Magnesium fertilizer application increases peanut growth and pod yield under reduced nitrogen application in southern China

This study investigated the effect of magnesium application on peanut growth and yield under two nitrogen(N)application rates in acidic soil in southern China.The chlorophyll content,net photosynthetic rate and dry matter accumulation of the N-sensitive cultivar decreased under reduced N treatments,whereas no effect was observed on the relevant indicators in the N-insensitive variety GH1026.Mg application increased the net photosynthetic rate by increasing the expression of genes involved in chlorophyll synthesis and Rubisco activity in the leaves during the pegging stage under 50%N treatment,while no effect on the net photosynthetic rate was observed under the 100%N treatment.The rate of dry matter accumulation at the early growth stage,total dry matter accumulation and pod yield at harvest increased after Mg application under 50%N treatment by increasing the transportation of assimilates from stems and leaves to pods in both peanut varieties,whereas no effect was found under 100%N treatment.Moreover,Mg application increased the NUE under 50%N treatment.No improvement of NUE in either peanut variety was found under 100%N treatment,while Mg application under the 50%N treatment can obtain a higher economic benefit than the 100%N treatment.In acidic soil,application of 307.5 kg ha^(-1)of Mg sulfate fertilizer under 50%reduced nitrogen application is a suitable fertilizer management measure for improving carbon assimilation,NUE and achieve high peanut yields in southern China.

MATRICES OVER A REDUCED RING AS SUMS OF THREE TRIPOTENTS

In this paper,we study reduced rings in which every element is a sum of three tripotents that commute,and determine the integral domains over which every n£n matrix is a sum of three tripotents.It is proved that for an integral domain R,every matrix in M_(n)(R)is a sum of three tripotents if and only if R■Zp with p=2,3,5 or 7.

Ultrahydrophobic melamine sponge via interfacial modification with reduced graphene oxide/titanium dioxide nanocomposite and polydimethylsiloxane for oily wastewater treatment

Three-dimensional(3D)porous absorbents have attracted significant attention in the oily wastewater treatment technology due to their high porosity and elasticity.Given their amphiphilic surface,they have a propensity to simultaneously absorb water and oil,which restricts their range of applications.In this study,a reduced graphene oxide and titanium dioxide nanocomposite(rGO/TiO_(2))was used to fabricate an ultra-hydrophobic melamine sponge(MS)through interfacial modification using a solution immersion technique.To further modify it,poly-dimethylsiloxane(PDMS)was grafted onto its surface to establish stronger covalent bonds with the composite.The water contact angle of the sponge(rGO/TiO_(2)/PDMS/MS)was 164.2°,which satisfies the condition for ultrahydrophobicity.The evidence of its water repellency was demonstrated by the Cassie-Baxter theory and the lotus leaf effect.As a result of the increased density of rGO/TiO_(2)/PDMS/MS,it recorded an initial capacity that was 2 g/g lower than the raw MS for crude oil absorption.The raw MS retained 53% of its initial absorption capacity after 20 cycles of absorption,while rGO/TiO_(2)/PDMS/MS retained 97%,suggesting good recyclability.Excellent oil and organic solvent recovery(90%-96%)was demonstrated by rGO/TiO_(2)/PDMS/MS in oil-water combinations.In a continuous separation system,it achieved a remarkable separation efficiency of 2.4×10^(6)L/(m^(3)·h),and in turbulent emulsion separation,it achieved a demulsification efficiency of 90%-91%.This study provides a practical substitute for massive oil spill cleaning.

