Urbanization promotes carbon storage or not? The evidence during the rapid process of China.

China's commitment to attaining carbon neutrality by 2060 has galvanized research into carbon sequestration, a critical approach for mitigating climate change. Despite the rapid urbanization observed since the turn of the millennium, a comprehensive analysis of how urbanization influences urban carbon storage throughout China remains elusive. Our investigation delves into the nuanced effects of urbanization on carbon storage, dissecting both the direct and indirect influences by considering urban-suburban gradients and varying degrees of urban intensity. We particularly scrutinize the roles of climatic and anthropogenic factors in mediating the indirect effects of urbanization on carbon storage. Our findings reveal that urbanization in China has precipitated a direct reduction in carbon storage by approximately 13.89 Tg of carbon (Tg C). Remarkably, urban sprawl has led to a diminution of vegetation carbon storage by 8.65 Tg C and a decrease in soil carbon storage by 5.24 Tg C, the latter resulting from the sequestration of impervious surfaces and the elimination of organic matter inputs following vegetation removal. Meanwhile, carbon storage in urban greenspaces has exhibited an increase of 6.90 Tg C and offsetting 49.70% of the carbon loss induced by direct urbanization effects. However, the indirect effects of urbanization predominantly diminish carbon storage in urban greenspaces by an average of 5.40%. The degree of urban vegetation management emerges as a pivotal factor influencing the indirect effects of urbanization on carbon storage. To bolster urban carbon storage, curbing urban sprawl and augmenting urban green spaces are imperative strategies. Insights from this study are instrumental in steering sustainable urban planning and advancing towards the goal of carbon neutrality.

Differential regulation of GUV mechanics via actin network architectures.

Actin networks polymerize and depolymerize to construct highly organized structures, thereby endowing the mechanical phenotypes found in a cell. It is generally believed that the amount of filamentous actin and actin network architecture determine cytoplasmic viscoelasticity of the whole cell. However, the intrinsic complexity of a cell and the presence of endogenous cellular components make it difficult to study the differential roles of distinct actin networks in regulating cell mechanics. Here, we model a cell by using giant unilamellar vesicles (GUVs) encapsulating actin filaments and networks assembled by various actin cross-linker proteins. Perturbation of these cytoskeletal vesicles using alternating current electric fields revealed that deformability depends on actin network architecture. While actin-free vesicles exhibited large electromechanical deformations, deformations of GUVs encapsulating actin filaments were significantly dampened. The suppression of electrodeformation of actin-GUVs can be similarly recapitulated by using aqueous poly(ethylene glycol) 8000 solutions at different concentrations to modulate solution viscoelasticity. Furthermore, networks cross-linked by alpha actinin resulted in decreased GUV deformability compared with actin-filament-encapsulating GUVs, and membrane-associated actin networks, through the formation of the dendritic actin cortex, greatly dampened electrodeformation of GUVs. These results highlight that the organization of actin networks regulates the mechanics of GUVs and shed insights into the origin of differential deformability of cells.

Driving forces and variation in water footprint before and after the COVID-19 lockdown in Fujian Province of China.

The COVID-19 outbreak has injured the global industrial supply chain, especially China as the world's largest manufacturing base. Since 2020, China has implemented a rigorous lockdown policy, which has sternly damaged sectoral trade in export-oriented coastal areas. Fujian Province, which mainly processes imported materials, has a more profound influence. Although the COVID-19 lockdown has had some detrimental consequences on the world economy, it also had some favorable benefits on the global ecology. Previous studies have shown that the lockdown has altered the physical water quantity and quality, but the lack of total, virtual, and physical water research that combines water quantity and water quality simultaneously to pinpoint the subject and responsibility of water resources consumption and pollution. This research quantified the physical, virtual, and total water consumption and water pollution among 30 sectors in Fujian Province based on the theory of water footprint and the Economic Input-Output Life Cycle Assessment model. SDA model was then used to investigate the socioeconomic elements that underpin variations in the water footprint. The results show that after the lockdown, the physical water quantity and the physical grey WF in Fujian Province decreased by 2.6 Gm3 (-6.7%) and 0.4 Gm3 (-1.3%) respectively. The virtual water quantity decreased by 2.3 Gm3 (-4.5%), whereas the virtual grey WF rose by 1.5 Gm3 (4.3%). The total water quantity dropped by 3.3 Gm3 (-4.9%), while the grey WF increased by 1.2 Gm3 (2.5%), i.e. the COVID-19 lockdown decreases physical water quantity and improves local water quality. More than 50% of the water comes from virtual water trade outside the province (virtual water is highly dependent on external), and around 60% of the grey WF comes from physical sewage in the province. The COVID-19 lockdown reduced water outsourcing across the province (paid nonlocally decrease) but increased pollution outsourcing (paid nonlocally increase). And gross capital formation's contribution to the growth in water footprint will continue to rise. As a result, this study suggested that Fujian should take advantage of sectoral trade network to enhance the transaction of green water-intensive intermediate products, reduce the physical water consumption of blue water-intensive sectors, and reduce the external dependence on water consumption. Achieving the shared responsibility of upstream and downstream water consumption and reducing the external dependence on water in water-rich regions is crucial to solving the world's water problems. This research provides empirical evidence for the long-term effects of COVID-19 lockdown on the physical and virtual water environment.

