Human neural stem cells promote mitochondrial genesis to alleviate neuronal damage in MPTP-induced cynomolgus monkey models.

Currently, there is no effective treatment for Parkinson's disease (PD), and the regenerative treatment of neural stem cells (NSCs) is considered the most promising method. This study aimed to investigate the protective effect and mechanism of NSCs on neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced cynomolgus monkey (Macaca fascicularis) model of PD. We first found that injecting NSCs into the subarachnoid space relieved motor dysfunction in PD cynomolgus monkeys, as well as reduced dopaminergic neuron loss and neuronal damage in the substantia nigra (SN) and striatum. Besides, NSCs decreased 17-estradiol (E2) level, an estrogen, in the cerebrospinal fluid (CSF) of PD cynomolgus monkeys, which shows NSCs may provide neuro-protection by controlling estrogen levels in the CSF. Furthermore, NSCs elevated proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a), mitofusin 2 (MFN2), and optic atrophy 1 (OPA1) expression, three genes mediating mitochondrial biogenesis, in the SN and striatum of PD monkeys. In addition, NSCs suppress reactive oxygen species (ROS) production caused by MPTP, as well as mitochondrial autophagy, therefore preserving dopaminergic neurons. In summary, our findings show that NSCs may preserve dopaminergic and neuronal cells in an MPTP-induced PD cynomolgus monkey model. These protective benefits might be attributed to NSCs' ability of modulating estrogen balance, increasing mitochondrial biogenesis, and limiting oxidative stress and mitochondrial autophagy. These findings add to our understanding of the mechanism of NSC treatment and shed light on further clinical treatment options.

Difluorocarbene-Triggered Acyl Rearrangement Reaction: A Strategy for the Direct Introduction of the gem-Difluoromethylene Group.

A novel metal- and catalyst-free dearomative reaction of 2-oxypyridines to construct gem-difluoromethylenated N-substituted 2-pyridones has been developed. The reaction involves an attractive acyl rearrangement from O to CF2 of difluorocarbene-derived pyridinium ylides, which provides a new strategy for the direct introduction of the gem-difluoromethylene group with high efficiency and selectivity as well as broad substrate scope. Gram-scale synthesis and synthetic transformations have also been demonstrated.

Merging the Non-Natural Catalytic Activity of Lipase and Electrosynthesis: Asymmetric Oxidative Cross-Coupling of Secondary Amines with Ketones.

We describe the enantioselective oxidative cross-coupling of secondary amines with ketones by combining the non-natural catalytic activity of lipase with electrosynthesis. Various 2,2-disubstituted 3-carbonyl indoles with a stereogenic quaternary carbon center were synthesized from 2-substituted indoles in yields up to 78 % with good enantio- and diastereoselectivities (up to 96 : 4 e.r. and >20 : 1 d.r.). This unprecedented protocol demonstrated that hydrolase catalysis is compatible with electrosynthesis, and the reaction can be carried out in organic solvents with a broad substrate scope and good stereoselectivity. This work provides insights into enzymatic electrosynthesis.

Knockdown of miR-384-3p Protects Against Myocardial Ischemia-Reperfusion Injury in Rats Through Targeting HSP70.

