基于激光雕刻石墨烯电极的伏安法实验教学新方案

伏安法是仪器分析课程的重要章节和教学难点,其现有实验教学方案在理论融合和应用拓展等方面存在不足。本文通过引入较为前沿的激光雕刻石墨烯电极体系,丰富内容如扩散电流理论和电催化现象模拟,延伸应用如奶粉香兰素检测,帮助学生深入理解方法的基本原理、研究动向和应用价值。实验综合成本低、电极可批量制备,适合教学开展。

Improved Diurnal Cycle of Precipitation on Land in a Global Non-Hydrostatic Model Using a Revised NSAS Deep Convective Scheme

In relatively coarse-resolution atmospheric models,cumulus parameterization helps account for the effect of subgridscale convection,which produces supplemental rainfall to the grid-scale precipitation and impacts the diurnal cycle of precipitation.In this study,the diurnal cycle of precipitation was studied using the new simplified Arakawa-Schubert scheme in a global non-hydrostatic atmospheric model,i.e.,the Yin-Yang-grid Unified Model for the Atmosphere.Two new diagnostic closures and a convective trigger function were suggested to emphasize the job of the cloud work function corresponding to the free tropospheric large-scale forcing.Numerical results of the 0.25-degree model in 3-month batched real-case simulations revealed an improvement in the diurnal precipitation variation by using a revised trigger function with an enhanced dynamical constraint on the convective initiation and a suitable threshold of the trigger.By reducing the occurrence of convection during peak solar radiation hours,the revised scheme was shown to be effective in delaying the appearance of early-afternoon rainfall peaks over most land areas and accentuating the nocturnal peaks that were wrongly concealed by the more substantial afternoon peak.In addition,the revised scheme enhanced the simulation capability of the precipitation probability density function,such as increasing the extremely low-and high-intensity precipitation events and decreasing small and moderate rainfall events,which contributed to the reduction of precipitation bias over mid-latitude and tropical land areas.

Searching for the Nano-Hertz Stochastic Gravitational Wave Background with the Chinese Pulsar Timing Array Data ReleaseⅠ

Observing and timing a group of millisecond pulsars with high rotational stability enables the direct detection of gravitational waves(GWs).The GW signals can be identified from the spatial correlations encoded in the times-of-arrival of widely spaced pulsar-pairs.The Chinese Pulsar Timing Array(CPTA)is a collaboration aiming at the direct GW detection with observations carried out using Chinese radio telescopes.This short article serves as a“table of contents”for a forthcoming series of papers related to the CPTA Data Release 1(CPTA DR1)which uses observations from the Five-hundred-meter Aperture Spherical radio Telescope.Here,after summarizing the time span and accuracy of CPTA DR1,we report the key results of our statistical inference finding a correlated signal with amplitude logA_(c)=-14.4_(-2.8)^(+1.0)for spectral index in the range ofα∈[-1.8,1.5]assuming a GW background(GWB)induced quadrupolar correlation.The search for the Hellings–Downs(HD)correlation curve is also presented,where some evidence for the HD correlation has been found that a 4.6σstatistical significance is achieved using the discrete frequency method around the frequency of 14 n Hz.We expect that the future International Pulsar Timing Array data analysis and the next CPTA data release will be more sensitive to the n Hz GWB,which could verify the current results.

Improving GPP estimates by partitioning green APAR from total APAR in two deciduous forest sites

