Purpose
The aim of the present study was to evaluate the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of remimazolam besylate following single ascending dose (SAD) and continuous ...infusion in healthy Chinese volunteers.
Methods
This was a randomized phase I study conducted in two parts. Part I was a double-blind, placebo- and midazolam-controlled, SAD study among healthy Chinese participants with a remimazolam dose of 0.025–0.4 mg/kg. Part II was an open-label, midazolam-controlled, continuous infusion study. Bispectral index (BIS) monitoring and Modified Observers Assessment of Alertness and Sedation (MOAA/S) score assessment were used to assess the PD properties.
Results
The half-life range of remimazolam was from 34.1 ± 8.1 to 59.8 ± 20.5 min in the SAD study. The sedation function was initially observed at the dose of 0.05 mg/kg remimazolam. Doses of ≥ 0.075 mg/kg exerted a peak sedation effect within 1–2 min after injection, resulting in a deeper and more rapid sedation. In the 2 h continuous infusion, remimazolam showed a deeper sedation and more rapid recovery than midazolam. For general anesthesia, an induction dosage of 0.2 mg/kg/min and a maintenance dosage of 1 mg/kg/h can achieve a satisfactory efficacy effect.
Conclusions
Remimazolam was safe and well tolerated in healthy Chinese participants. Based on the phase I clinical study, we suggest that remimazolam besylate demonstrates greater sedation and quicker recovery from sedation than midazolam.
Aqueous Zn-ion batteries (ZIBs) are a potential electrochemical energy storage device because of their highly intrinsic safety, low cost, and large capacity. However, it is still in the primary stage ...because of the limited selection of cathode materials with high rate and long-life cycling stability. In addition, the energy storage mechanisms of ZIBs have not been well established. In this work, we report the synthesis of porous V2O3@C materials with high conductivity and further illustrate its application as the intercalation cathode for aqueous zinc-ion batteries. The unique channel and appropriate pore size distribution of corundum-type V2O3 are beneficial to the rapid zinc ion intercalation and removal, leading to a high rate capability. Also, the carbon framework structure achieves a high cyclic stability. The porous V2O3@C cathode delivers high capacities of 350 mA h g–1 at 100 mA g–1, an excellent rate capability (250 mA h g–1 at 2 A g–1), and an impressive long-life cycling stability with 90% capacity retention over 4000 cycles at 5 A g–1. The storage mechanism of zinc ions in the Zn/V2O3 system was studied by various analytical methods and first-principles calculation.
We simulate vibrational strong coupling (VSC) and vibrational ultrastrong coupling (V-USC) for liquid water with classical molecular dynamics simulations. When the cavity modes are resonantly coupled ...to the O—H stretch mode of liquid water, the infrared spectrum shows asymmetric Rabi splitting. The lower polariton (LP) may be suppressed or enhanced relative to the upper polariton (UP) depending on the frequency of the cavity mode. Moreover, although the static properties and the translational diffusion of water are not changed under VSC or V-USC, we do find the modification of the orientational autocorrelation function of H2O molecules especially under V-USC, which could play a role in ground-state chemistry.
Identifying the timing of formation and geochemical nature of the Cenozoic granites along the Himalayan orogen is essential to test or formulate models that link crustal anatexis with tectonic ...transition during the evolution of large-scale collisional orogenic belts. The Malashan gneiss dome, one of the prominent domes within the Tethyan Himalaya, experienced Barrovian-type metamorphism and partial melting of pelitic rocks at relatively deep levels during the collision between India and Eurasia. New LA-MC-ICP-MS zircon U–Pb analyses yielded that the Malashan two-mica granites formed at a time span of 17.6±0.1 to 16.9±0.1Ma. The Malashan two-mica granites are characterized by: (1) high SiO2 (>71.3wt.%), Al2O3 (>14.8wt.%), and relatively high CaO (>1.3wt.%); (2) relatively high Sr (>146ppm), but low Rb/Sr ratios (<1.3) which are nearly constant relative to large variations in Ba concentrations; (3) enrichment in LREE, depletion in HREE, and no or weak negative Eu anomalies (Eu/Eu∗=0.7–0.9); (4) as compared to granites in the other Northern Himalayan Gneiss Domes and High Himalayan Belt, relatively lower initial 87Sr/86Sr ratios (0.7391–0.7484) and similar unradiogenic Nd isotope compositions (εNd(t)=−13.7 to −14.4). These characteristics imply that the two-mica granites were derived from fluid-fluxing melting of metapelite, possibly triggered by the E–W extension. Our new data in combination with literature data indicate that there are three types of granites with diverse geochemical characteristics and distinct formation mechanisms along the Himalayan orogen since the Cenozoic India–Eurasia continental collision. Conceivably, our new results will provide new insights on how the partial melting behavior of relatively deeper crustal rocks evolved as the tectonic evolution of large orogenic belts.