BACKGROUND: Myocardial infarction (MI) and heart failure remain critical states of heart disease with high mortality. Previous studies have indicated that miRNA has cardioprotective effects and can resist myocardial ischemia-reperfusion (I/R) injury. However, the role of mir-384-3p in MI has not been reported, and whether this miRNA can regulate the apoptosis of cardiomyocytes needs to be verified. METHODS: The effect of hypoxia-reperfusion (H/R) on cardiomyocyte activity was detected using MTT assay. MiR-384-3p was knocked down or overexpressed in cardiomyocytes H/R models by pretreatment with miR-384-3p mimic or inhibitor to verify the function of miR-384-3p in H/R. Circulating levels of miR-384-3p was detected by quantitative realtime PCR, and protein expression was detected by western blotting. TUNEL staining and flow cytometry demonstrated a high degree of myocardium apoptosis after H/R induction. Dual-Luciferase Reporter Assay detected dynamic expression of miR-384-3p and HSP70. The infarction size of I/R rats was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: MiR-384-3p was closely related to cardiomyocyte activity in H/R progression. Increased expression of mir-384-3p can promote the production of cleaved caspase-3 and cleaved PARP, thereby regulating cardiomyocyte apoptosis. HSP70 was a target of miR-384-3p and HSP70 silencing aggravated H/R-induced cardiomyocyte dysfunction. In an animal model, the expression level of HSP70 is regulated by miR-384-3p, and miR-384-3p inhibition remarkably reduced I/R-induced MI in rats. CONCLUSION: In conclusion, the present report identified that HSP70 was a potential target of miR-384-3p, and miR-384-3p inhibition remarkably reduced I/R-induced MI in rats. Therefore, this study provides a novel therapeutic approach for the treatment of MI from bench to clinic.

Palladium-Catalyzed C-H Bond Functionalization Reactions Using Phosphate/Sulfonate Hypervalent Iodine Reagents.

A new and operationally simple approach for palladium-catalyzed C-H functionalization reactions utilizing an organophosphorus/sulfonate hypervalent iodine reagent as both an oxidant and the source of a functional group has been developed. Through this method, the oxidative phosphorylation-, sulfonation-, and hydroxylation of unactivated benzyl C(sp3)-H bonds, along with the hydroxylation and arylation of aryl C(sp2)-H bonds, are successfully realized under mild conditions and with excellent site-selectivity. The versatile C-OSO2R bond provides a platform for a wide array of subsequent diversification reactions.

Defluorinative C(sp3 )-P Bond Construction for the Synthesis of Phosphorylation gem-Difluoroalkenes under Catalyst- and Oxidant-Free Conditions.

Defluorinative C(sp3 )-P bond formation of α-trifluoromethyl alkenes with phosphine oxides or phosphonates have been achieved under catalyst- and oxidant-free conditions, giving phosphorylation gem-difluoroalkenes as products. α-Trifluoromethyl alkenes bearing various of aryl substituents such as halogen, cyano, ester and heterocyclic groups are available in this transformation. The results of control experiments demonstrated that the mechanism of dehydrogenative/defluorinative cross-coupling reactions was not a radical route, but might be an SN 2' process involving phosphine oxide anion.

Unexpected reaction patterns enable simultaneous differentiation of H2S, H2Sn and biothiols.

A robust fluorescent probe, MCP1, was developed for triple-detection of H2S, H2Sn and biothiols for the first time. Introduction of H2S, H2Sn and biothiols to MCP1 lead to distinct emission peaks at 508, 576 and 469 nm, respectively, enabling simultaneous detection of H2S, H2Sn and biothiols from distinct emission channels.

I2-catalyzed intramolecular oxidative amination of C(sp3)-H bond: efficient access to 3-acylimidazo[1,2-a]pyridines under neat condition.

An efficient and "green" protocol for the synthesis of 3-acylimidazo[1,2-a]pyridines through intramolecular oxidative α-amination of carbonyl compounds has been developed. The reaction proceeds smoothly utilizing I2 as a catalyst and H2O2 as an oxidant under neat condition with broad substrate scope. Several complex nitrogen-containing fused rings are conveniently constructed, which are not easy to access by traditional methods.

A lysosome-targetable fluorescent probe for the simultaneous sensing of Cys/Hcy and GSH from different emission channels.

A lysosome-specific fluorescent probe, Lyso-AC, for biothiols was developed by incorporation of a 4-nitrophenol moiety into a coumarin dye. The Cys/Hcy-triggered substitution-rearrangement cascade, and GSH-induced substitution reaction lead to the corresponding blue emissive amino-coumarin and yellow emissive thiol-coumarin, thereby enabling Cys/Hcy and GSH detection from distinct emissions. Moreover, this probe displayed an excellent lysosome targeting property with a 0.92 Pearson's colocalization coefficient by using Neutral Red as a reference. Significantly, biological experiments indicated Lyso-AC has the potential to monitor lysosome Cys/Hcy and GSH simultaneously in living HeLa cells from distinct emissions.

