Tebufenozide,an efficient insect growth regulator(IGR)against lepidopteran pests,presents a novel mode of action with minimal non-target impact.By competing with ecdysteroids for ecdysone receptor(EcR)binding,it regul...Tebufenozide,an efficient insect growth regulator(IGR)against lepidopteran pests,presents a novel mode of action with minimal non-target impact.By competing with ecdysteroids for ecdysone receptor(EcR)binding,it regulates insect growth precisely.This study explores tebufenozide's potential as a multitarget IGR,targeting both EcR and Ostrinia furnacalis chitinase I(OfChtI).The inhibitory activity against OfChtI is comparable to that of substrates(GlcNAc)5,with an IC50 of 45.77μM.Our computational findings indicate that tebufenozide binds at the subsite1 to t1 of OfChtI through various interactions.Notably,tebufenozide establishes a pi-pi interaction with the flipped sidechain of Trp107,enabling tebufenozide to deeply penetrate into the S1 pocket,thereby obstructing substrate binding to OfChtI.These insights highlight the potency of multitarget strategies,laying the groundwork for innovative IGR designs that offer comprehensive pest management solutions.展开更多
BACKGROUND Thymic carcinoid(TC)is a rare entity among anterior mediastinal malignancies.TCs are neuroendocrine carcinomas that constitute approximately 2%–5%of all thymic epithelial tumors.CASE SUMMARY The study repo...BACKGROUND Thymic carcinoid(TC)is a rare entity among anterior mediastinal malignancies.TCs are neuroendocrine carcinomas that constitute approximately 2%–5%of all thymic epithelial tumors.CASE SUMMARY The study reported a rare TC with multiple bone metastases.A 77-year-old man presented with a 2-month history of lower back pain and weight loss of 5 kg.Magnetic resonance imaging scans revealed damage to the lumbar spine,sacrocaudal vertebrae and iliac crest,suggesting bone metastasis;computed tomography(CT)scan of the thorax showed a calcified anterior mediastinal mass;positron emission tomography-CT demonstrated multiple abnormal bone signals;and laboratory work-up showed no endocrine abnormalities.Fine-needle aspiration biopsy revealed predominantly single small,round to oval cells with scant cytoplasm and some loose clusters,suggesting endocrine manifestations.The pathological diagnosis was atypical carcinoid,which tend to originate from the thymus and was classified as intermediate-highly invasive.The patient underwent anlotinib-targeted therapy.Anlotinib(12 mg)was administered daily for 2 wk,after which the patient was allowed to rest for 21 d.Follow-up CT after one year demonstrated that the tumor had shrunk by approximately 29%after therapy.Treatment has a long stable disease benefit of more than 2.5 years.CONCLUSION These findings demonstrated that anlotinib is a promising treatment regimen for patients with TC and multiple bone metastases.展开更多
Alzheimer’s disease(AD)is one of the most common forms of neurodegenerative dementia.The etiology of AD is multifactorial,and its complex pathophysiology involves tau and amyloid-βdeposition,increased oxidative stre...Alzheimer’s disease(AD)is one of the most common forms of neurodegenerative dementia.The etiology of AD is multifactorial,and its complex pathophysiology involves tau and amyloid-βdeposition,increased oxidative stress,neuroinflammation,metabolic disorders,and massive neuronal loss.Due to its complex pathology,no effective cure for AD has been found to date.Therefore,there is an unmet clinical need for the development of new drugs against AD.Natural products are known to be good sources of compounds with pharmacological activity and have potential for the development of new therapeutic agents.Naringin,a naturally occurring flavanone glycoside,is predominantly found in citrus fruits and Chinese medicinal herbs.Mounting evidence shows that naringin and its aglycone,naringenin,have direct neuroprotective effects on AD,such as anti-amyloidogenic,antioxidant,anti-acetylcholinesterase,and anti-neuroinflammatory effects,as well as metal chelation.Furthermore,they are known to improve disordered glucose/lipid metabolism,which is a high risk factor for AD.In this review,we summarize the latest data on the impact of naringin and naringenin on the molecular mechanisms involved in AD pathophysiology.Additionally,we provide an overview of the current clinical applications of naringin and naringenin.The novel delivery systems for naringin and naringenin,which can address their widespread pharmacokinetic limitations,are also discussed.The literature indicates that naringin and naringenin could be multilevel,multitargeted,and multifaceted for preventing and treating AD.展开更多
An algorithm to track multiple sharply maneuvering targets without prior knowledge about new target birth is proposed. These targets are capable of achieving sharp maneuvers within a short period of time, such as dron...An algorithm to track multiple sharply maneuvering targets without prior knowledge about new target birth is proposed. These targets are capable of achieving sharp maneuvers within a short period of time, such as drones and agile missiles.The probability hypothesis density (PHD) filter, which propagates only the first-order statistical moment of the full target posterior, has been shown to be a computationally efficient solution to multitarget tracking problems. However, the standard PHD filter operates on the single dynamic model and requires prior information about target birth distribution, which leads to many limitations in terms of practical applications. In this paper,we introduce a nonzero mean, white noise turn rate dynamic model and generalize jump Markov systems to multitarget case to accommodate sharply maneuvering dynamics. Moreover, to adaptively estimate newborn targets’information, a measurement-driven method based on the recursive random sampling consensus (RANSAC) algorithm is proposed. Simulation results demonstrate that the proposed method achieves significant improvement in tracking multiple sharply maneuvering targets with adaptive birth estimation.展开更多