A guidance and control design with reduced information for a dual-spin stabilized projectile

In this paper,an integrated guidance and control method based on an adaptive path-following controller is proposed to control a spin-stabilized projectile with only translational motion information under the constraint of an actuator,uncertainties in aerodynamic parameters and measurements,and control system complexity.Owing to the fairly high rotation speed,the dynamic model of this missile is strongly nonlinear,uncertain and coupled in pitch,yaw and roll channels.A theoretical equivalent resultant force and uncertainty compensation method are comprehensively used to realize decoupling of pitch and yaw.In response to the strong nonlinear and time-varying characteristics of the dynamic system,the quasi-linear model whose parameters are obtained by interpolation of points selected as the segmentation points in the trajectory envelope,is used for calculation in each step.To cope with the system uncertainty caused by model approximation,parameter uncertainty and ballistic interference,an extended state estimator is used to compensate the output feedback according to the test ballistic angle.In order to improve the tracking efficiency and ensure the tracking error convergence with only translational motion information,the virtual guide point,whose derivative is deduced according to the Lyapunov principle,is calculated in real time according to the projection relationship between the real-time position and the reference trajectory,and a virtual line-of-sight angle and the backstepping method are used for the design of the guidance and control system.In order to avoid the influence of control input saturation on the guidance and control performance due to the actuator limitation and improve the robustness of the system,an anti-saturation compensator is designed according to the two-step method.The feasibility and effectiveness of the path-following controller is verified through closed-loop flight simulations with measurement,control,and condition uncertainties.The results indicate that the designed controller can converge to the reference path and evidently decrease the distance between the impact point and target under different uncertainties.

Development of Direct Reduced Iron in China:Challenges and Pathways

The steel industry is considered an important basic sector of the national economy,and its high energy consumption and carbon emissions make it a major contributor to climate change,especially in China.The majority of crude steel in China is produced via the energy-and carbon-intensive blast furnace–basic oxygen furnace(BF–BOF)route,which greatly relies on coking coal.In recent years,China’s steel sector has made significant progress in energy conservation and emission reduction,driven by decarbonization policies and regulations.However,due to the huge output of crude steel,the steel sector still produces 15%of the total national CO_(2) emissions.The direct reduced iron(DRI)plus scrap–electric arc furnace(EAF)process is currently considered a good alternative to the conventional route as a means of reducing CO_(2) emissions and the steel industry’s reliance on iron ore and coking coal,since the gas-based DRI plus scrap–EAF route is expected to be more promising than the coal-based one.Unfortunately,almost no DRI is produced in China,seriously restricting the development of the EAF route.Here,we highlight the challenges and pathways of the future development of DRI,with a focus on China.In the short term,replacing natural gas with coke oven gas(COG)and byproduct gas from the integrated refining and chemical sector is a more economically feasible and cleaner way to develop a gas-based route in China.As the energy revolution proceeds,using fossil fuels in combination with carbon capture,utilization,and storage(CCUS)and hydrogen will be a good alternative due to the relatively low cost.In the long term,DRI is expected to be produced using 100%hydrogen from renewable energy.Both the development of deep processing technologies and the invention of a novel binder are required to prepare high-quality pellets for direct reduction(DR),and further research on the one-step gas-based process is necessary.

Meta-Auto-Decoder:a Meta-Learning-Based Reduced Order Model for Solving Parametric Partial Differential Equations

Many important problems in science and engineering require solving the so-called parametric partial differential equations(PDEs),i.e.,PDEs with different physical parameters,boundary conditions,shapes of computational domains,etc.Typical reduced order modeling techniques accelerate the solution of the parametric PDEs by projecting them onto a linear trial manifold constructed in the ofline stage.These methods often need a predefined mesh as well as a series of precomputed solution snapshots,and may struggle to balance between the efficiency and accuracy due to the limitation of the linear ansatz.Utilizing the nonlinear representation of neural networks(NNs),we propose the Meta-Auto-Decoder(MAD)to construct a nonlinear trial manifold,whose best possible performance is measured theoretically by the decoder width.Based on the meta-learning concept,the trial manifold can be learned in a mesh-free and unsupervised way during the pre-training stage.Fast adaptation to new(possibly heterogeneous)PDE parameters is enabled by searching on this trial manifold,and optionally fine-tuning the trial manifold at the same time.Extensive numerical experiments show that the MAD method exhibits a faster convergence speed without losing the accuracy than other deep learning-based methods.