Rotational Spectroscopy of the 2,2,3,3,3-Pentafluoropropanol⋠⋠⋠Water Complex: Conformations and Large Amplitude Motions.

The 2,2,3,3,3-pentafluoropropanol (PFP) monomer can exist in five conformations defined by the CCCO and CCOH dihedral angles: four mirror-imaged pairs (G+g+/G-g-, G+g-/G-g+, G+t/G-t, Tg+/Tg-) and an achiral Tt form. We examined the conformational landscape of the PFP⋅⋅⋅water complex using chirped pulsed Fourier transform microwave spectroscopy and theoretical calculations. Rotational spectra of two PFP⋅⋅⋅water conformers, PFPG+g+⋅⋅⋅WH and PFPTg+⋅⋅⋅WH , and seven deuterated isotopologues of each, were assigned. Tunneling splittings were observed for both conformers and are attributed to the exchange of the bonded and non-bonded hydrogen atoms of water. On the other hand, the tunneling splitting associated with the OH flipping motion in PFPTg+/Tg- appears to be quenched upon hydrogen bonding with water. The large amplitude motions associated with the water subunits were examined in detail to explain the very different magnitudes of the experimental and theoretical permanent electric dipole moment components. The study highlights the challenge in correctly identifying the conformers observed when large amplitude motions are involved. Quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analyses, as well as electrostatic potential (ESP) calculations were carried out to explore the nature of the non-covalent interactions and to appreciate the effects of fluorination.

2,2,3,3,3-Pentafluoro-1-propanol and its dimer: structural diversity, conformational conversion, and tunnelling motion.

Rotational spectra of 2,2,3,3,3-pentafluoro-1-propanol (PFP) were measured using cavity and chirped pulse Fourier transform microwave spectrometers. Of the nine possible PFP configurations which include four mirror-imaged pairs and an achiral conformer, the two most stable monomeric PFP imaged pairs, i.e., PFPG+g+/G-g- and PFPTg+/Tg- were observed and assigned, along with the 13C, 18O and deuterated isotopologues of PFPG+g+/G-g-. The rotational transitions of PFPTg+/Tg- exhibit large tunnelling splittings and were analyzed in detail. CREST, a recently developed conformational search tool that was used for systematic conformational searches of possible binary PFP conformers and the subsequent DFT calculations at the B3LYP-D3(BJ)/def2-QZVP level produced nearly 80 stable, binary PFP geometries, where ten of them are within a narrow energy window of ∼1 kJ mol-1, highlighting the structural diversity of the system. Rotational spectra of five (PFP)2 conformers were assigned and were identified as the five most stable binary conformers predicted. A closer examination reveals that the assigned binary conformers are made exclusively of the two most stable PFP monomeric subunits observed experimentally. A combined kinetic and thermodynamic model was proposed to explain the observation or non-observation of low energy conformers, and the analysis was further verified by the 'argon test'. The non-covalent intermolecular interactions of PFP and its binary conformers are also discussed with the aid of quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analyses, as well as the effects of fluorination by comparing with 1-propanol and its dimers.

Rotational Spectrum and Molecular Structures of the Binary Aggregates of 1,1,1,3,3,3-Hexafluoro-2-propanol with Ne and Ar.

