SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, tha...SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.展开更多
Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include...Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.展开更多
Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown t...Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.展开更多
Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson...Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.展开更多
Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor(α7 n ACh R) activations by a potent ag...Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor(α7 n ACh R) activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons.To further investigate the underlying mechanism,we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water,twice a day during 4 days.Western blot assay results showed that the expression of heme oxygenase-1(HO-1),the key component of the cholinergic anti-inflammatory pathway,in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water,and that the increase in HO-1 expression was independent of change in α7 n ACh R expression.These findings suggest that HO-1 expression is unrelated to α7 n ACh R density and the increase in HO-1 expression likely contributes to α7 n ACh R activation-related neuroprotective effect in early-stage Huntington's disease.展开更多
The alpha–beta filter algorithm has been widely researched for various applications,for example,navigation and target tracking systems.To improve the dynamic performance of the alpha–beta filter algorithm,a new pred...The alpha–beta filter algorithm has been widely researched for various applications,for example,navigation and target tracking systems.To improve the dynamic performance of the alpha–beta filter algorithm,a new prediction learning model is proposed in this study.The proposed model has two main components:(1)the alpha–beta filter algorithm is the main prediction module,and(2)the learning module is a feedforward artificial neural network(FF‐ANN).Furthermore,the model uses two inputs,temperature sensor and humidity sensor data,and a prediction algorithm is used to predict actual sensor readings from noisy sensor readings.Using the novel proposed technique,prediction accuracy is significantly improved while adding the feed‐forward backpropagation neural network,and also reduces the root mean square error(RMSE)and mean absolute error(MAE).We carried out different experiments with different experimental setups.The proposed model performance was evaluated with the traditional alpha–beta filter algorithm and other algorithms such as the Kalman filter.A higher prediction accuracy was achieved,and the MAE and RMSE were 35.1%–38.2%respectively.The final proposed model results show increased performance when compared to traditional methods.展开更多
Optimization algorithms are applied to resolve the second-order pileup(SOP)issue from high counting rates occurring in digital alpha spectroscopy.These are antlion optimizer(ALO)and particle swarm optimization(PSO)alg...Optimization algorithms are applied to resolve the second-order pileup(SOP)issue from high counting rates occurring in digital alpha spectroscopy.These are antlion optimizer(ALO)and particle swarm optimization(PSO)algorithms.Both optimization algorithms are coupled to one of the three proposed peak finder algorithms.Three custom time-domain algorithms are proposed for retrieving SOP peaks,namely peak seek,slope tangent,and fast array algorithms.In addition,an average combinational algorithm is applied.The time occurrence of the retrieved peaks is tested for an elimination of illusive pulses.Conventional methods are inaccurate and timeconsuming.ALO and PSO optimizations are used for the localization of retrieved peaks.Optimum cost values that achieve the best fitness values are demonstrated.Thus,the optimum positions of the detected peak heights are achieved.Evaluation metrics of the optimized algorithms and their influences on the retrieved peaks parameters are established.Comparisons among such algorithms are investigated,and the algorithms are inspected in terms of their computational time and average error.The peak seek algorithm achieves the lowest average computational error for pulse parameters(amplitude and position).However,the fast array algorithm introduces the largest average error for pulse parameters.In addition,the peak seek algorithm coupled with an ALO or PSO algorithm is observed to realize a better performance in terms of the optimum cost and computational time.By contrast,the performance of the peak seek recovery algorithm is improved using the PSO.Furthermore,the computational time of the peak optimization using the PSO is much better than that of the ALO algorithm.As a final conclusion,the accuracy of the peaks detected by the PSO surpasses that for the peaks detected by the ALO.The implemented peak retrieval algorithms are validated through a comparison with experimental results from previous studies.The proposed algorithms achieve a notable precision for compensation of the SOP peaks within the alpha ray spectroscopy at a high counting rate.展开更多
Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player le...Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.展开更多
Objective To investigate the contraceptive mechanism of combination regimen of low- dose gossypol acetic acid (GA) with steroid hormones [desogestre/ethinylestradiol/ testosterone undeeanote(DSG/EE/TU)]. Methods A...Objective To investigate the contraceptive mechanism of combination regimen of low- dose gossypol acetic acid (GA) with steroid hormones [desogestre/ethinylestradiol/ testosterone undeeanote(DSG/EE/TU)]. Methods Adult male rats were randomly divided into four groups. Group GH: rats were fed orally with gossypol acetic acid (GA, 12.5 mg/kg) and desogestrel (DSG, 0.125 mg/kg)/ ethinylestradiol (EE, 0.025 mg/kg)/testosterone undecanoate (TU, 100 mg/kg per day, qd X4 weeks or 10 weeks); group G: a single dose of GA (12.5 mg/kg per day, qd X 4 weeks or I0 weeks); group H: the same dosage of DSG/EE/TUas in group GH; group C: rats were treated with vehicle (1% methyl cellulose) as the control. Expression of protein kinase C alpha (PKC-a) and cyclin D1 in rat testes were tested mainly by immunohistochemistry (IHC) and Western blotting. Results IHC results showed that protein PKC- a was expressed mainly in interstitial tissue of testis among seminiferous tubule. The expression of PKC-oc in groups H and GH at week 10 was decreased greatly compared with that in group C. The protein cyclin D1 was expressed mainly in residual body of seminiferous tubule eavosurface and interstitial tissue among seminiferous tubule of testis. Western blotting results showed that the expression of PKC-a in groups H and GH at week 10 was decreased significantly compared with that in group C (P〈0.05). The expression of cyclin D1 in groups G, H or GH at week 10 rose significantly compared with that in group C (P 〈0.05).Conclusion The administration of low-dose gossypol acetic acid with steroid hormones for 10 weeks can decrease the expression of PKC-a greatly.展开更多
Rotor clearance is necessary for the safe operation of twin-screw compressors,and it has a major impact on the performance of twin-screw compressors.The purpose of this study was to obtain a rotor tooth profile with r...Rotor clearance is necessary for the safe operation of twin-screw compressors,and it has a major impact on the performance of twin-screw compressors.The purpose of this study was to obtain a rotor tooth profile with reasonable meshing clearance on the rotor end surface,so that the clearance on the rotor contact line would be uniform and the rotor could be smoothly meshed.Under ideal conditions,the rotor of a screw compressor should have no clearance or interference.However,owing to assembly errors,thermal compression,stress deformation,and other factors,a rotor without backlash modification will inevitably produce interference during operation.A new design method based on the Alpha shape solution was proposed to achieve an efficient and high-precision design of the clearance of the twin-screw rotor profile.This method avoids the complex analytical calculations in the traditional envelope principle.The best approximation of the points on the rotor conjugate motion sweeping surface in the points is illuminated using a specific color.The sweeping surface of the screw rotor single-tooth profile is roughly scanned to capture the base point set of the sweeping surface boundary points.The chord length and tilt angle of each interval are calculated using the value of the base point set to adjust the position,phase,and magnification of each interval sweeping surface.Finally,the data point set is converted to the same coordinate system to generate the conjugated rotor profile.An example was used to verify the feasibility and adaptability of this method.Based on the equidistant profile method,the clearance between male and female rotors of a screw compressor was obtained under actual operation conditions.Therefore,this study provides a basis for the meshing clearance design in the machining of twin-screw compressor rotors.展开更多
