Mechanotransduction couples mechanical stimulation with ion flux, which is critical for normal biological processes involved in neuronal cell development, pain sensation, and red blood cell volume ...regulation. Although they are key mechanotransducers, mechanosensitive ion channels in mammals have remained difficult to identify. In 2010, Coste and colleagues revealed a novel family of mechanically activated cation channels in eukaryotes, consisting of Piezo1 and Piezo2 channels. These have been proposed as the long-sought-after mechanosensitive cation channels in mammals. Piezo1 and Piezo2 exhibit a unique propeller-shaped architecture and have been implicated in mechanotransduction in various critical processes, including touch sensation, balance, and cardiovascular regulation. Furthermore, several mutations in Piezo channels have been shown to cause multiple hereditary human disorders, such as autosomal recessive congenital lymphatic dysplasia. Notably, mutations that cause dehydrated hereditary xerocytosis alter the rate of Piezo channel inactivation, indicating the critical role of their kinetics in normal physiology. Given the importance of Piezo channels in understanding the mechanotransduction process, this review focuses on their structural details, kinetic properties and potential function as mechanosensors. We also briefly review the hereditary diseases caused by mutations in Piezo genes, which is key for understanding the function of these proteins.
An unprecedented copper-catalyzed reaction of sulfoxonium ylides and anthranils is reported that enables an easy access to 2,3-diaroylquinolines through a 4+1+1 annulation. Copper-catalyzed ...homocoupling of sulfoxonium ylides provided α,α,β-tricarbonyl sulfoxonium ylides, which provides a strategy to extend the carbon chain through C–C bond formation. The utility of the products as well as the mechanistic details of the process are presented.
A highly regioselective C–C bond cleavage/double cyclization of α‐ketoamides with o‐phenylene diamines has been developed for the synthesis of benzimidazo1,2‐cquinazolin‐6‐ones. Two new C–N and one ...new C=N bonds are simultaneously formed in the reaction, providing the gateway to access these fused heterocyclic scaffolds via copper catalysis under air atmosphere. This new protocol provides a novel and important foundation for the preparation of these heterocycles.
α‐Ketoamides have been successfully employed to synthesize benzimidazo1,2‐cquinazolin‐6‐ones through C–C bond cleavage/double cyclization, in which two new C–N and one new C=N bonds are simultaneously formed by copper catalysis under air atmosphere. This new protocol provides an important foundation for the preparation of benzimidazo1,2‐cquinazolin‐6‐ones in high yields.
Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with ...stroke due to intracerebral haemorrhage.
We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214.
We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio aOR 0·88, 95% CI 0·76–1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 9% deaths in the tranexamic acid group vs 123 11% deaths in the placebo group; aOR 0·73, 0·53–0·99, p=0·0406), there was no difference in case fatality at 90 days (250 22% vs 249 21%; adjusted hazard ratio 0·92, 95% CI 0·77–1·10, p=0·37). Fewer patients had serious adverse events after tranexamic acid than after placebo by days 2 (379 33% patients vs 417 36% patients), 7 (456 39% vs 497 43%), and 90 (521 45% vs 556 48%).
Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect.
National Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation.
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•A novel CP-based luminescent sensor was synthesized for simultaneous recognition of ascorbic acid and acetylacetone.•Both proposed sensing systems showed excellent performance with ...high KSV values and low limit of detection (LOD).•Probable sensing mechanism of CP 1 to the two types of analytes are discussed in more detail.
A new coordination polymer (CP), Co(μ3-HL)(μ-bpp)(H2O)n1 (H3L = 5-(3,4-dicarboxylphenoxy) nicotinic acid, bpp = 1,2-bis (4-pyridyl) propane)) has been successfully prepared under solvothermal conditions. Single-crystal X-ray diffraction analysis demonstrates that compound 1 possesses a 2-D layer structure with (3-c)(4-c) 2-nodal (42ˑ63ˑ8) (42ˑ6) topology, which then self-assembles into a final 3-D supramolecular network via the interlayer π⋯π interactions. Magnetic studies indicate that there exist weak-anti-ferromagnetic exchange interactions between CoII ions. More importantly, compound 1 represents a rare example of a fluorescent CP sensor which can dually probe ascorbic acid (AA) and acetylacetone (acac) in aqueous solution. The probable sensing mechanism of both analytes has also been discussed in this paper.
Memristors have been widely studied as artificial synapses in neuromorphic circuits, due to their functional similarity with biological synapses, low operating power, and high integration density. ...Currently, the synaptic weight symbolic limitation and weight update inaccuracy are two challenging issues to be solved. In this work, a novel memristive synapse and a matched mixed-signal neuron circuit are designed to implement robust yet accurate spike-timing-dependent plasticity learning in excitatory and inhibitory synapses. To break through the weight symbolic limitation, a four memristors and two resistors (4M2R) synapse composed of 4M2R for spiking neural network (SNN) is designed. The proposed synapse can be either excitatory or inhibitory (E/I) by rationally arranging the resistors in the circuit, and it is the first of its kind, enabling Hebbian and anti-Hebbian training without additional adjusting of neural signals. In addition, the high symmetricity, linearity, and stability against device variation of the 4M2R synapse can also greatly improve the weight update accuracy. To further address the inaccurate weight update issue caused by signal complexity, a neuron circuit is designed to generate square-wave pulses for spike transmission and synaptic weight modulation. Simulations are carried out in the MATLAB Simscape as well as Virtuoso using SMIC 0.18 <inline-formula> <tex-math notation="LaTeX">\mu </tex-math> </inline-formula>m process and a specially developed memristor model for SNN synapse simulation. The simulating results show good agreement with the weight change derived from the algorithmic methods, and the influence of weak signal-induced weight variation on circuit performance can be rigorously assessed.
