Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for ...Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.展开更多
MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are...MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.展开更多
Energetic nanofluid fuel has caught the attention of the field of aerospace liquid propellant for its high energy density(HED), but it suffers from the inevitable solid-liquid phase separation problem. To resolve this...Energetic nanofluid fuel has caught the attention of the field of aerospace liquid propellant for its high energy density(HED), but it suffers from the inevitable solid-liquid phase separation problem. To resolve this problem, herein we synthesized the high-Al-/B-containing(up to 30%(mass)) HED gelled fuels, with low-molecular-mass organic gellant Z, which show high net heat of combustion(NHOC), density, storage stability, and thixotropic properties. The characterizations indicate that the application of energetic particles to the gelled fuels obviously destroys their fibrous network structures but can provide the new particle-gellant gelation microstructures, resulting in the comparable stability between 1.0%(mass) Z/JP-10 + 30%(mass) Al or B and pure JP-10 gelled fuel. Moreover, the gelled fuels with high-content Al or B exhibit high shear-thinning property, recovery capability, and mechanical strength, which are favorable for their storage and utilization. Importantly, the prepared 1.0%(mass) Z/JP-10 + 30%(mass) B(or 1.0%(mass) Z/JP-10 + 30%(mass) Al) shows the density and NHOC 1.27 times(1.30) and 1.43 times(1.21)higher than pure JP-10, respectively. This work provides a facile and valid approach to the manufacturing of HED gelled fuels with high content of energetic particles for gel propellants.展开更多
The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its ...The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its potential molecular mechanism were investigated.Results showed that SCP3 at 25-100μg/m L increased viability and improved phagocytosis of RAW264.7 cells.Meanwhile,SCP3 could activate mitogen-activated protein kinase(MAPK)and nuclear factor kappa B(NF-κB)signaling pathways,which increased the phosphorylation of Erk1/2,JNK,p38 and NF-κB p65,promoting secretion of cytokines tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and nitric oxide(NO)as well as the production of reactive oxygen species(ROS).In addition,Toll-like receptor 4(TLR4)receptor inhibitors were able to block the production of NO and TNF-αby SCP3-stimulated macrophages.Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways,the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-αand NO production via TLR4-mediated MAPK and NF-κB pathways.In summary,SCP3 has significant immunomodulatory potential.The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production,which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.展开更多
Liver transplantation is the primary therapeutic intervention for end-stage liver disease.However,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.The clinical ...Liver transplantation is the primary therapeutic intervention for end-stage liver disease.However,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.The clinical manifestations associated with early arterial complications following liver transplantation are often non-specific.Without timely intervention,these complications can result in graft fai-lure or patient mortality.Therefore,early diagnosis and the formulation of an op-timal treatment plan are imperative.Ultrasound examination remains the pre-dominant imaging modality for detecting complications post liver transplan-tation.This article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these con-ditions.Overall,ultrasound offers the advantages of convenience,safety,effect-iveness,and non-invasiveness.It enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation assessments.INTRODUCTION Liver transplantation stands as the primary therapeutic approach for end-stage liver disease.Continuous advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation procedures.Despite these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.During the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood flow.During later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood supply.It is now understood that the establishment of effective collateral circulation is pivotal for determining the prognosis of hepatic artery complic-ations.The clinical manifestations of these complications are closely linked to factors such as timing,severity,and the specific type of onset.Insufficient hepatic arterial blood flow can lead to