Visualizing Immune Checkpoint Inhibitors Derived Inflammation in Atherosclerosis.

Background: Immune checkpoint inhibitor (ICI) usage has resulted in immune-related adverse events in patients with cancer, such as accelerated atherosclerosis. Of immune cells involved in atherosclerosis, the role of CCR2+ (CC motif chemokine receptor 2-positive) proinflammatory macrophages is well documented. However, there is no noninvasive approach to determine the changes of these cells in vivo following ICI treatment and explore the underlying mechanisms of immune-related adverse events.

Leveraging Pt/CeLaO To Elucidate Interfacial Oxygen Vacancy Active Sites for Aerobic Oxidation of 5-Hydroxymethylfurfural.

The interfacial oxygen-defective sites of oxide-supported metal catalysts are generally regarded as active centers in diverse redox reactions. Identification of their structure-property relationship at the atomic scale is of great importance but challenging. Herein, a series of La-doped three-dimensionally ordered macroporous CeO (3D-CeLaO) were synthesized and applied as supports for Pt nanoparticles.

The Latest Advances in Imaging Crosstalk Between the Immune System and Fibrosis in Cardiovascular Disease.

Inflammation and fibrosis are hallmarks of tissue repair processes and organ failure progression in cardiovascular diseases. Paradigm-shifting research on diverse immune cell populations within the cardiovascular system have enabled discovery of new biomarkers fostering development of diagnostic and therapeutic agents at the molecular level to better manage cardiovascular diseases. To date, a variety of molecular imaging agents have been developed to visualize the biomarkers expressed on immune cells and fibroblasts within their crosstalk network, which drives the pathogenesis of fibrosis triggered by both innate and adaptive immunity.

Advances in Chiral Metal-Organic and Covalent Organic Frameworks for Asymmetric Catalysis.

Asymmetric catalysis is of crucial importance owing to the huge and rising demand for optically pure substances. Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), as two emerging crystalline porous materials, have presented great promising applications for heterogeneous asymmetric catalysis. The unique properties, such as, highly regular porous structures, prominent structural tunability, and well-ordered catalytic sites, render chiral MOFs (CMOFs) and chiral COFs (CCOFs) highly active and enantioselective for a large number of asymmetric catalytic organic transformations.

CC Chemokine Receptor 2-Targeting Copper Nanoparticles for Positron Emission Tomography-Guided Delivery of Gemcitabine for Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with dire prognosis due to aggressive biology, lack of effective tools for diagnosis at an early stage, and limited treatment options. Detection of PDAC using conventional radiographic imaging is limited by the dense, hypovascular stromal component and relatively scarce neoplastic cells within the tumor microenvironment (TME). The CC motif chemokine 2 (CCL2) and its cognate receptor CCR2 (CCL2/CCR2) axis are critical in fostering and maintaining this kind of TME by recruiting immunosuppressive myeloid cells such as the tumor-associated macrophages, thereby presenting an opportunity to exploit this axis for both diagnostic and therapeutic purposes.

Asymmetric Oxygen Vacancies: the Intrinsic Redox Active Sites in Metal Oxide Catalysts.

To identify the intrinsic active sites in oxides or oxide supported catalysts is a research frontier in the fields of heterogeneous catalysis and material science. In particular, the role of oxygen vacancies on the redox properties of oxide catalysts is still not fully understood. Herein, some relevant research dealing with M-O-M or M-□-M linkages as active sites in mixed oxides, in oxide supported single-atom catalysts, and at metal/oxide interfaces of oxide supported nanometal catalysts for various reaction systems is reviewed.

Band-Gap and Charge Transfer Engineering in Red Phosphorus-Based Composites for Enhanced Visible-Light-Driven H Evolution.

It is known that the low lifetime of photogenerated carriers is the main drawback of elemental photocatalysts. Therefore, a facile and versatile one-step strategy to simultaneously achieve the oxygen covalent functionalization of amorphous red phosphorus (RP) and in situ modification of CdCO is reported. This strategy endows RP with enhanced charge carrier separation ability and photocatalytic activity by coupling band-gap engineering and heterojunction construction.

Germacrane Sesquiterpenoids as a New Type of Anticardiac Fibrosis Agent Targeting Transforming Growth Factor β Type I Receptor.

A germacrane sesquiterpenoid library containing 30 compounds (-) was constructed by structural modification of a major component aristolactone () from the traditional Chinese medicine . Compound was identified as a promising anticardiac fibrosis agent by systematic screening of this library. could inhibit the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagens in transforming growth factor β 1 (TGFβ1)-stimulated cardiac fibroblasts at a micromolar level and ameliorate myocardial fibrosis and heart function in abdominal aortic constriction (AAC) rats at 5 mg/kg dose.

(+)-Isobicyclogermacrenal and spathulenol from Aristolochia yunnanensis alleviate cardiac fibrosis by inhibiting transforming growth factor β/small mother against decapentaplegic signaling pathway.

Cardiac fibrosis contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. Antifibrotic therapies are likely to be a crucial strategy in curbing many fibrosis-related cardiac diseases. In our previous study, an ethyl acetate extract of a traditional Chinese medicine Aristolochia yunnanensis Franch.

Evodialones A and B: Polyprenylated Acylcyclopentanone Racemates with a 3-Ethyl-1,1-diisopentyl-4-methylcyclopentane Skeleton from Evodia lepta.

Two polyprenylated acylcyclopentanone racemates, evodialones A (1) and B (2), featuring a 3-ethyl-1,1-diisopentyl-4-methylcyclopentane skeleton, were isolated from an extract of the aerial parts of Evodia lepta. Evodialone A (1) was resolved by chiral-phase HPLC to afford a pair of enantiomers, (+)- and (-)-evodialones A (1b/1a), while evodialone B (2) could not be resolved. Their structures were elucidated by spectroscopic analysis and a combination of computational techniques including gauge-independent atomic orbital calculation of 1D NMR data and experimental and TDDFT-calculated ECD spectra.

