Nitric oxide and tumor necrosis factor-⍺ levels are negatively correlated in endotoxin tolerance recovery in vitro.

Endotoxin tolerance (ET) is the hyporesponsiveness to lipopolysaccharide (LPS) after prior exposure. It is characterized by the downregulation of pro-inflammatory cytokine levels. Although ET protects against inflammation, its abolishment or recovery is critical for immunity. Nitric oxide (NO) plays various roles in the development of ET; however, its specific role in ET recovery remains unknown. To induce ET, RAW264.7 cells (a murine macrophage cell line) were pre-exposed to LPS (LPS1, 100 ng/mL for 24 h) and subsequently re-stimulated with LPS (LPS2, 100 ng/mL for 24 h). Expression of cytokines, NO, nitrite and inducible NO synthase (iNOS) were measured after 0, 12, 24, and 36 h of resting after LPS1 treatment with or without the iNOS-specific inhibitor, 1400W. LPS2-induced tumor necrosis factor-⍺ (TNF-⍺) and interleukin-6 (IL-6) were downregulated after LPS1 treatment, confirming the development of ET. Notably, TNF-⍺ and IL-6 levels spontaneously rebounded after 12-24 h of resting following LPS1 treatment. In contrast, levles of NO, nitrite and iNOS increased during ET development and decreased during ET recovery. Moreover, 1400W inhibited ET development and blocked the early production of NO (<12 h) during ET recovery. Our findings suggest a negative correlation between iNOS-induced NO and cytokine levels in the abolishment of ET.

Rational synthesis of 1,3,4-thiadiazole based ESIPT-fluorescent probe for detection of Cu2+ and H2S in herbs, wine and fruits.

Here, 1,3,4-thiadiazole unit was employed as novel excited state intramolecular proton transfer (ESIPT) structure to prepare favorable fluorescent probe. High selectivity and rapid response to Cu2+ was obtained and the settling reaction was also used to recover ESIPT characteristics of probe to achieve sequential detection of H2S. Remarkable color change of solution from colorless to bright yellow and fluorescence emission from green to dark realized the visual detection of Cu2+ by naked eyes and transition of probe into portable fluorescent test strips. As expected, L-E could be utilized to quantitatively sense Cu2+ and H2S in different actual water and food samples including herbs, wine and fruits. The limits of detection for Cu2+ and H2S were as low as 34.5 nM and 38.6 nM. Also, probe L-E achieved real-time, portable, on-site quantitative detection of Cu2+ via a colorimeter and a smartphone platform with limit of detection to 90.3 nM.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

Highly sensitive fluorescent triarylimidazole derivatives for sensing of 2,4,6-trinitrophenol in aqueous solution and its application for actual environment detection.

Two highly sensitive fluorescent triarylimidazole derivatives were synthesized by modifying imidazole with coumarin and large conjugate rigid plane structure. XM-F and XM-L emitted bright yellow-green fluorescent light. Their intense conjugation system generated strong π-π electrostatic interactions with TNP, accompanied by the formation of hydrogen bonds to achieve rapid detection of TNP within 25 s. The detection limits were as low as 0.049 µM and 0.071 µM, respectively. Probes had been successfully applied to rapid detection of TNP in real water samples and manufactured into portable fluorescent test strips. In view of excellent performance of XM-F, it was used to achieve real-time, portable, on-site quantitative detection of TNP by a colorimeter and a smartphone platform. In addition, XM-F also successfully processed into probe-coated TLC plates for efficient detection of fingerprints contaminated with TNP.

Facile Synthesis of Pre-Lithiated LiTiO2 Nanoparticles for Quick Charge and Long Lifespan Anode in Lithium-Ion Batteries.