Primary cilia are distributed extensively within the corneal epithelium and endothelium. However, the presence of cilia in the corneal stroma and the dynamic changes and roles of endothelial and ...stromal cilia in corneal homeostasis remain largely unknown. Here, we present compelling evidence for the presence of primary cilia in the corneal stroma, both in vivo and in vitro. We also demonstrate dynamic changes of both endothelial and stromal cilia during corneal development. In addition, our data show that cryoinjury triggers dramatic cilium formation in the corneal endothelium and stroma. Furthermore, depletion of cilia in mutant mice lacking intraflagellar transport protein 88 compromises the corneal endothelial capacity to establish the effective tissue barrier, leading to an upregulation of α‐smooth muscle actin within the corneal stroma in response to cryoinjury. These observations underscore the essential involvement of corneal endothelial and stromal cilia in maintaining corneal homeostasis and provide an innovative strategy for the treatment of corneal injuries and diseases.
How metazoan mechanotransduction channels sense mechanical stimuli is not well understood. The NOMPC channel in the transient receptor potential (TRP) family, a mechanotransduction channel for ...Drosophila touch sensation and hearing, contains 29 Ankyrin repeats (ARs) that associate with microtubules. These ARs have been postulated to act as a tether that conveys force to the channel. Here, we report that these N-terminal ARs form a cytoplasmic domain essential for NOMPC mechanogating in vitro, mechanosensitivity of touch receptor neurons in vivo, and touch-induced behaviors of Drosophila larvae. Duplicating the ARs elongates the filaments that tether NOMPC to microtubules in mechanosensory neurons. Moreover, microtubule association is required for NOMPC mechanogating. Importantly, transferring the NOMPC ARs to mechanoinsensitive voltage-gated potassium channels confers mechanosensitivity to the chimeric channels. These experiments strongly support a tether mechanism of mechanogating for the NOMPC channel, providing insights into the basis of mechanosensitivity of mechanotransduction channels.
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•ARs are essential for NOMPC mechanogating in vitro and in vivo•Microtubule association is required for NOMPC mechanogating•ARs are a main component of the filaments that tether NOMPC to microtubules•Transferring the ARs to voltage-gated potassium channels confers mechanosensitivity
Study of mechanotransduction channel NOMPC reveals a tether mechanism of mechanogating in which the N-terminal ARs of NOMPC form a tether linking the channel and the microtubules that convey force exerted via cell deformation to gate the channel and activate touch-sensitive neurons.
Within the Himalayan collisional belt, granotoids occur along two sub-parallel belts, the Northern Himalayan Gneiss Domes (NHGD) and the High Himalayan Crystalline Series (HHCS). In the Yardoi area ...of NHGD, two-mica granite, a new type granite occurs in the core of the Yardoi gneiss dome (YGD), Dala and Quedang from north to south, and extends at least 50km long. These granites have similar mineral composition, elemental and radiogenic isotope geochemistry, and age of formation. SHRIMP zircon U/Pb dating indicates that the Yardoi and the Quedang two-mica granites formed at 42.6±1.1Ma and 42.8±0.6Ma, respectively, similar to the Dala pluton. These two-mica granites have (1) high SiO2 (>68wt.%), Al2O3 (>15wt.%), and A/CNK(>1.0); (2) relatively high Sr and LREE, but low Y(<10ppm) and Yb (<1ppm); (3) high Sr/Y (>40 and up to 250) and La/Yb (>30); (4) very weak or no Eu anomalies; and (5) as compared with those in the Himalayan leucogranites, low initial Sr (87Sr/86Sr(i)<0.7120) and similarly unradiogenic Nd (εNd(i)=−8.9–−15.0) isotopic compositions. These granites have initial Sr and Nd isotope compositions similar to those in the amphibolites but significantly different from those in the metapelite and granitic gneiss. Two-mica granites from the Yardoi area are of peraluminous granite with relatively high Na/K and Sr/Y ratios. Such features are distinct from those in the younger leucogranites along the HHCS as well as in the NHGD, and require melting of source consisting dominantly of amphibolite at thickened crustal conditions. This is also supported by the presence of amphibolites with similar Sr and Nd isotope compositions, and similar ages of metamorphism. Two-mica granites of similar age also occur in the other NHGD gneiss domes and along the HHCS belt, implying that Mid-Eocene melting of thickened crustal materials was widespread and might be a primary factor that led to the formation of high density materials (e.g. eclogitic rocks) beneath the Tethyan Himalaya.