For swarm robots moving in a harsh or uncharted outdoor environment without GPS guidance and global communication,algorithms that rely on global-based information are infeasible.Typically,traditional gene regulatory n...For swarm robots moving in a harsh or uncharted outdoor environment without GPS guidance and global communication,algorithms that rely on global-based information are infeasible.Typically,traditional gene regulatory networks(GRNs)that achieve superior performance in forming trapping pattern towards targets require accurate global positional information to guide swarm robots.This article presents a gene regulatory network with Self-organized grouping and entrapping method for swarms(SUNDER-GRN)to achieve adequate trapping performance with a large-scale swarm in a confined multitarget environment with access to only local information.A hierarchical self-organized grouping method(HSG)is proposed to structure subswarms in a distributed way.In addition,a modified distributed controller,with a relative coordinate system that is established to relieve the need for global information,is leveraged to facilitate subswarms entrapment toward different targets,thus improving the global multi-target entrapping performance.The results demonstrate the superiority of SUNDERGRN in the performance of structuring subswarms and entrapping 10 targets with 200 robots in an environment confined by obstacles and with only local information accessible.展开更多
Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor,which are being used in clinic.It can inhibit more than 80 kinds of receptor`s tyrosine kinase,including epidermal growth factor receptor (EGFR),p...Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor,which are being used in clinic.It can inhibit more than 80 kinds of receptor`s tyrosine kinase,including epidermal growth factor receptor (EGFR),platelet-derived growth factor receptors,vascular endothelial growth factor receptors (VEGFR),etc.And tyrosine kinase inhibitor is involved in connection with the generation and progression of many kinds of cancer including lung cancer.Several studies have evaluated the effect of Sunitinib on non-small cell lung cancer (NSCLC),by single agent,continuous daily dosing or in combination with chemotherapeutics (with docetaxel or gemcitabine plus cisplatin),which all showed certain effect.The test of Sunitinib in combination with gemcitabine plus cisplatin for advanced NSCLC shown that at the maximum tolerated dose:oral Sunitinib 37.5 mg/day intermittently (Schedule 2/1:2 weeks on treatment,1 week off treatment) schedule with intravenous infusions of gemcitabine (1000 mg/m2 days 1,8) and cisplatin (80 mg/m2 day 1),administered in 3-week cycles,66.7% patients achieved partial responses.And adverse effects were mild to moderate in severity (grades 1 to 2).Therapy was generally well tolerated.In summary,all the evidence above suggests that Sunitinib may play an important role in the treating of NSCLC.展开更多
In this paper we discuss the rationale of applying a “sequential” targeted therapy with a specific application in clinical practice, given our understanding of cancer heterogenous and dynamic biology. We explore the...In this paper we discuss the rationale of applying a “sequential” targeted therapy with a specific application in clinical practice, given our understanding of cancer heterogenous and dynamic biology. We explore the advantages of “single inhibition” to combinational therapies and dual inhibition on key pathways, as well as a multi-step approach to use “oncological addiction” and “oncogenic shock” as a suicide plan for cancer. We specifically explain how the downstream targets can be used to “create” feedback loops in an advantage for creating actionable targets in upstream signaling molecules. We apply this hypothesis in the clinical setting, with superior outcomes shown in a series of case studies. We conclude that “sequential and dual inhibition” can be considered a meaningful approach to checkmate the tumor, with minimum chance of tumor resistance. We recommend further clinical studies to generate further hypotheses based on each actionable target.展开更多
Multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program(2014).T...Multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program(2014).The United States Preventive Services Task Force(USPSTF) October 2015 draft recommendation for CRC screening included mt-s DNA as an "alternative" screening test that "may be useful in select clinical circumstances",despite its very high sensitivity for early stage CRC.The evidence supporting mt-s DNA for routine screening use is robust.The clinical efficacy of mt-s DNA as measured by sensitivity,specificity,life-years gained(LYG),and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document,especially those requiring annual testing adherence.In a population with primarily irregular screening participation,tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual adherence.This paper reviews the evidence supporting mt-s DNA for routine screening and demonstrates,using USPSTF's modeling data,that mt-s DNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing,high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening.展开更多
AIM To determine the uptake of noninvasive multitarget stool DNA (mt-s DNA) in a cohort of colorectal cancer(CRC) screening non-compliant average-risk Medicare patients.METHODS This cross sectional primary care office...AIM To determine the uptake of noninvasive multitarget stool DNA (mt-s DNA) in a cohort of colorectal cancer(CRC) screening non-compliant average-risk Medicare patients.METHODS This cross sectional primary care office-based study examined mt-s DNA uptake in routine clinical practice among 393 colorectal cancer screening non-compliant Medicare patients ages 50-85 ordered by 77 physicians in a multispecialty group practice (USMD Physician Services, Dallas, TX) from October, 2014-September, 2015. Investigators performed a Health Insurance Portability and Accountability Act compliant retrospective review of electronic health records to identify mt-s DNA use in patients who were either > 10 years since last colonoscopy and/or > 1 year since last fecal occult blood test. Test positive patients were advised to get diagnostic colonoscopy and thereafter patients were characterized by the most clinically significant lesion documented on histopathology of biopsies or excisional tissue. Descriptive statistics were employed. Key outcome measures included mt-s DNA compliance and diagnostic colonoscopy compliance on positive cases.RESULTS Over 12 mo, 77 providers ordered 393 mt-sD NA studies with 347 completed (88.3% compliance). Patient mean age was 69.8 (50-85) and patients were 64% female. Mt-sD NA was negative in 85.3%(296/347) and positive in 14.7%(51/347). Follow-up colonoscopy was performed in 49 positive patients (96.1% colonoscopy compliance) with two patients lost to follow up. Index findings included: colon cancer(4/49, 8.2%), advanced adenomas (21/49, 42.9%), non-advanced adenomas(15/49, 30.6%), and negative results (9/49, 18.4%). The positive predictive value for advanced colorectal lesions was 51.0% and for any colorectal neoplasia was 81.6%. The mean age of patients with colorectal cancer was 70.3 and all CRC's were localized Stage Ⅰ(2) and Stage Ⅱ (2), three were located in the proximal colon and one was located in the distal colon.CONCLUSION Mt-s DNA provided medical benefit to screening noncompliant Medicare population. High compliance with mt-s DNA and subsequent follow-up diagnostic colonoscopy identified patients with clinically critical advanced colorectal neoplasia.展开更多
