Eleutheroside B (EB) is the main active constituent derived from the Chinese herb Acanthopanax senticosus (AS) that has been reported to possess cardioprotective effects. In this study we ...investigated the effects of EB on cardiac electrophysiology and its suppression on atrial fibrillation (AF). Whole-cell recording was conducted in isolated rabbit atrial myocytes. The intracellular calcium (Ca
) concentration was measured using calcium indicator Fura-2/AM fluorescence. Monophasic action potential (MAP) and electrocardiogram (ECG) synchronous recordings were conducted in Langendorff-perfused rabbit hearts using ECG signal sampling and analysis system. We showed that EB dose-dependently inhibited late sodium current (I
), transient sodium current (I
), and sea anemone toxin II (ATX II)-increased I
with IC
values of 167, 1582, and 181 μM, respectively. On the other hand, EB (800 μM) did not affect L-type calcium current (I
), inward rectifier potassium channel current (I
), and action potential duration (APD). Furthermore, EB (300 μM) markedly decreased ATX II-prolonged the APD at 90% repolarization (APD
) and eliminated ATX II-induced early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and triggered activities (TAs). Moreover, EB (200 μM) significantly suppressed ATX II-induced Na
-dependent Ca
overload in atrial myocytes. In the Langendorff-perfused rabbit hearts, application of EB (200 μM) or TTX (2 μM) substantially decreased ATX II-induced incidences of atrial fibrillation (AF), ventricular fibrillation (VF), and heart death. These results suggest that augmented I
alone is sufficient to induce AF, and EB exerts anti-AF actions mainly via blocking I
, which put forward the basis of pharmacology for new clinical application of EB.
Reported herein is an asymmetric Pd/PC‐Phos‐catalyzed denitrogenative cyclization of benzotriazoles with allenes and N‐allenamides, representing the first example of enantioselective denitrogenative ...cyclizations of benzotriazoles. A series of optically active 3‐methyleneindolines were obtained in good yields with high ee values. The use of inexpensive and readily available starting materials, high regio‐ and enantioselectivity, a broad substrate scope, mild reaction conditions, no need for base, as well as versatile functionalization of the 3‐methyleneindolines make this approach attractive.
The first example of an enantioselective denitrogenative cyclization of benzotriazoles with allenes and N‐allenamides is enabled using Pd/PC‐Phos catalysis, and provides rapid access to optically active 3‐methyleneindolines in good yields with high ee values. The method features a general substrate scope, high regioselectivity, and mild reaction conditions. Tf=trifluoromethanesulfonyl.
This paper reviews the concentration, distribution, source, and potential risk of polycyclic aromatic hydrocarbons (PAHs) in surface soils of China through analysis of data from >6000 surface soil ...samples in nearly 100 references. The mean value of total 16 PAHs was 730ng·g−1 in surface soil in China, a relatively lower or moderate level than other countries. Based on the Maliszewska-Kordybach classification criteria, the proportions of heavily contaminated, contaminated, weakly contaminated, and non-contaminated soil samples were 21.4%, 11.9%, 49.5%, and 17.2%, respectively. There was a clear geographical distribution, with concentrations of the total 16 PAHs descending in the following order: Northeast China (1467ng·g−1)>North China (911ng·g−1)>East China (737ng·g−1)>South China (349ng·g−1)>West China (209ng·g−1). Moreover, it was found that the PAH concentrations in surface soil in China descended along the urban–suburban–rural gradient. The concentration and distribution of PAHs were mainly related to the degree of economic development, population density, climatic conditions, and soil organic matter, and the divergence of regional economic patterns and climatic conditions was the main reason for the observed PAH distribution in the soils. Traffic emissions, coal and biomass combustion mainly contributed to the PAH contamination of surface soil in China during the process of urbanization and industrialization, and the average Benzo(a)pyrene equivalent concentration of ∑PAH7c (seven carcinogenic PAHs) was 99ng·g−1, which indicated the soil samples had a small potential carcinogenic risk. Despite soil pollution being generally low, PAH concentrations in some areas were relatively high, therefore it is necessary to produce strategies, such as establishing effective guidelines and developing environmental-friendly technology to reduce PAH emissions, and prevent further contamination.
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•The overall contamination status of surface soil by PAHs in China was reviewed.•The total PAH concentrations descended in the order of Northeast > North > East > South > West.•The divergence of economic development was the main reason for PAHs distribution in the soils in China.•Traffic exhaust, coal combustion and biomass burning contributed to PAHs contamination of surface soil during urbanization and industrialization.
Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for ...systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.
Abstract Cosmic rays (CRs) travel throughout the Galaxy, leaving traces from radio to ultra-high-energy γ -rays due to interactions with the interstellar gas, radiation field, and magnetic field. ...Therefore, it is necessary to utilize multiwavelength investigations on the Galactic diffuse emission to shed light on the physics of CR production and propagation. In this work, we present a spatially dependent propagation scenario, taking account of a local source contribution, while making allowances for an additional CR component freshly accelerated near their sources. In this picture, after reproducing the particle measurements at the solar system, we calculated the intensity and compared the spectral energy distribution to observations from Fermi-LAT and LHAASO-KM2A in the γ -ray band, and from WMAP and Planck among other radio surveys at lower energies. Multiband data considered in conjunction, the former comparison exhibits sufficiently good consistency in favor of our model, while the latter calls for improvement in data subtraction and processing. From this standpoint, there remains potential for advanced observations at energies from milli-eVs to MeVs toward the Galactic plane, in order to evaluate our model further and more comprehensively in the future.
