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Sarcoplasmic reticulum (SR) Ca2+ cycling is tightly regulated by ryanodine receptor (RyR) Ca2+ release and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) Ca2+ uptake during each excitation–contraction coupling cycle. We previously showed that RyR refractoriness plays a key role in the onset of SR Ca2+ alternans in the intact rabbit heart, which contributes to arrhythmogenic action potential duration (APD) alternans. Recent studies have also implicated impaired SERCA function, a key feature of heart failure, in cardiac alternans and arrhythmias. However, the relationship between reduced SERCA function and SR Ca2+ alternans is not well understood. Simultaneous optical mapping of transmembrane potential (Vm) and SR Ca2+ was performed in isolated rabbit hearts (n = 10) using the voltage-sensitive dye RH237 and the low-affinity Ca2+ indicator Fluo-5N-AM. Alternans was induced by rapid ventricular pacing. SERCA was inhibited with cyclopiazonic acid (CPA; 1–10 μM). SERCA inhibition (1, 5, and 10 μM of CPA) resulted in dose-dependent slowing of SR Ca2+ reuptake, with the time constant (tau) increasing from 70.8 ± 3.5 ms at baseline to 85.5 ± 6.6, 129.9 ± 20.7, and 271.3 ± 37.6 ms, respectively (p < 0.05 vs. baseline for all doses). At fast pacing frequencies, CPA significantly increased the magnitude of SR Ca2+ and APD alternans, most strongly at 10 μM (pacing cycle length = 220 ms: SR Ca2+ alternans magnitude: 57.1 ± 4.7 vs. 13.4 ± 8.9 AU; APD alternans magnitude 3.8 ± 1.9 vs. 0.2 ± 0.19 AU; p < 0.05 10 μM of CPA vs. baseline for both). SERCA inhibition also promoted the emergence of spatially discordant alternans. Notably, at all CPA doses, alternation of SR Ca2+ release occurred prior to alternation of diastolic SR Ca2+ load as pacing frequency increased. Simultaneous optical mapping of SR Ca2+ and Vm in the intact rabbit heart revealed that SERCA inhibition exacerbates pacing-induced SR Ca2+ and APD alternans magnitude, particularly at fast pacing frequencies. Importantly, SR Ca2+ release alternans always occurred before the onset of SR Ca2+ load alternans. These findings suggest that even in settings of diminished SERCA function, relative refractoriness of RyR Ca2+ release governs the onset of intracellular Ca2+ alternans. [ABSTRACT FROM AUTHOR]

Strata movement control during coal seam's backfill mining is very much related to the mechanical properties of backfill body in goaf. A mechanical model of the structural water-resistant strata (SWRS) of stope overburden in backfill water-preserved mining (BWPM) was established on the basis of the key strata theory in ground control. This approach was conducted to investigate the mechanical properties of backfill body on the overburden water-resistant strata stability. The proposed model was based on the compressive mechanical properties of the filled gangue, which considered the linear and nonlinear elastic mechanical properties of backfill body. The stability mechanics criterion of the SWRS of stope overburden in BWPM on the nonlinear elastic foundation was deduced by introducing the tensile yield criterion. The maximum tensile stress (MTS) that acts on the SWRS of stope overburden decreased with the increase of the backfill body's linear elastic foundation coefficient of k1 and the nonlinear elastic foundation coefficients of k2 and k3. However, the MTS rapidly decreased with the increase of k1 and slowly decreased with the increase of k2 and k3. The sensitivity analysis indicated that k1 exhibited the greatest effect on the MTS that acts on the SWRS, thereby accounting for 72.38%. In addition, k2 and k3 showed less effect on the MTS that acts on the SWRS, thereby only accounting for 19.56% and 8.06%, respectively. Results showed that the backfill body's linear elastic foundation coefficient plays a very important role in controlling the stability of the SWRS of stope overburden in BWPM. Increasing k1 is more beneficial to the stability control of the water-resistant strata of stope overburden than increasing k2 and k3, especially the latter. [ABSTRACT FROM AUTHOR]

