Objectives:Lung cancer represents a major global healthcare challenge,characterized by high annual incidence and mortality rates worldwide.Although targeted therapies for lung cancer have advanced,treatment outcomes f...Objectives:Lung cancer represents a major global healthcare challenge,characterized by high annual incidence and mortality rates worldwide.Although targeted therapies for lung cancer have advanced,treatment outcomes for advanced-stage patients remain suboptimal.This investigation examines the role of the translocase of the inner mitochondrial membrane(TIMM)8A-TIMM13 complex in lung cancer and evaluates its potential as a novel therapeutic target.Methods:A co-immunoprecipitation(Co-IP)assay was conducted to verify the interaction between TIMM8A and TIMM13.Differential gene expression analysis of TIMM8A or TIMM13 was executed using the TNMplot database,with survival estimates derived from the Kaplan-Meier plotter.Lung cancer cell proliferation was evaluated through Cell Counting Kit 8(CCK-8)and colony formation assays,while cell migration was assessed via Transwell assay.RNA sequencing identified the downstream effectors of TIMM13.RNAi technology facilitated the inhibition of TIMM8A or TIMM13 expression,which was measured through immunoblotting or qRT-PCR.Results:This investigation revealed that components of the TIMM8A-TIMM13 complex exhibited elevated expression in human lung cancer tissues,correlating with disease progression and poor overall survival rates among lung cancer patients.The suppression of either TIMM8A or TIMM13 inhibited cell proliferation and migration.Mechanistic studies through transcriptome analysis identified cell cycle-related pathways as potential key downstream effectors of the TIMM8A-TIMM13 complex.Subsequent experiments confirmed that the TIMM8A-TIMM13 complex significantly regulated the expression of cyclin D1(CCND1)and cyclin-dependent kinase 6(CDK6)complex.Conclusion:The elevated expression of TIMM8A-TIMM13 complex components plays a crucial role in lung cancer cell growth,suggesting its potential as a promising therapeutic target for lung cancer treatment.展开更多
To avoid missing track caused by the target maneuvers in automatic target tracking system, a new maneuvering target tracking technique called threshold interacting multiple model （TIMM） is proposed. This algorithm i...To avoid missing track caused by the target maneuvers in automatic target tracking system, a new maneuvering target tracking technique called threshold interacting multiple model （TIMM） is proposed. This algorithm is based on the interacting multiple model （IMM） method and applies a threshold controller to improve tracking accuracy. It is also applicable to other advanced algorithms of IMM. In this research, we also compare the position and velocity root mean square （RMS） errors of TIMM and IMM algorithms with two different examples. Simulation results show that the TIMM algorithm is superior to the traditional IMM alzorithm in estimation accuracy.展开更多
Determining the minimal duration of status epilepticus （SE） that leads to the development of subsequent spontaneous seizures （i.e., epilepsy） is important, because it provides a critical timewindow for seizure int...Determining the minimal duration of status epilepticus （SE） that leads to the development of subsequent spontaneous seizures （i.e., epilepsy） is important, because it provides a critical timewindow for seizure intervention and epilepsy prevention. In the present study, male ICR （imprinting Control Region） mice were injected with pilocarpine to induce acute sei zures. SE was terminated by diazepam at 10 min, 30 min, 1 h, 2 h and 4 h after seizure onset. Spon taneous seizures occurred in the 1, 2 and 4 h SE groups, and the seizure frequency increased with the prolongation of SE. Similarly, the Morris water maze revealed that the escape latency was significantly increased and the number of target quadrant cross ings was markedly decreased in the 1, 2 and 4 h SE groups. Robust mossy fiber sprouting was observed in these groups, but not in the 10 or 30 min group. In contrast, FluoroJade B staining revealed significant cell death only in the 4 h SE group. The incidence and frequency of spontaneous seizures were corre lated with Timm score （P = 0.004） and escape latency （P = 0.004）. These data suggest that SE longer than one hour results in spontaneous motor seizures and memory deficits, and spontaneous seizures are likely associated with robust mossy fiber sprouting but not neuronal death.展开更多
BACKGROUND： Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state,...BACKGROUND： Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state, thereby inhibiting abnormal epileptic discharges, and eventually controlling epileptic seizure. OBJECTIVE： This study was designed to observe the effects of chaotic electrical stimulation to the subthalamic nucleus on mossy fiber sprouting, epileptic seizures, and electrical discharges, and to summarize the most suitable intervention. DESIGN, TIME AND SETTING： This randomized grouping, neuroelectrophysiological study was performed at the Laboratory of Neurology, Union Hospital Affiliated to Fujian Medical University in September 2007. MATERIALS： Fifty-five healthy, male, Sprague Dawley rats were subjected to an epileptic model by an intraperitoneal injection of pentylenetetrazol. The YC-2 programmed electrical stimulator was provided by Chengdu Instrument Factory, China; the video electroencephalographic system （KT-88-2400） and 24-hour