Titanium dioxide (TiO2) has been widely used as an alternative anodic material for lithium-ion batteries (LIBs) due to its ultrahigh capacity retention and long cycle lifespan. However, the restriction of lithium insertion, intrinsically poor electronic conductivity, and sluggish lithium ionic kinetics of bulk TiO2 hinder their specific capacity and rate performance. Herein, LiTiO2 nanoparticles (NPs) are synthesized via a facile ball milling method by the reaction of anatase TiO2 with LiH. The as-prepared LiTiO2 NPs have strong structural stability and a "zero strain" effect during the repeated intercalation/deintercalation, even at low potential. As anodic materials for LIBs, LiTiO2 NPs exhibit a superior rate performance of ∼100 mA h g-1 at 10C (3350 mA g-1) with a capacity retention of 100% after 1000 cycles, which is 5 times higher than that of the original commercial anatase TiO2 powder. The higher specific capacity of LiTiO2 NPs is attributed to the increased conversion of Ti3+ to Ti2+ on the porous surface of LiTiO2 NPs, which provides a more capacitive contribution. This study not only provides a new fabrication approach toward Ti-based anodes for ultrafast LIBs but also underscores the potential importance of embedding lithium into transition metal oxides as a strategy for boosting their electrochemical performance.

The value of TDI combined with myocardial strain parameters in quantitative evaluation of left heart function in parturient with pregnancy-induced hypertension.

This study aimed to investigate the value of tissue doppler imaging (TDI) and 4D myocardial strain parameters in evaluating left heart function of pregnant women with hypertension and the association between these parameters and relevant factors. Forty-five pregnant women with hypertensive disorder, including 20 with hypertension, 15 with mild preeclampsia, and 10 with severe preeclampsia, were recruited, and their cardiac functions were compared with those of 30 healthy pregnant women as controls. High Left ventricular end-systolic volume (LVESV), Left atrial volume index (LAVI), E/e were observed in hypertensive disorder, while Mitral peak diastolic velocity(E), Early diastolic peak velocity(e), E/A, Left ventricularglobal longitudinal strain (LVGLS), Left ventricularglobal area strain (LVGAS), and Left atrialglobal longitudinal strain (LAGLS) were decreased; for pre-eclampsia, Left ventricular end-systolic diameter (LVESD), Left atrial anteroposterior diameter (LAD-ap), LVESV, LAVI were significantly increased, LVGLS, LAGLS were significantly decreased, Left ventricular end-diastolic diameter (LVEDD), Left ventricular end-diastolic volume (LVEDV), A peak, E/e were increased, while E peak, E/A, e, Left ventricle global radial strain (LVGRS), Left ventricle global circumferential strain (LVGCS), LVGAS were decreased but not significantly; for severe preeclampsia, Left ventricular end diastolic diameter (LVEDD), LVESD, LAD-ap, Left ventricular end-diastolic volume (LVEDV), LVESV, LAVI, A, and E/e were significantly increased, while LVGLS, LVGRS, LVGCS, LVGAS, LAGLS, E peak, E/A, and e were significantly reduced. TDI combined with 4D myocardial strain parameters can detect early changes in cardiac function of hypertensive disorders in pregnancy, with LVGLS, LVGAS, and LAGLS being the most sensitive indicators for early changes. Such findings provide a basis for effective clinical treatment of these symptoms.

Impacts of air pollution and meteorological conditions on dry eye disease among residents in a northeastern Chinese metropolis: a six-year crossover study in a cold region.

The purpose of this study is to explore the associations among dry eye disease (DED), air pollution, and meteorological conditions in the cold region of a northeastern Chinese metropolis (i.e., Changchun). Data on ambient air pollutants and meteorological parameters as well as diagnosed DED outpatients during 2015-2021 were collected. The associations between DED and environmental factors were analysed at multiple time scales using various statistical methods (i.e., correlation, regression and machine learning). Among the 10,809 DED patients (21,617 eyes) studied, 64.60% were female and 35.40% were male. A higher frequency of DED was observed in March and April, followed by January, August and October. Individual and multiple factor models showed the positive importance of particles with aerodynamic diameters <10 µm (PM10), carbon monoxide (CO), and ozone (O3) among normal air pollutants and air pressure (AP), air temperature (AT) and wind speed (WS) among normal meteorological parameters. Air pollutants (PM10, nitrogen dioxide: NO2) and meteorological parameters (AT, AP) have combined impacts on DED occurrence. For the first time, we further explored the associations of detailed components of atmospheric particles and DED, suggesting potential emission sources, including spring dust from bare soil and roads and precursor pollutants of summer O3 formation from vehicles and industry in Northeast China. Our results revealed the quantitative associations among air pollutants, meteorological conditions and DED outpatients in cold regions, highlighting the importance of coordinated policies in air pollution control and climate change mitigation.