Non-photosynthetic components within a forest ecosystem account for a large proportion of the canopy but are not involved in photosynthesis.Therefore,the accuracy of gross primary production(GPP)estimates is expected to improve by removing these components.However,their infl uence in GPP estimations has not been quantitatively evaluated for deciduous forests.Several vegetation indices have been used recently to estimate the fraction of photosynthetically active radiation absorbed by photosynthetic components(FAPAR_(green))for partitioning APAR green(photosynthetically active radiation absorbed by photosynthetic components).In this study,the enhanced vegetation index(EVI)estimated FAPAR_(green)and to separate the photosynthetically active radiation absorbed by photosynthetic components(APAR green)from total APAR observations(APAR_(total))at two deciduous forest sites.The eddy covariance-light use effi ciency(EC-LUE)algorithm was employed to evaluate the infl uence of non-photosynthetic components and to test the performance of APAR green in GPP estimation.The results show that the infl uence of non-photosynthetic components have a seasonal pattern at deciduous forest sites,large diff erences are observed with normalized root mean square error(RMSE*)values of APAR green-based GPP and APAR_(total)-based GPP between tower-based GPP during the early and end stages,while slight diff erences occurred during peak growth seasons.In addition,daily GPP estimation was significantly improved using the APAR green-based method,giving a higher coeffi cient of determination and lower normalized root mean square error against the GPP estimated by the APAR_(total)-based method.The results demonstrate the signifi cance of partitioning APAR green from APAR_(total)for accurate GPP estimation in deciduous forests.

The magnetic field design of a solenoid for the cold-cathode Penning ion source of a miniature neutron tube

A high-yield and beam-stable neutron tube can be applied in many fields.It is of great significance to the optimal external magnetic field intensity of the cold-cathode Penning ion source(PIS)and precisely controls the movement of deuterium(D),tritium(T)ions and electrons in the source of the neutron tubes.A cold-cathode PIS is designed based on the solenoidal magnetic field to obtain better uniformity of the magnetic field and higher yield of the neutron tube.The degree of magnetic field uniformity among the magnetic block,double magnetic rings and solenoidal ion sources is compared using finite element simulation methods.Using drift diffusion approximation and a magnetic field coupling method,the plasma distribution of hydrogen and the relationship between plasma density and magnetic field intensity at 0.06 Pa pressure and a solenoid magnetic field are obtained.The results show that the solenoidal ion source has the most uniform magnetic field distribution.The optimum magnetic field strength of about 0.1 T is obtained in the ion source at an excitation voltage of 1 V.The maximum average number density of monatomic hydrogen ions(H+)is 1×108 m−3,and an ion-beam current of about 14.51μA is formed under the−5000 V extraction field.The study of the solenoidal magnetic field contributes to the understanding of the particle dynamics within the PIS and provides a reference for the further improvement of the source performance of the neutron tube in the future.

Novel learning framework for optimal multi-object video trajectory tracking

Background With the rapid development of Web3D, virtual reality, and digital twins, virtual trajectories and decision data considerably rely on the analysis and understanding of real video data, particularly in emergency evacuation scenarios. Correctly and effectively evacuating crowds in virtual emergency scenarios are becoming increasingly urgent. One good solution is to extract pedestrian trajectories from videos of emergency situations using a multi-target tracking algorithm and use them to define evacuation procedures. Methods To implement this solution, a trajectory extraction and optimization framework based on multi-target tracking is developed in this study. First, a multi-target tracking algorithm is used to extract and preprocess the trajectory data of the crowd in a video. Then, the trajectory is optimized by combining the trajectory point extraction algorithm and Savitzky-Golay smoothing filtering method. Finally, related experiments are conducted, and the results show that the proposed approach can effectively and accurately extract the trajectories of multiple target objects in real time. Results In addition, the proposed approach retains the real characteristics of the trajectories as much as possible while improving the trajectory smoothing index, which can provide data support for the analysis of pedestrian trajectory data and formulation of personnel evacuation schemes in emergency scenarios. Conclusions Further comparisons with methods used in related studies confirm the feasibility and superiority of the proposed framework.