Mixed‑Dimensional Assembly Strategy to Construct Reduced Graphene Oxide/Carbon Foams Heterostructures for Microwave Absorption,Anti‑Corrosion and Thermal Insulation

Considering the serious electromagnetic wave(EMW)pollution problems and complex application condition,there is a pressing need to amalgamate multiple functionalities within a single substance.However,the effective integration of diverse functions into designed EMW absorption materials still faces the huge challenges.Herein,reduced graphene oxide/carbon foams(RGO/CFs)with two-dimensional/three-dimensional(2D/3D)van der Waals(vdWs)heterostructures were meticulously engineered and synthesized utilizing an efficient methodology involving freeze-drying,immersing absorption,secondary freeze-drying,followed by carbonization treatment.Thanks to their excellent linkage effect of amplified dielectric loss and optimized impedance matching,the designed 2D/3D RGO/CFs vdWs heterostructures demonstrated commendable EMW absorption performances,achieving a broad absorption bandwidth of 6.2 GHz and a reflection loss of-50.58 dB with the low matching thicknesses.Furthermore,the obtained 2D/3D RGO/CFs vdWs heterostructures also displayed the significant radar stealth properties,good corrosion resistance performances as well as outstanding thermal insulation capabilities,displaying the great potential in complex and variable environments.Accordingly,this work not only demonstrated a straightforward method for fabricating 2D/3D vdWs heterostructures,but also outlined a powerful mixeddimensional assembly strategy for engineering multifunctional foams for electromagnetic protection,aerospace and other complex conditions.

基于REDUCE理论的高校图书馆服务营销高质量发展研究

在高校图书馆高质量发展的背景下,服务营销高质量发展是提升图书馆服务利用效率,助力图书馆整体内涵式变革的重要举措。面向高校图书馆服务营销效能的提升需要,结合REDUCE理论创新高校图书馆服务营销理念,从心理抗拒、禀赋效应、距离、不确定性和补强证据五个维度分析高校用户利用图书馆服务的决策障碍,提出相对应的用户决策障碍化解路径指南,旨在为图书馆服务营销行动的高质量开展提供方法指引,有效促进用户利用图书馆服务,提升图书馆用户服务的核心价值。

Oxidation of Partially Hydrolyzed Polyacrylamide from Polymer Flooding Processes Using Fenton Reagents

The degradation of partially hydrolyzed polyacrylamide(HPAM) found in alkaline/surfactant/polymer flooding sewage was investigated using Fenton-type reagents. Different Fenton reagent treatments for HPAM degradation were compared. The effects of pH, hydrogen peroxide(H_(2)O_(2)), ferrous ion(Fe^(2+)), and tartaric ion(C_(4)H_(4)O_(6)^(2-)) concentrations were studied. The degradation reaction occurred within a wide range of pH(3–9). The HPAM degradation performance of photo-Fenton processes using solar light and UV were compared with that of the Fenton process. The degradation rate was found to be strongly dependent on the H_(2)O_(2)/Fe^(2+)/C_(4)H_(4)O_(6)^(2-)molar ratio. The HPAM degradation efficiency was 90%, and the chemical oxygen demand removal efficiency was 85%. HPAM could be degraded into a compound with a lower molecular weight, but it was difficult to achieve complete mineralization to CO_(2). The presence of intermediate products hindered further oxidation in the Fenton process.

A review of complications of polyacrylamide hydrogel injection

Once a popular injectable filler,polyacrylamide hydrogel(PAAG)has been banned in China since 2006 due to its unclear safety and long-term complications.However,it is still being used worldwide because of its huge commercial profit,leading to emerging complications and an urgent need for standardized clinical management.This review aimed to assess the properties,safety,and complications of PAAG and treatment strategies for its removal.

