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MXenes, a new class of two-dimensional (2D) nanomaterials, have shown enormous potential for biological applications. Notably, the development of 2D MXenes in nanomedicine is still in its infancy. Herein, a distinct W1.33 C i-MXene with multiple theranostic functionalities, fast biodegradation, and satisfactory biocompatibility is explored. By designing a parent bulk laminate in-plane ordered (W2/3 Y1/3 )2 AlC ceramic and optionally etching aluminum (Al) and yttrium (Y) elements, 2D W1.33 C i-MXene nanosheets with ordered divacancies are efficiently fabricated. Especially, theoretical simulations reveal that W1.33 C i-MXene possesses a strong predominance of near-infrared (NIR) absorbance. The constructed ultrathin W1.33 C nanosheets feature excellent photothermal-conversion effectiveness (32.5% at NIR I and 49.3% at NIR II) with desirable biocompatibility and fast degradation in normal tissue rather than in tumor tissue. Importantly, the multimodal-imaging properties and photothermal-ablation performance of W1.33 C-BSA nanosheets are systematically revealed and demonstrated both in vitro and in vivo. The underlying mechanism and regulation factors for the W1.33 C-BSA nanosheets-induced hyperthermia ablation are also revealed by transcriptome and proteome sequencing. This work offers a paradigm that i-MXenes achieve the tailoring biomedical applications through composition and structure design on the atomic scale.

Objective To investigate the feasibility and safety of wire-guided pericardial access without contrast. Methods From January 2014 to February 2019, patients who received epicardial mapping and ablation of ventricular tachycardia in the Beijing Anzhen Hospital were entered into the current study. They were divided into contrast-guided access group or wire-guided access group according to the pericardial puncture technique used. The baseline variables, procedure parameters, complications were collected and compared. Results During the study period, a consecutive of 73 patients received epicardial access. The initial 32 patients received contrast-guided puncture with success achieved in 30 patients, the remaining 41 patients underwent wire-guided puncture with success achieved in 40 patients (30/32 and 40/41, P = .581). Fluoroscopy time (4.45 ± 0.52 and 4.38 ± 0.46 minutes, P = .891) and access time (5.14 ± 0.58 and 5.34 ± 0.50 minutes, P = .657) were comparable between the two groups. Inadvertent right ventricular puncture occurred more commonly in the contrast-guided group (5/32 and 1/41, P = .038). Though more pericardial effusions (2/32 and 1/41, P = .575), tamponade (2/32 and 1/41, P = .575), and surgical repair (1/32 and 0/41, P = .432) occurred in the contrast-guided group, they reached no statistical difference. Conclusion Wire-guided pericardial puncture exhibits better safety and similar success rates to contrast-guided technique with a trend towards less complications.

Angiogenesis is crucial for tumor growth and inhibition of angiogenesis has been regarded as a promising approach for cancer therapy. Vascular endothelial growth factor receptor-2 (VEGFR-2) is an important factor in angiogenesis. In this work, a novel series of thiazolo[5,4-d]pyrimidine derivatives inhibiting angiogenesis were rationally designed and synthesized. Their inhibitory activities against human umbilical vein endothelial cells (HUVEC) were investigated in vitro. 1-(4-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19b) and 1-(3-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19g) exhibited the most potent inhibitory effect on HUVEC proliferation (IC50 =12.8 and 5.3 μm, respectively). Compound 19g could inhibit the migration of human umbilical vein endothelial cells. These results support the further investigation of these compounds as potent anticancer agents.

A series of oxazolopyrimidine-based ureas and amides were designed, synthesized, and biologically evaluated for their antiproliferative and antiangiogenic activities. These compounds were identified to exhibit inhibitory activities against human umbilical vein endothelial cells (HUVEC) in vitro. Among these compounds, compound 22 effectively inhibited the migration and capillary-like tube formation of human umbilical vein endothelial cells. It also exhibited a concentration-dependent inhibition on capillary sprouting from the rat aorta rings. Preliminary mechanistic studies revealed that compound 22 suppressed protein kinases activation, by decreasing PI3K and ERK 1/2 phosphorylation. These results support the further investigation of this class of compounds as potential anticancer agents.