A Synthetic Study of the Position Difference of the Southern Branch Trough of the Qinghai-Tibet Plateau Based on Objective Identification

The southern branch trough (SBT) mainly appears in the winter half year (November to May of the following year), using the 4 times daily NCEP/NCAR re-analysis data nearly 41 years (1979-2019) to analyze the differences of the SBT distribution of spatial location, frequency in winter and spring, then selects the “eastern type” and “western type” of the 10 most typical SBT, using simplified vertical vorticity tendency equation, using simplified vertical vorticity tendency equation to diagnosis of the SBT in power, heat, water vapor and wave energy in different positions. The results show that: 1) The location of the SBT is more eastward in winter, and more westward in spring. 2) The diagnosis results of the vorticity equation show that the vorticity of the southern branch of the “western type” is mainly contributed by advection term;the vorticity of the “eastern type” south branch is mainly contributed by the non-adiabatic heating term. 3) The SBT of the “eastern type” has more obvious vorticity advection than the southern branch of the “western type”, and the dynamic action is stronger. The “western type” SBT has stronger Q1, specific humidity advection and water vapor flux than the “eastern type” SBT, which is greatly affected by thermal action and water vapor. When the “eastern type” and “western type” SBT occur, the T-N wave activity flux appears obvious abnormal energy fluctuation propagation.

机械制图课程混合式教学方法研究

混合式教学模式由信息技术支持下的传统课堂＋翻转课堂教学模式组成,是一种更适合在高等院校实施,更容易达成高等工程教育的核心目标的教学模式.混合式教学模式是机械制图课程改革发展的方向.设计合理的学习任务单是学生自主学习的支架,基于过程的评价、师生间的有效交流、采用“做中学”和“项目学习”等方法,可激发学生参与课堂学习的积极性,提高教与学的效率.

Mechanical Properties and Degradability of Electrospun PCL/PLGA Blended Scaffolds as Vascular Grafts

In our study, the mechanical properties and degradability of vascular grafts made from poly(ε-caprolactone)(PCL) and poly(lactic-co-glycolic acid)(PLGA) at different ratios were investigated. The results showed that the electrospun PCL/PLGA grafts possess good mechanical properties and biodegradability. The tensile and burst strength of the scaffolds met the demands of vascular grafts. In vitro degradation tests indicated that the degradation rate of the materials increased with the percentage of PLGA, and in vivo tests showed that increasing the amount of PLGA is an effective way to promote cell infiltration. Particularly, the electrospun PCL/PLGA blended scaffold with 10% PLGA exhibited a balance of mechanical and degradation properties, making it a promising tissue engineering material for vascular grafts.

Effects of ephedrine on expression of Nogo-A and synaptophysin in neonatal rats following hypoxic-ischemic brain damage

BACKGROUND： Central nervous system axons regenerate poorly following neonatal hypoxic-ischemic brain damage （HIBD）, partly due to inhibitors, such as Nogo-A. Very few studies have addressed the regulation of Nogo-A in neonatal rats following HIBD. However, numerous studies have shown that ephedrine accelerates neuronal remodeling and promotes recovery of neural function in neonatal rats following HIBD. OBJECTIVE： To investigate the effects of ephedrine on expression of Nogo-A and synaptophysin in brain tissues of neonatal rats following HIBD. DESIGN, TIME AND SETTING： A completely randomized, controlled study was performed at the Immunohistochemistry Laboratory of the Research Institute of Pediatrics, Children＇s Hospital of Chongqing Medical University from August 2008 to March 2009. MATERIALS： Ephedrine hydrochloride （Chifeng Pharmaceutical Group, China）, rabbit anti-Nogo-A polyclonal antibody （Abcam, UK）, and rabbit anti-synaptophysin polyclonal antibody （Lab Vision, USA） were used in this study. METHODS： A total of 96 healthy, neonatal, Sprague Dawley rats were randomly assigned to three groups （n = 32）： sham operation, HIBD, and ephedrine. The HIBD model was established by permanent occlusion of the left common carotid artery, followed by 2 hours of hypoxia （8% oxygen and 92% nitrogen）. In the sham operation group, the left common carotid artery was exposed, but was not ligated or subjected to hypoxia. Rats in the ephedrine group were intraperitoneally injected with ephedrine immediately following HIBD, with 1.5 mg/kg each time. Rats in the sham operation and HIBD groups were injected with an equal volume of saline. All neonatal rats were treated once daily for 7 days. MAIN OUTCOME MEASURES： Histopathological damage to the cortex and hippocampus was determined by hematoxylin-eosin staining. Expression of Nogo-A and synaptophysin was detected using immunohistochemical staining. RESULTS： Neuronal degeneration and edema were observed in the hypoxJc-Jschemic cortex and hippocampus by hematoxylin-eosin staining. Compared with the sham operation group, the levels of Nogo-A significantly increased in the HIBD group at various time points （P 〈 0.01）. Nogo-A expression was significantly reduced in the ephedrine group compared with the HIBD group （P 〈 0.01）. Synaptophysin expression was significantly decreased in the hypoxic-ischemJc cortex, compared with the sham operation group （P 〈 0.01）. Synaptophysin levels were significantly increased in the ephedrine group, compared with the HIBD group （P 〈 0.01）. CONCLUSION： Altered Nogo-A expression was associated with inversely altered synaptophysin expression. The use of ephedrine normalized expression levels of Nogo-A and synaptophysin following HIBD.