Engineering CoMoO_(4) in reduced graphene oxide as superior cathode hosts for advanced room-temperature sodium-sulfur batteries

Promising room-temperature sodium-sulfur(RT Na-S)battery systems rely on purposely designed highperforming and low-cost electrode materials.Nevertheless,there are the challenges of irreversible dissolution and slow redox kinetics of NaPSs in the complete discharge of sulfur capacity.Herein,engineered CoMoO_(4)in reduced graphene oxide(CoMoO_(4)@rGO)is reported as a class of superior cathode hosts for RT Na-S batteries.The CoMoO_(4)@rGO matrix is designed to facilitate the reversible sodiation and desodiation of sulfur,considering the strong chemisorption between sulfur(and short-chain sodium sulfides)and CoMoO_(4),which alleviates the shuttle effect of sodium sulfides and accelerates the electrochemical reaction rate at RT.The obtained S/CoMoO_(4)@rGO cathode with~52%S loading exhibits a high capacity of520.1 mA h g^(-1)after 100 cycles at 0.1 A g^(-1).Moreover,an enhanced long-term performance at high current densities(212.2 mA h g^(-1)at 4 A g^(-1)over 1000 cycles)with high Coulombic efficiency(~100%)is also achieved.This work demonstrates a novel multifunctional additive for RT Na-S battery cathodes,which is expected to promote the long-waited development towards practical applications of RT Na-S batteries.

Reduced graphene oxide aerogel decorated with Mo_(2)C nanoparticles toward multifunctional properties of hydrophobicity,thermal insulation and microwave absorption

Reduced graphene oxide(rGO)aerogels are emerging as very attractive scaffolds for high-performance electromagnetic wave absorption materials(EWAMs)due to their intrinsic conductive networks and intricate interior microstructure,as well as good compatibility with other electromagnetic(EM)components.Herein,we realized the decoration of rGO aerogel with Mo_(2)C nanoparticles by sequential hydrothermal assembly,freeze-drying,and high-temperature pyrolysis.Results show that Mo_(2)C nanoparticle loading can be easily controlled by the ammonium molybdate to glucose molar ratio.The hydrophobicity and thermal insulation of the rGO aerogel are effectively improved upon the introduction of Mo_(2)C nanoparticles,and more importantly,these nanoparticles regulate the EM properties of the rGO aerogel to a large extent.Although more Mo_(2)C nanoparticles may decrease the overall attenuation ability of the rGO aerogel,they bring much better impedance matching.At a molar ratio of 1:1,a desirable balance between attenuation ability and impedance matching is observed.In this context,the Mo_(2)C/r GO aerogel displays strong reflection loss and broad response bandwidth,even with a small applied thickness(1.7 mm)and low filler loading(9.0wt%).The positive effects of Mo_(2)C nanoparticles on multifunctional properties may render Mo_(2)C/r GO aerogels promising candidates for high-performance EWAMs under harsh conditions.

Mechanically flexible reduced graphene oxide/carbon composite films for high-performance quasi-solid-state lithium-ion capacitors

Practical applications of diverse flexible wearable electronics require electrochemical energy storage(EES)devices with multiple configurations.Moreover,to fabricate flexible EES devices with high energy density and stability,organic integration from electrode design to device assembly is required.To address these challenges,a free-standing reduced graphene oxide(rGO)/carbon film with a unique sandwich structure has been designed via the assistance of vacuum-assistant filtration for lithium-ion capacitors(LICs).The graphene acts as not only a binder to construct a three-dimensional conductive network but also an active material to provide additional capacitive lithium storage sites,thus enabling fast ion/electron transport and improving the capacity.The designed rGO/hard carbon(rGO/HC)and rGO/activated carbon(rGO/AC)free-standing films exhibit enhanced specific capacities(513.7 mA h g^(-1)for rGO/HC and 102.8 mA h g^(-1)for rGO/AC)and excellent stability.Moreover,the integrated flexible quasi-solid-state rGO/AC//rGO/HC LIC devices possess a maximum energy density of 138.3 Wh kg^(-1),a high power density of 11 kW kg^(-1),and improved cycling performance(84.4%capacitance maintained after 10,000 cycles),superior to the AC//HC LIC(43.5%retention).Such a strategy enlightens the development of portable flexible LICs.

