Chelativorans salis sp. nov., a slightly halophilic bacterium isolated from an enrichment system with saline lake sediment.

A Gram-stain-negative, non-motile, and slightly halophilic alphaproteobacterium, designated strain EGI FJ00035T, was isolated from enrichment sediment samples of a saline lake in Xinjiang Uygur Autonomous Region, PR China. The taxonomic position of the isolate was determined using the polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain EGI FJ00035T formed a distinct clade with 'Chelativorans alearense' UJN715 and 'Chelativorans xinjiangense' lm93 with sequence similarities of 98.44 and 98.22 %, respectively, while sharing less than 96.7 % with other valid type strains. The novel isolate could be distinguished from other species of the genus Chelativorans by its distinct phenotypic, physiological, and genotypic characteristics. Optimal growth of strain EGI FJ00035T occurred on marine agar 2216 at pH 7.0 and 30 °C. The major respiratory quinone was Q-10, while the major fatty acids (>5 %) were C19 : 0 cyclo ω8c, summed feature 8 (C17 : 1 ω6c and/or C17 : 1 ω7c), C16 : 0, C18 : 0, and iso-C17 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipids, unidentified glycolipids, and an unidentified lipid. Based on its genome sequence, the G+C content of strain EGI FJ00035T was 63.2 mol%. The average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values of strain EGI FJ00035T against related members of the genus Chelativorans were below the thresholds for delineation of a novel species. According our polyphasic taxonomic data, strain EGI FJ00035T represents a new species of the genus Chelativorans, for which the name Chelativorans salis sp. nov. is proposed. The type strain of the proposed novel isolate is EGI FJ00035T (=KCTC 92251T=CGMCC 1.19480T).

Rational Design of a Highly Sensitive Carboxylesterase Probe and Its Application in High-Throughput Screening for Uncovering Carboxylesterase Inhibitors.

Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.

Synthesis of 1-Aminoisoquinolines and Their Application in a Host-Guest Doped Strategy To Construct Ultralong Room-Temperature Phosphorescence Materials for Bioimaging.

Organic ultralong room-temperature phosphorescence (RTP) materials have attracted great attention for their wide applications in optoelectronic devices and bioimaging. However, the development of these materials remains a challenging task, partially due to the lack of rational molecular design strategies and unclear luminescence mechanisms. Herein, we present a method for facile access to structurally diverse substituted 1-aminoisoquinoline derivatives through a copper-catalyzed one-pot three-component coupling reaction that provides a promising approach to rapidly assemble a library of 1-aminoisoquinolines for exploring the regularity of the host-guest doped system. A series of host-guest RTP materials with wide-ranging lifetimes from 4.4 to 299.3 ms were constructed by doping various substituted isoquinolines derivatives into benzophenone (BP). Furthermore, 4 r/BP nanoparticles could be used for in-vivo imaging with a signal-to-noise ratio value as high as 32, revealing the potential of the isoquinoline framework for the construction of high-performance RTP materials.

Two Stable Bifunctional Zinc Metal-Organic Frameworks with Luminescence Detection of Antibiotics and Proton Conduction.

Functionalized crystalline solids based on metal-organic frameworks (MOFs) enable efficient luminescence detection and high proton conductivity, making them crucial in the realms of environmental monitoring and clean energy. Here, two structurally and functionally distinct zinc-based MOFs, [Zn(TTDPa)(bodca)]·H2O (1) and [Zn(TTDPb)(bodca)]·H2O (2), were successfully designed and synthesized using 3,6-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPa) and 2,5-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPb) as ligands, in the presence of bicyclo[2.2.2]octane-1,4-dicarboxylic acid (H2bodca). Both 1 and 2 display a three-dimensional (3D) structure with 5-fold interpenetration, and notably, 2 forms a larger one-dimensional pore measuring 17.16 × 10.81 Å2 in size. Fluorescence experiments demonstrate that 1 and 2 can function as luminescent sensors for nitrofurantoin (NFT) and nitrofurazone (NFZ) with low detection limits, remarkable selectivity, and good recyclability. A comprehensive analysis was conducted to investigate the differing sensing effects of compounds 1 and 2 and to explore potential sensing mechanisms. Additionally, at 328 K and 98% relative humidity, 1 and 2 exhibit proton conductivity values of 2.13 × 10-3 and 4.91 × 10-3 S cm-1, respectively, making them suitable proton-conducting materials. Hence, the integration of luminescent sensing and proton conductivity in monophasic 3D Zn-MOFs holds significant potential for application in intelligent multitasking devices.