The structures and binding topologies of two binary van der Waals complexes 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)···Ne and ···Ar were investigated. The rotational spectra of these two complexes including several isotopic species containing 20Ne, 22Ne, 40Ar, 13C, and hydroxyl D were measured using a chirped pulse Fourier transform microwave spectrometer and a cavity-based Fourier transform microwave spectrometer. While HFIP was shown to exist in both the gauche and trans configurations based on previous reports, the rare gas atom is predicted to attach to HFIP in several different binding topologies, leading to a total of nine possible structural isomers for each complex. Only one isomer was detected for each species, and it corresponds to the most stable one predicted, based on the comparison of the experimental rotational constants and electric dipole moment components with the theoretical predictions and on the isotopic data. We applied quantum theory of atoms in molecules (QTAIM) and electrostatic potential calculations to examine the different rare gas binding sites and to explore the nature of the interactions in these two complexes and several previously reported alcohol···Ar complexes. The effects of fluorination are also discussed by comparison with the binary complexes of isopropanol···Ne and ···Ar.

Higher-Energy Hexafluoroisopropanol···Water Isomer and Its Large Amplitude Motions: Rotational Spectra and DFT Calculations.

Rotational spectra of the 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)···water complex were measured using a chirped pulse Fourier-transform microwave spectrometer. The spectral analyses, aided by density functional theory calculations, reveal two HFIP···water isomers: one previously reported, trans HFIP (HFIPt)···water (Phys. Chem. Chem. Phys. 2015, 119, 5650-5657), and a new isomer, gauche HFIP (HFIPg)···water. To confirm the identity of the new isomer, rotational spectra of seven of its deuterated species were also measured and analyzed. Both the experimental and theoretical pieces of evidence indicate that the intermolecular interaction with water preferentially stabilizes the HFIPg monomer configuration over the global minimum configuration, HFIPt. The relative energy difference between these monomeric forms is 4.1 kJ mol-1 and decreases to 2.5 kJ mol-1 in the respective monohydrates at the B3LYP-D3(BJ)/def2-QZVP level of theory. Both rigid and relaxed potential energy surface scans were carried out to gain insights into the large-amplitude water motions in HFIPg···water. The nonobservation of a water tunneling splitting in HFIPt···water has been explained to be a result of a barrier-less (after zero-point-energy correction) pathway for the water motion, whereas in HFIPg···water, a relatively large water tunneling barrier was identified as the cause of barely resolved water tunneling splittings. Noncovalent interaction and quantum theory of atoms and molecule analyses were used to evaluate the changes in HFIPg···water when going from the minimum to the transition state in terms of attractive interactions such as the OH···H and OH···F contacts. The effect of fluorination is discussed by comparing the vastly different binding topologies of isopropanol···water and HFIP···water.

The Agonist of Inward Rectifier Potassium Channel (IK1) Attenuates Rat Reperfusion Arrhythmias Linked to CaMKII Signaling.

Inward rectifier potassium channels (IK1, Kir) are known to play critical roles in arrhythmogenesis. Thus, how IK1 agonist affects reperfusion arrhythmias needs to be clarified, and its underlying mechanisms should be determined. Reperfusion arrhythmias were modeled by coronary ligation (ischemia, 15 minutes) and release (reperfusion, 15 minutes). Zacopride (1.5-50 µg/kg in vivo, or 0.1-10 µmol/Lex vivo) was applied in the settings of pretreatment (3 minutes before coronary ligation) and posttreatment (5 minutes after coronary ligation). Hypoxia (45 minutes) /reoxygenation (30 minutes) model was established in cultured H9c2 (2-1) cardiomyocytes. Zacopride or KN93 was applied before hypoxia (pretreatment). In the setting of pre- or posttreatment, zacopride at 15 µg/kg in vivo or 1 µmol/Lin vitro exhibited superlative protections on reperfusion arrhythmias or intracellular calcium overload. Western blot data from ex vivo hearts or H9c2 (2-1) cardiomyocytes showed that I/R (H/R) induced the inhibition of Kir2.1 (the dominant subunit of IK1 channel in ventricle), phosphorylation and oxidation of CaMKII, downregulation of SERCA2, phosphorylation of phospholamban (at Thr17), and activation of caspase-3. Zacopride treatment (1 µmol/L) was noted to strikingly restore the expression of Kir2.1 and SERCA2 and decrease the activity of CaMKII, phospholamban, and caspase-3. These effects were largely eliminated by co-application of IK1 blocker BaCl2. CaMKII inhibitor KN93 attenuated calcium overload and p-PLB (Thr17) in an IK1-independent manner. IK1-depedent inhibition of CaMKII activity is found to be a key cardiac salvage signaling under Ca2+ dyshomeostasis and reactive oxygen species (ROS) stress. IK1 might be a novel target for pharmacological conditioning of reperfusion arrhythmia, especially for the application after unpredictable ischemia.