Reduced graphene oxide-embedded nerve conduits loaded with bone marrow mesenchymal stem cell-derived extracellular vesicles promote peripheral nerve regeneration

We previously combined reduced graphene oxide(rGO)with gelatin-methacryloyl(GelMA)and polycaprolactone(PCL)to create an rGO-GelMA-PCL nerve conduit and found that the conductivity and biocompatibility were improved.However,the rGO-GelMA-PCL nerve conduits differed greatly from autologous nerve transplants in their ability to promote the regeneration of injured peripheral nerves and axonal sprouting.Extracellular vesicles derived from bone marrow mesenchymal stem cells(BMSCs)can be loaded into rGO-GelMA-PCL nerve conduits for repair of rat sciatic nerve injury because they can promote angiogenesis at the injured site.In this study,12 weeks after surgery,sciatic nerve function was measured by electrophysiology and sciatic nerve function index,and myelin sheath and axon regeneration were observed by electron microscopy,immunohistochemistry,and immunofluorescence.The regeneration of microvessel was observed by immunofluorescence.Our results showed that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles were superior to rGO-GelMA-PCL conduits alone in their ability to increase the number of newly formed vessels and axonal sprouts at the injury site as well as the recovery of neurological function.These findings indicate that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles can promote peripheral nerve regeneration and neurological function recovery,and provide a new direction for the curation of peripheral nerve defect in the clinic.

Drag reduction behavior of hydrolyzed polyacrylamide/xanthan gum mixed polymer solutions

Partially hydrolyzed polyacrylamide（HPAM）as the main component of slickwater fracturing fluid is a shear-sensitive polymer,which suffers from mechanical degradation at turbulent flow rates.Five different concentrations of HPAM as well as mixtures of polyacrylamide/xanthan gum were prepared to investigate the possibility of improving shear stability of HPAM.Drag reduction（DR）measurements were performed in a closed flow loop.For HPAM solutions,the extent of DR increased from 30%to67%with increasing HPAM concentration from 100 to1000 wppm.All the HPAM solutions suffered from mechanical degradation and loss of DR efficiency over the shearing period.Results indicated that the resistance to shear degradation increased with increasing polymer concentration.DR efficiency of 600 wppm xanthan gum（XG）was 38%,indicating that XG was not as good a drag reducer as HPAM.But with only 6%DR decline,XG solution exhibited a better shear stability compared to HPAM solutions.Mixed HPAM/XG solutions initially exhibited greater DR（40%and 55%）compared to XG,but due to shear degradation,DR%dropped for HPAM/XG solutions.Compared to 200 wppm HPAM solution,addition of XG did not improve the drag reduction efficiency of HPAM/XG mixed solutions though XG slightly improved the resistance against mechanical degradation in HPAM/XG mixed polymer solutions.

Preparation of cationic polyacrylamide microsphere emulsion and its performance for permeability reduction

In this paper, cationic polyacrylamide microspheres （CPAM） were synthesized using acrylamide （AM） and methacryloyloxyethyl trimethyl ammonium chloride （TMAEMC） as monomers, ammonium sulfate as dispersant, poly（acryloyloxyethyl trimethyl ammonium chloride） （PAETAC） as dispersion stabilizer, and ammonium persulfate as initiator. The synthetic method was dispersion polymerization. The effects of monomer ratio （AM/TMAEMC）, dispersant concentration, and dispersion stabilizer dosage on dispersion polymerization were systematically studied to determine the optimal preparation conditions. The structure and viscosity of the synthesized polymer were characterized by FTIR and capillary viscometry, respectively, and the particle sizes and distribution of the polymer microspheres were characterized by microscopy and dynamic light scattering, respectively. Finally, flow tests were conducted to measure the permeability reduction performance of the microspheres at various concentrations in sand packs with different permeability. Results show that CPAM emulsion of a solids content of 1 wt% has excellent performance in low-to-medium permeability formations （〈 1,000 mD）, and the efficiency may reach above 90%.