abnormal liver function,hepatic infarction,and the formation of hepatic abscesses.Additionally,since the hepatic artery is the sole blood supply to the biliary tract,hepatic artery-related ischemia may result in biliary stricture,obstruction,and the formation of bile ducts.Ultrasound examination remains the primary imaging modality for diagnosing complications post liver transplantation.This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and outlines abnormal sonographic findings for accurately diagnosing these conditions.NORMAL HEPATIC ARTERY During the intraoperative phase,an ultrasound examination is typically conducted to evaluate the hepatic artery anas-tomosis.The normal internal diameter of the hepatic artery typically ranges from 2 to 5 mm.Two strong echo points are typically identified near the anastomosis.To assess blood flow dynamics,peak systolic velocity,end-diastolic velocity,and resistance index are measured at the donor and recipient sides of the anastomosis following angle correction.Anastomotic stenosis presence and severity can be evaluated by comparing the velocity at the anastomotic site with that at the recipient side.Postoperatively,direct visualization of the anastomosis site through gray ultrasound scans is often challenging.The surgical approach has a significant impact on the proper hepatic artery’s position,resulting in a lower overall success rate of continuous visualization.Color Doppler ultrasound is primarily employed to trace the artery’s path,and spectral measurements are taken at the brightest position of the Color Doppler blood flow signal,primarily used to identify the presence of high-speed turbulence.Hepatic artery spectrum examination plays a crucial role,as a favorable arterial spectral waveform and appropriate hepatic artery flow velocity typically indicate a successful anastomosis,even in cases where the hepatic artery anastomosis cannot be directly visualized by ultrasound.The hepatic artery runs alongside the portal vein,often selected as a reference due to its larger inner diameter.A normal hepatic artery spectrum displays a regular pulsation pattern with a rapid rise in systole and a slow decline in diastole.Parameters for assessing hepatic artery resistance include a resistance index between 0.5 to 0.8 and an artery systolic acceleration of less than 80 ms.Instantaneous increases in the resistance index(RI>0.8)often occur within 2 d after surgery,followed by a subsequent return to normal hepatic arterial parameters.It has been established that the maximum blood flow velocity during systole in the hepatic artery should not exceed 200 cm/s[1].展开更多
BACKGROUND:Patients with hypertension coupled with metabolic syndrome(MetS) are among the high risk population in cardiovascular and cerebrovascular diseases.To reduce the prevalence of cardiovascular and cerebrovascu...BACKGROUND:Patients with hypertension coupled with metabolic syndrome(MetS) are among the high risk population in cardiovascular and cerebrovascular diseases.To reduce the prevalence of cardiovascular and cerebrovascular diseases,it is essential to appropriately control blood pressure together with other cardiovascular risk factors. OBJECTIVE:The current study was designed to investigate the therapeutic effects on blood pressure,blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula,a compound traditional Chinese herbal medicine,in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN,SETTING,PARTICIPANTS AND INTERVENTIONS:A total of 43 patients with hypertension coupled with MetS were recruited into this study.The enrolled patients were randomly divided into the Chinese herbal formula group(anti-hypertensive drugs plus Yiqi Huaju Formula,CHF) and the control group(anti-hypertensive drugs plus placebo).The CHF group enrolled 22 patients while the control group received 21 cases.Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES:Parameters examined include 24-hour ambulatory blood pressure monitoring,body mass index,waist circumference,waist-to-hip ratio,homeostatic model assessment for insulin resistance(HOMA-IR),fasting glycosylated hemoglobin(HbA1c),fasting plasma glucose,2-hour postprandial plasma glucose(PPG),fasting plasma insulin,serum lipid,etc. RESULTS:Compared with the control group,the CHF group had significant improvement (PO.01) in anthropometric parameters,FPG,HOMA-IR,blood pressure amplitude,blood pressure variability and blood pressure load. CONCLUSION:This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors.The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER:ChiCTR-TRC-11001633.展开更多
The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue an...The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.展开更多