LiF-Rich Interfacial Protective Layer Enables Air-Stable Lithium Metal Anodes for Dendrite-Free Lithium Metal Batteries.

Lithium (Li) metal is considered as a promising anode candidate for high-energy-density batteries. However, the high reactivity of Li metal leads to poor air stability, limiting its practical application. Additionally, the interfacial instability, such as dendrite growth and an unstable solid electrolyte interphase layer, further complicates its utilization. Herein, a dense lithium fluoride (LiF)-rich interfacial protective layer is constructed on the Li surface through a simple reaction between Li and fluoroethylene carbonate (denoted as LiF@Li). The LiF-rich interfacial protective layer consists of both organic (ROCO2Li and C-F-containing species, which only exist on the outer layer) and inorganic (LiF and Li2CO3, distribute throughout the layer) components with a thickness of ∼120 nm. Specifically, chemically stable LiF and Li2CO3 play an important role in blocking air and hence improve the air durability of LiF@Li anodes. Notably, LiF with high Li+ diffusivity facilitates uniform Li+ deposition, while organic components with high flexibility relieve volume change upon cycling, thereby enhancing the dendrite inhibition capacity of LiF@Li. Consequently, LiF@Li exhibits remarkable stability and excellent electrochemical performance in both symmetric cells and LiFePO4 full cells. Moreover, LiF@Li maintains its initial color and morphology even after air exposure for 30 min, and the air-exposed LiF@Li anode still retains its superior electrochemical performance, further establishing its outstanding air-defendable capability. This work proposes a facile approach in constructing air-stable and dendrite-free Li metal anodes toward reliable Li metal batteries.

Mangiferin depresses vesicular glutamate release in synaptosomes from the rat cerebral cortex by decreasing synapsin I phosphorylation.

Mangiferin is a glucosyl xanthone that has been shown to be a neuroprotective agent against brain disorders involving excess glutamate. However, the effect of mangiferin on the function of the glutamatergic system has not been investigated. In this study, we used synaptosomes from the rat cerebral cortex to investigate the effect of mangiferin on glutamate release and identify the possible underlying mechanism. We observed that mangiferin produced a concentration-dependent reduction in the release of glutamate elicited by 4-aminopyridine with an IC50 value of 25 µM. Inhibition of glutamate release was blocked by removing extracellular calcium and by treatment with the vacuolar-type H+-ATPase inhibitor bafilomycin A1, which prevents the uptake and storage of glutamate in vesicles. Moreover, we showed that mangiferin decreased the 4-aminopyridine-elicited FM1-43 release and synaptotagmin 1 luminal domain antibody (syt1-L ab) uptake from synaptosomes, which correlated with decreased synaptic vesicle exocytosis. Transmission electron microscopy in synaptosomes also showed that mangiferin attenuated the 4-aminopyridine-elicited decrease in the number of synaptic vesicles. In addition, antagonism of Ca2+/calmodulin-dependent kinase II (CaMKII) and protein kinase A (PKA) counteracted mangiferin's effect on glutamate release. Mangiferin also decreased the phosphorylation of CaMKII, PKA, and synapsin I elicited by 4-aminopyridine treatment. Our data suggest that mangiferin reduces PKA and CaMKII activation and synapsin I phosphorylation, which could decrease synaptic vesicle availability and lead to a subsequent reduction in vesicular glutamate release from synaptosomes.

Cynarin, a caffeoylquinic acid derivative in artichoke, inhibits exocytotic glutamate release from rat cortical nerve terminals (synaptosomes).

