Calcium-Dependent Protein Kinase 5 and 13 enhance salt tolerance in rice by directly activating OsMPK3/6 kinases.

Mitogen-activated protein kinases (MAPKs/MPKs) are pivotal regulators in many stress-signaling pathways in plants. The dual phosphorylation of the TXY motif by MAP Kinase Kinases (MKKs) is essential for activating MAPKs. Here, we reveal a mechanism for MAPK activation that bypasses the need for MKKs. We identified rice (Oryza sativa) calcium-dependent protein kinase 5 (OsCPK5) and OsCPK13as positive regulators in salt stress tolerance. These kinases are essential for the full activation of OsMPK3 and OsMPK6 in response to elevated sodium levels, with both OsMPK3 and OsMPK6 also acting as positive regulators in rice salt tolerance. Biochemical analysis demonstrated that OsCPK5/13 directly interact with and activate OsMPK3/6 by phosphorylating the TXY motif in vitro and in vivo. Additionally, we have discovered that OsCPK5/13 relocate from the cell membrane to the nucleus in response to salt stress. This process relies on their N-terminal myristoylation and a calcium-dependent phosphorylation event within the N-terminus. Our results elucidate a MAPK activation pathway in rice that is independent of traditional MKK-mediated phosphorylation, highlighting the crucial roles of OsCPK5 and OsCPK13 in directly phosphorylating and activating OsMPK3/6, which are important for rice tolerance to salt stress.

Catalyst Selection over an Electrochemical Reductive Coupling Reaction toward Direct Electrosynthesis of Oxime from NOx and Aldehyde.

Aqueous electrochemical coupling reactions, which enable the green synthesis of complex organic compounds, will be a crucial tool in synthetic chemistry. However, a lack of informed approaches for screening suitable catalysts is a major obstacle to its development. Here, we propose a pioneering electrochemical reductive coupling reaction toward direct electrosynthesis of oxime from NOx and aldehyde. Through integrating experimental and theoretical methods, we screen out the optimal catalyst, i.e., metal Fe catalyst, that facilitates the enrichment and C-N coupling of key reaction intermediates, all leading to high yields (e.g., ∼99% yield of benzaldoxime) for the direct electrosynthesis of oxime over Fe. With a divided flow reactor, we achieve a high benzaldoxime production of 22.8 g h-1 gcat-1 in ∼94% isolated yield. This work not only paves the way to the industrial mass production of oxime via electrosynthesis but also offers references for the catalyst selection of other electrochemical coupling reactions.

Co─Mn Bimetallic Nanowires by Interfacial Modulation with/without Vacancy Filling as Active and Durable Electrocatalysts for Water Splitting.

Active and stable nonnoble electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are required for water splitting by sustainable electricity. Here, Mn bonded with O and P is incorporated to modulate Co3S4 and Co2P respectively to enhance the catalytic activity and extend the catalyst lifetime. Mn3O4 adjusts the electronic structure of Co3S4 and Co atom fills the oxygen vacancy in Mn3O4. The interfacial interaction endows Co3S4/Mn3O4 to a lower reaction barrier due to ideal binding energies for OER intermediates. Structure stability of active sites and enhanced Co─S bonds by Operando Raman spectroscopy and theoretical calculations reduce the dissolution of Co3S4/Mn3O4, resulting in a lifetime of 500 h at 50 mA cm-2 for OER. The modulation of Co2P by MnP weakens the interaction between Co sites and adsorbed H*, achieving a high activity under a large current for HER. The assembled electrolyzer affords 50 mA cm-2 at 1.58 V and exhibits a lifetime of 350 h at 50 mA cm-2. The calculations disclose the electron interaction for the activity and stability, as well as the enhanced conductivity. The findings develop new avenues toward promoting catalytic activity and stability, making Co─Mn bimetallic nanowires efficient electrocatalysts for nonnoble water electrolyzers.

Strong Interface Coupling Enables Stability of Amorphous Meta-Stable State in CoS/Ni3S2 for Efficient Oxygen Evolution.