Grain size dependence of annealing strengthening of an extruded Mg-Gd-Zn alloy subjected to pre-compression deformation

In this work, pre-strain annealing strengthening(PSAS) effect was investigated in an extruded Mg-1.0Gd-1.5 Zn(wt.%) alloy with respect to different grain sizes. The evolution of microstructures was provided by scanning electron microscopy(SEM), electron backscattered diffraction(EBSD), transmission electron microscopy(TEM) and high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM) under the initial state, pre-compression, intermediate annealing and re-compression conditions. The obtained results showed a grain size-dependent PSAS effect in the alloy. The sample with larger grain sizes corresponded to a higher strengthening effect, which mainly resulted from a more remarkable hindrance for the growth of existing twins and a larger proportion of activation for the nucleation of new twins. This was closely associated with the increase of back stress and friction stress for twin boundary motion impeded by the larger restraint of dislocations, the higher stress field surrounding solutes and the more Zn segregation. In addition to twinning behavior, Guinier Preston(G.P.) zones on basaldislocations were found after intermediate annealing and provided an extra strengthening by inhibiting the motions of gilding pre-existing dislocations and newly formed ones, but it was independent on the grain size.

Optimal compatible doses and effects of ephedrine and naloxone on neural plasticity in cerebral ischemia/reperfusion rats

BACKGROUND： Ephedrine promotes neural plasticity in rats following cerebral ischemia/reperfusion injury. Ephedrine has been combined with naloxone in some studies, and it has been confirmed that their combination has synergistic effects on increasing neural plasticity following cerebral ischemia/reperfusion injury. OBJECTIVE： To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity and to find an optimal dose of naloxone in rats after cerebral ischemia/reperfusion injury by analyzing growth associated protein-43 （GAP-43）, synaptophysin and β-endorphin expression in the hippocampal CA3 area. DESIGN, TIME AND SETTING： This immunohistochemical, randomized, controlled, animal experiment was performed at the Chongqing Research Institute of Pediatrics, China from September 2007 to June 2008. MATERIALS： Ephedrine hydrochloride injection and naloxone hydrochloride injection were respectively purchased from Shandong Lvliang Pharmaceutical Factory, China and Sichuan Jingwei Pharmaceutical Co., Ltd., China. A total of 192 healthy adult Sprague Dawley rats were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. METHODS： At 2 hours following cerebral ischemia, the rats were intraperitoneally injected with 1.5 mg/kg/d ephedrine （ephedrine group）, with 0.1, 0.2, or 0.3 mg/kg/d naloxone （low, moderate and high doses of naloxone groups）, with 1.5 mg/kg/d ephedrine ＋ 0.1, 0.2, or 0.3 mg/kg/d naloxone （ephedrine ＋ low, moderate and high doses of naloxone groups）, and with 0.5 mL saline （model group）, respectively. MAIN OUTCOME MEASURES： GAP-43, synaptophysin and β -endorphin expression were detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery. Sensorimotor integration in rats was assessed using the beam walking test. RESULTS： GAP-43 and synaptophysin expression was greater in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups compared with the model group. GAP-43 and synaptophysin expression was greatest in the ephedrine ＋ high dose of naloxone group at 2 and 3 weeks alter surgery. β -endorphin expression was significantly lower in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups compared with the model group （P 〈 0.05）. β -endorphin expression was persistently low in the ephedrine ＋ high dose of naloxone group. At 1-3 weeks after surgery, the beam walking test score was significantly higher in the ephedrine group and ephedrine ＋ various doses of naloxone groups than in the model group （P 〈 0.05）. The score was higher in the ephedrine ＋ moderate and high doses of naloxone groups than in the ephedrine group （P 〈 0.05）. Moreover, the score was increased as the dose of naloxone increased in the ephedrine ＋ various doses of naloxone groups. CONCLUSION： Ephedrine promotes GAP-43 and synaptophysin expression, inhibits /3 -endorphin expression in the hippocampal CA3 area, and improves motor function in rats following cerebral ischemia/reperfusion injury. Naloxone does not have the above-mentioned effects. During combined treatment with ephedrine and naloxone, however, the above-described effects are enhanced with an increased dose of naloxone. The combination of ephedrine （1.5 mg/kg/d） and naloxone （0.3 mg/kg/d） can produce optimal therapeutic efficacy in treatment of cerebral ischemic injury.