In radar systems of automatic detection, an estimate of background clutter power is used to set the detection threshold. An interference saturated environment is frequently encountered in these systems (multiple targe...In radar systems of automatic detection, an estimate of background clutter power is used to set the detection threshold. An interference saturated environment is frequently encountered in these systems (multiple target situations). Therefore, the detection of signals in such an environment becomes one of the most important problems to be solved. The double-threshold algorithm is one of the more interesting detectors used in these situations. While the first threshold operation ensures that the calculation of the detection (second) threshold is based on a set of samples which is free of strong interferers and is therefore much more representative of the noise level, the second threshold is used to declare the presence or the absence of the radar target. The object of the present paper is to analyze the performance of such type of CFAR schemes when the radar receiver contains a noncoherent integrator amongst its basic elements. It is found that the processor detectabil ity loss is very low and the performance degradation, caused by interferers is quite small even if the number of outlying targets is large, given that the first threshold is properly chosen.展开更多
A fast joint probabilistic data association （FJPDA） algorithm is proposed in tiffs paper. Cluster probability matrix is approximately calculated by a new method, whose elements βi^t（K） can be taken as evaluation ...A fast joint probabilistic data association （FJPDA） algorithm is proposed in tiffs paper. Cluster probability matrix is approximately calculated by a new method, whose elements βi^t（K） can be taken as evaluation functions. According to values of βi^t（K）, N events with larger joint probabilities can be searched out as the events with guiding joint probabilities, tiros, the number of searching nodes will be greatly reduced. As a result, this method effectively reduces the calculation load and nnkes it possible to be realized on real-thne, Theoretical ,analysis and Monte Carlo simulation results show that this method is efficient.展开更多
The yield of bremsstrahlung (BS) from collisions of fast electrons (energy at least 6 MeV) with a Tungsten target can be significantly improved by exploitation of Tungsten wall scatter in a multi-layered target. A sim...The yield of bremsstrahlung (BS) from collisions of fast electrons (energy at least 6 MeV) with a Tungsten target can be significantly improved by exploitation of Tungsten wall scatter in a multi-layered target. A simplified version of a previously developed principle is also able to focus on small angle scattered electrons by a Tungsten wall. It is necessary that the thickness of each Tungsten layer does not exceed 0.04 mm—a thickness of 0.03 mm is suitable for accelerators in medical physics. Further focusing of electrons results from suitable magnetic fields with field strength between 0.5 Tesla and 1.2 Tesla (if the cone with multi-layered targets is rather narrow). Linear accelerators in radiation therapy only need to be focused by wall scatter without further magnetic fields (a standard case: 31 plates with 0.03 mm thickness and 1 mm distance between the plates). We considered three cases with importance in medical physics: A very small cone with an additional magnetic field for focusing (the field diameter at 90 cm depth: 6 cm), a medium cone with an optional magnetic field (field diameter at 90 cm depth: 13 cm) and a broad cone without a magnetic field (the field diameter at 90 cm depth: 30 cm). All these cases can be positioned in a carousel. Measurements have been performed in the existing carousel positioned in the plane of the flattening filter and scatter foils for electrons.展开更多
For data association in multisensor and multitarget tracking, a novel parallel algorithm is developed to improve the efficiency and real-time performance of FGAs-based algorithm. One Cluster of Workstation （COW） wit...For data association in multisensor and multitarget tracking, a novel parallel algorithm is developed to improve the efficiency and real-time performance of FGAs-based algorithm. One Cluster of Workstation （COW） with Message Passing Interface （MPI） is built. The proposed Multi-Deme Parallel FGA （MDPFGA） is run on the platform. A serial of special MDPFGAs are used to determine the static and the dynamic solutions of generalized m-best S-D assignment problem respectively, as well as target states estimation in track management. Such an assignment-based parallel algorithm is demonstrated on simulated passive sensor track formation and maintenance problem. While illustrating the feasibility of the proposed algorithm in multisensor multitarget tracking, simulation results indicate that the MDPFGAs-based algorithm has greater efficiency and speed than the FGAs-based algorithm.展开更多
The computer control techniques applicable to electronically scanned multifunction radars are presented. The software and hardware architecture for the real time control and the data processing within a phased array ...The computer control techniques applicable to electronically scanned multifunction radars are presented. The software and hardware architecture for the real time control and the data processing within a phased array radar are described. The software system comprising a number of tasks is written in C language and implemented. The results show that the algorithm for the multitask adaptive scheduling and the multitarget data processing is suitable for multifunction phased array radars.展开更多