Simultaneous Discrimination of Cysteine, Homocysteine, Glutathione, and H2S in Living Cells through a Multisignal Combination Strategy.

Biothiols are essential reactive sulfur species (RSS), which play crucial roles in various critical physiological activities. To clarify their complex correlations in signal transduction and metabolism pathways, methods to distinguish H2S, cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) at the same time are highly needed. Herein, we deliberately integrate 7-diethylcoumarin and resorufin through an ether bond to develop RC for simultaneous differentiation of Cys, Hcy, GSH, and H2S for the first time. RC displays distinct fluorescence colors in response to H2S, Cys, Hcy, and GSH as red, blue-red, blue-green-red, and green-red, respectively, both in aqueous media and living cells. This work not only reported a robust molecule, RC, to disentangle the intricate interplay networks among different biothiols in biosystems but also demonstrated a strategy for the design of multisignal fluorescent probes for the simultaneous sensing of diverse RSS species as well as other biological species.

Thoracic splenosis presenting as pulmonary space-occupying lesion.

BACKGROUND: Spleen leaves its normal anatomical position and appears in other locations, which is called ectopic spleen. It is most commonly found in the abdomen or pelvis with seeding of the peritoneum, omentum or mesentery. A few of cases of thoracic splenosis associated with traumatic diaphragmatic rupture have been reported. CASE PRESENTATION: We make a report on a case of intrapulmonary thoracic splenosis. A 44-year-old male patient underwent splenectomy due to a high fall accident injury in 2008. After ten years, thoracic splenosis were found in the lungs and chest wall. Clinical diagnosis was unidentified masses, benign tumor of lungs and chest wall. The radiological imaging was suggestive of the thoracic splenosis, After surgery, the diagnosis of thoracic splenosis was confirmed by pathological diagnosis. CONCLUSIONS: Thoracic splenosis may occur after the injury to spleen and surgical treatment may not be the preferred method for asymptomatic or less symptomatic thoracic splenosis.

A Lysosome-Targetable Fluorescent Probe for Simultaneously Sensing Cys/Hcy, GSH, and H2S from Different Signal Patterns.

Biothiols, a vital branch of reactive sulfur species (RSS) family, are indispensable in human physiology. However, the exact functional roles of each biothiol involved in complicated physiological activities are still not fully clarified. A critical barrier is a lack of robust molecular tools which can simultaneously visualize different biothiols with distinct emission signals. Herein, the first lysosome-targetable fluorescent probe, Lyso-RC, which could respond to Cys/Hcy, GSH, and H2S with different sets of signal patterns was developed. Lyso-RC responds to Cys/Hcy, GSH, and H2S with the fluorescence signal patterns of blue-red, green-red, and red, respectively. Significantly, Lyso-RC is capable of discriminating lysosomal Cys/Hcy, GSH, and H2S in HeLa cells.

Cytotoxic Triterpenoids from Roots of Actinidia chinensis.

Phytochmical investigation of roots of Actinidia chinensisPlanch. led to the isolation triterpenoids 1 - 16, including a new compound 2α,3α,23,24-tetrahydroxyursa-12,20(30)-dien-28-oic acid (1). Their structures were identified on the basis of spectroscopic analysis, including 1D- and 2D-NMR, HR-ESI mass spectrometry, and by comparison with the literatures. The cytotoxicities of triterpenoids 1 - 16 against a panel of cultured human cancer cell lines (HepG2, A549, MCF-7, SK-OV-3, and HeLa) were evaluated. The new compound 1 exhibited moderate antitumor activities with IC50 values of 19.62 ± 0.81, 18.86 ± 1.56, 45.94 ± 3.62, 62.41 ± 2.29, and 28.74 ± 1.07 µm, respectively. The experiment data might be available to explain the use of roots of A. chinensis to treat various cancers in traditional Chinese medicine.

Metal-free oxidative isocyanides insertion with aromatic aldehydes to aroylated N-heterocycles.