► The Yardoi two-mica granites in the NHGD formed at ~43-44 Ma. ► Amphibolite experienced high grade metamorphism and partial melting at ~43 Ma. ► These high Sr/Y granites were derived from high pressure melting of amphibolite.
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•Unique hierarchical CoS2 nanosheet arrays coated on carbon cloth are fabricated.•The formation mechanism and influence of vulcanizing agent activity are meticulously analyzed.•The ...structural superiorities of the electrode are explored by electrochemical characterization.•An all-solid-state flexible HSC delivers ultrahigh energy and power densities.•The HSC also exhibits good reliability under mechanical deformations and thermal circumstances.
Although all-solid-state hybrid supercapacitors (HSCs) based on cobalt sulfides are revealed to procure high density of redox species, their rate performance and power are severely restricted by adverse bulk structure of the electrode materials. Here, through regulating the sulfuric agents with mutative activities to rationally vulcanize cobalt-MOF, we fabricate hierarchical CoS2 nanosheet arrays directly coated on the conductive carbon cloth (CC@CoS2). These nanosheets are featured with unique macropore-mesopore-micropore porous architecture providing multi-level channels for rapid diffusion of ions, as well as abundant periphery sites from the refined nanoparticles in favor of the pseudocapacitive reaction. Electrochemical studies indicate that the structural superiorities of the CC@CoS2 effectually accelerate ions diffusion and retard the kinetic hysteresis. Consequently, an all-solid-state HSC with the CC@CoS2 and nitrogen-doped carbon nanosheet arrays grown vertically on carbon cloth as cathode and anode, respectively, achieves synchronous high energy density of 3.16 mWh·cm−3 and power density up to 1.61 W·cm−3, as well as robust cyclic stability (86.2% retention after 16,000 cycles). Besides, the electrochemical behavior of the HSC also shows good reliability under multiple mechanical deformation conditions and thermal circumstances. This work demonstrates a universal, effective strategy to produce advanced textile electrodes for flexible all-solid-state energy storage applications.
•Methods to measure the albedo of limited-extent targets are summarized.•A new mask-free method is proposed.•The mask-free method does not need a known-albedo mask(s) for calibration.
Albedo is a ...non-dimensional parameter used to quantify the proportion of solar radiation reflected by a surface. While a couple of methods are available for measuring the albedo of limited-extent targets, these methods require known-albedo mask(s) for calibration, which interrupt the measurement by manual intervention and make continuous albedo measurements difficult. Here we propose a mask-free method for measuring the albedo of limited-extent diffuse targets without the aid of known-albedo masks for calibration. The albedo of a limited extent target can be measured by leveling an albedometer over the target and assembling a baffle around the lower detector of the albedometer to make the detector receive reflected radiation from the target only. The view factor from the detector through the baffle to the target is found by leveling the albedometer over a large open field with uniform background and then dividing the reflected radiation at the baffle-on case from that at the baffle-off case. Albedos of seven 1 m × 1 m flexible uniform sheets with different colors were measured using the proposed mask-free method and the methods with known-albedo masks for calibration. The results indicated that the mask-free method measured the albedo of limited extent targets as accurately as the methods with known-albedo masks for calibration.
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