Constructing Flexible Crystalline Porous Organic Salts via a Zwitterionic Strategy.

The unique ionic channels and highly polar pore structures have distinguished crystalline porous organic salts (CPOSs) from conventional porous frameworks in the past decade. Up to now, CPOSs were all constructed by a monoionic strategy, in which two types of building units individually bearing anionic or cationic groups were introduced, thus increasing complexity in the synthesis of CPOSs. In this study, by utilizing stereoisomeric compounds of TPE-NS-Z or TPE-NS-E bearing both anionic and cationic groups as a single building unit, the zwitterionic strategy was proven feasible in constructing CPOSs.

Visualizing Triplet Energy Transfer in Organic Near-Infrared Phosphorescent Host-Guest Materials.

Limited by the energy gap law, purely organic materials with efficient near-infrared room temperature phosphorescence are rare and difficult to achieve. Additionally, the exciton transition process among different emitting species in host-guest phosphorescent materials remains elusive, presenting a significant academic challenge. Herein, using a modular nonbonding orbital-π bridge-nonbonding orbital (n-π-n) molecular design strategy, we develop a series of heavy atom-free phosphors.

Conformational cycle of human polyamine transporter ATP13A2.

Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson's disease and autosomal recessive spastic paraplegia 78, is a transporter with a critical role in balancing the polyamine concentration between the lysosome and the cytosol. Here, to better understand human ATP13A2-mediated polyamine transport, we use single-particle cryo-electron microscopy to solve high-resolution structures of human ATP13A2 in six intermediate states, including the putative E2 structure for the P5 subfamily of the P-type ATPases.

Engineering Platelets with PDL1 Antibodies and Iron Oxide Nanoparticles for Postsurgical Cancer Immunotherapy.

Recently, immune checkpoint blockade (ICB) therapy has achieved great success in inhibition of the recurrence and metastasis of tumor. However, this therapy is challenged by the poor delivery efficiency of ICB agents and the insufficient activation of antitumor immunity by ICB only. Here, we describe a strategy using platelets as carriers for co-delivery of ICB agents (anti-PDL1 antibodies, aPDL1) and photothermal agents (iron oxide nanoparticles, IONPs) to the postsurgical tumor site, which simultaneously provides photothermal therapy for ablation of residual tumor cells and ICB therapy for blocking the immunoinhibitory signals in the tumor microenvironment.

A new PLA-Tween composited drug-carrying C60-FeO multifunctional ultrasound contrast agent based on three kinds of lesions.

A PLA-Tween composited drug-carrying C60-FeO microbubble was designed and prepared. Using FeO as a targeting factor and C60 as a drug carrier, warfarin (WF), netimixin (NET) and doxorubicin (DOX) respectively were loaded on a C60-FeO complex through π-π conjugate effect, and C60-FeO-WF, C60-FeO-NET and C60-FeO-DOX targeted drug-loading complexes were obtained. The three drug-loading complexes were respectively combined into PLA and Tween membrane material, PLA-Tween composited C60-FeO-DOX microbubbles, PLA-Tween composited C60-FeO-NET microbubbles and PLA-Tween composited C60-FeO-WF microbubbles were obtained, respectively.

Ag-Catalyzed Asymmetric Interrupted Barton-Zard Reaction Enabling the Enantioselective Dearomatization of 2- and 3-Nitroindoles.

We disclose a Ag-catalyzed asymmetric interrupted Barton-Zard reaction of α-aryl-substituted isocyanoacetates with 2- and 3-nitroindoles, which enables the dearomatization of nitroindoles and hence offers rapid access to an array of optically active tetrahydropyrrolo[3,4-]indole derivatives bearing three contiguous stereogenic centers, including two tetrasubstituted chiral carbon atoms with pretty outcomes (up to 99% yield, 91:9 dr, and 96% ee). The synthetic potential of the protocol was showcased by the gram-scale reaction and versatile transformations of the product.

Layer-by-Layer Assembly of Lipid Nanobubbles on Microneedles for Ultrasound-Assisted Transdermal Drug Delivery.