Rational Design of a Near-Infrared Ratiometric Probe with a Large Stokes Shift: Visualization of Polarity Abnormalities in Non-Alcoholic Fatty Liver Model Mice.

Tracking liver polarity with noninvasive and dynamic imaging techniques is helpful to better understand the non-alcoholic fatty liver (NAFL). Herein, a novel near-infrared (NIR) fluorescent probe Cy-Mp is constructed using a "symmetry collapse" strategy. The structure modification leads to the conversion of locally excited state fluorescence to charge transfer state fluorescence. Cy-Mp emits at near-infrared (NIR) wavelengths with high photostability as well as a large Stokes shift. Cy-Mp exhibits a ratiometric response to polarity, providing more accurate analysis of intracellular polarity via the built-in internal reference correction. Most importantly, the in vivo studies indicate that Cy-Mp can accumulate in the liver and the decreased polarity in the liver of mice with NAFL is verified by the ratiometric imaging, implying the great potential of Cy-Mp in the diagnosis of NAFL.

Dysprosium(III) Metal-Organic Framework Demonstrating Ratiometric Luminescent Detection of pH, Magnetism, and Proton Conduction.

A multifunctional metal-organic framework, (Hdmbpy)[Dy(H2dobdc)2(H2O)]·3H2O (Dy-MOF, H4dobdc = 2,5-dihydroxyterephthalic acid, dmbpy = 4,4'-dimethyl-2,2'-bipyridine), was synthesized and structurally characterized. The metal center DyIII is connected by four carboxyl groups to form the [Dy2(CO2)4] binuclear nodes, which are further interconnected by eight separate H2dobdc2- ligands to form a three-dimensional (3D) framework including hydrophilic triangular channels and abundant hydrogen-bonding networks. Dy-MOF has good stability in aqueous solution as well as in harsh acidic or alkaline solutions (pH range: 2.0-12.0). Furthermore, the luminescence signal of Dy-MOF undergoes a visualized color change as the acidity of the solution alters, which is the typical behavior of pH ratiometric probe. At a 100% relative humidity, Dy-MOF exhibits a high proton conductivity σ (1.70 × 10-4 S cm-1 at 303 K; 1.20 × 10-3 S cm-1 at 343 K) based on the proton hopping mechanism, which can be classified as a superionic conductor with σ exceeding 10-4 S cm-1. Additionally, the ferromagnetic interaction and magnetic relaxation behavior are simultaneously achieved in Dy-MOF. Herein, the combination of luminescence sensing, magnetism, and proton conduction in a single-phase 3D MOF may offer great potential applications in smart multitasking devices.

Selective Synthesis of ß-Ketonitriles via Catalytic Carbopalladation of Dinitriles.

A practical, convenient, and highly selective method of synthesizing ß-ketonitriles from the Pd-catalyzed addition of organoboron reagents to dinitriles has been developed. This method provides excellent functional-group tolerance, a broad scope of substrates, and the convenience of using commercially available substrates. The method is expected to show further utility in future synthetic procedures.

Tracking Labile Copper Fluctuation In Vivo/Ex Vivo: Design and Application of a Ratiometric Near-Infrared Fluorophore Derived from 4-Aminostyrene-Conjugated Boron Dipyrromethene.

Specimen differences, tissue-dependent background fluorescence and scattering, and deviated specimen position and sensor concentration make optical imaging for labile copper fluctuation in animals questionable, and a signal comparison between specimens is infeasible. We proposed ratiometric optical imaging as an alternative to overcome these disadvantages, and a near-infrared (NIR) ratiometric sensor, BDPS1, was devised therefore by conjugating boron dipyrromethene (BODIPY) with 4-aminostyrene and modifying the 4-amino group as a Cu+ chelator. BDPS1 possessed an excitation ratiometric copper-sensing ability to show the ratio of NIR emission (710 nm) upon excitation at 600 nm to that at 660 nm, Fex600/Fex660, increasing from 2.8 to 10.7. This sensor displayed still the opposite copper response of its internal charge transfer (ICT; 670 nm) and local (581 nm) emission bands. Ratiometric imaging with this sensor disclosed a higher labile copper region near the nucleus apparatus, and HEK-293T cells were more sensitive to copper incubation than MCF-7 cells. Dual excitation ratiometric imaging with this sensor realized tracking of labile copper fluctuation in mice, and the whole-body imaging found that tail intravenous injection of CUTX-101, a therapeutical agent for Menkes disease, led to a distinct labile copper increase in the upper belly. The ex vivo imaging of the resected viscera of mice revealed that CUTX-101 injection enhanced the labile copper level in the liver, intestine, lung, and gall bladder in sequence, yet the kidney, heart, and spleen showed almost no response. This study indicated that modifying BODIPY as an extended ICT fluorophore, with its electron-donating group being derived as a metal chelator, is an effective design rationale of NIR ratiometric sensors for copper tracking in vivo/ex vivo.