In this paper, an adaptive digital filter algorithm is presented to optimize the signal-to-noise ratio of an antenna array with multiuser signal inputs. These synchronous communication signals have constant envelope p...In this paper, an adaptive digital filter algorithm is presented to optimize the signal-to-noise ratio of an antenna array with multiuser signal inputs. These synchronous communication signals have constant envelope property and are transmitted through a Multiple-Input/Multiple-Output （MIMO） linear channel. This Multiuser Constant Modulus Algorithm （MU-CMA） using an antenna array can compensate for both Interuser Interference （IUI） and Intersymbol Interference （ISI）. The method is derived by minimizing the cost function of the constant modulus signals as well as cross-correlations between them. The simulation result in this paper shows the performance of this algorithm.展开更多
Rasagiline,a monoamine oxidase-B inhibitor,and bis（propyl）-cognitin（B3C）,a novel dimer are reported to be neuroprotective.Herein,the synergistical neuroprotection produced by rasagiline and B3 C was investigated i...Rasagiline,a monoamine oxidase-B inhibitor,and bis（propyl）-cognitin（B3C）,a novel dimer are reported to be neuroprotective.Herein,the synergistical neuroprotection produced by rasagiline and B3 C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced mice of Parkinsonism.By using neurobehavioural tests,high-performance liquid chromatography and western blot assay,we showed that B3 C at 0.3 mg/kg,rasagiline at 0.02 mg/kg,as well as co-treatment with B3 C and rasagiline prevented MPTP-induced behavioural abnormities,increased the concentrations of dopamine and its metabolites in the striatum,and up-regulated the expression of tyrosine hydroxylase in the substantia nigra.However,the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3 C or rasagiline alone.Collectively,we have demonstrated that B3 C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.展开更多
Objective： To study the relationship between traditional Chinese medicine （TCM） research and network pharmacology. Methods： Discuss the common features of TCM and network pharmacology through the analysis of the c...Objective： To study the relationship between traditional Chinese medicine （TCM） research and network pharmacology. Methods： Discuss the common features of TCM and network pharmacology through the analysis of the characteristics of TCM, the background of network pharmacology, so as better interpretation of TCM and in-depth understanding of TCM research and network pharmacology. Results： Multicomponent and multitarget characteristics of TCM as same as the study thought of network pharmacology. Network pharmacology breaks through the research model of linear and coincides with the complexity of TCM, provides technical support for rational design of TCM formulae, both and a new way in the research of TCM. It becomes a new strategy for modern TCM research. Conclusion： Network pharmacology is an important breakthrough in TCM research, its research promote modernization and internationalization process of TCM conduce to the research and development of TCM and have important significance for the integration of Chinese and Western medicine.展开更多
The quantization of circuits has received to be rather attractive in domains of solid state—molecular—and biophysics, since the quanta referred to as Q-bits play a significant role in the design of the quantum compu...The quantization of circuits has received to be rather attractive in domains of solid state—molecular—and biophysics, since the quanta referred to as Q-bits play a significant role in the design of the quantum computer and entangled structures. Quantized circuits cannot be applied without modifications, since the energy differences are not equidistant and the polarization of the excited states has to be accounted for having particular importance for the creation of virtual states. Applications of the presented theory are scanning methods in radiotherapy without multi-leaf collimators, which may be realized in tomo-scanning radiotherapy and in the keV domain, which provides a new design of CT. The problem of lateral scatter in the target and energy storage by heat production is significantly reduced by a multilayer system with focusing the impinging electrons at the walls and by a magnetic field. The verification of the Heisenberg-Euler scatter of crossing beams of 9 MV is a central problem of photon physics and can be solved by the new bremsstrahlung technique. A comparison with GEANT 4 Monte-Carlo data indicates that the presented method also works in the GeV domain, and a multi-target can improve the bremsstrahlung yield. GEANT 4 provides the spatial distribution, whereas the virtual oscillator states only show the created energy spectrum. In every case, the exploitation yield can be drastically improved by the superiority of the focused multitarget system compared to a single standard target, and the door to new technologies is opened.展开更多
For many multigene or multifactorial diseases,the one-drug therapy for inhibiting a defined molecular target is often less effective than combined treatments.Typically,drug combination therapies are multitargeted,so t...For many multigene or multifactorial diseases,the one-drug therapy for inhibiting a defined molecular target is often less effective than combined treatments.Typically,drug combination therapies are multitargeted,so the mechanisms or even interactions are often complementary.These drug-drug interactions may promote alteration of pharmacokinetic or pharmacodynamic activities of one drug by another drug.Other interactions may change the expected effect of medications through polymorphisms that alter the expression or activity of the drug-mediated enzyme and the cell signaling cascade,such as drug-gene interactions and drug-drug-gene interactions.The number of possible existing interactions requires appropriate methods of study.In this review,we summarized combination therapies for cancer,as well as for viral,cardiovascular,and neurological diseases.Here,we also highlight known methodologies,such as in vitro methods based on Loewe’s and Bliss’s pioneer models and in silico methods based on online available data.With more elaborate methods and reliable results,multitarget therapies through drug combinations may increasingly benefit patients suffering from complex diseases.展开更多
基金financially supported by the National Natural Science Foundation of China(No.22177132 and 21977114).