The accurate determination of the height of the water-conducting fractured zone (HWCFZ) in a coal seam covered by thin bedrock and thick clay layer is crucial for aquifer protection, mine safety, and eco-environmental conservation. Using the Sanyuan coal mine in North China as a case study, theoretical analysis, numerical simulation, and field measurements were used to analyze the regularity of the HWCFZ in this area. Per mechanical theory, a geometrical model for calculating rock bending and subsidence was established. Two arcs of equal curvature and lengths and opposite curvature direction were used to fit the curve section of intermediate rock layer after bending. The theoretical method for solving the HWCFZ was given by calculating the rock layer's tensile ratio. In addition, rock failure process analysis (RFPA) software was used to simulate the development of the water-conducting fractured zone (WCFZ) during the mining process, and the HWCFZ was measured by the drilling fluid loss measurement, both which verified the feasibility of the theoretical calculation. To determine the primary controlling factors affecting the HWCFZ, the seepage characteristics and plastic properties of the Quaternary clay layer were also analyzed using laboratory tests. Results show that the Quaternary clay with a depth greater than 130 m has a permeability coefficient of E−10 m/s, a liquidity index less than 0.25, and a plasticity index more than 17, indicating the clay layer is impermeable and of great importance to inhibiting the development of WCFZ. The research can provide significant theoretical insights for effectively preventing water hazards on mine roofs. [ABSTRACT FROM AUTHOR]

Tight oil reservoirs account for a large portion of hydrocarbon resources in continental basins. The Chang 7 Member of the Upper Triassic Yanchang Formation in the Ordos Basin is a well-known high-quality source rock in China and considerable petroleum resources have been found in its tight oil sandstone reservoirs. This study uses thin sections, constant-rate mercury injection, mercury injection, scanning electron microscopy, and the fractal dimension to study its mineral compositions and pore structure and to discuss the effects of cement mineralogy and pore structure on reservoir physical property. Tight oil sandstone reservoirs in Chang 7 Member mainly consist of gray and grayish green medium-fine-grained lithic arkose, feldspathic litharenite, and litharenite. Feldspar dissolved pores are the most developed pores in the reservoirs, followed by intergranular pores and lithic dissolved pores. Throats of the reservoirs are mainly in pore shrinkage type, neck type, sheet type, and bent sheet type. The tight oil sandstone reservoirs have complex pore structure and with the increasing radius, the structure of throats becomes simpler, while the structure of pores becomes more complex. According to median radius of pore-throat, the maximum mercury intrusion saturation, and extrusion efficiency, the reservoirs can be divided into three types: micro throat-high mercury intrusion saturation type with high physical property, adsorptive throat-medium mercury intrusion saturation type with medium physical property, and micro adsorptive throat-low mercury intrusion saturation type with low physical property. Ferrocalcite and illite are the main cements reducing reservoir physical property, while chlorite cement can protect the reservoir physical property to some extent. In microscopic pore structure parameters, except pore-throat skewness, median radius of pore-throat, pore-throat ratio, pore-throat sorting coefficient, and the fractal dimension of big pore-throats, can affect reservoir physical property. [ABSTRACT FROM AUTHOR]

A mechanical model for the tilted workface floor along the tilted direction of coal seam was proposed. Stress expressions of an arbitrary point inside the tilted workface floor were deduced. Calculation formula for the maximum failure depth of the lateral floor strata of the tilted workface was also deduced. Based on the Mohr-Coulomb yield criterion, the tilted workface floor's stress distribution, and failure depth and shape were simulated by using FLAC3D software for different coal seam's dip angles, buried depths, and workface widths. Results show that the concentration coefficient, the peak value and the distance between the peak position of the lateral abutment pressure and the roadway on both sides of the tilted workface decreases with the increases in coal seam's dip angle. The vertical stress isoclines present a "spoon-shaped" distribution along the tilted direction of workface. Both sides of the workface form "bubble-shaped" distribution shear stress and its peak value increases first and then decreases with the increases in coal seam's dip angle and reaches maximum at 30°–35°. The tilted workface floor's plastic failure zone presents a "spoon-shaped" distribution along the tilted direction of workface, which is large on the lower side and small on the upper side. The plastic zone's failure depth increases first and then decreases with the increases in the dip angle of coal seam and reaches maximum at 30°. [ABSTRACT FROM AUTHOR]