The diffuse brain injury model was conducted in Sprague-Dawley rats, according to Marmarou's free-fall attack. The water content in brain tissue, expression of metabotropic glutamate receptor la mRNA and protein w...The diffuse brain injury model was conducted in Sprague-Dawley rats, according to Marmarou's free-fall attack. The water content in brain tissue, expression of metabotropic glutamate receptor la mRNA and protein were significantly increased after injury, reached a peak at 24 hours, and then gradually decreased. After treatment with the competitive antagonist of metabotropic glutamate receptor la, (RS)-l-aminoindan-1,5-dicarboxylic acid, the water content of brain tissues decreased between 12-72 hours after injury, and neurological behaviors improved at 2 weeks. These experimental findings suggest that the 1-aminoindan-1, 5-dicarboxylic acid may result in marked neuroprotection against diffuse brain injury.展开更多
Soil microbial communities are key factors in maintaining ecosystem multifunctionality(EMF).However,the distribution patterns of bacterial diversity and how the different bacterial taxa and their diversity dimensions ...Soil microbial communities are key factors in maintaining ecosystem multifunctionality(EMF).However,the distribution patterns of bacterial diversity and how the different bacterial taxa and their diversity dimensions affect EMF remain largely unknown.Here,we investigated variation in three measures of diversity(alpha diversity,community composition and network complexity)among rare,intermediate,and abundant taxa across a latitudinal gradient spanning five forest plots in Yunnan Province,China and examined their contributions on EMF.We aimed to characterize the diversity distributions of bacterial groups across latitudes and to assess the differences in the mechanisms underlying their contributions to EMF.We found that multifaceted diversity(i.e.,diversity assessed by the three different metrics)of rare,intermediate,and abundant bacteria generally decreased with increasing latitude.More importantly,we found that rare bacterial taxa tended to be more diverse,but they contributed less to EMF than intermediate or abundant bacteria.Among the three dimensions of diversity we assessed,only community composition significantly affected EMF across all locations,while alpha diversity had a negative effect,and network complexity showed no significant impact.Our study further emphasizes the importance of intermediate and abundant bacterial taxa as well as community composition to EMF and provides a theoretical basis for investigating the mechanisms by which belowground microorganisms drive EMF along a latitudinal gradient.展开更多
基金supported by Science Foundation Ireland (Grant 19/FFP/6666),Cure Parkinson’s (Grant CP:GO01)a PhD studentship from the Anatomical Society。
文摘SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN)。
文摘Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.
基金supported by grants from Tianjin Scientific Research Project in Key Areas of Traditional Chinese Medicine,Tianjin Municipal Health Commission,No.2024012(to JL)Tianjin Municipal Education Commission Project,No.2021KJ217(to CS)。
文摘Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.
基金supported by the Spanish Ministry of Science and Innovation via a doctoral grant[FPU22/03656].supported by the Spanish Ministry of Science and Innovation(PID2022-137963OB-I00)Generalitat de Catalunya(2021-SGR-00635 AGAUR)+1 种基金CERCA Programme(Generalitat de Catalunya)by ICREA,ICREA-Academia 2020(to SV)。
文摘Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.
基金supported by the Région Centre-Val de Loire(2014 00094049–AP 2014-850)the European Union’s Seventh Framework Programme(FP7/2007-2013)under grant agreement n°278850(INMiND)
文摘Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor(α7 n ACh R) activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons.To further investigate the underlying mechanism,we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water,twice a day during 4 days.Western blot assay results showed that the expression of heme oxygenase-1(HO-1),the key component of the cholinergic anti-inflammatory pathway,in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water,and that the increase in HO-1 expression was independent of change in α7 n ACh R expression.These findings suggest that HO-1 expression is unrelated to α7 n ACh R density and the increase in HO-1 expression likely contributes to α7 n ACh R activation-related neuroprotective effect in early-stage Huntington's disease.
基金supported by the Institute of Information&communications Technology Planning&Evaluation(IITP)grant funded by the Korea government(MSIT)(No.2020‐0‐01441,Artificial Intelligence Convergence Research Center(Chungnam National University))“Regional Innovation Strategy(RIS)”through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(MOE)(2021RIS‐004).