Rational design of heterostructure catalysts through phase engineering strategy plays a critical role in heightening the electrocatalytic performance of catalysts. Herein, a novel amorphous/crystalline (a/c) heterostructure (a-CoS/Ni3S2) is manufactured by a facile hydrothermal sulfurization method. Strikingly, the interface coupling between amorphous phase (a-CoS) and crystalline phase (Ni3S2) in a-CoS/Ni3S2 is much stronger than that between crystalline phase (c-CoS) and crystalline phase (Ni3S2) in crystalline/crystalline (c/c) heterostructure (c-CoS/Ni3S2) as control sample, which makes the meta-stable amorphous structure more stable. Meanwhile, a-CoS/Ni3S2 has more S vacancies (Sv) than c-CoS/Ni3S2 because of the presence of an amorphous phase. Eventually, for the oxygen evolution reaction (OER), the a-CoS/Ni3S2 exhibits a significantly lower overpotential of 192 mV at 10 mA cm-2 compared to the c-CoS/Ni3S2 (242 mV). An exceptionally low cell voltage of 1.51 V is required to achieve a current density of 50 mA cm-2 for overall water splitting in the assembled cell (a-CoS/Ni3S2 || Pt/C). Theoretical calculations reveal that more charges transfer from a-CoS to Ni3S2 in a-CoS/Ni3S2 than in c-CoS/Ni3S2, which promotes the enhancement of OER activity. This work will bring into play a fabrication strategy of a/c catalysts and the understanding of the catalytic mechanism of a/c heterostructures.

Synergy of Interface Coupling and Sulfur Vacancies in Ni3S2/Fe2P for Water Splitting.

Integrated application of interface engineering and vacancy engineering is a promising and effective strategy for the design and fabrication of high-performance electrocatalysts. Herein, the heterointerface catalyst with rich sulfur vacancies, vs-Ni3S2/Fe2P, was successfully designed and constructed. The strong heterointerface coupling and rich sulfur vacancies in vs-Ni3S2/Fe2P significantly optimize the electronic structure of the catalyst and synergistically improve the inherent catalytic activity. Benefiting from the optimization of the electronic structure, vs-Ni3S2/Fe2P exhibits excellent bifunctional electrocatalytic performance in alkaline electrolytes. The overpotentials for hydrogen and oxygen evolution reactions (HER and OER) are 99 and 169 mV at a current density of 10 mA cm-2, respectively. Particularly, it achieves an ultrahigh OER performance with an overpotential of 251 mV at 300 mA cm-2. Moreover, the catalyst also displays outstanding long-term durability. Density functional theory (DFT) computations reveal that the synergy of interface coupling and sulfur vacancies is crucial to optimizing the electronic structure. This study offers a hopeful pathway for the design and construction of durable and efficient electrocatalysts.

Tip-like Fe-N4 Sites Induced Surface Microenvironments Regulation Boosts the Oxygen Reduction Reaction.

Single atom catalysts with defined local structures and favorable surface microenvironments are significant for overcoming slow kinetics and accelerating O2 electroreduction. Here, enriched tip-like FeN4 sites (T-Fe SAC) on spherical carbon surfaces were developed to investigate the change in surface microenvironments and catalysis behavior. Finite element method (FEM) simulations, together with experiments, indicate the strong local electric field of the tip-like FeN4 and the more denser interfacial water layer, thereby enhancing the kinetics of the proton-coupled electron transfer process. In situ spectroelectrochemical studies and the density functional theory (DFT) calculation results indicate the pathway transition on the tip-like FeN4 sites, promoting the dissociation of O-O bond via side-on adsorption model. The adsorbed OH* can be facilely released on the curved surface and accelerate the oxygen reduction reaction (ORR) kinetics. The obtained T-Fe SAC nanoreactor exhibits excellent ORR activities (E1/2 =0.91 V vs. RHE) and remarkable stability, exceeding those of flat FeN4 and Pt/C. This work clarified the in-depth insights into the origin of catalytic activity of tip-like FeN4 sites and held great promise in industrial catalysis, electrochemical energy storage, and many other fields.

Vacancy-induced catalytic mechanism for alcohol electrooxidation on nickel-based electrocatalyst.