The purpose of this study was to evaluate the effect of cynarin, a caffeoylquinic acid derivative in artichoke, on glutamate release elicited by 4-aminopyridine (4-AP) in rat cortical nerve terminals (synaptosomes). We observed that cynarin decreased 4-aminopyridine-elicited glutamate release, which was prevented by the removal of external free Ca2+ with ethylene glycol bis (ß-aminoethyl ether)-N,N,N,N-tetraacetic acid (EGTA) or the blockade of P/Q-type calcium channels with ω-agatoxin IVA. Molecular docking also revealed that cynarin formed a hydrogen bond with the P/Q-type Ca2+ channel, indicating a mechanism of action involving Ca2+ influx inhibition. Additionally, the inhibitory effect of cynarin on glutamate release is associated with a change in the available synaptic vesicles, as cynarin decreased 4-AP-elicited FM1-43 release or hypertonic sucrose-evoked glutamate release from synaptosomes. Furthermore, the suppression of protein kinase A (PKA) prevented the effect of cynarin on 4-AP-elicited glutamate release. 4-AP-elicited PKA and synapsin I or synaptosomal-associated protein of 25 kDa (SNAP-25) phosphorylation at PKA-specific residues were also attenuated by cynarin. Our data indicate that cynarin, through the suppression of P/Q-type Ca2+ channels, inhibits PKA activation and attenuates synapsin I and SNAP-25 phosphorylation at PKA-specific residues, thus decreasing synaptic vesicle availability and contributing to glutamate release inhibition in cerebral cortex terminals.

A multifunctional fluorescent probe based on Schiff base with AIE and ESIPT characteristics for effective detections of Pb2+, Ag+ and Fe3.

In this work, three Schiff-based fluorescent probes with aggregation-induced emission (AIE) and excited intramolecular proton transfer (ESIPT) characters were synthesized by grafting 2-aminobenzothiazole group onto 4-substituted salicylaldehydes. More important, a rare tri-responsive fluorescent probe (SN-Cl) was developed by purposeful variation of substituents in the molecule. It could selectively identify Pb2+, Ag+ and Fe3+ in different solvent systems or with the help of masking agent and show complete fluorescence enhancement without interference of other ions. Meanwhile, the other two probes (SN-ON and SN-N) could only recognize Pb2+ in DMSO/Tris-HCl buffer (3: 7, v/v, pH = 7.4). According to Job's plot, density functional theory (DFT) calculations and NMR analysis, coordination between SN-Cl and Pb2+/Ag+/Fe3+ was determined. The LOD values for three ions were as low as 0.059 µM, 0.012 µM and 8.92 µM, respectively. Ideally, SN-Cl showed satisfactory performance in real water samples detection and test paper experiments for three ions. Also, SN-Cl could be used as an excellent imaging agent for Fe3+ in HeLa cells. Therefore, SN-Cl has the ability to be a "single fluorescent probe for three targets".

Plantainoside D Reduces Depolarization-Evoked Glutamate Release from Rat Cerebral Cortical Synaptosomes.

Inhibiting the excessive release of glutamate in the brain is emerging as a promising therapeutic option and is efficient for treating neurodegenerative disorders. The aim of this study is to investigate the effect and mechanism of plantainoside D (PD), a phenylenthanoid glycoside isolated from Plantago asiatica L., on glutamate release in rat cerebral cortical nerve terminals (synaptosomes). We observed that PD inhibited the potassium channel blocker 4-aminopyridine (4-AP)-evoked release of glutamate and elevated concentration of cytosolic Ca2+. Using bafilomycin A1 to block glutamate uptake into synaptic vesicles and EDTA to chelate extracellular Ca2+, the inhibitory effect of PD on 4-AP-evoked glutamate release was prevented. In contrast, the action of PD on the 4-AP-evoked release of glutamate in the presence of dl-TBOA, a potent nontransportable inhibitor of glutamate transporters, was unaffected. PD does not alter the 4-AP-mediated depolarization of the synaptosomal membrane potential, suggesting that the inhibitory effect of PD on glutamate release is associated with voltage-dependent Ca2+ channels (VDCCs) but not the modulation of plasma membrane potential. Pretreatment with the Ca2+ channel blocker (N-type) ω-conotoxin GVIA abolished the inhibitory effect of PD on the evoked glutamate release, as did pretreatment with the protein kinase C inhibitor GF109203x. However, the PD-mediated inhibition of glutamate release was eliminated by applying the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 or dantrolene, which inhibits Ca2+ release through ryanodine receptor channels. These data suggest that PD mediates the inhibition of evoked glutamate release from synaptosomes primarily by reducing the influx of Ca2+ through N-type Ca2+ channels, subsequently reducing the protein kinase C cascade.