Microneedles as a typical device for transdermal drug delivery provide an alternative route for drug administration with minimal digestion by organs and better patient compliance. However, diffusion of passively released drug molecules within the skin tissue mainly depends on the interstitial fluid, which may be affected by different physiological conditions of individuals. Herein, we propose a nanobubble-modified microneedle patch for ultrasound-assisted drug delivery, which provides additional driving force for penetration and diffusion of the drug molecules.

Fasting augments pyrrolizidine alkaloid-induced hepatotoxicity.

Pyrrolizidine alkaloids (PAs) are phytotoxins widely present in various natural products and foodstuffs. The present study aims to investigate the effects of fasting on PA-induced hepatotoxicity and the underlying biochemical mechanisms. The results of hepatotoxic study showed that 15-h overnight fasting significantly exacerbated the hepatotoxicity of retrorsine (RTS, a representative toxic PA) in fasted rats compared to fed rats, as indicated by remarkably elevated plasma ALT and bilirubin levels and obvious liver histological changes.

Multiple-relaxation-time finite-difference lattice Boltzmann model for the nonlinear convection-diffusion equation.

In this paper, a multiple-relaxation-time finite-difference lattice Boltzmann method (MRT-FDLBM) is developed for the nonlinear convection-diffusion equation (NCDE). Through designing the equilibrium distribution function and the source term properly, the NCDE can be recovered exactly from MRT-FDLBM. We also conduct the von Neumann stability analysis on the present MRT-FDLBM and its special case, i.

Chiral Indoline-2-carboxylic Acid Enables Highly Enantioselective Catellani-type Annulation with 4-(Bromomethyl)cyclohexanone.

Chiral indoline-2-carboxylic acid has been identified to enable a highly enantioselective Catellani-type annulation of (hetero)aryl, alkenyl triflate and conjugated vinyl iodides with 4-(bromomethyl)cyclohexanone, directly assembling a diverse range of chiral all-carbon bridged ring systems. Control experiments and DFT calculations suggest that the coordinating orientation of the chiral amino acid to the arylpalladium(II) center allows for high levels of stereochemical control.

Characterization of liver injury induced by a pyrrolizidine alkaloid in rats.

Background: Pyrrolizidine alkaloids (PAs) are common phytotoxins. PA intoxication is reported to cause severe acute liver damage, typically known as hepatic sinusoidal obstruction syndrome (HSOS), but it remains obscure whether the acute liver damage may progress into chronic liver disease characterized by hepatic fibrosis.

Purpose: This study aims to characterize the biochemical markers of liver injury and histological features of regressive and progressive liver fibrosis, and to examine changes in hepatic gene expression that may underpin mechanisms of fibrogenesis in rats induced by retrorsine (RTS), a representative toxic PA.

A Maitake () polysaccharide ameliorates Alzheimer's disease-like pathology and cognitive impairments by enhancing microglial amyloid-β clearance.

Alzheimer's disease (AD) is characterized by the deposition of amyloid-β (Aβ) plaques, neuronal loss and neurofibrillary tangles. In addition, neuroinflammatory processes are thought to contribute to AD pathophysiology. Maitake (), an edible/medicinal mushroom, exhibits high nutritional value and contains a great amount of health-beneficial, bioactive compounds.

Organocatalytic Asymmetric Dearomatization of 3-Nitroindoles and 3-Nitrobenzothiophenes via Thiol-Triggered Diastereo- and Enantioselective Double Michael Addition Reaction.

Organocatalytic asymmetric dearomatization of 3-nitroindoles and 3-nitrobenzothiophenes by reaction with ethyl 4-mercapto-2-butenoate has been developed. A range of chiral tetrahydrothiopheneindolines and tetrahydrothiophenebenzothiophenes bearing three contiguous stereocenters are obtained in high yields with good diastereoselectivities and excellent enantioselectivities. This is the first example of thiol-triggered catalytic asymmetric dearomatization of 3-nitroindoles and 3-nitrobenzothiophenes.

Pyrrole-Hemoglobin Adducts, a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure.

Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants. The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity. The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.