Management of delayed-onset skin flap complications after pediatric cochlear implantation.

PURPOSE: To review delayed-onset skin flap complications associated with pediatric cochlear implantation (CI) in our institute, analyze the etiology, and explore effective treatment strategies. METHODS: Retrospective analyses of 811 children who had undergone cochlear implantation between January 2003 and March 2019 were performed. Twelve (1.48%) patients developed skin flap complications after CI. We present a classification of flap issues and wound histopathology following cochlear implantation. The interventions for flap problems included drug treatment, aspiration, local wound care, revision surgery, and explantation depending on the clinical situation. The temporalis myofascial reconstructive option is discussed. RESULTS: Seven subjects were cured with conservative treatment. Five cases with flap infection or necrosis underwent revision surgery, with wound closure in three cases (60%) and revision surgery with explantation in the remaining two cases (40%). Explantation ultimately led to wound healing in all cases. They all achieved excellent performance through re-implantation. CONCLUSION: Flap complications after CI are rare but treatable. Comprehensive treatments should be developed to achieve a stable and healed wound for CI.

An Optical/Photoacoustic Dual-Modality Probe: Ratiometric in/ex Vivo Imaging for Stimulated H2S Upregulation in Mice.

Tracking signaling H2S in live mice demands responsive imaging with fine tissue imaging depth and low interferences from tissue scattering/autofluorescence and probe concentration. With complementary advantages of fluorescence and photoacoustic (PA) imaging, optical/PA dual-modality imaging was suggested for in/ex vivo H2S imaging. Therefore, a meso-benzoyloxyltricarboheptamethine cyanine, HS-CyBz, was prepared as the first ratiometric optical/PA dual-modality probe for H2S, profiting from a keto-enol transition sensing mechanism. Tail intravenous injection of this probe leads to probe accumulation in the liver of mice, and the endogenous H2S upregulation triggered by S-adenosyl-l-methionine has been verified by ratiometric optical/PA imaging, suggesting the promising potential of this ratiometric dual-modality imaging.

Cardioprotection of post-ischemic moderate ROS against ischemia/reperfusion via STAT3-induced the inhibition of MCU opening.

Enhanced reactive oxygen species (ROS) at the beginning of reperfusion activated signal transducer and activator of transcription 3 (STAT3) in intermittent hypobaric hypoxia (IHH)-afforded cardioprotection against ischemia/reperfusion (I/R). However, its mechanism remains largely unknown. This study aimed to investigate the role and the downstream of STAT3 in exogenous enhanced post-ischemic ROS-induced cardioprotection using the model of moderate hydrogen peroxide postconditioning (H2O2PoC) mimicking endogenous ROS in IHH. Moderate H2O2PoC not only improved the post-ischemic myocardial contractile recovery and reduced the infarct size in isolated rat I/R hearts, but also alleviated mitochondrial calcium overload and ameliorated Ca2+ transients, cell contraction, and mitochondrial membrane potential in rat I/R cardiomyocytes. However, the cardioprotective effects of moderate H2O2PoC were abrogated by Janus kinase 2 (JAK2)/STAT3 inhibitor AG490 in rat hearts as well as adenovirus-delivered short hairpin RNA specific for STAT3 and the opener of mitochondrial calcium uniporter (MCU) spermine in rat cardiomyocytes. Notably, the moderate H2O2PoC-afforded cardioprotection abrogated by spermine could be rescued by STAT3 over-expression with adenovirus in rat I/R cardiomyocytes. Besides, moderate H2O2PoC enhanced mitochondrial STAT3 expression during I/R. A co-localization/interaction of STAT3 or phospho-STAT3ser727 and MCU was observed in rat cardiomyocytes with moderate H2O2PoC at 5 and 30 min of reperfusion but not in rat I/R cardiomyocytes. Further, STAT3 interacted with the N-terminal domain (NTD) of MCU in rat cardiomyocytes with moderate H2O2PoC. These findings indicated that post-ischemic moderate ROS activate STAT3 against cardiac I/R by inhibiting MCU opening via its interaction with the NTD of MCU to alleviate mitochondrial calcium overload.