Owing to outstanding performances, nickel-based electrocatalysts are commonly used in electrochemical alcohol oxidation reactions (AORs), and the active phase is usually vacancy-rich nickel oxide/hydroxide (NiOx Hy ) species. However, researchers are not aware of the catalytic role of atom vacancy in AORs. Here, we study vacancy-induced catalytic mechanisms for AORs on NiOx Hy species. As to AORs on oxygen-vacancy-poor ß-Ni(OH)2 , the only redox mediator is electrooxidation-induced electrophilic lattice oxygen species, which can only catalyze the dehydrogenation process (e.g., the electrooxidation of primary alcohol to carboxylic acid) instead of the C-C bond cleavage. Hence, vicinal diol electrooxidation reaction involving the C-C bond cleavage is not feasible with oxygen-vacancy-poor ß-Ni(OH)2 . Only through oxygen vacancy-induced adsorbed oxygen-mediated mechanism, can oxygen-vacancy-rich NiOx Hy species catalyze the electrooxidation of vicinal diol to carboxylic acid and formic acid accompanied with the C-C bond cleavage. Crucially, we examine how vacancies and vacancy-induced catalytic mechanisms work during AORs on NiOx Hy species.

Preliminary study on the anti-CO2 stress and growth ability of hypsizygus marmoreus mutant strain HY68.

BACKGROUND: A high concentration of CO2 will stagnate the development of the newly formed primordia of Hypsizygus marmoreus, hinder the development of the mushroom cap, thereby inhibiting the normal differentiation of the fruiting body. Moreover, in the previous experiment, our research group obtained the mutant strain HY68 of H. marmoreus, which can maintain normal fruiting under the condition of high concentration of CO2. Our study aimed to evaluate the CO2 tolerance ability of the mutant strain HY68, in comparison with the starting strain HY61 and the control strain HY62. We analyzed the mycelial growth of these strains under various conditions, including different temperatures, pH levels, carbon sources, and nitrogen sources, and measured the activity of the cellulose enzyme. Additionally, we identified and predicted ß-glucosidase-related genes in HY68 and analyzed their gene and protein structures. RESULTS: Our results indicate that HY68 showed superior CO2 tolerance compared to the other strains tested, with an optimal growth temperature of 25 °C and pH of 7, and maltose and beef paste as the ideal carbon and nitrogen sources, respectively. Enzyme activity assays revealed a positive correlation between ß-glucosidase activity and CO2 tolerance, with Gene14147 identified as the most closely related gene to this activity. Inbred strains of HY68 showed trait segregation for CO2 tolerance. CONCLUSIONS: Both HY68 and its self-bred offspring could tolerate CO2 stress. The fruiting period of the strains resistant to CO2 stress was shorter than that of the strains not tolerant to CO2 stress. The activity of ß-GC and the ability to tolerate CO2 were more closely related to the growth efficiency of fruiting bodies. This study lays the foundation for understanding how CO2 regulates the growth of edible fungi, which is conducive to the innovation of edible fungus breeding methods. The application of the new strain HY68 is beneficial to the research of energy-saving production in factory cultivation.

Selective Anchoring by Surface Sulfur Species Coupled with Rapid Interface Electron Transfer for Ultrahigh Capacity Extraction of Uranium from Seawater.

Improving the adsorption selectivity, enhancing the extraction capacity, and ensuring the structural stability of the adsorbent are the key to realize the high efficiency recovery of uranium. In this work, we utilized the strong Lewis acid-base interaction between S2- and U(VI)O22+ coupling rapid electron transfer at the MnS/U(VI)O22+ solid-liquid interface to achieve excellent selectivity, high adsorption capacity, and rapid extraction of uranium. The as-synthesized MnS adsorbent exhibited an ultrahigh uranium extraction capacity (2457.05 mg g-1) and a rapid rate constant (K = 9.11 × 10-4 g h-1 mg-1) in seawater with 100.7 ppm of UO2(NO3)2 electrolyte. The kinetic simulation reveals that this adsorption process is a chemical adsorption process and conforms to a pseudo-second-order kinetic model, indicating electron transfer at the MnS/U(VI)O22+ solid-liquid interface. The relevant (quasi) in situ spectroscopic characterization and theoretical calculation results further revealed that the outstanding uranium extraction property of MnS could be attributed to the highly selective UO22+ adsorption of MnS with lower adsorption energy as a result of the strong interaction between S2- and UO22+ and the rapid mass transfer and interface electron transfer from S2- and low-valent Mn(II) to U(VI)O22+.

Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia.

PURPOSE: As a public health emergency of international concern, coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia. MATERIALS AND METHODS: 62 patients were randomly assigned to a treatment group (LIPUS treatment area - Group 1; self-control area - Group 2) and an external control group (Group 3). The primary outcomes were the volume absorption rate (VAR) and the area absorption rate (AAR) of lung inflammation in CT images. RESULTS: After an average duration of treatment 7.2 days, there were significant differences in AAR and VAR between Group 1 and Group 2 (AAR 0.25 vs 0.12, p=0.013; VAR 0.35 vs 0.11, p=0.005), and between Group 1 and Group 3 (AAR 0.25 vs 0.11, p=0.047; VAR 0.35 vs 0.19, p=0.042). Neither AAR nor VAR was statistically different between Group 2 and Group 3. After treatment, C-reactive protein, interleukin-6, leukocyte, and fingertip arterial oxygen saturation (SaO2) improved in Group 1, while in Group 3 only fingertip SaO2 increased. CONCLUSION: LIPUS therapy reduced lung inflammation and serum inflammatory factor levels in hospitalized COVID-19 patients, which might be a major advancement in COVID-19 pneumonia therapy.

Electrocatalytic Synthesis of Nylon-6 Precursor at Almost 100 % Yield.

Synthesis of cyclohexanone oxime via the cyclohexanone-hydroxylamine process is widespread in the caprolactam industry, which is an upstream industry for nylon-6 production. However, there are two shortcomings in this process, harsh reaction conditions and the potential danger posed by explosive hydroxylamine. In this study, we presented a direct electrosynthesis of cyclohexanone oxime using nitrogen oxides and cyclohexanone, which eliminated the usage of hydroxylamine and demonstrated a green production of caprolactam. With the Fe electrocatalysts, a production rate of 55.9 g h-1 gcat -1 can be achieved in a flow cell with almost 100 % yield of cyclohexanone oxime. The high efficiency was attributed to their ability of accumulating adsorbed hydroxylamine and cyclohexanone. This study provides a theoretical basis for electrocatalyst design for C-N coupling reactions and illuminates the tantalizing possibility to upgrade the caprolactam industry towards safety and sustainability.

Tailoring Oxygen-Containing Groups on Graphene for Ratiometric Electrochemical Measurements of Ascorbic Acid in Living Subacute Parkinson's Disease Mouse Brains.

Ascorbic acid (AA), a major antioxidant in the central nervous system (CNS), is involved in withstanding oxidative stress that plays a significant role in the pathogenesis of Parkinson's disease (PD). Exploring the AA disturbance in the process of PD is of great value in understanding the molecular mechanism of PD. Herein, by virtue of a carbon fiber electrode (CFE) as a matric electrode, a three-step electrochemical process for tailoring oxygen-containing groups on graphene was well designed: potentiostatic deposition was carried out to fabricate graphene oxide on CFE, electrochemical reduction that assisted in removing the epoxy groups accelerated the electron transfer kinetics of AA oxidation, and electrochemical oxidation that increased the content of the carbonyl group (C═O) generated an inner-reference signal. The mechanism was solidified by ab initio calculations by comparing AA absorption on defected models of graphene functionalized with different oxygen groups including carboxyl, hydroxyl, epoxy, and carbonyl. It was found that epoxy groups would hinder the physical absorption of AA onto graphene, while other functional groups would be beneficial to it. Biocompatible polyethylenedioxythiophene (PEDOT) was further rationally assembled to improve the antifouling property of graphene. As a result, a new platform for ratiometric electrochemical measurements of AA with high sensitivity, excellent selectivity, and reproducibility was established. In vivo determination of AA levels in different regions of living mouse brains by the proposed method demonstrated that AA decreased remarkably in the hippocampus and cortex of a subacute PD mouse than those of a normal mouse.

Dexamethasone induces an imbalanced fetal-placental-maternal bile acid circulation: involvement of placental transporters.