Simulation of the hydrodynamics and mass transfer in a falling film wavy microchannel

The flow in a liquid falling film is predominantly laminar,and the liquid-side mass transfer is limited by molecular diffusion.The effective way to enhance the mass transfer is to improve the liquid film flow behavior.The falling film behaviors of water,ethanol and ethylene glycol in nine different wavy microchannels were simulated by Computational Fluid Dynamics.The simulation results show that the falling film thickness exhibits a waveform distribution resulting in a resonance phenomenon along the wavy microchannel.The fluctuation of liquid film surface increases the gas-liquid interface area,and the internal eddy flow inside the liquid film also improves the turbulence of liquid film,the gas-liquid mass transfer in falling film microchannels is intensified.Compared with flat microchannel,the CO_(2) absorption efficiency in water in the wavy microchannel is improved over 41%.Prediction models of liquid film amplitude and average liquid film thickness were established respectively.

Comprehensive report on China's Long-Term Low-Carbon Development Strategies and Pathways

1.Introduction 2020 is an unusual year in which the COVID-19 pandemic has raged through the globe,infecting tens of millions of people and killing hundreds of thousands.The pandemic has not only wreaked havoc on public health systems,economic activities,and people's lives,but also has greatly affected and will continue to reshape the world's political,economic,and trade patterns.

Ammonia promotes the proliferation of bone marrow-derived mesenchymal stem cells by regulating the Akt/mTOR/S6k pathway

Ammonia plays an important role in cellular metabolism.However,ammonia is considered a toxic product.In bone marrow-derived mesenchymal stem cells,multipotent stem cells with high expression of glutamine synthetase(GS)in bone marrow,ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs.As a major nutritional amino acid for biosynthesis,glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation.The activation of mTOR can promote cell entry into S phase,thereby enhancing DNA synthesis and cell proliferation.Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity.Then,the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation.These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia.