文摘Tebufenozide,an efficient insect growth regulator(IGR)against lepidopteran pests,presents a novel mode of action with minimal non-target impact.By competing with ecdysteroids for ecdysone receptor(EcR)binding,it regulates insect growth precisely.This study explores tebufenozide's potential as a multitarget IGR,targeting both EcR and Ostrinia furnacalis chitinase I(OfChtI).The inhibitory activity against OfChtI is comparable to that of substrates(GlcNAc)5,with an IC50 of 45.77μM.Our computational findings indicate that tebufenozide binds at the subsite1 to t1 of OfChtI through various interactions.Notably,tebufenozide establishes a pi-pi interaction with the flipped sidechain of Trp107,enabling tebufenozide to deeply penetrate into the S1 pocket,thereby obstructing substrate binding to OfChtI.These insights highlight the potency of multitarget strategies,laying the groundwork for innovative IGR designs that offer comprehensive pest management solutions.
基金Supported by Guangxi Guilin Science and Technology Fund,No.20190218-7-6.
文摘BACKGROUND Thymic carcinoid(TC)is a rare entity among anterior mediastinal malignancies.TCs are neuroendocrine carcinomas that constitute approximately 2%–5%of all thymic epithelial tumors.CASE SUMMARY The study reported a rare TC with multiple bone metastases.A 77-year-old man presented with a 2-month history of lower back pain and weight loss of 5 kg.Magnetic resonance imaging scans revealed damage to the lumbar spine,sacrocaudal vertebrae and iliac crest,suggesting bone metastasis;computed tomography(CT)scan of the thorax showed a calcified anterior mediastinal mass;positron emission tomography-CT demonstrated multiple abnormal bone signals;and laboratory work-up showed no endocrine abnormalities.Fine-needle aspiration biopsy revealed predominantly single small,round to oval cells with scant cytoplasm and some loose clusters,suggesting endocrine manifestations.The pathological diagnosis was atypical carcinoid,which tend to originate from the thymus and was classified as intermediate-highly invasive.The patient underwent anlotinib-targeted therapy.Anlotinib(12 mg)was administered daily for 2 wk,after which the patient was allowed to rest for 21 d.Follow-up CT after one year demonstrated that the tumor had shrunk by approximately 29%after therapy.Treatment has a long stable disease benefit of more than 2.5 years.CONCLUSION These findings demonstrated that anlotinib is a promising treatment regimen for patients with TC and multiple bone metastases.
基金supported by the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.TGD23C050001)by National Natural Science Foundation of China(No.82074186).
文摘Alzheimer’s disease(AD)is one of the most common forms of neurodegenerative dementia.The etiology of AD is multifactorial,and its complex pathophysiology involves tau and amyloid-βdeposition,increased oxidative stress,neuroinflammation,metabolic disorders,and massive neuronal loss.Due to its complex pathology,no effective cure for AD has been found to date.Therefore,there is an unmet clinical need for the development of new drugs against AD.Natural products are known to be good sources of compounds with pharmacological activity and have potential for the development of new therapeutic agents.Naringin,a naturally occurring flavanone glycoside,is predominantly found in citrus fruits and Chinese medicinal herbs.Mounting evidence shows that naringin and its aglycone,naringenin,have direct neuroprotective effects on AD,such as anti-amyloidogenic,antioxidant,anti-acetylcholinesterase,and anti-neuroinflammatory effects,as well as metal chelation.Furthermore,they are known to improve disordered glucose/lipid metabolism,which is a high risk factor for AD.In this review,we summarize the latest data on the impact of naringin and naringenin on the molecular mechanisms involved in AD pathophysiology.Additionally,we provide an overview of the current clinical applications of naringin and naringenin.The novel delivery systems for naringin and naringenin,which can address their widespread pharmacokinetic limitations,are also discussed.The literature indicates that naringin and naringenin could be multilevel,multitargeted,and multifaceted for preventing and treating AD.
基金supported by the National Natural Science Foundation of China (61773142)。
文摘An algorithm to track multiple sharply maneuvering targets without prior knowledge about new target birth is proposed. These targets are capable of achieving sharp maneuvers within a short period of time, such as drones and agile missiles.The probability hypothesis density (PHD) filter, which propagates only the first-order statistical moment of the full target posterior, has been shown to be a computationally efficient solution to multitarget tracking problems. However, the standard PHD filter operates on the single dynamic model and requires prior information about target birth distribution, which leads to many limitations in terms of practical applications. In this paper,we introduce a nonzero mean, white noise turn rate dynamic model and generalize jump Markov systems to multitarget case to accommodate sharply maneuvering dynamics. Moreover, to adaptively estimate newborn targets’information, a measurement-driven method based on the recursive random sampling consensus (RANSAC) algorithm is proposed. Simulation results demonstrate that the proposed method achieves significant improvement in tracking multiple sharply maneuvering targets with adaptive birth estimation.