Nonvolatile molecular memory with the multilevel states based on MoS2 nanochannel field effect transistor through tuning gate voltage to control molecular configurations.

A new flexible memory element is crucial for mobile and wearable electronics. A new concept for memory operation and innovative device structure with new materials is certainly required to address the bottleneck of memory applications now and in the future. We report a new nonvolatile molecular memory with a new operating mechanism based on two-dimensional (2D) material nanochannel field-effect transistors (FETs). The smallest channel length for our 2D material nanochannel FETs was approximately 30 nm. The modified molecular configuration for charge induced in the nanochannel of the MoS2 FET can be tuned by applying an up-gate voltage pulse, which can vary the channel conductance to exhibit memory states. Through controlling the amounts of triggered molecules through either different gate voltage pulses or gate duration time, multilevel states were obtained in the molecular memory. These new molecular memory transistors exhibited an erase/program ratio of more than three orders of current magnitude and high sensitivity, of a few picoamperes, at the current level. Reproducible operation and four-level states with stable retention and endurance were achieved. We believe this prototype device has potential for use in future memory devices.

Toward Antibiofouling PVDF Membranes.

Membranes for biologically and biomedically related applications must be bioinert, that is, resist biofouling by proteins, human cells, bacteria, algae, etc. Hydrophobic materials such as polysulfone, polypropylene, or poly(vinylidene fluoride) (PVDF) are often chosen as matrix materials but their hydrophobicity make them prone to biofouling, which in turn limits their application in biological/biomedical fields. Here, we designed PVDF-based membranes by precipitation from the vapor phase and zwitterionized them in situ to reduce their propensity to biofouling. To achieve this goal, we used a copolymer containing phosphorylcholine groups. An in-depth physicochemical characterization revealed not only the controlled presence of the copolymer in the membrane but also that bicontinuous membranes could be formed. Membrane hydrophilicity was greatly improved, resulting in the mitigation of a variety of biofoulants: the attachment of Stenotrophomonas maltophilia, Streptococcus mutans, and platelets was reduced by 99.9, 99.9, and 98.9%, respectively. Besides, despite incubation in a plasma platelet-poor medium, rich in plasma proteins, a flux recovery ratio of 75% could be measured while it was only 40% with a hydrophilic commercial membrane of similar structure and physical properties. Similarly, the zwitterionic membrane severely mitigated biofouling by microalgae during their harvesting. All in all, the material/process combination presented in this work leads to antibiofouling porous membranes with a large span of potential biomedically and biologically related applications.

On the risk concerns of zacopride, a moderate IK1 channel agonist with cardiac protective action.

Zacopride, an IK1 agonist with moderate potency, could exert significant antiarrhythmic and cardiac protective effects. To date, there is no report to show that zacopride is proarrhythmic in both experimental studies and clinical trials. However, in certain cardiac pathological conditions, especially short QT syndrome and certain reentry tachycardia, zacopride is not suggested. Further studies are needed to precisely evaluate the potential arrhythmogenic risk of zacopride.

Activation of IK1 channel by zacopride attenuates left ventricular remodeling in rats with myocardial infarction.