Modulating Magnetic Property of Phthalocyanine Supported MII-DyIII (M = Ni, Zn) Heterodinuclear Complexes.

Three heterometallic dinuclear compounds, [MIIDyIII(L)(Pc)(ROH)]·ROH (R = CH3, M = Ni (1), Zn (2); R = C2H5, M = Zn (3)), were stepwise synthesized based on phthalocyanine (H2Pc) and one tripodal Schiff-base ligand 1,1,1-tris[(salicylideneamino)methyl]ethane (H3L). All of them have been studied structurally and magnetically. The six-coordinate MII ion and the seven-coordinate DyIII ion are bridged by two phenolic oxygen atoms to form an MII-LnIII heterodinuclear unit. Magnetic measurements indicate that the ferromagnetic NiII-DyIII interaction is operative in compound 1 and all three compounds exhibit the field-induced slow relaxation of magnetizations. In particular, compounds 2 and 3 have the improved magnetic performance. Ab initio calculations indicate that the weak NiII-DyIII interaction decreases the energy barrier, while the replacement of the paramagnetic NiII ion by the diamagnetic ZnII in compound 2 and 3 not only controls the magnetic interaction but also alters the local magnetic axes of DyIII ions to optimize the magnetic relaxation behavior.

Temporal dynamics of immune response following prolonged myocardial ischemia/reperfusion with and without cyclosporine A.

Understanding the dynamics of the immune response following late myocardial reperfusion is critical for the development of immunomodulatory therapy for myocardial infarction (MI). Cyclosporine A (CSA) possesses multiple therapeutic applications for MI, but its effects on the inflammation caused by acute MI are not clear. This study aimed to determine the dynamics of the immune response following myocardial ischemia/reperfusion (I/R) and the effects of CSA in a mouse model of prolonged myocardial ischemia designated to represent the human condition of late reperfusion. Adult C57BL/6 mice were subjected to 90 min of closed-chest myocardial I/R, which induced severe myocardial injury and excessive inflammation in the heart. Multicomponent analysis of the immune response caused by prolonged I/R revealed that the peak of cytokines/chemokines in the systemic circulation was synchronized with the maximal influx of neutrophils and T-cells in the heart 1 day after MI. The peak of cytokine/chemokine secretion in the infarcted heart coincided with the maximal macrophage and natural killer cell infiltration on day 3 after MI. The cellular composition of the mediastinal lymph nodes changed similarly to that of the infarcted hearts. CSA (10 mg/kg/day) given after prolonged I/R impaired heart function, enlarged the resulting scar, and reduced heart vascularization. It did not change the content of immune cells in hearts exposed to prolonged I/R, but the levels of MCP-1 and MIP-1α (hearts) and IL-12 (hearts and serum) were significantly reduced in the CSA-treated group in comparison to the untreated group, indicating alterations in immune cell function. Our findings provide new knowledge necessary for the development of immunomodulatory therapy targeting the immune response after prolonged myocardial ischemia/reperfusion.

A Two-Dimensional Iron(II) Coordination Polymer with Synergetic Spin-Crossover and Luminescent Properties.

A composite material, {[Fe(L)(TPPE)0.5 ]⋅3 CH3 OH}n , has been constructed by integrating the spin-crossover (SCO) subunit FeII {diethyl(E,E)-2,2'-[1,2-phenyl-bis(iminomethylidyne)]bis(3-oxobutanoate)-(2-)-N,N',O3 ,O3 '} and the highly luminescent connector 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)-ethene. Its structure contains four staggered 4×4 layers and intercalated methanol. The packing is dominated by considerable H-bonds either between adjacent layers and between layers and guests. A crystal-structure transformation was detected upon removal of the guest molecules. The SCO transition of the solvated crystals is centered at ca. 215 K with a non-symmetrical hysteresis of 25 K wide, and the desolvated [Fe(L)(TPPE)0.5 ]n exhibits gradual SCO without hysteresis. Intriguingly, the intensity of the fluorescence at 460 nm for the latter is maximized at the SCO transition. The energy transfer between luminescent and SCO entities is achievable as confirmed by theoretical calculations.