A new approach for the total synthesis of ammosamide B was realized. The strategy is based on an intermolecular Pd-catalyzed N-arylation of 4-chloro-1-methylindoline-2,3-dione (2), which enables construction of the key pyrroloquinoline skeleton precursor 6 within three steps in an overall yield of 80 %. The ammosamide B total synthesis is achieved in 12 simple transformations by starting from a commercially available starting material and proceeds with an overall yield of 23 %. Additionally, key precursor 6 represents an important intermediate in the synthesis of other pyrroloquinoline-containing natural products.

A new approach for the total synthesis of ammosamide B was realized. The strategy is based on an intermolecular Pd-catalyzed N-arylation of 4-chloro-1-methylindoline-2,3-dione (2), which enables construction of the key pyrroloquinoline skeleton precursor 6 within three steps in an overall yield of 80 %. The ammosamide B total synthesis is achieved in 12 simple transformations by starting from a commercially available starting material and proceeds with an overall yield of 23 %. Additionally, key precursor 6 represents an important intermediate in the synthesis of other pyrroloquinoline-containing natural products.

A convenient method for the regioselective synthesis of unsaturated nucleoside analogs in water under microwave irradiation was developed. All pyrimidine and purine nucleoside derivatives were exclusively alkylated at N1 and N9 respectively in good to excellent yields. In addition, this system could tolerate a broad range of functional groups, such as chloro, bromo, iodo, alkyl, amino, and hydroxyl groups. More importantly, the reaction scale could be enlarged to 50 mmol which made this route attractive for industrial application.

A novel ligand-based pharmacophore model for KDR kinase was generated on the basis of chemical features of 30 KDR kinase inhibitors. This pharmacophore model consists of one hydrogen-bond acceptor, one hydrogen-bond donor and two hydrophobic groups. Several methods have been used to validate the model, suggesting that it can serve as a reliable tool for virtual screening to facilitate the discovery of novel KDR inhibitors. The model was then used as database search query from the National Cancer Institute (NCI) database for the rational design to identify new hit compound.

1. In the present study, the temporal and concentration-dependent cardioprotective effects of rapamycin against ischaemia-reperfusion (I/R) injury, as well as the underlying mechanisms, were investigated. 2. Rat Langendorff-perfused isolated hearts were exposed to 40 min global ischaemia followed by 120 min reperfusion. Hearts were perfused with different concentrations of rapamycin before and after ischaemia. Myocardial injury was assessed in terms of infarct size and the release of lactate dehydrogenase (LDH) and creatine kinase (CK). The phosphorylation of Akt, extracellular signal-regulated kinase (ERK) 1/2 and endothelial nitric oxide synthase (eNOS) was determined at the end of reperfusion. 3. When administered prior to ischaemia, 25, 50 and 100 nmol/L rapamycin significantly reduced infarct size compared with control (40.1 ± 1.5, 26.3 ± 4.1 and 21.2 ± 3.4 vs 52.5 ± 4.5%, respectively) without affecting the recovery of ventricular function. No reduction in infarct size was observed when 50 nmol/L rapamycin was administered 10 or 120 min into the reperfusion period. 4. Rapamycin (50 nmol/L) enhanced the phosphorylation of Akt kinase but did not affect the phosphorylation of ERK1/2 or eNOS at the end of reperfusion. The cardioprotective effect of rapamycin was blocked by the phosphatidylinositol 3-kinase (Akt) inhibitor LY294002 (15 nmol/L). 5. In conclusion, rapamycin mediates cardioprotection prior to ischaemia and after reperfusion. This protection may involve activation of the phosphatidylinositol 3-kinase pathway.