Increasing evidence shows that Curcumin (Cur) has a protective effect against cardiovascular diseases. However, the role of Cur in the electrophysiology of cardiomyocytes is currently not entirely ...understood. Therefore, the present study was conducted to investigate the effects of Cur on the action potential and transmembrane ion currents in rabbit ventricular myocytes to explore its antiarrhythmic property. The whole-cell patch clamp was used to record the action potential and ion currents, while the multichannel acquisition and analysis system was used to synchronously record the electrocardiogram and monophasic action potential. The results showed that 30 μmol/L Cur shortened the 50 and 90% repolarization of action potential by 17 and 7%, respectively. In addition, Cur concentration dependently inhibited the Late-sodium current (
I
Na.L
), Transient-sodium current (
I
Na.T
), L-type calcium current (
I
Ca.L
), and Rapidly delayed rectifying potassium current (
I
Kr
), with IC
50
values of 7.53, 398.88, 16.66, and 9.96 μmol/L, respectively. Importantly, the inhibitory effect of Cur on
I
Na.L
was 52.97-fold higher than that of
I
Na.T
. Moreover, Cur decreased ATX II-prolonged APD, suppressed the ATX II-induced early afterdepolarization (EAD) and Ca
2+
-induced delayed afterdepolarization (DAD) in ventricular myocytes, and reduced the occurrence and average duration of ventricular tachycardias and ventricular fibrillations induced by ischemia–reperfusion injury. In conclusion, Cur inhibited
I
Na.L
,
I
Na.T
,
I
Ca.L
, and
I
Kr
; shortened APD; significantly suppressed EAD and DAD-like arrhythmogenic activities at the cellular level; and exhibited antiarrhythmic effect at the organ level. It is first revealed that Cur is a multi-ion channel blocker that preferentially blocks
I
Na.L
and may have potential antiarrhythmic property.
Both Global Positioning System (GPS) measurements and studies of Late Quaternary faulting are consistent with a slip rate of ∼10 mm/yr along the central segment of the Altyn Tagh Fault and a ...systematic decrease in that rate toward the eastern end of the fault. Dates of terraces above and below laterally offset terrace risers yield bounds on Quaternary slip rates that range from those that agree with GPS measurements to values as much as three times faster. We argue that offset terrace risers that are protected by topography upstream of them are more closely dated by the age of the upper terrace than by that of the lower terrace. In some cases, valleys upstream of the fault have been incised into bedrock, and few if any terrace risers can be seen within the valleys. Such streams debouch onto alluviated floodplains or fans that become incised, presumably during climate changes, to create terrace risers. The terrace risers are then displaced so that they lie downslope from bedrock ridges on the upstream side of the fault, and thus the risers become protected from further incision. In such cases, dates of upper terraces should more closely approximate the ages of the risers than those of lower terraces. Such dates yield slip rates of ∼10 mm/yr in the central segment of the fault and decreasing rates eastward. Although we cannot with certainty rule out the higher slip rates along the Altyn Tagh Fault, our analysis does show that viable interpretations consistent with GPS measurements are more likely, at least along some segments of the fault. Not only do these rates support the view that the Tibetan Plateau deforms internally by slip on a distributed network of faults in the shallow brittle crust, and hence behaves as a continuum at depth, but the gradual decrease toward the east also shows that the Altyn Tagh Fault does not separate two effectively rigid lithospheric plates. Correspondingly, the relatively low slip rate and the eastward decrease in slip rate suggest that the Altyn Tagh Fault does not transfer a significant portion of the convergence between India and Asia into northeastward extrusion of the Tibetan Plateau. Thus, large‐scale extrusion of crustal material in India's path into Eurasia seems to be limited largely to the confines of the Tibetan Plateau.
An asymmetric 1,6‐conjugate addition of thioacetic acid with para‐quinone methides has been developed by using chiral phosphoric acid catalysis in the presence of water. A series of sulfur‐containing ...compounds were thus obtained in high yields with good to excellent enantioselectivities. Theoretical studies indicated that the water‐bridged proton transfer is a potentially favorable reaction pathway. An unprecedented O−H⋅⋅⋅π interaction between water and the aromatic nucleus of chiral phosphoric acid was discovered to contribute significantly to the stereocontrol in the catalysis.
Building bridges: The title reaction was realized in the presence of water, and successfully solved the challenge of remote stereocontrol for the para‐quinone methide substrates. Theoretical studies indicated that the water‐bridged proton transfer and an unprecedented O−H⋅⋅⋅π interaction, between water and the aromatic nucleus of the chiral phosphoric acid, play important roles in the transition state.
Two skeleton isomers, CaL(H2O)(DMF)2•DMF (1) (H2L=5‐(1,3‐dioxo‐1H‐benzodeisoquinolin‐2(3H)‐yl)isophthalic acid) with a 1 dimensional chain structure and CaL(DMF)1.72• (DMF)0.28 (2) with a 2 ...dimensional layer structure were synthesized. Mechanochromic luminescence studies reveal that 1 and 2 exhibit luminescent red‐shift and blue‐shift respectively under grinding stimuli. The different influence of grinding stimuli on the π⋅⋅⋅π interaction in the two structures are proposed to be the main reason for such different responses. In addition, 1 has a rare broad sensing ability for halogenated hydrocarbons and can distinguish seven halogenated hydrocarbons out of 17 solvents. 1 can also be used for rapid detection of trace water in DMF with a calculated detection limit of 0.0078 v/v %. The relevant recognition mechanism is the decomposition of the structure during the recognition process due to the water instability of the ionic bond. The above results reveal that both compounds have the potential to be used as multi‐stimulus‐responsive materials.
Present here are two framework isomers that exhibit grinding and volatile organic solvent stimulus response properties. In addition, one can also be used to detect H2O in DMF with detection limit of 0.0078 v/v%.
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