The establishment of efficient oxygen evolution electrocatalysts is of great value but also challenging.Herein,a durable metal–organic framework(MOF)with minor atomically dispersed ruthenium and an optimized electron...The establishment of efficient oxygen evolution electrocatalysts is of great value but also challenging.Herein,a durable metal–organic framework(MOF)with minor atomically dispersed ruthenium and an optimized electronic structure is constructed as an efficient electrocatalyst.Significantly,the obtained NiRu_(0.08)-MOF with doping Ru only needs an overpotential of 187 mV at 10 mA cm^(-2) with a Tafel slop of 40 mV dec^(-1) in 0.1M KOH for the oxygen evolution reaction,and can work continuously for more than 300 h.Ultrahigh Ru mass activity is achieved,reaching 56.7 Ag^(-1)_(Ru) at an overpotential of 200 mV,which is 36 times higher than that of commercial RuO_(2).X-ray adsorption spectroscopy and density function theory calculations reveal that atomically dispersed ruthenium on metal sites in MOFs is expected to optimize the electronic structure of nickel sites,thus improving the conductivity of the catalyst and optimizing the adsorption energy of intermediates,resulting in significant optimization of electrocatalytic performance.This study could provide a new avenue for the design of efficient and stable MOF electrocatalysts.展开更多
为探究G蛋白信号调节蛋白2(Regulator of G Protein Signaling 2,RGS2)在泛癌中的表达与预后和免疫浸润的关系,利用生物信息学方法、结合R语言与多个数据库进行了深入分析。首先,通过TCGA数据库分析RGS2在33种癌症肿瘤组织与正常组织中...为探究G蛋白信号调节蛋白2(Regulator of G Protein Signaling 2,RGS2)在泛癌中的表达与预后和免疫浸润的关系,利用生物信息学方法、结合R语言与多个数据库进行了深入分析。首先,通过TCGA数据库分析RGS2在33种癌症肿瘤组织与正常组织中的差异表达,并通过GEO数据库对部分结果进行验证;再通过Cox回归分析与log-rank检验进行预后分析。接着进行免疫浸润分析,并通过ssGSEA分析RGS2对免疫微环境的影响;根据RGS2表达的高低分组获取差异基因,并通过Gene Ontology(GO)、Kyoto Encyclopedia of Genes and Genomes(KEGG)富集分析找到与RGS2相关的分子通路。最后,通过STRING数据库、GENEMANIA数据库获取RGS2的相关基因,搭建蛋白互作网络(Protein-Protein Interaction Networks,PPI)。结果表明,RGS2表达量在24种癌症肿瘤组织显著下调,在4种癌症中显著上调。RGS2在膀胱尿路上皮癌、肾透明细胞癌、肝细胞肝癌、胃腺癌中为危险因素,但在皮肤黑色素瘤、子宫癌肉瘤为保护因素。免疫浸润分析结果表明,RGS2表达与多数免疫细胞表达量显著正相关,但与Th17细胞表达量显著负相关。富集分析表明,RGS2与补体活化、免疫球蛋白受体结合等功能和通路密切相关。PPI蛋白互作网络显示RGS2与RGS4、GNA11、GNA14等基因具有显著相关性。综上所述,RGS2在28种癌症中显著差异表达,可作6种癌症的独立预后因子,与多种癌症的免疫浸润水平显著相关。因此,RGS2有望成为多种癌症的诊断、预后、免疫浸润的新型生物标志物,有望成为一种新的治疗靶点。展开更多
The harmonic balance method(HBM)is one of the most widely used methods in solving nonlinear vibration problems,and its accuracy and computational efficiency largely depend on the number of the harmonics selected.The a...The harmonic balance method(HBM)is one of the most widely used methods in solving nonlinear vibration problems,and its accuracy and computational efficiency largely depend on the number of the harmonics selected.The adaptive harmonic balance(AHB)method is an improved HBM method.This paper presents a modified AHB method with the asymptotic harmonic selection(AHS)procedure.This new harmonic selection procedure selects harmonics from the frequency spectra of nonlinear terms instead of estimating the contribution of each harmonic to the whole nonlinear response,by which the additional calculation is avoided.A modified continuation method is proposed to deal with the variable size of nonlinear algebraic equations at different values of path parameters,and then all solution branches of the amplitude-frequency response are obtained.Numerical experiments are carried out to verify the performance of the AHB-AHS method.Five typical nonlinear dynamic equations with different types of nonlinearities and excitations are chosen as the illustrative examples.Compared with the classical HBM and Runge-Kutta methods,the proposed AHB-AHS method is of higher accuracy and better convergence.The AHB-AHS method proposed in this paper has the potential to investigate the nonlinear vibrations of complex high-dimensional nonlinear systems.展开更多
An 80-GHz DCO based on modified hybrid tuning banks is introduced in this paper.To achieve sub-MHz frequency res-olution with reduced circuit complexity,the improved circuit topology replaces the conventional circuit ...An 80-GHz DCO based on modified hybrid tuning banks is introduced in this paper.To achieve sub-MHz frequency res-olution with reduced circuit complexity,the improved circuit topology replaces the conventional circuit topology with two binary-weighted SC cells,enabling eight SC-cell-based improved SC ladders to achieve the same fine-tuning steps as twelve SC-cell-based conventional SC ladders.To achieve lower phase noise and smaller chip size,the promoted binary-weighted digi-tally controlled transmission lines(DCTLs)are used to implement the coarse and medium tuning banks of the DCO.Compared to the conventional thermometer-coded DCTLs,control bits of the proposed DCTLs are reduced from 30 to 8,and the total length is reduced by 34.3%(from 122.76 to 80.66μm).Fabricated in 40-nm CMOS,the DCO demonstrated in this work fea-tures a small fine-tuning step(483 kHz),a high oscillation frequency(79-85 GHz),and a smaller chip size(0.017 mm^(2)).Com-pared to previous work,the modified DCO exhibits an excellent figure of merit with an area(FoMA)of-198 dBc/Hz.展开更多
Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal g...Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal growth factor receptor(EGFR)-targeted therapy of head and neck squamous cell carcinoma(HNSCC)remaining to be elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC cell lines(HSC-3,SCC-25,SCC-9,and H-400)and the human oral keratinocyte(HOK)cell lines were assessed for GC receptor(GR)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.展开更多
BACKGROUND: Exertional heatstroke(EHS) is a life-threatening disease without ideal prognostic markers for predicting hospital mortality.METHODS: This is a single-center retrospective study. Clinical data from EHS pati...BACKGROUND: Exertional heatstroke(EHS) is a life-threatening disease without ideal prognostic markers for predicting hospital mortality.METHODS: This is a single-center retrospective study. Clinical data from EHS patients admitted to the Intensive Care Unit(ICU) of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. Univariate and multivariate logistic regression were used to identify the factors for mortality. The prediction model was developed with the prognostic markers, and a nomogram was established.RESULTS: The study ultimately enrolled 156 patients, and 15(9.6%) of patients died before discharge. The lymphocyte count(Lym) and percentage(Lym%) were significantly lower in nonsurvivors(P<0.05). The univariate and multivariate logistic regression analyses indicated that Lym% at the third day of admission(Lym% D3)(OR=0.609, 95%CI: 0.454–0.816) and hematocrit(HCT)(OR=0.908, 95%CI: 0.834–0.988) were independent protective factors for hospital mortality. A nomogram incorporating Lym% D3 with HCT was developed and demonstrated good discrimination and calibration ability. The comparison between the prediction model and scoring systems revealed that the prediction model had the largest area under the curve(AUC)(0.948, 95%CI: 0.900–0.977), with 100.00% sensitivity and 83.69% specificity, and a greater clinical net benefit.CONCLUSION: Severe EHS patients had a higher risk of experiencing prolonged lymphopenia. A nomogram based on Lym% D3 and HCT was developed to facilitate early identification and timely treatment of patients with potentially unfavorable prognoses.展开更多
A gliding arc plasma fuel atomization actuator suitable for aeroengines was designed,and a gliding arc plasma fuel spray experimental platform was built to address the fuel atomization problem in aeroengine combustion...A gliding arc plasma fuel atomization actuator suitable for aeroengines was designed,and a gliding arc plasma fuel spray experimental platform was built to address the fuel atomization problem in aeroengine combustion chambers.The spray characteristics for different airflows,fuel flows,and discharge voltages were analyzed using laser particle size analysis.The research shows that the fuel atomization effect is improved from the increased airflow.The decreased fuel flow not only reduces the injection pressure of the fuel but also changes the discharge mode of the gliding arc,which affects reductions in the discharge power and inhibits fuel atomization.Gliding arc discharges accelerate the breaking,atomization,and evaporation of fuel droplets while reducing the particle size,which increases the proportion of small droplets.Compared with the working conditions of plasma-assisted atomization without the gliding arc,the D0.5,D0.9,and average particle size of the fuel droplets are reduced by 4.7%,6.5%,and 4.1%,respectively,when the modulation voltage of the gliding arc power supply is 200 V.展开更多
基金supported by the National Natural Science Foundation of China,No.31970906(to WLei)the Natural Science Foundation of Guangdong Province,No.2020A1515011079(to WLei)+4 种基金Key Technologies R&D Program of Guangdong Province,No.2018B030332001(to GC)Science and Technology Projects of Guangzhou,No.202206060002(to GC)the Youth Science Program of the National Natural Science Foundation of China,No.32100793(to ZX)the Pearl River Innovation and Entrepreneurship Team,No.2021ZT09 Y552Yi-Liang Liu Endowment Fund from Jinan University Education Development Foundation。
文摘Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.