基金supported in part by National Key R&D Program of China(Grant Nos.2021ZD0111501,2021ZD0111502)the Key Laboratory of Digital Signal and Image Processing of Guangdong Province+8 种基金the Key Laboratory of Intelligent Manufacturing Technology(Shantou University)Ministry of Education,the Science and Technology Planning Project of Guangdong Province of China(Grant No.180917144960530)the Project of Educational Commission of Guangdong Province of China(Grant No.2017KZDXM032)the State Key Lab of Digital Manufacturing Equipment&Technology(grant number DMETKF2019020)National Natural Science Foundation of China(Grant Nos.62176147,62002369)STU Scientific Research Foundation for Talents(Grant No.NTF21001)Science and Technology Planning Project of Guangdong Province of China(Grant Nos.2019A050520001,2021A0505030072,2022A1515110660)Science and Technology Special Funds Project of Guangdong Province of China(Grant Nos.STKJ2021176,STKJ2021019)Guangdong Special Support Program for Outstanding Talents(Grant No.2021JC06X549)。
文摘For swarm robots moving in a harsh or uncharted outdoor environment without GPS guidance and global communication,algorithms that rely on global-based information are infeasible.Typically,traditional gene regulatory networks(GRNs)that achieve superior performance in forming trapping pattern towards targets require accurate global positional information to guide swarm robots.This article presents a gene regulatory network with Self-organized grouping and entrapping method for swarms(SUNDER-GRN)to achieve adequate trapping performance with a large-scale swarm in a confined multitarget environment with access to only local information.A hierarchical self-organized grouping method(HSG)is proposed to structure subswarms in a distributed way.In addition,a modified distributed controller,with a relative coordinate system that is established to relieve the need for global information,is leveraged to facilitate subswarms entrapment toward different targets,thus improving the global multi-target entrapping performance.The results demonstrate the superiority of SUNDERGRN in the performance of structuring subswarms and entrapping 10 targets with 200 robots in an environment confined by obstacles and with only local information accessible.
文摘Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor,which are being used in clinic.It can inhibit more than 80 kinds of receptor`s tyrosine kinase,including epidermal growth factor receptor (EGFR),platelet-derived growth factor receptors,vascular endothelial growth factor receptors (VEGFR),etc.And tyrosine kinase inhibitor is involved in connection with the generation and progression of many kinds of cancer including lung cancer.Several studies have evaluated the effect of Sunitinib on non-small cell lung cancer (NSCLC),by single agent,continuous daily dosing or in combination with chemotherapeutics (with docetaxel or gemcitabine plus cisplatin),which all showed certain effect.The test of Sunitinib in combination with gemcitabine plus cisplatin for advanced NSCLC shown that at the maximum tolerated dose:oral Sunitinib 37.5 mg/day intermittently (Schedule 2/1:2 weeks on treatment,1 week off treatment) schedule with intravenous infusions of gemcitabine (1000 mg/m2 days 1,8) and cisplatin (80 mg/m2 day 1),administered in 3-week cycles,66.7% patients achieved partial responses.And adverse effects were mild to moderate in severity (grades 1 to 2).Therapy was generally well tolerated.In summary,all the evidence above suggests that Sunitinib may play an important role in the treating of NSCLC.
文摘In this paper we discuss the rationale of applying a “sequential” targeted therapy with a specific application in clinical practice, given our understanding of cancer heterogenous and dynamic biology. We explore the advantages of “single inhibition” to combinational therapies and dual inhibition on key pathways, as well as a multi-step approach to use “oncological addiction” and “oncogenic shock” as a suicide plan for cancer. We specifically explain how the downstream targets can be used to “create” feedback loops in an advantage for creating actionable targets in upstream signaling molecules. We apply this hypothesis in the clinical setting, with superior outcomes shown in a series of case studies. We conclude that “sequential and dual inhibition” can be considered a meaningful approach to checkmate the tumor, with minimum chance of tumor resistance. We recommend further clinical studies to generate further hypotheses based on each actionable target.
文摘Multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program(2014).The United States Preventive Services Task Force(USPSTF) October 2015 draft recommendation for CRC screening included mt-s DNA as an "alternative" screening test that "may be useful in select clinical circumstances",despite its very high sensitivity for early stage CRC.The evidence supporting mt-s DNA for routine screening use is robust.The clinical efficacy of mt-s DNA as measured by sensitivity,specificity,life-years gained(LYG),and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document,especially those requiring annual testing adherence.In a population with primarily irregular screening participation,tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual adherence.This paper reviews the evidence supporting mt-s DNA for routine screening and demonstrates,using USPSTF's modeling data,that mt-s DNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing,high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening.