Therapeutic benefits of neoadjuvant and post-operative denosumab on sacral giant cell tumor: a retrospective cohort study of 30 cases.

PURPOSE: Denosumab, a new monoclonal antibody that inhibits receptor activator for nuclear factor Kß ligand (RANKL), has recently been approved by FDA for the treatment of aggressive giant cell tumor of bone (GCTB). So we initiated this study to evaluate the clinical benifits of denosumab used preoperatively or postoperatively. METHODS: Patients diagnosed with classic sacral GCT without metastasis were included in this study. Patients were assigned into 3 groups according to the use of denosumab: control group 1, post-operative group 2 and neoadjuvant group 3. The latter two groups were treated with 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle. The primary endpoints were event-free-survival (EFS) and objective response rate (OPR) based on RECIST criteria. A system (MUD system) proposed by our center was applied to score the sacral nerve deficit changes before surgery in group 3. RESULTS: A total 30 patients (13 men and 17 women, mean age 34.7 years, range 15-56) were enrolled from April 2014 to July 2016. Group 1 included 10 patients, group 2 9 and group 3 11. The study ended in March 01, 2017, and followup ranged from 3 to 36 months (mean 18.3). Two patients with PET-CT showed SUV max uptake down to muscle tissue level. In the neoadjuvant group 3 7 patients had partial responses and 4 stable disease (ORR 63.6%; 95% CI 35-92). Most (80%) patients achieved significant improvement in pain and great relief in the bladder and bowel functions. In 4 patients the urocatheter was removed after neoadjuvant denosumab. CONCLUSION: Neoadjuvant therapy with denosumab can significantly relieve the symptoms and neurologic deficits.

A New Approach to Sensitize Antitumor Monofunctional Platinum(II) Complexes via Short Time Photo-Irradiation.

Sensitizing the antitumor activity of monofunctional PtII complexes is a reliable approach to developing antitumor agents different from the classic Pt-based drugs. Considering the poor intracellular accumulation of monofunctional PtII complexes, in this study, the photosensitizing monofunctional PtII complex Pt-BA was derived from a weak BODIPY (boron-dipyrromethene)-derived photosensitizer BA, with the purpose to improve its antitumor cytotoxicity via enhancing its intracellular accumulation with a short time photo-irradiation. Photoinduced reactive oxygen species (ROS) determination indicated that the PtII center in Pt-BA is able to improve the photoinduced ROS production ability of BA, which makes Pt-BA a mild photosensitizer. Fluorescence imaging disclosed that dark incubation makes Pt-BA accumulate mainly on the surface of cell membrane, and the later short time photo-irradiation (5 min) promotes distinctly the intracellular accumulation of Pt-BA, which has been confirmed by inductively coupled plasma-mass spectrometry determination. Flow cytometric Annexin V-FITC assay indicated that the short time irradiation of Pt-BA induces in situ the cell membrane damage, which might finally enhance the intracellular accumulation of this monofunctional complex. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay confirmed that the short time photo-irradiation promotes distinctly the antitumor cytotoxicity of Pt-BA against MCF-7, SGC-7901, A549, and HeLa cell lines. The photopromoted antitumor activity of Pt-BA implies that modifying monofunctional PtII complex as a mild photosensitizer to promote its cell accumulation is a useful approach to sensitizing the antitumor activity of monofunctional PtII complex and renders the possibility of monofunctional PtII prodrugs for precise chemotherapy via only short time photoactivation.

Expression profiles of histone lysine demethylases during cardiomyocyte differentiation of mouse embryonic stem cells.