基金supported by Science and Technology Innovation Enhancement Project of Army Medical University(to LX).
文摘MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.
基金support from the National Natural Science Foundation of China (22222808, 21978200)the Haihe Laboratory of Sustainable Chemical Transformations for financial support
文摘Energetic nanofluid fuel has caught the attention of the field of aerospace liquid propellant for its high energy density(HED), but it suffers from the inevitable solid-liquid phase separation problem. To resolve this problem, herein we synthesized the high-Al-/B-containing(up to 30%(mass)) HED gelled fuels, with low-molecular-mass organic gellant Z, which show high net heat of combustion(NHOC), density, storage stability, and thixotropic properties. The characterizations indicate that the application of energetic particles to the gelled fuels obviously destroys their fibrous network structures but can provide the new particle-gellant gelation microstructures, resulting in the comparable stability between 1.0%(mass) Z/JP-10 + 30%(mass) Al or B and pure JP-10 gelled fuel. Moreover, the gelled fuels with high-content Al or B exhibit high shear-thinning property, recovery capability, and mechanical strength, which are favorable for their storage and utilization. Importantly, the prepared 1.0%(mass) Z/JP-10 + 30%(mass) B(or 1.0%(mass) Z/JP-10 + 30%(mass) Al) shows the density and NHOC 1.27 times(1.30) and 1.43 times(1.21)higher than pure JP-10, respectively. This work provides a facile and valid approach to the manufacturing of HED gelled fuels with high content of energetic particles for gel propellants.
基金the financial supports by the National Natural Science Foundation of China(82060594)the Natural Science Foundation of Jiangxi Province,China(20202BAB205006)。
文摘The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its potential molecular mechanism were investigated.Results showed that SCP3 at 25-100μg/m L increased viability and improved phagocytosis of RAW264.7 cells.Meanwhile,SCP3 could activate mitogen-activated protein kinase(MAPK)and nuclear factor kappa B(NF-κB)signaling pathways,which increased the phosphorylation of Erk1/2,JNK,p38 and NF-κB p65,promoting secretion of cytokines tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and nitric oxide(NO)as well as the production of reactive oxygen species(ROS).In addition,Toll-like receptor 4(TLR4)receptor inhibitors were able to block the production of NO and TNF-αby SCP3-stimulated macrophages.Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways,the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-αand NO production via TLR4-mediated MAPK and NF-κB pathways.In summary,SCP3 has significant immunomodulatory potential.The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production,which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.
基金Supported by the Shenzhen Science and Technology R&D Fund,No.JCYJ20220530163011026and Shenzhen Third People’s Hospital,No.G2022008 and No.G2021008。
文摘Liver transplantation is the primary therapeutic intervention for end-stage liver disease.However,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.The clinical manifestations associated with early arterial complications following liver transplantation are often non-specific.Without timely intervention,these complications can result in graft fai-lure or patient mortality.Therefore,early diagnosis and the formulation of an op-timal treatment plan are imperative.Ultrasound examination remains the pre-dominant imaging modality for detecting complications post liver transplan-tation.This article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these con-ditions.Overall,ultrasound offers the advantages of convenience,safety,effect-iveness,and non-invasiveness.It enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation assessments.INTRODUCTION Liver transplantation stands as the primary therapeutic approach for end-stage liver disease.Continuous advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation procedures.Despite these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.During the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood flow.During later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood supply.It is now understood that the establishment of effective collateral circulation is pivotal for determining the prognosis of hepatic artery complic-ations.The clinical manifestations of these complications are closely linked to factors such as timing,severity,and the specific type of onset.Insufficient hepatic arterial blood flow can lead to abnormal liver function,hepatic infarction,and the formation of hepatic abscesses.Additionally,since the hepatic artery is the sole blood supply to the biliary tract,hepatic artery-related ischemia may result in biliary stricture,obstruction,and the formation of bile ducts.Ultrasound examination remains the primary imaging modality for diagnosing complications post liver transplantation.This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and outlines abnormal sonographic findings for accurately diagnosing these conditions.NORMAL HEPATIC ARTERY During the intraoperative phase,an ultrasound examination is typically conducted to evaluate the hepatic artery anas-tomosis.The