Impact of vericiguat on heart failure with reduced ejection fraction:a review

Introduction:Heart failure is a major public health issue with a prevalence of about 26 million people worldwide.Reduced nitric oxide availability,lower soluble guanylate cyclase(sGC)activity,and decreased cyclic guanosine monophosphate(cGMP)production are the causes of HF's development.Vericiguat prescribed under the brand name Verquvo was approved by U.S.Food and Drug Administration(FDA)in January 2021.It is a novel agent and the first sGC stimulator which helps to treat patients suffering from heart failure with reduced ejection fraction(HFrEF).Objective:The mechanism of action(cGMP pathway)of vericiguat,its clinical trials,its use in the treatment of heart failure,and its possible future aspects in therapeutic recommendations are all covered in this review.It will also raise awareness amongst healthcare professionals about the pharmacokinetic and pharmacodynamic parameters,dosing,administration,and drug-related problems of this new drug.Methods:Various databases for drug review were used in this review like PubMed,Medline,Google scholar,Drug bank,U.s.FDA,Medscape,and European society of cardiology guidelines.A total of 58 articles were screened out of which 39 articles were included in this review.Results:This review discusses vericiguat's mechanism of action(cGMP pathway),clinical studies,application in the treatment of heart failure,and potential future considerations in therapeutic recommendations.It will also educate healthcare professionals about the new drug's pharmacokinetics and pharmacodynamics,dose,administration,and drug-related problems.Conclusion:After hospitalization for HFrEF,the 5-year survival rate is just 25%,and disease morbidity and death are stil significant.As adjunctive therapy for individuals with heart failure and a low ejection fraction,vericiguat has a moderate level of effectiveness.Vericiguat's efficacy as an adjunct therapy to different drugs used to cure HF has to be further investigated.Vericiguat's safety and dosage in patients who have severe renal or hepatic illness need to be studied further.

Deep learning-based magnetic resonance imaging reconstruction for improving the image quality of reduced-field-of-view diffusionweighted imaging of the pancreas

BACKGROUND It has been reported that deep learning-based reconstruction(DLR)can reduce image noise and artifacts,thereby improving the signal-to-noise ratio and image sharpness.However,no previous studies have evaluated the efficacy of DLR in improving image quality in reduced-field-of-view(reduced-FOV)diffusionweighted imaging(DWI)[field-of-view optimized and constrained undistorted single-shot(FOCUS)]of the pancreas.We hypothesized that a combination of these techniques would improve DWI image quality without prolonging the scan time but would influence the apparent diffusion coefficient calculation.AIM To evaluate the efficacy of DLR for image quality improvement of FOCUS of the pancreas.METHODS This was a retrospective study evaluated 37 patients with pancreatic cystic lesions who underwent magnetic resonance imaging between August 2021 and October 2021.We evaluated three types of FOCUS examinations:FOCUS with DLR(FOCUS-DLR+),FOCUS without DLR(FOCUS-DLR−),and conventional FOCUS(FOCUS-conv).The three types of FOCUS and their apparent diffusion coefficient(ADC)maps were compared qualitatively and quantitatively.RESULTS FOCUS-DLR+(3.62,average score of two radiologists)showed significantly better qualitative scores for image noise than FOCUS-DLR−(2.62)and FOCUS-conv(2.88)(P<0.05).Furthermore,FOCUS-DLR+showed the highest contrast ratio and 600 s/mm^(2)(0.72±0.08 and 0.68±0.08)and FOCUS-DLR−showed the highest CR between cystic lesions and the pancreatic parenchyma for the b-values of 0 and 600 s/mm2(0.62±0.21 and 0.62±0.21)(P<0.05),respectively.FOCUS-DLR+provided significantly higher ADCs of the pancreas and lesion(1.44±0.24 and 3.00±0.66)compared to FOCUS-DLR−(1.39±0.22 and 2.86±0.61)and significantly lower ADCs compared to FOCUS-conv(1.84±0.45 and 3.32±0.70)(P<0.05),respectively.CONCLUSION This study evaluated the efficacy of DLR for image quality improvement in reduced-FOV DWI of the pancreas.DLR can significantly denoise images without prolonging the scan time or decreasing the spatial resolution.The denoising level of DWI can be controlled to make the images appear more natural to the human eye.However,this study revealed that DLR did not ameliorate pancreatic distortion.Additionally,physicians should pay attention to the interpretation of ADCs after DLR application because ADCs are significantly changed by DLR.