The goal of this study was to determine the mechanisms of n-3 polyunsaturated fatty acids (n-3 PUFA) on anti-arrhythmias and prevention of sudden death. The calcium-tolerant Sprague-Dawley rat ventricular myocytes were isolated by enzyme digestion. Effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on action potentials and transient outward potassium currents (I (to)) of epicardial ventricular myocytes were investigated using whole-cell patch clamp techniques. Action potential durations (APDs) and I (to) were observed in different concentrations of DHA and EPA. APD(25), APD(50), and APD(90) with 0.1 μmol/L DHA and EPA were prolonged less than 15% and 10%. However, APDs were prolonged in concentration-dependent manners when DHA and EPA were more than 1 μmol/L. APD(25), APD(50), and APD(90) were 7.7 ± 2.0, 21.2 ± 3.5, and 100.1 ± 9.8 ms respectively with 10 μmol/L DHA, and 7.2 ± 2.5, 12.8 ± 4.2, and 70.5 ± 10.7 ms respectively with 10 μmol/L EPA. I (to) currents were gradually reduced with the increased concentrations of DHA and EPA from 1 to 100 μmol/L, and their half-inhibited concentrations were 2.3 ± 0.2 and 3.8 ± 0.6 μmol/L. The results showed APDs were prolonged and I (to) current densities were gradually reduced with the increased concentrations of DHA and EPA. The anti-arrhythmia mechanisms of n-3 PUFA are complex, however, the effects of n-3 PUFA on action potentials and I (to) may be one of the important mechanisms.

Three MnII coordination supramolecular complexes [Mn(pdc)(H2O)]n1, {[Mn(pdc) (phen)(H2O)]·3H2O}n2, and {[Mn(cyan)2(H2O)4]·2HCl·2(Hcyan)} 3 (H2pdc = pyridine-2,3-dicarboxylic acid, Hcyan = cyanuric acid, phen = 1,10-phenanthroline) were hydrothermally synthesized and their structures determined by single-crystal X-ray diffraction. The pdc group in complex 1 bridges the MnII ions to form an infinite 3D structure. In complex 2, the MnII ion is bridged to a 1D infinite chain by pdc groups and the chain is further connected to a 2D structure by hydrogen bonds. The 3D structure of complex 3 is formed by hydrogen bonds and O···Cl weak interactions. Surface photovoltage spectroscopy (SPS) of complexes 1–3 indicate that they all possess positive SPV response in the range of 300–800 nm and show p-type semiconductor characteristic. The intensities of the SPV responses are obviously different, and this can mainly be attributed to the differences in their structures. Field-induced surface photovoltage spectroscopy (FISPS) of complexes 1–3 confirms their p-type semiconductor characteristic.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Three cadmium(II) coordination polymers [Cd(NA)2(H2O)2]n (1), {[Cd(NA)(phen)(NO3)]·(H2O)1/2}n (2), {[Cd(NA)(CH3C6H4COO)(H2O)2]·(CH3C6H4COOH)}n (3) (HNA = nicotinic acid, phen = 1, 10-phenanthroline) have been synthesized by hydrothermal method. Their single-crystal structures were determined by X-ray diffractometry. The absorption, excitation and emission spectra were investigated and all the complexes emit strong fluorescence: λemmax = 544 nm (λex = 492 nm), 1; λemmax = 466 nm (λex = 393 nm), 2; λemmax = 430 nm (λex = 313 nm), 3. At room temperature in the solid state the fluorescence lifetimes of the complexes were investigated and the relationships between the spectra were discussed as well as the connections of luminescence and crystal structures.

A practical and efficient synthesis of 2-substituted 7-azaindoles has been developed using a cross-coupling-heteroannulation approach.