normal internal diameter of the hepatic artery typically ranges from 2 to 5 mm.Two strong echo points are typically identified near the anastomosis.To assess blood flow dynamics,peak systolic velocity,end-diastolic velocity,and resistance index are measured at the donor and recipient sides of the anastomosis following angle correction.Anastomotic stenosis presence and severity can be evaluated by comparing the velocity at the anastomotic site with that at the recipient side.Postoperatively,direct visualization of the anastomosis site through gray ultrasound scans is often challenging.The surgical approach has a significant impact on the proper hepatic artery’s position,resulting in a lower overall success rate of continuous visualization.Color Doppler ultrasound is primarily employed to trace the artery’s path,and spectral measurements are taken at the brightest position of the Color Doppler blood flow signal,primarily used to identify the presence of high-speed turbulence.Hepatic artery spectrum examination plays a crucial role,as a favorable arterial spectral waveform and appropriate hepatic artery flow velocity typically indicate a successful anastomosis,even in cases where the hepatic artery anastomosis cannot be directly visualized by ultrasound.The hepatic artery runs alongside the portal vein,often selected as a reference due to its larger inner diameter.A normal hepatic artery spectrum displays a regular pulsation pattern with a rapid rise in systole and a slow decline in diastole.Parameters for assessing hepatic artery resistance include a resistance index between 0.5 to 0.8 and an artery systolic acceleration of less than 80 ms.Instantaneous increases in the resistance index(RI>0.8)often occur within 2 d after surgery,followed by a subsequent return to normal hepatic arterial parameters.It has been established that the maximum blood flow velocity during systole in the hepatic artery should not exceed 200 cm/s[1].
基金supported by grants from the National Traditional Chinese Medicine Administration Bureau, Chinathe project of Science and Technology Commission of Shanghai Municipality(No.08dj 1400600),Shanghaithe National Natural Science Foundation(No.81001574)
文摘BACKGROUND:Patients with hypertension coupled with metabolic syndrome(MetS) are among the high risk population in cardiovascular and cerebrovascular diseases.To reduce the prevalence of cardiovascular and cerebrovascular diseases,it is essential to appropriately control blood pressure together with other cardiovascular risk factors. OBJECTIVE:The current study was designed to investigate the therapeutic effects on blood pressure,blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula,a compound traditional Chinese herbal medicine,in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN,SETTING,PARTICIPANTS AND INTERVENTIONS:A total of 43 patients with hypertension coupled with MetS were recruited into this study.The enrolled patients were randomly divided into the Chinese herbal formula group(anti-hypertensive drugs plus Yiqi Huaju Formula,CHF) and the control group(anti-hypertensive drugs plus placebo).The CHF group enrolled 22 patients while the control group received 21 cases.Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES:Parameters examined include 24-hour ambulatory blood pressure monitoring,body mass index,waist circumference,waist-to-hip ratio,homeostatic model assessment for insulin resistance(HOMA-IR),fasting glycosylated hemoglobin(HbA1c),fasting plasma glucose,2-hour postprandial plasma glucose(PPG),fasting plasma insulin,serum lipid,etc. RESULTS:Compared with the control group,the CHF group had significant improvement (PO.01) in anthropometric parameters,FPG,HOMA-IR,blood pressure amplitude,blood pressure variability and blood pressure load. CONCLUSION:This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors.The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER:ChiCTR-TRC-11001633.
基金supported by grants from the National Natural Science Foundation of China(21566024)。
文摘The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.
基金National Natural Science Foundation of China,Grant/Award Number:51632008。
文摘The establishment of efficient oxygen evolution electrocatalysts is of great value but also challenging.Herein,a durable metal–organic framework(MOF)with minor atomically dispersed ruthenium and an optimized electronic structure is constructed as an efficient electrocatalyst.Significantly,the obtained NiRu_(0.08)-MOF with doping Ru only needs an overpotential of 187 mV at 10 mA cm^(-2) with a Tafel slop of 40 mV dec^(-1) in 0.1M KOH for the oxygen evolution reaction,and can work continuously for more than 300 h.Ultrahigh Ru mass activity is achieved,reaching 56.7 Ag^(-1)_(Ru) at an overpotential of 200 mV,which is 36 times higher than that of commercial RuO_(2).X-ray adsorption spectroscopy and density function theory calculations reveal that atomically dispersed ruthenium on metal sites in MOFs is expected to optimize the electronic structure of nickel sites,thus improving the conductivity of the catalyst and optimizing the adsorption energy of intermediates,resulting in significant optimization of electrocatalytic performance.This study could provide a new avenue for the design of efficient and stable MOF electrocatalysts.