active electroencephalographic system were products of Contec Medical System Co., Ltd., China; pentylenetetrazol was purchased from Sigma, USA. METHODS： The present interventional method consisted of electrical stimulation to the subthalamic nucleus with an intensity of 500 μA, pulse width 0.05 ms, frequency 30 Hz, and a duration of 20 minutes for 14 successive days. Fifty-five rats were divided into 6 groups： （1） pre-stimulation （n = 10）, pentylenetetrazol was administered and 30 minutes later, chaotic electrical stimulation was performed; （2） synchronous stimulation （n = 10）, rats received pentylenetetrazol and chaotic electrical stimulation concurrently; （3） post-administration stimulation （n = 10）, after pentylenetetrazol administration, chaotic electrical stimulation was performed immediately after cessation of a seizure; （4） sham-stimulation （n = 10）, following pentylenetetrazol administration, an electrode was connected to the stimulator, but electrical stimulation was not performed; （5） control （n = 10）, pentylenetetrazol administration, but no electrode was implanted; （6） blank control （n = 50）, administration of the same amount of physiological saline and chaotic electrical stimulation. MAIN OUTCOME MEASURES： Timm-stained granule change was scored. Simultaneously, electroencephalography was performed to acquire seizure counts and time course of epileptic discharge within 24 hours. RESULTS： Timm scores were lower in the electrically stimulated rats than in the non-stimulated rats （P 〈 0.01）. Timm scores were lowest in the synchronous stimulation group. When the rats suffered from tonic clonic seizure, the electroencephalogram primarily showed a persistent spike-slow wave and sharp wave. For the electrically stimulated rats, the mean values of seizure counts and time course of epileptic discharge during each hour were noticeably decreased compared with the non-stimulated rats. The synchronous stimulation group, however, had the lowest seizure counts and the shortest time course, followed by the pre-stimulation group, and lastly the post-administration stimulation group. Significant differences existed among the groups （P 〈 0.01）. Compared with the pre-stimulation group and the post-administration stimulation group, the latent period of grades Ⅰ and Ⅳ epileptic seizures was significantly prolonged, and the time course of tonic clonic seizure, as well as total time course, were significantly shortened in the synchronous stimulation group （P 〈 0.01）. CONCLUSION： Simultaneous administration of pentylenetetrazol together with chaotic electrical stimulation produced the greatest inhibitory effects on epileptic seizures. This is possibly related to inhibition of abnormal mossy fiber spouting in the hippocampus.展开更多
基金supported by Beijing Natural Science Foundation(7242268)Beijing Hospitals Authority Youth Programme(QML20230807)Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University(CCMU2023ZKYXZ007).
文摘Objectives:Lung cancer represents a major global healthcare challenge,characterized by high annual incidence and mortality rates worldwide.Although targeted therapies for lung cancer have advanced,treatment outcomes for advanced-stage patients remain suboptimal.This investigation examines the role of the translocase of the inner mitochondrial membrane(TIMM)8A-TIMM13 complex in lung cancer and evaluates its potential as a novel therapeutic target.Methods:A co-immunoprecipitation(Co-IP)assay was conducted to verify the interaction between TIMM8A and TIMM13.Differential gene expression analysis of TIMM8A or TIMM13 was executed using the TNMplot database,with survival estimates derived from the Kaplan-Meier plotter.Lung cancer cell proliferation was evaluated through Cell Counting Kit 8(CCK-8)and colony formation assays,while cell migration was assessed via Transwell assay.RNA sequencing identified the downstream effectors of TIMM13.RNAi technology facilitated the inhibition of TIMM8A or TIMM13 expression,which was measured through immunoblotting or qRT-PCR.Results:This investigation revealed that components of the TIMM8A-TIMM13 complex exhibited elevated expression in human lung cancer tissues,correlating with disease progression and poor overall survival rates among lung cancer patients.The suppression of either TIMM8A or TIMM13 inhibited cell proliferation and migration.Mechanistic studies through transcriptome analysis identified cell cycle-related pathways as potential key downstream effectors of the TIMM8A-TIMM13 complex.Subsequent experiments confirmed that the TIMM8A-TIMM13 complex significantly regulated the expression of cyclin D1(CCND1)and cyclin-dependent kinase 6(CDK6)complex.Conclusion:The elevated expression of TIMM8A-TIMM13 complex components plays a crucial role in lung cancer cell growth,suggesting its potential as a promising therapeutic target for lung cancer treatment.
文摘To avoid missing track caused by the target maneuvers in automatic target tracking system, a new maneuvering target tracking technique called threshold interacting multiple model （TIMM） is proposed. This algorithm is based on the interacting multiple model （IMM） method and applies a threshold controller to improve tracking accuracy. It is also applicable to other advanced algorithms of IMM. In this research, we also compare the position and velocity root mean square （RMS） errors of TIMM and IMM algorithms with two different examples. Simulation results show that the TIMM algorithm is superior to the traditional IMM alzorithm in estimation accuracy.