Key points: Cardiac electrophysiology and Ca2+ handling change rapidly during the fight‐or‐flight response to meet physiological demands.Despite dramatic differences in cardiac electrophysiology, the cardiac fight‐or‐flight response is highly conserved across species.In this study, we performed physiological sympathetic nerve stimulation (SNS) while optically mapping cardiac action potentials and intracellular Ca2+ transients in innervated mouse and rabbit hearts.Despite similar heart rate and Ca2+ handling responses between mouse and rabbit hearts, we found notable species differences in spatio‐temporal repolarization dynamics during SNS.Species‐specific computational models revealed that these electrophysiological differences allowed for enhanced Ca2+ handling (i.e. enhanced inotropy) in each species, suggesting that electrophysiological responses are fine‐tuned across species to produce optimal cardiac fight‐or‐flight responses. Sympathetic activation of the heart results in positive chronotropy and inotropy, which together rapidly increase cardiac output. The precise mechanisms that produce the electrophysiological and Ca2+ handling changes underlying chronotropic and inotropic responses have been studied in detail in isolated cardiac myocytes. However, few studies have examined the dynamic effects of physiological sympathetic nerve activation on cardiac action potentials (APs) and intracellular Ca2+ transients (CaTs) in the intact heart. Here, we performed bilateral sympathetic nerve stimulation (SNS) in fully innervated, Langendorff‐perfused rabbit and mouse hearts. Dual optical mapping with voltage‐ and Ca2+‐sensitive dyes allowed for analysis of spatio‐temporal AP and CaT dynamics. The rabbit heart responded to SNS with a monotonic increase in heart rate (HR), monotonic decreases in AP and CaT duration (APD, CaTD), and a monotonic increase in CaT amplitude. The mouse heart had similar HR and CaT responses; however, a pronounced biphasic APD response occurred, with initial prolongation (50.9 ± 5.1 ms at t = 0 s vs. 60.6 ± 4.1 ms at t = 15 s, P < 0.05) followed by shortening (46.5 ± 9.1 ms at t = 60 s, P = NS vs. t = 0). We determined the biphasic APD response in mouse was partly due to dynamic changes in HR during SNS and was exacerbated by β‐adrenergic activation. Simulations with species‐specific cardiac models revealed that transient APD prolongation in mouse allowed for greater and more rapid CaT responses, suggesting more rapid increases in contractility; conversely, the rabbit heart requires APD shortening to produce optimal inotropic responses. Thus, while the cardiac fight‐or‐flight response is highly conserved between species, the underlying mechanisms orchestrating these effects differ significantly. Key points: Cardiac electrophysiology and Ca2+ handling change rapidly during the fight‐or‐flight response to meet physiological demands.Despite dramatic differences in cardiac electrophysiology, the cardiac fight‐or‐flight response is highly conserved across species.In this study, we performed physiological sympathetic nerve stimulation (SNS) while optically mapping cardiac action potentials and intracellular Ca2+ transients in innervated mouse and rabbit hearts.Despite similar heart rate and Ca2+ handling responses between mouse and rabbit hearts, we found notable species differences in spatio‐temporal repolarization dynamics during SNS.Species‐specific computational models revealed that these electrophysiological differences allowed for enhanced Ca2+ handling (i.e. enhanced inotropy) in each species, suggesting that electrophysiological responses are fine‐tuned across species to produce optimal cardiac fight‐or‐flight responses. [ABSTRACT FROM AUTHOR]