A metal-free, mild and efficient protocol for the construction of aroylated N-heterocycles via radical cascade aroylation of phenyl or vinyl isocyanides with aromatic aldehydes has been developed. Both phenanthridine and isoquinoline derivatives are delivered quickly in moderate to good yields with high regioselectivity.

[Chemical constituents from roots of Actinidia rufa and their cytotoxicity].

To investigate the chemical compounds from the roots of Actinidia rufa, nine compounds were isolated by various column chromatography on silica gel and Sephadex LH-20, and high performance liquid chromatography (HPLC). Their structures were elucidated as 2α, 3ß, 19α, 23, 24-pentahydroxyurs-12-en-28-oic acid-28-O-ß-D-glucopyranoside (1), 2α, 3α, 19α, 24-tetrahydroxyurs-12-en-28-oic acid-28-O-ß-D-glucopyranoside (2), 2α, 3α, 24-trihydroxyurs-12-en-28-oic acid (3), 2α, 3α, 24-trihydroxyolean-12-en-28-oic acid (4), 2α, 3α, 23, 24-tetrahydroxyurs -12-en-28-oic acid (5), 2α, 3ß, 23, 24-tetrah-ydroxyurs-12-en-28-oic acid (6), 2α, 3ß, 23-trihydroxy-12-en-28-oic acid (7), 2α, 3ß, 23-trihydroxyurs-12, 20(30)-dien-28-oic acid (8), and 2α, 3α, 23-trihydroxyurs-12, 20(30)-dien-28-oic acid (9). Compounds 1 and 2 were isolated from the Actinidia genus for the first time. Compounds 2, 3, and 4 showed cytotoxic activity against human SKVO3 and TPC-1 cancer cell lines with IC50 values ranging from 10.99 to 16.41 µmol•L⁻¹, compounds 3 and 4 have cytotoxic activity against human HeLa cancer cell line with IC50 values of 15.53 and 13.07 µmol•L⁻¹, respectively.

Simultaneous Detection of Glutathione and Hydrogen Polysulfides from Different Emission Channels.

Glutathione (GSH) and hydrogen polysulfides (H2Sn) play crucial roles in many physiological processes. To unravel the complicated interrelationship and cellular cross-talk between GSH and H2Sn, the development of single-molecule fluorescent probes that can selectively sense GSH and H2Sn simultaneously from different emission channels is highly desirable. In this report, we have developed the first dual-detection fluorescent probe, ACC-SePh, which responded to GSH with green fluorescence emission, whereas it reacted with H2Sn and emitted blue fluorescence. The probe exhibited excellent selectivity and sensitivity toward GSH and H2Sn over other common reactive sulfur species, such as Cys, Hcy and H2S. Importantly, we also demonstrated that ACC-SePh can be used for dual-channel imaging of endogenous GSH and H2Sn in living RAW264.7 cells.

External Noise and External Signal Induced Transition of Gene Switch and Coherence Resonance in the Genetic Regulatory System.

The transition of gene switch induced by external noises (multiplicative external noise and additive external noise) and external signals is investigated in the genetic regulatory system. Results show that the state-to-state transition of gene switch as well as resonant behaviors, such as the explicit coherence resonance (ECR), implicit coherence resonance (ICR) and control parameter coherence biresonance (CPCBR), can appear when noises are injected into the genetic regulatory system. The ECR is increased with the increase of the control parameter value when starting from the supercritical Hopf bifurcation parameter point, and there exists a critical control parameter value for the occurrence of ECR. However, the ICR is decreased as the control parameter value is increased when starting from the subcritical Hopf bifurcation point. In particular, the coherence of ECR is higher and more sensitive to noise than that of ICR. When an external signal is introduced into the system, the enhancement or suppression of the CPCBR and the number of peaks strongly depend on the frequency and amplitude of the external signal. Furthermore, the gene regulation system can selectively enhance or decrease the noise-induced oscillation signals at preferred frequency and amplitude of an external signal.