AIM: Histone lysine demethylases (KDMs) control the lineage commitments of stem cells. However, the KDMs involved in the determination of the cardiomyogenic lineage are not fully defined. The aim of this study was to investigate the expression profiles of KDMs during the cardiac differentiation of mouse embryonic stem cells (mESCs). METHODS: An in vitro cardiac differentiation system of mESCs with Brachyury (a mesodermal specific marker) and Flk-1(+)/Cxcr4(+) (dual cell surface biomarkers) selection was used. The expression profiles of KDMs during differentiation were analyzed using Q-PCR. To understand the contributions of KDMs to cardiomyogenesis, the mESCs on differentiation d 3.5 were sorted by FACS into Brachyury(+) cells and Brachyury(-) cells, and mESCs on d 5.5 were sorted into Flk-1(+)/Cxcr4(+) and Flk-1(-)/Cxcr4(-) cells. RESULTS: mESCs were differentiated into spontaneously beating cardiomyocytes that were visible in embryoid bodies (EBs) on d 7. On d 12-14, all EBs developed spontaneously beating cardiomyocytes. Among the 16 KDMs examined, the expression levels of Phf8, Jarid1a, Jhdm1d, Utx, and Jmjd3 were increased by nearly 2-6-fold on d 14 compared with those on d 0. Brachyury(+) cells showed higher expression levels of Jmjd3, Jmjd2a and Jhdm1d than Brachyury(-) cells. A higher level of Jmjd3 was detected in Flk-1(+)/Cxcr4(+) cells, whereas the level of Jmjd2c was lower in both Brachyury(+) cells and Flk-1(+)/Cxcr4(+) cells. CONCLUSION: KDMs may play important roles during cardiomyogenesis of mESCs. Our results provide a clue for further exploring the roles of KDMs in the cardiac lineage commitment of mESCs and the potential interference of cardiomyogenesis.

[Expression profile of microRNAs in the cardiomyocytes derived from mouse embryonic stem cells].

Embryonic stem cells (ESCs), derived from the inner cell mass of blastocysts, are self-renewing and pluripotent cells with the ability to differentiate into all derivatives of three primary germ layers, including cardiomyocytes. Recent studies have revealed that posttranscriptional regulations of lineage specific genes by microRNAs (miRNAs) emerge as a new class of cell fate and lineage determinants of ESCs. However, the miRNAs that control ESC differentiation are still largely unexplored. In the present study, we aimed to identify miRNAs that might be involved in cardiac differentiation of ESCs. Using a hanging drop technique, mouse ESCs (mESCs) were differentiated into cardiomyocytes. We then used the Aligent miRNAs chip (miRbase V16.0) to evaluate miRNA expression levels between the ESC-derived beating area enriched with cardiomyocytes and non-beating area. The expression levels of 19 miRNAs changed over 5-fold between two areas (n = 3, P < 0.05). Among them, 5 miRNAs were upregulated and 14 miRNAs were downregulated in the beating area compared with the non-beating area (P < 0.05). Then quantitative real-time-PCR was used to analyze the miRNAs with the differentiated expression level over 10-fold seen in the Aligent miRNAs chip. miR-196a, miR-196b and miR-467e were confirmed to be significantly lower in the beating area than those in the non-beating area (n = 3, P < 0.05). TargetScan analysis further suggested that miR-196a and miR-196b might be negatively related to the cardiomyocytes differentiation. Our findings provide a new clue for exploring roles of miRNAs in cardiac lineage commitment of mESCs.

Markovnikov Hydrochlorination of Unactivated Alkenes with FeCl3 via a HAT/XAT Sequence.

Hydrochlorination of alkenes is a practical strategy for accessing organic chlorides. Herein, we report the hydrochlorination of unactivated alkenes via a hydrogen atom transfer/halogen atom transfer process using earth-abundant and biocompatible FeCl3 as a chlorine source under extraordinarily mild reaction conditions. The protocol is easy to operate with notable features such as excellent chemoselectivity, remarkable efficiency, a broad substrate scope, and good functional group tolerance. Importantly, the synthetic utility is highlighted by scaled-up reactions, late-stage derivatizations of products, and the modification of sulfonamides.

A Review of N-(1,3-Dimethylbutyl)-N'-phenyl-p-Phenylenediamine (6PPD) and Its Derivative 6PPD-Quinone in the Environment.

As an antioxidant and antiozonant, N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is predominantly used in the rubber industry to prevent degradation. However, 6PPD can be ozonated to generate a highly toxic transformation product called N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone), which is toxic to aquatic and terrestrial organisms. Thus, 6PPD and 6PPD-quinone, two emerging contaminants, have attracted extensive attention recently. This review discussed the levels and distribution of 6PPD and 6PPD-quinone in the environment and investigated their toxic effects on a series of organisms. 6PPD and 6PPD-quinone have been widely found in air, water, and dust, while data on soil, sediment, and biota are scarce. 6PPD-quinone can cause teratogenic, developmental, reproductive, neuronal, and genetic toxicity for organisms, at environmentally relevant concentrations. Future research should pay more attention to the bioaccumulation, biomagnification, transformation, and toxic mechanisms of 6PPD and 6PPD-quinone.