Activating IK1 channels is considered to be a promising antiarrhythmic strategy. Zacopride has been identified as a selective IK1 channel agonist and can suppress triggered arrhythmias. Whether this drug also exerts a beneficial effect on cardiac remodeling is unknown, and the present study sought to address this question. Cardiac remodeling was induced through coronary ligation-induced myocardial infarction (MI) in male Sprague-Dawley rats. Zacopride (15 µg/kg) was administered (intraperitoneally) daily for 28 days after MI to determine whether it could attenuate MI-induced cardiac remodeling. A 4-week treatment with zacopride attenuated post-MI cardiac remodeling, as shown by the reduced left ventricular end-diastolic dimension and left ventricular end-systolic dimension and the increased ejection fraction and fractional shortening in zacopride-treated animals compared with animals treated with vehicle (all P < 0.05). Furthermore, zacopride significantly decreased myocardial collagen deposition, cardiomyocyte hypertrophy, the plasma level of brain natriuretic peptide, and cardiomyocyte ultrastructural injury. Zacopride also upregulated the expression of the IK1 channel protein and downregulated the expression of phosphorylated p70S6 kinase (p-p70S6K) and mTOR. These beneficial effects of zacopride were partially abolished by the IK1 channel blocker chloroquine. We conclude that the activation of IK1 channel by zacopride attenuates post-MI cardiac remodeling by suppressing mTOR-p70S6 kinase signaling.

Revealing the spatiotemporal evolution pattern and convergence law of agricultural land transfer in China.

The transfer of land plays a crucial role in revitalizing land resources, acting as a catalyst for promoting the high-quality development of agriculture. The land transfer ratio is a crucial metric for assessing the progress of rural land transfer and the effective allocation of rural land resources. Thus, this study examines the rural land transfer ratio across 30 provinces in China from 2005 to 2020. The study explores the distribution characteristics of the ratio using the rank-size rule and trend surface analysis. The LISA space-time transition method is employed to analyze the spatial and temporal dynamics of the rural land transfer ratio and examine its convergence. The study aims to comprehensively analyze the spatial distribution characteristics and evolutionary patterns of rural land transfer in China, illustrating the convergence and influencing factors during the development process. The results indicate that: (1) The rural land transfer ratio in China is generally increasing, with a spatial pattern showing an upward trend from west to east and from north to south. The main spatial contrast is between the eastern and western regions, with a relatively minor distinction between the southern and northern regions. (2) The LISA space-time transition highlights a significant spatial locking effect in China's rural land transfer ratio, suggesting strong spatial integration in its evolution. (3) Clear indications of σ convergence, absolute ß convergence, and club convergence are evident in China's rural land transfer ratio. This suggests a gradual reduction in internal disparities among provinces and regions, where areas with higher land transfer ratios influence spatial spillover effects on adjacent lower areas. (4) Factors such as transportation infrastructure, irrigation, water conservancy construction, and farmers' per capita income collectively influence the spatial and temporal evolution of China's rural land transfer ratio, with dominant driving factors varying across different periods.

Energy-Trapping Characteristics of Lateral Field Excited GdCOB Crystal Bulk Acoustic Wave Devices Based on Stepped Electrodes.

In this work, high-frequency forced vibrations of lateral field excitation (LFE) devices with stepped electrodes based on monoclinic crystals GdCOB are modeled, and the influence laws of the device parameters (the step number, size, and thickness of the stepped electrodes) on the energy-trapping effects of the device are revealed. The results show that the step number has a significant effect on the energy-trapping effect of the device: with the increase in the step number, the stronger energy-trapping effect of the device can be obtained; with the increase in the thickness difference of two layers of electrodes, the energy-trapping effect of the device becomes stronger; with the increase in the difference of the electrode radius, the energy-trapping effect of the device is enhanced gradually. The results of this work can provide an important theoretical basis for the design of stepped-electrode LFE resonators and sensors with high-quality factors based on monoclinic crystals.

A novel discovery of IK1 channel agonist: zacopride selectively enhances IK1 current and suppresses triggered arrhythmias in the rat.

Modulation of the inward rectifier K current (IK1) has profound effect on cardiac excitability and underlies new antiarrhythmic strategies. However, IK1-specific pharmacological tools, especially the selective IK1 agonists, are still lacking in the market. Zacopride, a gastrointestinal prokinetic drug, was found to be a selective IK1 channel agonist. By using the whole-cell patch clamp technique, it was found that zacopride (0.1-10 µmole/L) dose dependently enhanced the IK1 current in isolated rat cardiomyocytes, had no effects on other ion channels, transporters, or pumps. At the same dosage range, zacopride hyperpolarized the resting potential and shortened the action potential duration. When applied at the optimal dose of 1.0 µmole/L, zacopride could prevent or eliminate aconitine induced after depolarization and triggered activity in isolated cardiomyocytes. In a rat model of aconitine-induced arrhythmias both ex vivo and in vivo, zacopride (1.0 µmole/L or 25 µg/kg, respectively) treatment apparently protected the heart from ventricular tachyarrhythmias, which compares favorably with 7.5 mg/kg of lidocaine, a classical aconitine antidote. In conclusion, zacopride was found to be a selective IK1 agonist, and agonizing IK1 could prevent or eliminate aconitine-induced arrhythmias in the rat.