文摘The alpha–beta filter algorithm has been widely researched for various applications,for example,navigation and target tracking systems.To improve the dynamic performance of the alpha–beta filter algorithm,a new prediction learning model is proposed in this study.The proposed model has two main components:(1)the alpha–beta filter algorithm is the main prediction module,and(2)the learning module is a feedforward artificial neural network(FF‐ANN).Furthermore,the model uses two inputs,temperature sensor and humidity sensor data,and a prediction algorithm is used to predict actual sensor readings from noisy sensor readings.Using the novel proposed technique,prediction accuracy is significantly improved while adding the feed‐forward backpropagation neural network,and also reduces the root mean square error(RMSE)and mean absolute error(MAE).We carried out different experiments with different experimental setups.The proposed model performance was evaluated with the traditional alpha–beta filter algorithm and other algorithms such as the Kalman filter.A higher prediction accuracy was achieved,and the MAE and RMSE were 35.1%–38.2%respectively.The final proposed model results show increased performance when compared to traditional methods.
文摘Optimization algorithms are applied to resolve the second-order pileup(SOP)issue from high counting rates occurring in digital alpha spectroscopy.These are antlion optimizer(ALO)and particle swarm optimization(PSO)algorithms.Both optimization algorithms are coupled to one of the three proposed peak finder algorithms.Three custom time-domain algorithms are proposed for retrieving SOP peaks,namely peak seek,slope tangent,and fast array algorithms.In addition,an average combinational algorithm is applied.The time occurrence of the retrieved peaks is tested for an elimination of illusive pulses.Conventional methods are inaccurate and timeconsuming.ALO and PSO optimizations are used for the localization of retrieved peaks.Optimum cost values that achieve the best fitness values are demonstrated.Thus,the optimum positions of the detected peak heights are achieved.Evaluation metrics of the optimized algorithms and their influences on the retrieved peaks parameters are established.Comparisons among such algorithms are investigated,and the algorithms are inspected in terms of their computational time and average error.The peak seek algorithm achieves the lowest average computational error for pulse parameters(amplitude and position).However,the fast array algorithm introduces the largest average error for pulse parameters.In addition,the peak seek algorithm coupled with an ALO or PSO algorithm is observed to realize a better performance in terms of the optimum cost and computational time.By contrast,the performance of the peak seek recovery algorithm is improved using the PSO.Furthermore,the computational time of the peak optimization using the PSO is much better than that of the ALO algorithm.As a final conclusion,the accuracy of the peaks detected by the PSO surpasses that for the peaks detected by the ALO.The implemented peak retrieval algorithms are validated through a comparison with experimental results from previous studies.The proposed algorithms achieve a notable precision for compensation of the SOP peaks within the alpha ray spectroscopy at a high counting rate.
文摘Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.
文摘Objective To investigate the contraceptive mechanism of combination regimen of low- dose gossypol acetic acid (GA) with steroid hormones [desogestre/ethinylestradiol/ testosterone undeeanote(DSG/EE/TU)]. Methods Adult male rats were randomly divided into four groups. Group GH: rats were fed orally with gossypol acetic acid (GA, 12.5 mg/kg) and desogestrel (DSG, 0.125 mg/kg)/ ethinylestradiol (EE, 0.025 mg/kg)/testosterone undecanoate (TU, 100 mg/kg per day, qd X4 weeks or 10 weeks); group G: a single dose of GA (12.5 mg/kg per day, qd X 4 weeks or I0 weeks); group H: the same dosage of DSG/EE/TUas in group GH; group C: rats were treated with vehicle (1% methyl cellulose) as the control. Expression of protein kinase C alpha (PKC-a) and cyclin D1 in rat testes were tested mainly by immunohistochemistry (IHC) and Western blotting. Results IHC results showed that protein PKC- a was expressed mainly in interstitial tissue of testis among seminiferous tubule. The expression of PKC-oc in groups H and GH at week 10 was decreased greatly compared with that in group C. The protein cyclin D1 was expressed mainly in residual body of seminiferous tubule eavosurface and interstitial tissue among seminiferous tubule of testis. Western blotting results showed that the expression of PKC-a in groups H and GH at week 10 was decreased significantly compared with that in group C (P〈0.05). The expression of cyclin D1 in groups G, H or GH at week 10 rose significantly compared with that in group C (P 〈0.05).Conclusion The administration of low-dose gossypol acetic acid with steroid hormones for 10 weeks can decrease the expression of PKC-a greatly.