Prenylated flavonoids as potent phosphodiesterase-4 inhibitors from Morus alba: Isolation, modification, and structure-activity relationship study.

The bioassay-guided phytochemical study of a traditional Chinese medicine Morus alba led to the isolation of 18 prenylated flavonoids (1-18), of which (±)-cyclomorusin (1/2), a pair of enantiomers, and 14-methoxy-dihydromorusin (3) are the new ones. Subsequent structural modification of the selected components by methylation, esterification, hydrogenation, and oxidative cyclization led to 14 more derivatives (19-32). The small library was screened for its inhibition against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease (COPD).

Design, Synthesis, and Biological Evaluation of Novel Selenium-Containing Isocombretastatins and Phenstatins as Antitumor Agents.

Two series of structurally related organoselenium compounds designed by fusing the anticancer agent methyl(phenyl)selane into the tubulin polymerization inhibitors isocombretastatins or phenstatins were synthesized and evaluated for antiproliferative activity. Most of these selenium containing hybrids exhibited potent cytotoxicity against a panel of cancel cell lines, with IC values in the submicromolar concentration range. Among them, 11a, the 3-methylseleno derivative of isocombretastatin A-4 (isoCA-4) represented the most active compound with IC values of 2-34 nM against 12 cancer cell lines, including two drug-resistant cell lines.

Identification of 4-arylidene curcumin analogues as novel proteasome inhibitors for potential anticancer agents targeting 19S regulatory particle associated deubiquitinase.

The proteasomal 19S regulatory particle (RP) associated deubiquitinases (DUBs) have attracted much attention owing to their potential as a therapeutic target for cancer therapy. Identification of new entities against 19S RP associated DUBs and illustration of the underlying mechanisms is crucial for discovery of novel proteasome blockers. In this study, a series of 4-arylidene curcumin analogues were identified as potent proteasome inhibitor by preferentially blocking deubiquitinase function of proteasomal 19S RP with moderate 20S CP inhibition.

Biscembranoids and Cembranoids from the Soft Coral Sarcophyton elegans.

Two novel biscembranoids, sarelengans A and B ( and ), five new cembranoids, sarelengans C-G (-), along with two known cembranoids ( and ) were isolated from the South China Sea soft coral . Their structures were determined by spectroscopic and chemical methods, and those of , , , and were confirmed by single crystal X-ray diffraction. Compounds and represent the first example of biscembranoids featuring a -fused A/B-ring conjunction between the two cembranoid units.

Synthesis of the novel PARP-1 inhibitor AG-690/11026014 and its protective effects on angiotensin II-induced mouse cardiac remodeling.

We previously identified AG-690/11026014 (6014) as a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor that effectively prevented angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. In the present study, we reported a new synthesis route for 6014, and investigated its protective effects on Ang II-induced cardiac remodeling and cardiac dysfunction and the underlying mechanisms in mice. We designed a new synthesis route to obtain a sufficient quantity of 6014 for this in vivo study.

Versiquinazolines A-K, Fumiquinazoline-Type Alkaloids from the Gorgonian-Derived Fungus Aspergillus versicolor LZD-14-1.

Eleven fumiquinazoline-type alkaloids, namely, versiquinazolines A-K (1-11), along with cottoquinazolines B-D, were isolated from the gorgonian-derived fungus Aspergillus versicolor LZD-14-1. Their structures were determined by extensive analyses of the spectroscopic data (1D and 2D NMR, HRESIMS), in addition to the experimental and calculated ECD data and X-ray single-crystal diffraction analysis for the assignments of the absolute configurations. Versiquinazolines A, B, and F (1, 2, and 6), bearing a methanediamine or an aminomethanol unit and representing a unique subtype of fumiquinazolines, were found from nature for the first time.

New lanostane-type triterpenoids from the fruiting body of Ganoderma hainanense.

Five new lanostane-type triterpenoids, ganoderenses A-E (1-5), two new lanostane nor-triterpenoids, ganoderenses F and G (6 and 7), along with 13 known analogues (8-20) were isolated from the fruiting body of Ganoderma hainanense. Their structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds 1 and 13 were confirmed by single crystal X-ray diffraction. All compounds were evaluated for inhibitory activity against thioredoxin reductase (TrxR), a potential target for cancer chemotherapy with redox balance and antioxidant functions, but were inactive.

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents.

The phytochemical study of Pedilanthus tithymaloides led to the isolation of 13 jatrophane diterpenoids (1-13), of which eight (1-8) are new. Subsequent structural modification of the major components by esterification, hydrolysis, hydrogenation, or epoxidation yielded 22 new derivatives (14-35). Thus, a jatrophane library containing two series of compounds was established to screen for P-glycoprotein (Pgp)-dependent MDR modulators.

Degradation of polycyclic aromatic hydrocarbons in crumb tyre rubber catalysed by rutile TiO2 under UV irradiation.

The polycyclic aromatic hydrocarbons (PAHs) in crumb tyre rubber were firstly degraded under UV irradiation in the presence of rutile TiO2 and hydrogen peroxide. The effects of light intensity, catalyst amount, oxidant amount, initial pH value, co-solvent content, and reaction time on degradation efficiency of typical PAHs in crumb tyre rubber were studied. The results indicated that UV irradiation, rutile TiO2, and hydrogen peroxide were beneficial to the degradation of PAHs and co-solvent could accelerate the desorption of PAHs from crumb tyre rubber.