文摘为探究G蛋白信号调节蛋白2(Regulator of G Protein Signaling 2,RGS2)在泛癌中的表达与预后和免疫浸润的关系,利用生物信息学方法、结合R语言与多个数据库进行了深入分析。首先,通过TCGA数据库分析RGS2在33种癌症肿瘤组织与正常组织中的差异表达,并通过GEO数据库对部分结果进行验证;再通过Cox回归分析与log-rank检验进行预后分析。接着进行免疫浸润分析,并通过ssGSEA分析RGS2对免疫微环境的影响;根据RGS2表达的高低分组获取差异基因,并通过Gene Ontology(GO)、Kyoto Encyclopedia of Genes and Genomes(KEGG)富集分析找到与RGS2相关的分子通路。最后,通过STRING数据库、GENEMANIA数据库获取RGS2的相关基因,搭建蛋白互作网络(Protein-Protein Interaction Networks,PPI)。结果表明,RGS2表达量在24种癌症肿瘤组织显著下调,在4种癌症中显著上调。RGS2在膀胱尿路上皮癌、肾透明细胞癌、肝细胞肝癌、胃腺癌中为危险因素,但在皮肤黑色素瘤、子宫癌肉瘤为保护因素。免疫浸润分析结果表明,RGS2表达与多数免疫细胞表达量显著正相关,但与Th17细胞表达量显著负相关。富集分析表明,RGS2与补体活化、免疫球蛋白受体结合等功能和通路密切相关。PPI蛋白互作网络显示RGS2与RGS4、GNA11、GNA14等基因具有显著相关性。综上所述,RGS2在28种癌症中显著差异表达,可作6种癌症的独立预后因子,与多种癌症的免疫浸润水平显著相关。因此,RGS2有望成为多种癌症的诊断、预后、免疫浸润的新型生物标志物,有望成为一种新的治疗靶点。
基金Project supported by the National Natural Science Foundation of China(Nos.11972129 and12372008)the National Major Science and Technology Projects of China(No.2017-IV-0008-0045)+3 种基金the Natural Science Foundation of Heilongjiang Province of China(No.YQ2022A008)the Fundamental Research Funds for the Central Universities of China(No.HIT.OCEF.2023006)the Polish National Science Centre of Poland under the OPUS 18 grant(No.2019/35/B/ST8/00980)the Tianjin University Independent Innovation Foundation of China(No.2023XJS-0038)。
文摘The harmonic balance method(HBM)is one of the most widely used methods in solving nonlinear vibration problems,and its accuracy and computational efficiency largely depend on the number of the harmonics selected.The adaptive harmonic balance(AHB)method is an improved HBM method.This paper presents a modified AHB method with the asymptotic harmonic selection(AHS)procedure.This new harmonic selection procedure selects harmonics from the frequency spectra of nonlinear terms instead of estimating the contribution of each harmonic to the whole nonlinear response,by which the additional calculation is avoided.A modified continuation method is proposed to deal with the variable size of nonlinear algebraic equations at different values of path parameters,and then all solution branches of the amplitude-frequency response are obtained.Numerical experiments are carried out to verify the performance of the AHB-AHS method.Five typical nonlinear dynamic equations with different types of nonlinearities and excitations are chosen as the illustrative examples.Compared with the classical HBM and Runge-Kutta methods,the proposed AHB-AHS method is of higher accuracy and better convergence.The AHB-AHS method proposed in this paper has the potential to investigate the nonlinear vibrations of complex high-dimensional nonlinear systems.
基金This work is supported by the National Natural Science Foundation of China(No.61674036)the National Key Research and Development Program of China(No.2018YFB2202200).