Novel N-Doped Carbon Dots/ß-Cyclodextrin Nanocomposites for Enantioselective Recognition of Tryptophan Enantiomers.

Based on N-doped carbon dots/ß-cyclodextrin nanocomposites modified glassy carbon electrodes (N-CDs/ß-CD/GCE), an effective electrochemical sensor for enantioselective recognition of tryptophan (Trp) enantiomers was developed by differential pulse voltammograms (DPVs). Fluorescent N-CDs were synthesized through a hydrothermal method and characterized by spectroscopic approaches. The N-CDs/ß-CD nanocomposites were efficiently electrodeposited on the surface of GCE through C-N bond formation between N-CDs and electrode. The obtained N-CDs/ß-CD/GCE was characterized by multispectroscopic and electrochemical methods. Such N-CDs/ß-CD/GCE generated a significantly lower Ip and more negative Ep in the presence of l-Trp in DPVs, which was used for the enantioselective recognition of Trp enantiomers. The N-CDs/ß-CD nanocomposites showed different binding constants for tryptophan enantiomers, and they further selectively bonded with l-Trp to form inclusion complexes. This N-CDs/ß-CD/GCE combined advantages of N-CDs with strong C-N binding ability and ß-CD with specific recognition of Trp enantiomers to fabricate a novel sensing platform for enantioselective recognition of Trp enantiomers. This strategy provided the possibility of using a nanostructured sensor to discriminate the chiral molecules in bio-electroanalytical applications.

Systematical investigation of in vitro interaction of InP/ZnS quantum dots with human serum albumin by multispectroscopic approach.

Cadmium-free quantum dots (QDs) have attracted great attention in biological and biomedical applications due to their less content of toxic metals, but their potential toxicity investigations on molecular biology level are rarely involved. Since few studies have addressed whether InP/ZnS QDs could bind and alter the structure and function of human serum albumin (HSA), in vitro interaction between InP/ZnS QDs and HSA was systematically characterized by multispectroscopic approaches. InP/ZnS QDs could quench the intrinsic fluorescence of HSA via static mode. The binding site of InP/ZnS QDs was mainly located at subdomain IIA of HSA. Some thermodynamic parameters suggested that InP/ZnS QDs interacted with HSA mainly through electrostatic interactions. As further revealed by three-dimensional spectrometry, FT-IR spectrometry and circular dichroism technique, InP/ZnS QDs caused more global and local conformational change of HSA than CdSe/ZnS QDs, which illustrated the stronger binding interaction and higher potential toxicity of InP/ZnS QDs on biological function of HSA. Our results offer insights into the in vitro binding mechanism of InP/ZnS QDs with HSA and provide important information for possible toxicity risk of these cadmium-free QDs to human health.

Systematical investigation of binding interaction between novel ruthenium(II) arene complex with curcumin analogs and ctDNA.

In this study, the interaction between a novel ruthenium(II) arene complex with curcumin analogs and calf thymus DNA (ctDNA) was investigated systematically by viscosity measurement, the DNA melting approach, multispectroscopic techniques and electrochemical methods. The absorption spectra of the ctDNA-drug complex showed a slight red shift and a weak hypochromic effect. The relative viscosity and melting temperature of ctDNA increased on addition of the drug. The evidence obtained from fluorescence competitive experiments indicated that the binding mode of the drug with ctDNA was intercalative. Using acridine orange (AO) as a fluorescence probe, the drug statically quenched the fluorescence of the ctDNA-AO complex, and hydrogen bonding and van der Waals interactions played vital roles in the binding interaction between the drug and ctDNA. The influences of ionic strength, chemical denaturants and pH on the binding interaction were also investigated. Circular dichroism and Fourier transform infrared spectra suggested that this drug might bond with the G-C base pairs of ctDNA and the right-handed B-form helicity of ctDNA remained after drug binding. The intercalative binding between the drug and ctDNA was further investigated using electrochemical techniques. All these results suggested that the biological activity of ctDNA was affected by ruthenium(II) arene complex with curcumin analogs. Copyright © 2016 John Wiley & Sons, Ltd.