Effect of Intense Pulsed Light to Mitigate Meibomian Gland Dysfunction for Dry Eye Disease.

BACKGROUND: This retrospective study aimed to evaluate the effect of intense pulsed light treatment (IPL) combined with meibomian gland expression (MGX) in treating meibomian gland dysfunction (MGD) related dry eye disease (DED) for the first time in Northeast China. METHODS: Thirty-one MGD-related dry eye patients were managed by IPL-MGX from October to December 2019 in The First Hospital of Jilin University. Those patients had single IPL-MGX treatment with one follow-up visit, and no topical eye drops used were included in the study. General checkup and data collection helped in determining the age, sex, diagnosis, status of the MG, first noninvasive tear break-up time (1st NIBUT), average NIBUT, the height of tear film, and additional medical history. RESULTS: There was an improvement in the function of the meibomian gland (MG), with a significant decrease in the MG dropouts in the upper eyelid (Rt eye, p = 0.0047; Lt eye, p = 0.0158) and lower eyelid (Rt eye, p = 0.0017; Lt eye, p = 0.0027) plus the average NIBUT (Rt eye, p = 0.0264) also showed improvement after the IPL-MGX treatment. Though no significant difference was reached with the average NIBUT of the Lt eye (p = 0.5256) and the NIBUT grade (Rt eye, p = 0.0578; Lt eye, p = 0.0588), there was an increased duration of the average NIBUT and improved NIBUT grading. The negative results may be because of the maximum severity of DED and the limited treatment times. CONCLUSIONS: The result suggests that IPL-MGX was effective in treating MGD-related DED.

Unexpected delayed reversal of rocuronium-induced neuromuscular blockade by sugammadex: A case report and review of literature.

BACKGROUND: Rocuronium, a nondepolarizing muscle relaxant, is usually administered during general anesthesia to facilitate endotracheal intubation and keep patients immobile during the surgery. Sugammadex, the selective reversal agent of rocuronium, fully reverses the neuromuscular blockade (NMB) at the end of surgery. Most reports show that sugammadex rapidly achieves a ratio of train-of-four (TOF), a quantitative method of neuromuscular monitoring, of 0.9 which ensures adequate recovery for safe extubation. However, very rare patients with neuromuscular diseases may respond poorly to sugammadex. CASE SUMMARY: A 69-year-old female presented with abdominal fullness and nausea, and was diagnosed with gastroparesis. She underwent gastric peroral endoscopic myotomy under general anesthesia with rocuronium (0.7 mg/kg). At the end of surgery, sugammadex 3.6 mg/kg was administered when TOF showed 2 counts. Afterward, the TOF ratio recovered to 0.65 in 30 min. She was awake but could not fully open her eyelids. The tidal volume during spontaneous breathing was low. After additional doses of sugammadex (up to 7.3 mg/kg) in the following 3 h, the TOF ratio was 0.9, and the endotracheal tube was smoothly removed. After excluding possible mechanisms underlying the prolonged recovery course, we speculated our patient may have had an undiagnosed neuromuscular disease, hinted by her involuntary movement of the tongue and mouth. Furthermore, her poor renal function and history of delayed recovery from general anesthesia may be related to the long duration of rocuronium. CONCLUSION: In our case, both prolonged rocuronium-induced NMB and poor response to sugammadex were noted. To optimize the dose of rocuronium, perioperative TOF combined with other neuromuscular monitoring is suggested.