Three novel NiII coordination polymers [Ni2(HCOO)4(H2O)4]n (1), [Na2Ni(btec)(H2O)8]n (2; H4btec = 1,2,4,5-benzenetetracarboxylic acid) and [{Ni(pdc)(H2O)2}·H2O]n (3; H2pdc = pyridine-2,5-dicarboxylic acid) have been hydrothermally synthesized and their structures determined by single-crystal X-ray diffraction. The formate groups in complex 1 bridge the NiII ions to form a infinite 3D structure. Complex 2 also possesses a infinite 3D structure and the coordination environment of the NiII ion is a perfect octahedron. Complex 3 is a 2D infinite coordination polymer. The surface photovoltage spectra of complexes 1–3 indicate that they all show three positive surface photovoltage (SPV) responses in the range of 300–800 nm and all show p-type semiconductor characteristics. Although the intensities of the SPV responses are obviously different, this can mainly be attributed to the difference of their structures. The field-induced surface photovoltage spectra (FISPS) of complexes 1–3 confirm their p-type semiconductor characteristics. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

A Rh-catalyzed oxidative cross-coupling of 2-amino-substituted 1,4-naphthoquinones with activated olefins is developed.

The title tandem reaction proceeds through substrate tautomerization, C—H activation, oxidative addition, cyclization, and aromatization.

A novel Pd(II)-catalyzed dehydrogenative cross-coupling reaction of thiazolo[5,4- d ]pyrimidine with unactivated (hetero)arenes via C–H bond activation was achieved. This protocol provides a straightforward and operationally simple method for the synthesis of 2-arylsubstituted thiazolo[5,4- d ]pyrimidines of interest in pharmaceutical sciences.

Background Statins reduce the incidence of cardiovascular events after percutaneous coronary intervention (PCI), but no clinical studies have investigated the role of statins in ischemia-reperfusion injury after PCI. Hypothesis Rosuvastatin could reduce ischemia-reperfusion injury in patients with acute coronary syndrome treated with PCI. Objectives We investigated the effects of rosuvastatin on ischemia-reperfusion injury in patients with acute coronary syndrome after PCI and evaluated short-term prognosis. Methods Patients scheduled for emergent PCI were given either rosuvastatin for ≥6 months (10 mg/d, every night; n = 55) or no statins (control group; n = 65). Serum superoxide dismutase activity, malondialdehyde, brain natriuretic peptide (BNP), and high-sensitivity C-reactive protein (hs-CRP) were determined before and after PCI, as well as left ventricular ejection fraction and left ventricular end-diastolic volume. Major adverse cardiac events were observed at follow-ups for 6 months. Results Superoxide dismutase activity in the rosuvastatin-treated group was higher than that of the control group; serum levels of malondialdehyde were lower. BNP and hs-CRP levels in the rosuvastatin-treated group were lower than that of the control group. Four weeks after PCI, the left ventricular ejection fraction in the treatment group was higher than that of the control group, and the left ventricular end-diastolic volume was lower. At the 6-month follow-up, there was no difference in major adverse cardiac events between the 2 groups. Conclusions Rosuvastatin before PCI reduced ischemia-reperfusion injury in patients with acute coronary syndrome, which suggests the importance of application of rosuvastatin before PCI for early intervention.

Key step is an intramolecular C—O cross-coupling of ortho chloropyrimidine amide via a copper(I)-mediated cyclization.

Dichloro carbamate (I) undergoes a CuCl/amino acid catalyzed reaction with primary amines to give 6-chloropurin derivatives (III).

A novel and general synthesis of indoles has been established by utilizing 2-aminophenols as the starting materials. The key step is a modified Pd(0)–Cu(I)-catalyzed cross-coupling of 1-alkynes with 2-carboxamidoaryl triflates in the presence of n-Bu4NI as the additive. The 2-alkynylanilides obtained were subjected to an alkoxide-mediated cyclization to provide a number of indole containing compounds possessing substituents at the C2, C4, C5, and/or C6 position(s) in good overall yields.

A novel and efficient strategy for the synthesis of 2‐substituted 4‐azaindoles from 2‐chloro‐3‐nitropyridine through Pd‐catalyzed Sonogashira cross‐coupling, followed by reduction and heteroannulation on t‐BuOK, is reported.