基金supported by grants from the National Nature Science Foundation of China (8107262)the Zhejiang Provincial Natural Science Foundation of China (Y2100417)+1 种基金the Foundation of Qianjiang Talents (QJD1002012)the Foundation of Health Department of Zhejiang Province for Outstanding Youths (2010)
文摘Determining the minimal duration of status epilepticus （SE） that leads to the development of subsequent spontaneous seizures （i.e., epilepsy） is important, because it provides a critical timewindow for seizure intervention and epilepsy prevention. In the present study, male ICR （imprinting Control Region） mice were injected with pilocarpine to induce acute sei zures. SE was terminated by diazepam at 10 min, 30 min, 1 h, 2 h and 4 h after seizure onset. Spon taneous seizures occurred in the 1, 2 and 4 h SE groups, and the seizure frequency increased with the prolongation of SE. Similarly, the Morris water maze revealed that the escape latency was significantly increased and the number of target quadrant cross ings was markedly decreased in the 1, 2 and 4 h SE groups. Robust mossy fiber sprouting was observed in these groups, but not in the 10 or 30 min group. In contrast, FluoroJade B staining revealed significant cell death only in the 4 h SE group. The incidence and frequency of spontaneous seizures were corre lated with Timm score （P = 0.004） and escape latency （P = 0.004）. These data suggest that SE longer than one hour results in spontaneous motor seizures and memory deficits, and spontaneous seizures are likely associated with robust mossy fiber sprouting but not neuronal death.
基金Research and Development Foundation of Fujian Medical University, No. FJGXY04041
文摘BACKGROUND： Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state, thereby inhibiting abnormal epileptic discharges, and eventually controlling epileptic seizure. OBJECTIVE： This study was designed to observe the effects of chaotic electrical stimulation to the subthalamic nucleus on mossy fiber sprouting, epileptic seizures, and electrical discharges, and to summarize the most suitable intervention. DESIGN, TIME AND SETTING： This randomized grouping, neuroelectrophysiological study was performed at the Laboratory of Neurology, Union Hospital Affiliated to Fujian Medical University in September 2007. MATERIALS： Fifty-five healthy, male, Sprague Dawley rats were subjected to an epileptic model by an intraperitoneal injection of pentylenetetrazol. The YC-2 programmed electrical stimulator was provided by Chengdu Instrument Factory, China; the video electroencephalographic system （KT-88-2400） and 24-hour active electroencephalographic system were products of Contec Medical System Co., Ltd., China; pentylenetetrazol was purchased from Sigma, USA. METHODS： The present interventional method consisted of electrical stimulation to the subthalamic nucleus with an intensity of 500 μA, pulse width 0.05 ms, frequency 30 Hz, and a duration of 20 minutes for 14 successive days. Fifty-five rats were divided into 6 groups： （1） pre-stimulation （n = 10）, pentylenetetrazol was administered and 30 minutes later, chaotic electrical stimulation was performed; （2） synchronous stimulation （n = 10）, rats received pentylenetetrazol and chaotic electrical stimulation concurrently; （3） post-administration stimulation （n = 10）, after pentylenetetrazol administration, chaotic electrical stimulation was performed immediately after cessation of a seizure; （4） sham-stimulation （n = 10）, following pentylenetetrazol administration, an electrode was connected to the stimulator, but electrical stimulation was not performed; （5） control （n = 10）, pentylenetetrazol administration, but no electrode was implanted; （6） blank control （n = 50）, administration of the same amount of physiological saline and chaotic electrical stimulation. MAIN OUTCOME MEASURES： Timm-stained granule change was scored. Simultaneously, electroencephalography was performed to acquire seizure counts and time course of epileptic discharge within 24 hours. RESULTS： Timm scores were lower in the electrically stimulated rats than in the non-stimulated rats （P 〈 0.01）. Timm scores were lowest in the synchronous stimulation group. When the rats suffered from tonic clonic seizure, the electroencephalogram primarily showed a persistent spike-slow wave and sharp wave. For the electrically stimulated rats, the mean values of seizure counts and time course of epileptic discharge during each hour were noticeably decreased compared with the non-stimulated rats. The synchronous stimulation group, however, had the lowest seizure counts and the shortest time course, followed by the pre-stimulation group, and lastly the post-administration stimulation group. Significant differences existed among the groups （P 〈 0.01）. Compared with the pre-stimulation group and the post-administration stimulation group, the latent period of grades Ⅰ and Ⅳ epileptic seizures was significantly prolonged, and the time course of tonic clonic seizure, as well as total time course, were significantly shortened in the synchronous stimulation group （P 〈 0.01）. CONCLUSION： Simultaneous administration of pentylenetetrazol together with chaotic electrical stimulation produced the greatest inhibitory effects on epileptic seizures. This is possibly related to inhibition of abnormal mossy fiber spouting in the hippocampus.