•The effective segregation coefficient of Ce in Cs2LiYCl6 (CLYC) crystals is 0.22.•The scintillation properties of Ce-doped CLYC crystals are nonuniform across the length of the ingot.•Appropriate Ce ...doping concentration (2 %) was proposed.
Ce-doped Cs2LiYCl6 (CLYC) has widespread applications in homeland security owing to its excellent neutron/gamma discrimination ability. Ce3+ ions, as luminescent centers of CLYC, have a significant difference in effective ionic radius compared with Y3+, hinting at the severe inhomogeneous distribution of Ce3+ in CLYC. Still, only the relation between scintillation properties and nominal doping concentrations in CLYC crystals has been reported. The segregation behavior of Ce3+ ions along the ingot are still open for research. Herein, we measured the actual Ce3+ doping concentration along the CLYC ingot. Gamma-ray energy spectrum and powder XRD patterns of different samples were utilized to study the effects of Ce segregation on CLYC crystals. The effective segregation coefficient of Ce in CLYC crystals, keff = 0.22, was calculated. In most part of the ingots, the concentration of Ce3+ ions was lower than the nominal doping amount and rose rapidly at the tail. The scintillation properties of CLYC crystals along the ingot were affected by the distribution of Ce concentrations. This work may guide the optimization of properties for large-size CLYC crystals by modifying the distribution of Ce3+ ions.
The direct synthesis of metastable olivine phase NaMnPO4 still remains a challenge. In this study, single crystals of the olivine NaMnPO4 were synthesized for the first time by a facile hydrothermal ...reaction. Single-crystal X-ray diffraction analysis provides precise structure information on the olivine structure of NaMnPO4. Moreover, the olivine NaMnPO4 can be completely transformed to its maricite phase after heating at 600 °C under Ar atmosphere, confirming the metastable nature of the olivine phase. Electrochemical performance of the olivine NaMnPO4 as anode material for Li-ion batteries (LIBs) was characterized. It delivers a capacity of 645.0 mAh g−1 at 0.1 A g−1 after 200 cycles. In contrast, the maricite phase NaMnPO4 exhibits very low lithium storage capacity.
Single crystals of the metastable olivine phase NaMnPO4 were synthesized for the first time which exhibits much higher capacity as anode material of Li-ion batteries than that of the maricite phase. Display omitted
•Single crystals of the metastable olivine phase NaMnPO4 were synthesized for the first time.•The olivine to maricite phase transformation of NaMnPO4 was verified.•The olivine phase NaMnPO4 exhibits much higher capacity than maricite phase as anode material of Li-ion battery.
The copper hydroxyphosphate Cu
2
(OH)PO
4
was synthesized under mild hydrothermal conditions and structurally characterized by single-crystal X-ray diffraction. The electrochemical performance of Cu
...2
(OH)PO
4
as anode material for lithium-ion batteries (LIBs) was investigated. The Cu
2
(OH)PO
4
anode delivers a capacity of 741.1 mAh g
−1
at 0.1 A g
−1
over 300 cycles. The electrochemical and structural analyses suggest that the Cu
2
(OH)PO
4
anode undergoes the conversion reaction with Li
+
ions during lithium storage process. The in situ generated ion conductive Li
3
PO
4
is much beneficial to enhance Li
+
diffusion that leads to good rate capability and cycling stability. Besides the diffusion-controlled process, the surface capacitive effect also considerably contributes to the achieved capacity of the electrode. The results indicate that the polyanionic metal phosphate compounds are potential candidates for conversion-type anode materials for LIBs.
COVID-19 is an acute, complex disorder that was caused by a new β-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on current reports, it was surprising that the ...characteristics of many patients with COVID-19, who fulfil the Berlin criteria for acute respiratory distress syndrome (ARDS), are not always like those of patients with typical ARDS and can change over time. While the mechanisms of COVID-19–related respiratory dysfunction in COVID-19 have not yet been fully elucidated, pulmonary microvascular thrombosis is speculated to be involved. Considering that thrombosis is highly related to other inflammatory lung diseases, immunothrombosis, a two-way process that links coagulation and inflammation, seems to be involved in the pathophysiology of COVID-19, including respiratory dysfunction. Thus, the current manuscript will describe the proinflammatory milieu in COVID-19, summarize current evidence of thrombosis in COVID-19, and discuss possible interactions between these two.
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