BACKGROUND: The use of prenatal dexamethasone remains controversial. Our recent studies found that prenatal dexamethasone exposure can induce maternal intrahepatic cholestasis and have a lasting adverse influence on bile acid (BA) metabolism in the offspring. The purpose of this study was to investigate the effects of dexamethasone on fetal-placental-maternal BA circulation during the intrauterine period, as well as its placental mechanism. METHODS: Clinical data and human placentas were collected and analyzed. Pregnant Wistar rats were injected subcutaneously with dexamethasone (0.2 mg/kg per day) from gestational day 9 to 20. The metabolomic spectra of BAs in maternal and fetal rat serum were determined by LC-MS. Human and rat placentas were collected for histological and gene expression analysis. BeWo human placental cell line was treated with dexamethasone (20-500 nM). RESULTS: Human male neonates born after prenatal dexamethasone treatment showed an increased serum BA level while no significant change was observed in females. Moreover, the expression of organic anion transporter polypeptide-related protein 2B1 (OATP2B1) and breast cancer resistance protein (BCRP) in the male neonates' placenta was decreased, while multidrug resistance-associated protein 4 (MRP4) was upregulated. In experimental rats, dexamethasone increased male but decreased female fetal serum total bile acid (TBA) level. LC-MS revealed that primary BAs were the major component that increased in both male and female fetal serum, and all kinds of BAs were significantly increased in maternal serum. The expression of Oatp2b1 and Bcrp were reduced, while Mrp4 expression was increased in the dexamethasone-treated rat placentas. Moreover, dexamethasone increased glucocorticoid receptor (GR) expression and decreased farnesoid X receptor (FXR) expression in the rat placenta. In BeWo cells, dexamethasone induced GR translocation into the nucleus; decreased FXR, OATP2B1, and BCRP expression; and increased MRP4 expression. Furthermore, GR was verified to mediate the downregulation of OATP2B1, while FXR mediated dexamethasone-altered expression of BCRP and MRP4. CONCLUSIONS: By affecting placental BA transporters, dexamethasone induces an imbalanced fetal-placental-maternal BA circulation, as showed by the increase of primary BA levels in the fetal serum. This study provides an important experimental and theoretical basis for elucidating the mechanism of dexamethasone-induced alteration of maternal and fetal BA metabolism and for exploring early prevention and treatment strategies.

Facile Ratiometric Electrochemical Sensor for In Vivo/Online Repetitive Measurements of Cerebral Ascorbic Acid in Brain Microdiaysate.

The in vivo monitoring of ascorbic acid (AA) following physiological and pathological events is of great importance because AA plays a critical role in brain functions. The conventional electrochemical sensors (ECSs) usually suffered from poor selectivity and sluggish electron transfer kinetics for cerebral AA oxidation. The exploitation of ECSs adapt to the electrochemical detection (ECD)-microdialysis system, here we reported a facile ratiometric electrochemical sensor (RECS) for in vivo/online repetitive measurements of cerebral AA in brain microdiaysate. The sensor were constructed by careful electrodeposition of graphene oxide (GO) onto glassy carbon (GC) electrodes. Methylene blue (MB) was electrostatically adsorbed onto the GO surface as a built-in reference to achieve ratiometric detection of AA. The subsequent proper electroreduction treatment was able to readily facilitate the oxidation of AA at a relatively negative potential (-100 mV) and the oxidation of MB at separated potential (-428 mV). The in vitro experiments demonstrated that the RECS exhibited high sensitivity (detection limit: 10 nM), selectivity, and stability toward AA determination, enabling the in vivo/online repetitive measurement of cerebral AA in brain microdiaysate with high reliability. As a result, the designed RECS was successfully applied in the ECD-microdialysis system to in vivo/online repetitive monitoring the dynamic change of cerebral AA in the progress of the global cerebral ischemia/reperfusion events. More, the microinjection of endogenous AA and AA oxidase (AAOx) verified the reliability of the proposed RECS for in vivo/online repetitive cerebral AA detection. This proposed sensor filled the gap that no rational electrochemical sensor has been developed for the ECD-microdialysis system since its creation by the Mao group in 2005, which provided a reliable and effective method for brain chemistry research.

Antinociceptive Effect of Spirocyclopiperazinium Salt Compound DXL-A-24 and the Underlying Mechanism.