Preconditioning limits mitochondrial [Ca.sup.2+] during ischemia in rat hearts: role of [K.sub.ATP] channels. Am J Physiol Heart Circ Physiol 280: H2321-H2328, 2001.--Prolonged myocardial ischemia results in an increase in intracellular calcium concentration ([[[Ca.sup.2+]].sub.i]), which is thought to play a critical role in ischemia-reperfusion injury. Ischemic preconditioning (PC) improves myocardial function during ischemia-reperfusion, a process that may involve opening mitochondrial ATP-sensitive potassium ([K.sub.ATP]) channels. Because pharmacological limitation of mitochondrial calcium concentration ([[[Ca.sup.2+]].sub.m]) overload during ischemia-reperfusion has been shown to improve myocardial function, we hypothesized that PC would reduce [[[Ca.sup.2+]].sub.m] during ischemia-reperfusion and that this effect was mediated by opening mitochondrial [K.sub.ATP] channels. Isolated rat hearts were subjected to 25 min of global ischemia and 30 min of reperfusion with or without PC in the presence of mitochondrial [K.sub.ATP] channel opening (diazoxide, 100 [micro]M) and blockade [5-hydroxydecanoic acid (5-HD), 100 [micro]M]. Contracture during ischemia (end-diastolic pressure) and functional recovery on reperfusion (developed pressure) were assessed. Total [[[Ca.sup.2+]].sub.i] and [[[Ca.sup.2+]].sub.m] were measured using indo 1 fluorescence. Both PC and diazoxide limited the increase in end-diastolic pressure and resulted in greater functional recovery after 30 min of reperfusion, functional effects that were partially or completely abolished by 5-HD. PC and diazoxide also significantly limited the increase in [[[Ca.sup.2+]].sub.m] during ischemia-reperfusion. In addition, PC lowered [[[Ca.sup.2+]].sub.i] during reperfusion, whereas diazoxide paradoxically resulted in increased [[[Ca.sup.2+]].sub.i] during reperfusion. There was an inverse linear relationship between [[[Ca.sup.2+]].sub.m] and developed pressure during reperfusion. PC limits the ischemia-induced increase in mitochondrial, but not total, [[[Ca.sup.2+]].sub.i], an effect mediated by opening mitochondrial [K.sub.ATP] channels. These data suggest that the lowering of mitochondrial calcium overload is a mechanism of cardioprotection in PC. ischemia; reperfusion; mitochondria; calcium

• A versatile hybrid nanoplatform with great stability was synthesized through the self-polymerization of dopamine on the surfaces of Prussian blue nanoparticle. • Our synthesized nanocomposites possess precise photothermal conversion capacity for exhibiting anti-plaque photothermal therapy under NIR laser in mild temperature. • PP NPs scavenge excess ROS in gingival tissues due to their intrinsic enzyme-like characteristics and acceleration of the irradiation of NIR laser. Given the limitations of clinical curettage for periodontitis, the thorough removal of dental plaque at deep periodontal pockets and periodontal tissue repair require improvement with the assistance of appropriate medical therapy. Despite the significant developments of various local drug delivery systems (LDDSs) for adjuvant periodontitis therapy, several issues exist, such as the relatively low anti-biofilm effect and the tissue damage caused by excessive reactive oxygen species (ROS). To address the issues, we fabricated the versatile nanoplatforms (PPM NPs) via coating polydopamine (PDA) on the surface of monodispersed Prussian blue nanoparticles (PB NPs) through the facile yet efficient self-polymerization of dopamine (PP NPs), and then loading minocycline (Mino). Notedly, these integrative nanocomposites-based PB NPs as photothermal agents enhanced the therapeutic effect of plaque biofilms in vitro utilizing the antibacterial photothermal therapy (PTT) under irradiation of NIR laser. Further, the designed nanocomposites efficiently scavenged ROS over oxidative-stress Raw267.4 cells and human periodontal ligament cells, attributing to the enzyme-like activity of PB nanozymes and the reducibility of catechol in PDA. In vitro and in vivo consequences demonstrate the significantly augmented antibacterial and anti-inflammatory effects from the live/dead staining of biofilms and western blot results of inflammatory factors compared with free Mino solution in periodontitis. Our fabricated nanoplatforms-based PB NPs conveniently modified with PDA not only significantly improved the antibacterial effect via the combinational therapies but also efficiently scavenged cellular ROS utilizing the enzyme-like activity of nanozymes contributing to the treatment of periodontitis. [ABSTRACT FROM AUTHOR]