文摘Rotor clearance is necessary for the safe operation of twin-screw compressors,and it has a major impact on the performance of twin-screw compressors.The purpose of this study was to obtain a rotor tooth profile with reasonable meshing clearance on the rotor end surface,so that the clearance on the rotor contact line would be uniform and the rotor could be smoothly meshed.Under ideal conditions,the rotor of a screw compressor should have no clearance or interference.However,owing to assembly errors,thermal compression,stress deformation,and other factors,a rotor without backlash modification will inevitably produce interference during operation.A new design method based on the Alpha shape solution was proposed to achieve an efficient and high-precision design of the clearance of the twin-screw rotor profile.This method avoids the complex analytical calculations in the traditional envelope principle.The best approximation of the points on the rotor conjugate motion sweeping surface in the points is illuminated using a specific color.The sweeping surface of the screw rotor single-tooth profile is roughly scanned to capture the base point set of the sweeping surface boundary points.The chord length and tilt angle of each interval are calculated using the value of the base point set to adjust the position,phase,and magnification of each interval sweeping surface.Finally,the data point set is converted to the same coordinate system to generate the conjugated rotor profile.An example was used to verify the feasibility and adaptability of this method.Based on the equidistant profile method,the clearance between male and female rotors of a screw compressor was obtained under actual operation conditions.Therefore,this study provides a basis for the meshing clearance design in the machining of twin-screw compressor rotors.
文摘The diffuse brain injury model was conducted in Sprague-Dawley rats, according to Marmarou's free-fall attack. The water content in brain tissue, expression of metabotropic glutamate receptor la mRNA and protein were significantly increased after injury, reached a peak at 24 hours, and then gradually decreased. After treatment with the competitive antagonist of metabotropic glutamate receptor la, (RS)-l-aminoindan-1,5-dicarboxylic acid, the water content of brain tissues decreased between 12-72 hours after injury, and neurological behaviors improved at 2 weeks. These experimental findings suggest that the 1-aminoindan-1, 5-dicarboxylic acid may result in marked neuroprotection against diffuse brain injury.
基金supported by the Fundamental Research Funds of Chinese Academy of Forestry(Nos.CAFYBB2022SY037,CAFYBB2021ZA002 and CAFYBB2022QC002)the Basic Research Foundation of Yunnan Province(Grant No.202201AT070264).
文摘Soil microbial communities are key factors in maintaining ecosystem multifunctionality(EMF).However,the distribution patterns of bacterial diversity and how the different bacterial taxa and their diversity dimensions affect EMF remain largely unknown.Here,we investigated variation in three measures of diversity(alpha diversity,community composition and network complexity)among rare,intermediate,and abundant taxa across a latitudinal gradient spanning five forest plots in Yunnan Province,China and examined their contributions on EMF.We aimed to characterize the diversity distributions of bacterial groups across latitudes and to assess the differences in the mechanisms underlying their contributions to EMF.We found that multifaceted diversity(i.e.,diversity assessed by the three different metrics)of rare,intermediate,and abundant bacteria generally decreased with increasing latitude.More importantly,we found that rare bacterial taxa tended to be more diverse,but they contributed less to EMF than intermediate or abundant bacteria.Among the three dimensions of diversity we assessed,only community composition significantly affected EMF across all locations,while alpha diversity had a negative effect,and network complexity showed no significant impact.Our study further emphasizes the importance of intermediate and abundant bacterial taxa as well as community composition to EMF and provides a theoretical basis for investigating the mechanisms by which belowground microorganisms drive EMF along a latitudinal gradient.