Inhibition of Synaptic Glutamate Exocytosis and Prevention of Glutamate Neurotoxicity by Eupatilin from Artemisia argyi in the Rat Cortex.

The inhibition of synaptic glutamate release to maintain glutamate homeostasis contributes to the alleviation of neuronal cell injury, and accumulating evidence suggests that natural products can repress glutamate levels and associated excitotoxicity. In this study, we investigated whether eupatilin, a constituent of Artemisia argyi, affected glutamate release in rat cortical nerve terminals (synaptosomes). Additionally, we evaluated the effect of eupatilin in an animal model of kainic acid (KA) excitotoxicity, particularly on the levels of glutamate and N-methyl-D-aspartate (NMDA) receptor subunits (GluN2A and GluN2B). We found that eupatilin decreased depolarization-evoked glutamate release from rat cortical synaptosomes and that this effect was accompanied by a reduction in cytosolic Ca2+ elevation, inhibition of P/Q-type Ca2+ channels, decreased synapsin I Ca2+-dependent phosphorylation and no detectable effect on the membrane potential. In a KA-induced glutamate excitotoxicity rat model, the administration of eupatilin before KA administration prevented neuronal cell degeneration, glutamate elevation, glutamate-generating enzyme glutaminase increase, excitatory amino acid transporter (EAAT) decrease, GluN2A protein decrease and GluN2B protein increase in the rat cortex. Taken together, the results suggest that eupatilin depresses glutamate exocytosis from cerebrocortical synaptosomes by decreasing P/Q-type Ca2+ channels and synapsin I phosphorylation and alleviates glutamate excitotoxicity caused by KA by preventing glutamatergic alterations in the rat cortex. Thus, this study suggests that eupatilin can be considered a potential therapeutic agent in the treatment of brain impairment associated with glutamate excitotoxicity.

Lockdown-induced Urban Aerosol Change over Changchun, China During COVID-19 Outbreak with Polarization LiDAR.

Depending on various government policies, COVID-19 (Corona Virus Disease-19) lockdowns have had diverse impacts on global aerosol concentrations. In 2022, Changchun, a provincial capital city in Northeast China, suffered a severe COVID-19 outbreak and implemented a very strict lockdown that lasted for nearly two months. Using ground-based polarization Light Detection and Ranging (LiDAR), we detected real-time aerosol profile parameters (EC, extinction coefficient; DR, depolarization ratio; AOD, aerosol optical depth), as well as air-quality and meteorological indexes from 1 March to 30 April in 2021 and 2022 to quantify the effects of lockdown on aerosol concentrations. The period in 2022 was divided into three stages: pre-lockdown (1-10 March), strict lockdown (11 March to 10 April), and partial lockdown (11-30 April). The results showed that, during the strict lockdown period, compared with the pre-lockdown period, there were substantial reductions in aerosol parameters (EC and AOD), and this was consistent with the concentrations of the atmospheric pollutants PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 µm) and PM10 (particulate matter with an aerodynamic diameter ≤ 10 µm), and the O3 concentration increased by 8.3%. During the strict lockdown, the values of EC within 0-1 km and AOD decreased by 16.0% and 11.2%, respectively, as compared to the corresponding period in 2021. Lockdown reduced the conventional and organized emissions of air pollutants, and it clearly delayed the time of seasonal emissions from agricultural burning; however, it did not decrease the number of farmland fire points. Considering meteorological factors and eliminating the influence of wind-blown dust events, the results showed that reductions from conventional organized emission sources during the strict lockdown contributed to a 30% air-quality improvement and a 22% reduction in near-surface extinction (0-2 km). Aerosols produced by urban epidemic prevention and disinfection can also be identified using the EC. Regarding seasonal sources of agricultural straw burning, the concentrated burning induced by the epidemic led to the occurrence of heavy pollution from increased amounts of atmospheric aerosols, with a contribution rate of 62%. These results indicate that there is great potential to further improve air quality in the local area, and suggest that the comprehensive use of straw accompanied by reasonable planned burning is the best way to achieve this.