The antinociceptive effects of spirocyclopiperazinium salt compound DXL-A-24 on neuropathic pain and chemical-stimulated pain were investigated in this study. After the administration of DXL-A-24, the paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) were increased in rats suffering from neuropathic pain (chronic constriction injury, CCI) on days 1, 3, 5, 7 and 14 after surgery, and pain responses were inhibited in mice stimulated with chemicals (formalin or acetic acid). In the analysis of antinociceptive targets, the effect of DXL-A-24 was blocked by a peripheral nicotinic acetylcholine receptor (nAChR) antagonist (hexamethonium, Hex) or α7 nAChR antagonist (methyllycaconitine, MLA) in the formalin test. Meanwhile, the effect of DXL-A-24 was also blocked by a peripheral muscarinic acetylcholine receptor (mAChR) antagonist (atropine methylnitrate, Amn) or M4 mAChR antagonist (tropicamide, TRO). The antinociceptive signalling pathway was explored using molecular biology methods in ipsilateral dorsal root ganglions (DRGs) of CCI rats after the administration of DXL-A-24 for 7 days. Western blot analyses showed that the increased levels of phosphorylation of calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) and cAMP response element-binding protein (CREB) were eliminated, and the qRT-PCR assay showed that the increase in the expression of Tumor necrosis factor alpha (TNF-α) mRNA was reduced. Meanwhile, immunofluorescence staining revealed that the increase in calcitonin gene related peptide (CGRP) expression was inhibited by the administration of DXL-A-24, and the effect was blocked by MLA or TRO. In conclusion, DXL-A-24 exerts significant antinociceptive effects on neuropathic pain and chemical-stimulated pain. The antinociceptive effect of DXL-A-24 is probably attributed to the activation of peripheral α7 nAChR and M4 mAChR, the subsequent inhibition of the CaMKIIα/CREB signalling pathway, and finally the inhibition of TNF-α and CGRP expression.

Chemical vapor deposition growth of sub-centimeter single crystal WSe2 monolayer by NaCl-assistant.

Monolayer WSe2 exhibits unique optical and electronic properties, showing great potential applications in functional integrated devices, such as electronic devices and optoelectronics. Understanding the growth behavior and process are the key points for the salt-assisted growth of large domain WSe2 monolayers, it is also very important for its further application in on-chip laser and opto-devices. Here, we report a NaCl-assistant method for controlled growth of single crystal monolayer WSe2 with a domain size up to 0.57 mm on SiO2/Si substrate. Atomic-resolution scanning transmission electron microscopy reveals that the Se1 and Se2 vacancy point defects are the main defect type of those materials. The growth behavior of the salt-assisted method have been systemly investigated. The loading mass of NaCl powder prefers to be less with the controllable vapor process. The flow of hydrogen gas was also preferred to be suitable with a weak etching effect. The morphology of monolayer WSe2 shows a sensitive temperature dependence evolution with the growth temperature increasing. A screw dislocation growth behavior with 15° angle is also observed with the NaCl-assistant method. The results provide a deep understanding of the mechanism for the NaCl-assistant growth of large size monolayer WSe2.

A Density Functional Theoretical Study on the Charge-Transfer Enhancement in Surface-Enhanced Raman Scattering.

The chemical enhancement due to ground-state charge transfer (GSCT) and photon-driven charge transfer (PDCT) in surface-enhanced Raman scattering (SERS) has been investigated by density functional theory. Para-substituted thiophenol derivatives adsorbed on silver and gold surfaces are selected as model systems to evaluate the chemical enhancement factor. By changing the functional groups on thiophenol, we are allowed to modulate the chemical interactions between the thiophenol and the metal cluster in both ground state and charge transfer excited state. Both off-resonance and pre-resonance SERS spectra are simulated to calculate the chemical enhancement factors. The GSCT enhancement factor, EFGSCT , shows a roughly linear relationship to (ωTP /ωM-TP )4 , where ωTP denotes the HOMO-LUMO gap of free molecule, and ωM-TP denotes the energy difference between the HOMO of the molecule and the LUMO of the metal. The PDCT enhancement factor, EFPDCT , is governed by the energy difference between the incident light energy and the excitation energy to the CT excited state. EFPDCT first increases and then decreases with the increase of incident light energy.