文摘AIM To determine the uptake of noninvasive multitarget stool DNA (mt-s DNA) in a cohort of colorectal cancer(CRC) screening non-compliant average-risk Medicare patients.METHODS This cross sectional primary care office-based study examined mt-s DNA uptake in routine clinical practice among 393 colorectal cancer screening non-compliant Medicare patients ages 50-85 ordered by 77 physicians in a multispecialty group practice (USMD Physician Services, Dallas, TX) from October, 2014-September, 2015. Investigators performed a Health Insurance Portability and Accountability Act compliant retrospective review of electronic health records to identify mt-s DNA use in patients who were either > 10 years since last colonoscopy and/or > 1 year since last fecal occult blood test. Test positive patients were advised to get diagnostic colonoscopy and thereafter patients were characterized by the most clinically significant lesion documented on histopathology of biopsies or excisional tissue. Descriptive statistics were employed. Key outcome measures included mt-s DNA compliance and diagnostic colonoscopy compliance on positive cases.RESULTS Over 12 mo, 77 providers ordered 393 mt-sD NA studies with 347 completed (88.3% compliance). Patient mean age was 69.8 (50-85) and patients were 64% female. Mt-sD NA was negative in 85.3%(296/347) and positive in 14.7%(51/347). Follow-up colonoscopy was performed in 49 positive patients (96.1% colonoscopy compliance) with two patients lost to follow up. Index findings included: colon cancer(4/49, 8.2%), advanced adenomas (21/49, 42.9%), non-advanced adenomas(15/49, 30.6%), and negative results (9/49, 18.4%). The positive predictive value for advanced colorectal lesions was 51.0% and for any colorectal neoplasia was 81.6%. The mean age of patients with colorectal cancer was 70.3 and all CRC's were localized Stage Ⅰ(2) and Stage Ⅱ (2), three were located in the proximal colon and one was located in the distal colon.CONCLUSION Mt-s DNA provided medical benefit to screening noncompliant Medicare population. High compliance with mt-s DNA and subsequent follow-up diagnostic colonoscopy identified patients with clinically critical advanced colorectal neoplasia.
文摘In radar systems of automatic detection, an estimate of background clutter power is used to set the detection threshold. An interference saturated environment is frequently encountered in these systems (multiple target situations). Therefore, the detection of signals in such an environment becomes one of the most important problems to be solved. The double-threshold algorithm is one of the more interesting detectors used in these situations. While the first threshold operation ensures that the calculation of the detection (second) threshold is based on a set of samples which is free of strong interferers and is therefore much more representative of the noise level, the second threshold is used to declare the presence or the absence of the radar target. The object of the present paper is to analyze the performance of such type of CFAR schemes when the radar receiver contains a noncoherent integrator amongst its basic elements. It is found that the processor detectabil ity loss is very low and the performance degradation, caused by interferers is quite small even if the number of outlying targets is large, given that the first threshold is properly chosen.
文摘A fast joint probabilistic data association （FJPDA） algorithm is proposed in tiffs paper. Cluster probability matrix is approximately calculated by a new method, whose elements βi^t（K） can be taken as evaluation functions. According to values of βi^t（K）, N events with larger joint probabilities can be searched out as the events with guiding joint probabilities, tiros, the number of searching nodes will be greatly reduced. As a result, this method effectively reduces the calculation load and nnkes it possible to be realized on real-thne, Theoretical ,analysis and Monte Carlo simulation results show that this method is efficient.
文摘The yield of bremsstrahlung (BS) from collisions of fast electrons (energy at least 6 MeV) with a Tungsten target can be significantly improved by exploitation of Tungsten wall scatter in a multi-layered target. A simplified version of a previously developed principle is also able to focus on small angle scattered electrons by a Tungsten wall. It is necessary that the thickness of each Tungsten layer does not exceed 0.04 mm—a thickness of 0.03 mm is suitable for accelerators in medical physics. Further focusing of electrons results from suitable magnetic fields with field strength between 0.5 Tesla and 1.2 Tesla (if the cone with multi-layered targets is rather narrow). Linear accelerators in radiation therapy only need to be focused by wall scatter without further magnetic fields (a standard case: 31 plates with 0.03 mm thickness and 1 mm distance between the plates). We considered three cases with importance in medical physics: A very small cone with an additional magnetic field for focusing (the field diameter at 90 cm depth: 6 cm), a medium cone with an optional magnetic field (field diameter at 90 cm depth: 13 cm) and a broad cone without a magnetic field (the field diameter at 90 cm depth: 30 cm). All these cases can be positioned in a carousel. Measurements have been performed in the existing carousel positioned in the plane of the flattening filter and scatter foils for electrons.
基金Supported by National Defence Scientific Research Foundation
文摘For data association in multisensor and multitarget tracking, a novel parallel algorithm is developed to improve the efficiency and real-time performance of FGAs-based algorithm. One Cluster of Workstation （COW） with Message Passing Interface （MPI） is built. The proposed Multi-Deme Parallel FGA （MDPFGA） is run on the platform. A serial of special MDPFGAs are used to determine the static and the dynamic solutions of generalized m-best S-D assignment problem respectively, as well as target states estimation in track management. Such an assignment-based parallel algorithm is demonstrated on simulated passive sensor track formation and maintenance problem. While illustrating the feasibility of the proposed algorithm in multisensor multitarget tracking, simulation results indicate that the MDPFGAs-based algorithm has greater efficiency and speed than the FGAs-based algorithm.