The Effect of Isosaponarin Derived from Wasabi Leaves on Glutamate Release in Rat Synaptosomes and Its Underlying Mechanism.

Excessive glutamate release is known to be involved in the pathogenesis of neurological diseases, and suppression of glutamate release from nerve terminals is considered to be a treatment strategy. In this study, we investigated whether isosaponarin, a flavone glycoside isolated from wasabi leaves, could affect glutamate release in rat cerebral cortex nerve terminals (synaptosomes). The release of glutamate was evoked by the K+ channel blocker 4-aminopyridine (4-AP) and measured by an online enzyme-coupled fluorimetric assay. Isosaponarin produced a concentration-dependent inhibition of 4-AP-evoked glutamate release with a half-maximum inhibition of release value of 22 µM. The inhibition caused by isosaponarin was prevented by eliminating extracellular Ca2+ or by using bafilomycin A1, an inhibitor of synaptic vesicle exocytosis. Isosaponarin decreased intrasynaptosomal rises in Ca2+ levels that were induced by 4-AP, without affecting the synaptosomal membrane potential. The isosaponarin-induced inhibition of glutamate release was significantly prevented in synaptosomes that were pretreated with a combination of the calcium channel blockers ω-conotoxin GVIA (N-type) and ω-agatoxin IVA (P/Q-types). The protein kinase C (PKC) pan-inhibitor GF109203X and the Ca2+-dependent PKC inhibitor Go6976 abolished the inhibition of glutamate release by isosaponarin, while the Ca2+-independent PKC inhibitor rottlerin did not show any effect. The results from immunoblotting assays also showed that isosaponarin lowered PKC, PKCα, synaptosomal-associated protein of 25 kDa (SNAP-25), and myristoylated alanine-rich C-kinase substrate (MARCKS) phosphorylation induced by 4-AP. In addition, FM1-43-labeled synaptic vesicles in synaptosomes showed that treatment with isosaponarin resulted in an attenuation of the 4-AP-induced decrease in fluorescence intensity that is consistent with glutamate release. Transmission electron microscopy of synaptosomes also provided evidence that isosaponarin altered the number of synaptic vesicles. These results indicate that isosaponarin suppresses the Ca2+-dependent PKC/SNAP-25 and MARCKS pathways in synaptosomes, causing a decrease in the number of available synaptic vesicles, which inhibits vesicular glutamate release from synaptosomes.

Appropriate dosing of sugammadex for reversal of rocuronium-/vecuronium-induced muscle relaxation in morbidly obese patients: a meta-analysis of randomized controlled trials.

OBJECTIVE: To conduct a meta-analysis to compare different dosing scalars of sugammadex in a morbidly obese population for reversal of neuromuscular blockade (NMB). METHODS: PubMed®, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar were searched for relevant randomized controlled trials (RCTs) comparing lower-dose sugammadex using ideal body weight (IBW) or corrected body weight (CBW) as dosing scalars with standard-dose sugammadex based on total body weight (TBW) among morbidly obese people after NMB. Mean difference with SD was used to estimate the results. RESULTS: The analysis included five RCT with a total of 444 morbidly obese patients. The reversal time was significantly longer in patients receiving sugammadex with dosing scalar based on IBW than in patients receiving sugammadex with dosing scalar based on TBW (mean difference 55.77 s, 95% confidence interval [CI] 32.01, 79.53 s), but it was not significantly different between patients receiving sugammadex with dosing scalars based on CBW versus TBW (mean difference 2.28 s, 95% CI -10.34, 14.89 s). CONCLUSION: Compared with standard-dose sugammadex based on TBW, lower-dose sugammadex based on IBW had 56 s longer reversal time whereas lower-dose sugammadex based on CBW had a comparable reversal time.