文摘An 80-GHz DCO based on modified hybrid tuning banks is introduced in this paper.To achieve sub-MHz frequency res-olution with reduced circuit complexity,the improved circuit topology replaces the conventional circuit topology with two binary-weighted SC cells,enabling eight SC-cell-based improved SC ladders to achieve the same fine-tuning steps as twelve SC-cell-based conventional SC ladders.To achieve lower phase noise and smaller chip size,the promoted binary-weighted digi-tally controlled transmission lines(DCTLs)are used to implement the coarse and medium tuning banks of the DCO.Compared to the conventional thermometer-coded DCTLs,control bits of the proposed DCTLs are reduced from 30 to 8,and the total length is reduced by 34.3%(from 122.76 to 80.66μm).Fabricated in 40-nm CMOS,the DCO demonstrated in this work fea-tures a small fine-tuning step(483 kHz),a high oscillation frequency(79-85 GHz),and a smaller chip size(0.017 mm^(2)).Com-pared to previous work,the modified DCO exhibits an excellent figure of merit with an area(FoMA)of-198 dBc/Hz.
基金supported by the Research Funding(No.RCDWJS 2020-20)Research and Development Program(RD-02-202002)from West China School/Hospital of Stomatology Sichuan University+1 种基金the Natural Science Foundation of China(81902784&81872207)Sichuan Provincial Fund of China(2022YFSY0058).
文摘Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal growth factor receptor(EGFR)-targeted therapy of head and neck squamous cell carcinoma(HNSCC)remaining to be elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC cell lines(HSC-3,SCC-25,SCC-9,and H-400)and the human oral keratinocyte(HOK)cell lines were assessed for GC receptor(GR)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.
基金supported by the Natural Science Foundation of Guangdong Province (2022A1515010353)Science and Technology Projects of Guangzhou (SL2024A03J00951)Military Medical Innovation Project (18CXZ032)。
文摘BACKGROUND: Exertional heatstroke(EHS) is a life-threatening disease without ideal prognostic markers for predicting hospital mortality.METHODS: This is a single-center retrospective study. Clinical data from EHS patients admitted to the Intensive Care Unit(ICU) of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. Univariate and multivariate logistic regression were used to identify the factors for mortality. The prediction model was developed with the prognostic markers, and a nomogram was established.RESULTS: The study ultimately enrolled 156 patients, and 15(9.6%) of patients died before discharge. The lymphocyte count(Lym) and percentage(Lym%) were significantly lower in nonsurvivors(P<0.05). The univariate and multivariate logistic regression analyses indicated that Lym% at the third day of admission(Lym% D3)(OR=0.609, 95%CI: 0.454–0.816) and hematocrit(HCT)(OR=0.908, 95%CI: 0.834–0.988) were independent protective factors for hospital mortality. A nomogram incorporating Lym% D3 with HCT was developed and demonstrated good discrimination and calibration ability. The comparison between the prediction model and scoring systems revealed that the prediction model had the largest area under the curve(AUC)(0.948, 95%CI: 0.900–0.977), with 100.00% sensitivity and 83.69% specificity, and a greater clinical net benefit.CONCLUSION: Severe EHS patients had a higher risk of experiencing prolonged lymphopenia. A nomogram based on Lym% D3 and HCT was developed to facilitate early identification and timely treatment of patients with potentially unfavorable prognoses.
基金supported by National Natural Science Foundation of China(Nos.91741112 and 52276142)。
文摘A gliding arc plasma fuel atomization actuator suitable for aeroengines was designed,and a gliding arc plasma fuel spray experimental platform was built to address the fuel atomization problem in aeroengine combustion chambers.The spray characteristics for different airflows,fuel flows,and discharge voltages were analyzed using laser particle size analysis.The research shows that the fuel atomization effect is improved from the increased airflow.The decreased fuel flow not only reduces the injection pressure of the fuel but also changes the discharge mode of the gliding arc,which affects reductions in the discharge power and inhibits fuel atomization.Gliding arc discharges accelerate the breaking,atomization,and evaporation of fuel droplets while reducing the particle size,which increases the proportion of small droplets.Compared with the working conditions of plasma-assisted atomization without the gliding arc,the D0.5,D0.9,and average particle size of the fuel droplets are reduced by 4.7%,6.5%,and 4.1%,respectively,when the modulation voltage of the gliding arc power supply is 200 V.