[Cardiac inwardly rectifying potassium channel and arrhythmias].

The cardiac inwardly rectifying potassium channel (I(K1)), which is mainly expressed in mammalian atrial and ventricular myocytes, has been considered as the primary conductance controlling the resting potential (RP) and permitting a significant repolarizing current during the terminal phase of action potential. Therefore, I(K1) is highly influential on the RP, and the modulation of I(K1) would likely have profound effects on cardiac excitability and arrhythmogenesis. This article may shed light on the fundamental properties of cardiac I(K1), the mechanisms of inward rectification and I(K1) subunits composition. Furthermore, the article discusses the role of I(K1) in ventricular excitability and arrhythmogenesis and explores the possibility of modulating I(K1) as an antiarrhythmic mechanism. In fact, both blocking and enhancing I(K1) could be antiarrhythmic, but have proarrhythmic potential at the same time. Action potential duration (APD) prolongation has been accepted as an important antiarrhythmic strategy with some evidence in animal models of arrhythmogenesis that I(K1) blockade can prolongate APD and be antiarrhythmic. However, the potential of I(K1) blockade has not resulted in the development of specific I(K1) blockers used clinically. Safety concerns are probably the main reason, and the therapeutic potential for I(K1) blockers seems somewhat small. On the contrary, the up to date reports indicate that moderately activating I(K1) and hyperpolarizing the RP which has been depolarized by pathologic injury are to be feasible and effective to alleviate some kinds of ventricular arrhythmias.

Global Landscape of m6A Methylation of Differently Expressed Genes in Muscle Tissue of Liaoyu White Cattle and Simmental Cattle.

Liaoyu white cattle (LYWC) is a local breed in Liaoning Province, China. It has the advantages of grow quickly, high slaughter ratew, high meat quality and strong anti-stress ability. N6 methyladenosine (m6A) is a methylation modification of N6 position of RNA adenine, which is an important modification mechanism affecting physiological phenomena. In this study, we used the longissimus dorsi muscle of LYWC and SIMC for m6A-seq and RNA-seq high-throughput sequencing, and identified the key genes involved in muscle growth and m6A modification development by bioinformatics analysis. There were 31532 m6A peaks in the whole genome of LYWC and 47217 m6A peaks in the whole genome of SIMC. Compared with Simmental cattle group, LYWC group had 17,351 differentially expressed genes: 10,697 genes were up-regulated, 6,654 genes were down regulated, 620 differentially expressed genes were significant, while 16,731 differentially expressed genes were not significant. Among the 620 significantly differentially expressed genes, 295 genes were up-regulated and 325 genes were down regulated. In order to explore the relationship between m6A and mRNA expression in the muscles of LYWC and SIMC, the combined analysis of MeRIP-seq and RNA-seq revealed that 316 genes were m6A modified with mRNA expression. To identify differentially methylated genes related to muscle growth, four related genes were selected for quantitative verification in LYWC and SIMC. GO enrichment and KEGG analysis showed that the differentially expressed genes modified by m6A are mainly involved in skeletal muscle contraction, steroid biosynthesis process, redox process, PPAR pathway and fatty acid metabolism, and galactose metabolism. These results provide a theoretical basis for further research on the role of m6A in muscle growth and development.

Dynamic Polarization Behaviors of Equimolar CoCrFeNi High-Entropy Alloy Compared with 304 Stainless Steel in 0.5 M H2SO4 Aerated Aqueous Solution.

Three corrosion potentials and three corrosion current densities are clearly identified before the passivation for both dynamic polarization curves of equimolar CoCrFeNi high-entropy alloy (HEA) and 304 stainless steel (304SS) in 0.5 M H2SO4 aerated aqueous solution, by decomposing anodic and cathodic polarization curves. The passivated current density of the former is greater than the latter, compliant with not only the constant of solubility product (ksp) and redox equilibrium potential (Eeq) of each metal hydroxide but also the sequence of bond energy (Eb) for monolayer hydroxide on their facets derived from the first principle founded on density function theory. However, the total amount of ion releasing from HEA is less than 304SS, since the hydroxide/oxide film formed in the air of the latter containing greater amounts of Fe(Ⅱ) and Mn(Ⅱ) is less stable around corrosion potentials while they are further oxidized into more stable Fe(Ⅲ) and Mn(ⅢorⅣ) with much lower ksp, leading to the much less increasing ratios of ion releases from 0.25 to 0.6 V.