Synthesis and Flocculation of Polyacrylamide with Low Water Absorption for Non-dispersible Underwater Concrete

The polyacrylamide which is directly added into concrete shows strong water absorption property.Thus the construction of underwater constructure would demand high amount of water,resulting in poor workability of concrete and strength shrinkage after hardening.Herein,a kind of anionic polyacrylamide(APAM)grafted with water reducing functional group(-COOH)was synthesized at low temperatures by partial factor design and response surface design.The structure and morphology of APAM were characterized by UV,FTIR and SEM methods.The experimental results show that the molecular weight of the synthesized APAM could reach 11 million,under the condition that the temperature was 35℃,the pH value was 8,the monomer concentration was 27wt%,the initiator dosage was 0.6wt%,and the monomer ratio(n(AM):n(AA))was 3.When the APAM was applied into the underwater slurry,it presented good flocculation and low water demand.When the dosage was 1%of the mass of the cement,the water demand increased by 12%,which could meet the self-leveling and anti-dispersity of the underwater slurry at the same time.This technology provides technical guidance for the large-scale industrial production of polyacrylamide for underwater concrete construction while achieving environmental protection during production.

N-acetylcysteine and reduced glutathione reverse flupirtine-induced liver injury and pro⁃duce other beneficial effects in combination with flupirtine

OBJECTIVE To assess whether N-acetylcysteine(NAC)and reduced glutathione(GSH)are effective in reversing flupirtine-induced hepatotoxicity and whether they have other beneficial effects when combined with flupirtine.METHODS The analgesic effects of NAC and flupirtine were first evaluated in carrageenaninduced inflammatory pain and paclitaxel-induced neuropathic pain.The combination subthreshold⁃ing approach was then used to determine whether the combination of NAC and flupirtine produced synergistic analgesic effects.Hepatotoxicity markers and histopathological examination of the liver were used to assess the efficacy of NAC and GSH in reversing flupirtine-induced hepato⁃toxicity.Finally,the effect of GSH on the safe range of flupirtine was assessed in an acute tox⁃icity assay.RESULTS Flupirtine and NAC pro⁃duced dose-dependent antiallodynic effects evoked by carrageenan and paclitaxel in mice.In the above model,the combination of NAC and flupirtine produced an unexpected synergistic analgesic effect.There were no significant differ⁃ences observed in the hepatotoxicity markers and liver histopathology between the experimen⁃tal group and the control group under NAC and GSH treatment.Finally,GSH(200 mg·kg^(-1))expanded the therapeutic index of flupirtine by 1.77 times.CONCLUSION NAC and GSH are effective in preventing liver damage caused by long-term flupirtine use,which provides a solu⁃tion for the safe and effective treatment of chronic pain with flupirtine.In addition,the other benefi⁃cial effects of NAC and GSH when combined with flupirtine may provide the basis for the devel⁃opment of a new therapy with minimal sideeffects and good efficacy.