Anti-inflammatory effect and mechanism of the spirocyclopiperazinium salt compound LXM-15 in rats and mice.

OBJECTIVE: This study aimed to investigate the anti-inflammatory effects of a novel spirocyclopiperazinium salt compound LXM-15, and explore the underlying mechanisms. METHODS: Xylene-induced mouse ear oedema and carrageenan-induced rat paw oedema tests were used to evaluate the anti-inflammatory effects of LXM-15. The protein levels of TNF-α, IL-6, phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were detected by ELISA or Western blot analysis. Additionally, receptor blocking test was performed to explore the possible target. RESULTS: Intragastric administration with LXM-15 (2, 1, 0.5 mg/kg in mice, and 6, 3, 1.5 mg/kg in rats) produced distinct anti-inflammatory effects in vivo, the highest inhibition percentage was 60 and 52%, respectively (P < 0.01). Following treatment with LXM-15 (6 mg/kg, i.g.), the levels of TNF-α and IL-6 in the rats paws were attenuated by 40 and 41%; and the phosphorylation of JAK2 and STAT3 was restrained by 35 and 45%, respectively (P < 0.01). All effects of LXM-15 were blocked by pretreatment with methyllycaconitine citrate or tropicamide. CONCLUSION: This study provides the first report that the spirocyclopiperazinium salt compound LXM-15 displays considerable anti-inflammatory effects. The underlying mechanism may be through activating the peripheral α7 nicotinic acetylcholine receptor and M4 muscarinic acetylcholine receptor, leading to the inhibition of the JAK2/STAT3 signalling pathway, eventually resulting in the reduction of TNF-α and IL-6.

Antinociception of the spirocyclopiperazinium salt compound LXM-15 via activating α7 nAChR and M4 mAChR and inhibiting CaMKIIα/cAMP/CREB/CGRP signalling pathway in mice.

The aim of this study was to investigate the analgesic effect of the spirocyclopiperazinium salt compound LXM-15 by intragastric administration in thermal and chemical pain models and further to elucidate the possible molecular mechanisms. The results showed that LXM-15 exerted significant antinociception in hot-plate test, formalin test and acetic acid writhing test. Western blot analysis showed that LXM-15 significantly reduced the upregulation of phosphorylation of calcium/calmodulin -dependent protein kinase IIα (CaMKIIα) and cAMP response element-binding protein (CREB), and further decreased the elevation of calcitonin gene related peptide (CGRP) in the dorsal root ganglion (DRG) and spinal cord in mice. ELISA analysis showed the level of cAMP in the spinal cord was decreased by LXM-15. All effects of LXM-15 could be blocked by methyllycaconitine citrate (MLA, a selective α7 nicotinic receptor antagonist) or tropicamide (TRO, a selective M4 muscarinic receptor antagonist). This study first reported that intragastric administration of LXM-15 produced significant analgesic effect, which may be related to the activation of α7 nicotinic acetylcholine receptor and M4 muscarine acetylcholine receptor, and thereby inhibiting CaMKIIα/cAMP/CREB/CGRP signalling pathway.

Why granular media are thermal, and quite normal, after all.

Two approaches exist to account for granular dynamics: The athermal one takes grains as elementary, the thermal one considers the total entropy that includes microscopic degrees of freedom such as phonons and electrons. Discrete element method (DEM), granular kinetic theory and athermal statistical mechanics (ASM) belong to the first, granular solid hydrodynamics (GSH) to the second one. A discussion of the conceptual differences between both is given here, leading, among others, to the following insights: 1) While DEM and granular kinetic theory are well justified to take grains as athermal, any entropic consideration is far less likely to succeed. 2) In addition to modeling grains as a gas of dissipative, rigid mass points, it is very helpful take grains as a thermal solid that has been sliced and diced. 3) General principles that appear invalid in granular media are repaired and restored once the true entropy is included. These abnormalities (such as invalidity of the fluctuation-dissipation theorem, granular temperatures failing to equilibrate, and grains at rest unable to explore the phase space) are consequences of the athermal approximation, not properties of granular media.