文摘The computer control techniques applicable to electronically scanned multifunction radars are presented. The software and hardware architecture for the real time control and the data processing within a phased array radar are described. The software system comprising a number of tasks is written in C language and implemented. The results show that the algorithm for the multitask adaptive scheduling and the multitarget data processing is suitable for multifunction phased array radars.
基金Supported by the National Natural Science Foundation ofChina (60671040)
文摘In this paper, an adaptive digital filter algorithm is presented to optimize the signal-to-noise ratio of an antenna array with multiuser signal inputs. These synchronous communication signals have constant envelope property and are transmitted through a Multiple-Input/Multiple-Output （MIMO） linear channel. This Multiuser Constant Modulus Algorithm （MU-CMA） using an antenna array can compensate for both Interuser Interference （IUI） and Intersymbol Interference （ISI）. The method is derived by minimizing the cost function of the constant modulus signals as well as cross-correlations between them. The simulation result in this paper shows the performance of this algorithm.
基金supported by grants from the Natural Science Foundation of Guangdong Province of China,No.2015A030313317a grant from the Science and Technology Program of Guangzhou City of China,No.2014J4100097+3 种基金partially by a grant from the Science and Technology Development Fund(FDCT) of Macao Special Administrative Region,No.134/2014/A3a grant from the Research Committee of University of Macao,No.MYRG139(Y1-L4)-ICMS12-LMY and MYRG2015-00214-ICMS-QRCMgrants from the Research Grants Council of Hong Kong Special Administrative Region of China,No.561011,15101014the Hong Kong Polytechnic University of China,No.G-SB10,G-UC15 and G-YBGQ
文摘Rasagiline,a monoamine oxidase-B inhibitor,and bis（propyl）-cognitin（B3C）,a novel dimer are reported to be neuroprotective.Herein,the synergistical neuroprotection produced by rasagiline and B3 C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced mice of Parkinsonism.By using neurobehavioural tests,high-performance liquid chromatography and western blot assay,we showed that B3 C at 0.3 mg/kg,rasagiline at 0.02 mg/kg,as well as co-treatment with B3 C and rasagiline prevented MPTP-induced behavioural abnormities,increased the concentrations of dopamine and its metabolites in the striatum,and up-regulated the expression of tyrosine hydroxylase in the substantia nigra.However,the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3 C or rasagiline alone.Collectively,we have demonstrated that B3 C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.
文摘Objective： To study the relationship between traditional Chinese medicine （TCM） research and network pharmacology. Methods： Discuss the common features of TCM and network pharmacology through the analysis of the characteristics of TCM, the background of network pharmacology, so as better interpretation of TCM and in-depth understanding of TCM research and network pharmacology. Results： Multicomponent and multitarget characteristics of TCM as same as the study thought of network pharmacology. Network pharmacology breaks through the research model of linear and coincides with the complexity of TCM, provides technical support for rational design of TCM formulae, both and a new way in the research of TCM. It becomes a new strategy for modern TCM research. Conclusion： Network pharmacology is an important breakthrough in TCM research, its research promote modernization and internationalization process of TCM conduce to the research and development of TCM and have important significance for the integration of Chinese and Western medicine.
文摘The quantization of circuits has received to be rather attractive in domains of solid state—molecular—and biophysics, since the quanta referred to as Q-bits play a significant role in the design of the quantum computer and entangled structures. Quantized circuits cannot be applied without modifications, since the energy differences are not equidistant and the polarization of the excited states has to be accounted for having particular importance for the creation of virtual states. Applications of the presented theory are scanning methods in radiotherapy without multi-leaf collimators, which may be realized in tomo-scanning radiotherapy and in the keV domain, which provides a new design of CT. The problem of lateral scatter in the target and energy storage by heat production is significantly reduced by a multilayer system with focusing the impinging electrons at the walls and by a magnetic field. The verification of the Heisenberg-Euler scatter of crossing beams of 9 MV is a central problem of photon physics and can be solved by the new bremsstrahlung technique. A comparison with GEANT 4 Monte-Carlo data indicates that the presented method also works in the GeV domain, and a multi-target can improve the bremsstrahlung yield. GEANT 4 provides the spatial distribution, whereas the virtual oscillator states only show the created energy spectrum. In every case, the exploitation yield can be drastically improved by the superiority of the focused multitarget system compared to a single standard target, and the door to new technologies is opened.
文摘For many multigene or multifactorial diseases,the one-drug therapy for inhibiting a defined molecular target is often less effective than combined treatments.Typically,drug combination therapies are multitargeted,so the mechanisms or even interactions are often complementary.These drug-drug interactions may promote alteration of pharmacokinetic or pharmacodynamic activities of one drug by another drug.Other interactions may change the expected effect of medications through polymorphisms that alter the expression or activity of the drug-mediated enzyme and the cell signaling cascade,such as drug-gene interactions and drug-drug-gene interactions.The number of possible existing interactions requires appropriate methods of study.In this review,we summarized combination therapies for cancer,as well as for viral,cardiovascular,and neurological diseases.Here,we also highlight known methodologies,such as in vitro methods based on Loewe’s and Bliss’s pioneer models and in silico methods based on online available data.With more elaborate methods and reliable results,multitarget therapies through drug combinations may increasingly benefit patients suffering from complex diseases.