Organocatalyzed Asymmetric Dearomative Aza-Michael/Michael Addition Cascade of 2-Nitrobenzofurans and 2-Nitrobenzothiophenes with 2-Aminochalcones.

An organocatalyzed dearomative aza-Michael/Michael addition cascade of 2-nitrobenzofurans and 2-nitrobenzothiophenes with 2-aminochalcones has been developed, opening a new channel to access a series of optically active tetrahydrobenzofuro[3,2- b]quinolines and tetrahydrobenzo[4,5]thieno[3,2- b]quinolines bearing three contiguous stereocenters with excellent diastereo- and enantioselectivities (all cases >20:1 dr, up to 99% ee). This study features the first asymmetric dearomative cascade reaction of 2-nitrobenzofurans and 2-nitrobenzothiophenes beginning with aza-Michael addition. The potential applications of the methodology were demonstrated by the preparative-scale experiment and the versatile transformations of the products.

Competitive McLafferty-type rearrangements of sodium adduct of 2,3-dihydroxy-1-phenylpentane-1,4-dione compounds in tandem mass spectrometry.

Sodium adducts of -2,3-dihydroxy-1-phenylpentane-1,4-dione compounds with different substituents were studied by collision-induced dissociation. McLafferty-type rearrangements preceding fragmentation were found as their main fragmentation pathway. Coordination of sodium cation to the oxygen functions may either lead to formation of a five-membered or a six-membered ring.

Simultaneous quantification of imatinib and its main metabolite N-demethyl-imatinib in human plasma by liquid chromatography-tandem mass spectrometry and its application to therapeutic drug monitoring in patients with gastrointestinal stromal tumor.

The aim of this study was to improve and validate a more stable and less time-consuming method based on liquid chromatography and tandem mass spectrometry (LC- MS/MS) for the quantitative measurement of imatinib and its metabolite N-demethyl-imatinib (NDI) in human plasma. Separation of analytes was performed on a Waters XTerra RP column (50 × 2.1 mm i.

pDHS-SVM: A prediction method for plant DNase I hypersensitive sites based on support vector machine.

DNase I hypersensitive sites (DHSs) are accessible chromatin regions hypersensitive to cleavages by DNase I endonucleases. DHSs are indicative of cis-regulatory DNA elements (CREs), all of which play important roles in global gene expression regulation. It is helpful for discovering CREs by recognition of DHSs in genome.

Effect of Ginkgo Biloba Extract on the Pharmacokinetics and Metabolism of Clopidogrel in Rats.

Ginkgo biloba extract (GBE), a traditional herbal product used worldwide as both medicine and supplement, is often supplied with clopidogrel for the treatment of cerebrovascular diseases. The aim of the current study was to explore the effect of GBE on the metabolism and pharmacokinetics of clopidogrel. The in vitro study using rat liver microsomes revealed that GBE significantly induced the conversion of clopidogrel into its active metabolite.

Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy.

Aim: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A receptor (TXA receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A (Lp-PLA, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy.

Mechanistic understanding of the effect of Dengzhan Shengmai capsule on the pharmacokinetics of clopidogrel in rats.

Ethnopharmacological Relevance: The Dengzhan Shengmai capsule (DZSM) is known in China for its remarkable curative effect as a treatment of cardiovascular diseases, such as coronary heart disease and ischemic stroke. DZSM is a Chinese herbal compound preparation that consists of four ingredients, including Erigeron breviscapus (Vaniot) Hand.-Mazz.

Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke.

Aim: There is a high incidence of the antiplatelet drug clopidogrel resistance (CR) in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NR1I2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke.

3',4',5',5,7-pentamethoxyflavone sensitizes Cisplatin-resistant A549 cells to Cisplatin by inhibition of Nrf2 pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important redox-sensitive transcription factor that regulates the expression of several cytoprotective genes. More recently, genetic analyses of human tumors have indicated that Nrf2 may cause resistance to chemotherapy. In this study, we found that the expression levels of Nrf2 and its target genes GCLC, HO-1, NQO1 were significantly higher in cisplatin-resistant A549 (A549/CDDP) cells than those in A549 cells, and this resistance was partially reversed by Nrf2 siRNA.