Tetramisole is a new IK1 channel agonist and exerts IK1 -dependent cardioprotective effects in rats.

Cardiac ischemia, hypoxia, arrhythmias, and heart failure share the common electrophysiological changes featured by the elevation of intracellular Ca2+ (Ca2+ overload) and inhibition of the inward rectifier potassium (IK1 ) channel. IK1 channel agonists have been considered a new type of anti-arrhythmia and cardioprotective agents. We predicted using a drug repurposing strategy that tetramisole (Tet), a known anthelminthic agent, was a new IK1 channel agonist. The present study aimed to experimentally identify the above prediction and further demonstrate that Tet has cardioprotective effects. Results of the whole-cell patch clamp technique showed that Tet at 1-100 µmol/L enhanced IK1 current, hyperpolarized resting potential (RP), and shortened action potential duration (APD) in isolated rat cardiomyocytes, while without effects on other ion channels or transporters. In adult Sprague-Dawley (SD) rats in vivo, Tet showed anti-arrhythmia and anticardiac remodeling effects, respectively, in the coronary ligation-induced myocardial infarction model and isoproterenol (Iso, i.p., 3 mg/kg/day, 10 days) infusion-induced cardiac remodeling model. Tet also showed anticardiomyocyte remodeling effect in Iso (1 µmol/L) infused adult rat ventricular myocytes or cultured H9c2 (2-1) cardiomyocytes. Tet at 0.54 mg/kg in vivo or 30 µmol/L in vitro showed promising protections on acute ischemic arrhythmias, myocardial hypertrophy, and fibrosis. Molecular docking was performed and identified the selective binding of Tet with Kir2.1. The cardioprotection of Tet was associated with the facilitation of IK1 channel forward trafficking, deactivation of PKA signaling, and inhibition of intracellular calcium overload. Enhancing IK1 may play dual roles in anti-arrhythmia and antiventricular remodeling mediated by restoration of Ca2+ homeostasis.

Cardioprotection of an IK1 channel agonist on L-thyroxine induced rat ventricular remodeling.

Downregulation of inward rectifier potassium (IK1) channel is a hallmark in cardiac hypertrophy and failure. The cardioprotection of zacopride (a selective IK1 agonist) and underlying mechanisms were investigated in L-thyroxine (T4) or Triiodothyronine (T3)-induced cardiac remodeling. In the in vivo study, adult male Sprague-Dawley (SD) rats were randomly divided into control, L-thyroxine, L-thy+zacopride, and L-thy+zacopride+chloroquine (an IK1 antagonist) groups. Echocardiography, histopathology, TUNEL assay, western blotting and confocal imaging for intracellular Ca2+ fluorescence were performed. In the in vitro study, zacopride and nifedipine (a LTCC blocker) were used to compare their effects on Kir2.1, SAP97, autophagy, and [Ca2+]i in H9C2 (2-1) cardiomyocytes. Zacopride treatment attenuated L-thyroxine- or T3 induced cardiac remodeling and dysfunction which manifested as cardiac hypertrophy and collagen deposition, dilated ventricle, decreased ejection fraction (EF), increased cardiomyocytes apoptosis, hyper-activation of CaMKII and PI3K/Akt/mTOR signaling, decreased cardiac autophagy, and increased expression of integrin ß3. The cardioprotection of zacopride is strongly associated with the upregulation of IK1, SAP97, and [Ca2+]i homeostasis in cardiomyocytes. IK1 antagonist chloroquine or BaCl2 reversed these effects. Nifedipine could attenuate intracellular Ca2+ overload with no significant effects on IK1, SAP97, and autophagy. This study showed that zacopride could improve cardiac remodeling via facilitating Kir2.1 forward trafficking, and negatively regulating calcium-activated and PI3K/Akt/mTOR signalings, in an IK1-dependent manner.