Side effects of different doses of ephedrine in rats with cerebral ischemia/reperfusion injury

Ephedrine has a protective effect against cerebral ischemia,but its side effects limit its clinical application.Results from a previous study showed that 1.5 mg/kg per day ephedrine can promote motion recovery in rats following cerebral ischemia/reperfusion without significant side effects.In the present study,ephedrine at doses of 3.0,2.5 and 2.0 mg/kg was used to treat rats with cerebral ischemia/reperfusion and the effects of ephedrine on the heart,liver,kidney and cerebrum were observed.Results showed that the blood pressure of rats with cerebral ischemia/reperfusion injury following ephedrine treatment was lower than in rats that recovered naturally from cerebral ischemia/reperfusion,but the pressure decreased with increasing doses of ephedrine.In addition,serum aspartate transaminase,alkaline phosphatase and creatinine concentration in rats with cerebral ischemia/reperfusion injury following ephedrine treatment were greater than in rats that recovered naturally from cerebral ischemia/reperfusion.The concentrations of these enzymes were decreased with increasing doses of ephedrine.Ephedrine-treated rats displayed hyperemia,degeneration and edema in the cerebrum,liver,heart and kidney.Results demonstrated that ephedrine exhibited side effects on the cerebrum,heart,liver and kidney in rats following cerebral ischemia/reperfusion in a dose-dependent manner.

Suppression of partially irreversible phase transition in O′3-Na_(3)Ni_(2)SbO_(6)cathode for sodium-ion batteries by interlayered structural modulation

As a promising cathode material for sodium ion batteries,honeycomb-ordered layered Na_(3)Ni_(2)Sb O_(6)still suffers from rapid capacity fading because of partially irreversible phase transition.Herein,a substitution of Na+by Rb+with a larger ionic radius in honeycomb layered Na_(3)-xRbxNi_(2)Sb O_(6)is proposed to modulate the interlayer structure.The results unveil that biphasic transition reversibility of the intermediate P′3phase is substantially enhanced,and the structure evolution behavior during the charge/discharge process changes due to the structural modulation,which contributes to a suppression of the unfavorable O_(1)phase and an alleviation of the lattice distortion.Moreover,Rb substituted samples exhibited an improved Na+(de)intercalation thermodynamics and kinetics.Attributed to the modifications,the sample with optimized Rb content delivers superior cycle stability and rate capacity,demonstrating a feasible strategy for suppressing irreversible phase transition and developing high-performance honeycomb layered materials for sodium ion batteries.

Effects of exogenous ganglioside-1 on learning and memory in a neonatal rat model of hypoxia-ischemia brain injury

BACKGROUND： Exogenous ganglioside-1 （GM1） can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage. OBJECTIVE： To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass, pathological morphology, growth-associated protein-43 expression, and neurobehavioral manifestations. DESIGN, TIME AND SETTING： A randomized block-design study was performed at the Immunohistochemistry Laboratory of the Pediatric Research Institute, Children＇s Hospital of Chongqing Medical University from August 2005 to August 2006. MATERIALS： A total of 36 neonatal, 7-day-old, Sprague Dawley rats were used in this experiment. The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery, followed by oxygen inhalation at a low concentration （8% O2, 92% N2） for 2 hours, METHODS： All rats were randomly divided into the following groups： GMI, model, and sham operation, with 12 rats each group. Rats in the GM 1 and model groups received hypoxic/ischemic-induced brain damage. Rats in the GM1 group received injections of GM1 （i.p., 20 mg/kg） at 0, 24, 48, 72, 96, 120, and 144 hours following models established, and rats in the model group were administered （i.p.） the same amount of saline. The right carotid artery was separated, but not ligated, in the sham operation group rats. MAIN OUTCOME MEASURES： At 1 week after surgery, expression of growth-associated protein-43, a marker of neural development and plasticity, was detected in the hippocampal CA3 region by immunohistochemistry. Brain mass was measured, and the pathological morphology was observed. At 4 weeks after surgery, behavioral changes in the remaining rats were tested by Morris water maze, and growth-associated protein-43 expression was measured. RESULTS： （1） In the GMI and sham operation groups, growth-associated protein-43 expression was greater in the hippocampal CA3 region compared to the model group 1 week after surgery （P 〈 0.05）. In all three groups, brain weight of the right hemisphere was significantly less than the left hemisphere, in particular in the model group （P 〈 0.05）. In the GMI group, the weight difference between two hemispheres, as well as the extent of damage in the right hemisphere, was less than the model group （P 〈 0.01 ）. In the sham operation Uoup, brain tissue consisted of integrated structures and ordered cells. In the model group, the cerebral cortex layers of the right hemisphere were not defined, neurons were damaged, and neurons were disarranged in the hippocampal area. In the GM1 group, neurons were dense in the right cerebral cortex and hippocampal area, with no significant change in glial proliferation. （2） The average time of escape latency in the GM1 group was shortened 4 weeks alter surgery, and significantly less than the model group （P 〈 0.05）. In addition, the frequency platform passing in the GMI group was significantly greater than the model group （P 〈 0.01）. CONCLUSION： Exogenous GM1 may reduce brain injury and improve learning and memory in hypoxia-ischemia-induced brain damage rats. This protection may be associated with increased growth-associated protein-43 expression, which is involved in neuronal remodeling processes.

Optimal Timing of Antiretroviral Therapy Initiation in Acquired Immunodeficiency Syndrome-Associated Toxoplasmic Encephalitis:A Prospective Observational Multicenter Study in China

Background:Toxoplasmic encephalitis(TE)is the most frequent cause of expansive brain lesions among patients with acquired immunodeficiency syndrome(AIDS).However,the optimal timing of antiretroviral therapy(ART)initiation in these patients remains controversial.This study aims to investigate the differences in outcomes of ART initiation at different times,in order to help clarify the treatment timing of AIDS-associated TE.Methods:This multicenter prospective observational study included 87 patients recruited from 11 research centers in China(from March 2019 to December 2022).Of the patients,38 were assigned to the early ART group(initiating ART within 2 weeks after anti-Toxoplasma treatment initiation),and the remaining 49 patients received deferred ART(initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation).The main outcomes includedmortality and emergence of immune reconstitution inflammatory syndrome(IRIS).Human immunodeficiency virus(HIV)-1 viral load and CD4^(+)T-cell counts at weeks 24 and 48 were observed.Results:The number of deaths(1 vs.5,P=0.225)and incidence of IRIS(2.6%vs.0,P=0.437)were not significantly different between the early and deferred ART groups at week 48.Early ART initiation did not contribute significantly to HIV-1 viral load control(<50 copies/mL,n=8 vs.n=3 at week 24,P=0.142;n=7 vs.n=7 atweek 48,P=1.000).The median CD4^(+)T-cell counts between the two groups were not significantly different,either at week 24(155 vs.91 cells/mm^(3),P=0.837)or atweek 48(181 vs.146 cells/mm^(3),P=0.219).Conclusion:In patients with AIDS-associated TE,early ART initiation was not significantly different from deferred ART initiation in terms of incidence of mortality,IRIS,and HIV virological and immunological outcomes.Trial registration:This study was registered(registration number:ChiCTR1900021195)as one of 12 clinical trials under the title of a general project at the Chinese Clinical Trial Registry(chictr.gov)on February 1,2019.Enrollment for this study began inMarch 2019.

Phenylalanine diminishes M1 macrophage inflammation

Emerging evidence suggests that amino acids dictate the effector functions of immune cells;however, whether and how phenylalanine(Phe) orchestrates the polarization of macrophages is not understood. Here, we determined that Phe attenuated lipopolysaccharide(LPS) and P. multocida serotype A strain CQ2(PmCQ2) infection-induced inflammation in vivo. Furthermore, we demonstrated that Phe inhibited the production of interleukin(IL)-1β and tumor necrosis factor(TNF)-α in proinflammatory(M1) macrophages. Phe reprogrammed the transcriptomic and metabolic profiles and enhanced oxidative phosphorylation in M1 macrophages, which reduced the activation of caspase-1. Notably, the valine-succinyl-CoA axis played a critical role in Phe-mediated inhibition of IL-1β production in M1 macrophages. Taken together, our findings suggest that manipulating the valine-succinyl-CoA axis provides a potential target for preventing and/or treating macrophage-related diseases.