The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor...Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).展开更多
Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily...Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.展开更多
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b...Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histo...Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.展开更多
Dopamine,often termed the"feel-good"neurotransmitter,plays a crucial role in myriad physiological and psychological brain processes.While dopamine is primarily associated with pleasure,reward,and motivation,...Dopamine,often termed the"feel-good"neurotransmitter,plays a crucial role in myriad physiological and psychological brain processes.While dopamine is primarily associated with pleasure,reward,and motivation,its effects can be quite complex;and this complexity is further compounded when examining how dopamine functions in typical versus disease-affected neural circuits.In pa rticula r,epilepsy,characte rized by heightened brain excitability,is linked to cognitive dysfunction,and dopamine is implicated in elements of both its pathology and treatment.Neuroscience has been successful in describing the synaptic abnormalities believed to contribute to memory issues in epilepsy,aiding in the search for effective therapies for what persists as a major medical issue.展开更多
A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to ...A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.展开更多
Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Cu...Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.展开更多
Dopamine(DA)is a vital neurotransmitter,and accurate detection of its concentration is critical for both clinical diagnos-tics and neuroscience research.Due to its electrochemical activity,DA is commonly detected usin...Dopamine(DA)is a vital neurotransmitter,and accurate detection of its concentration is critical for both clinical diagnos-tics and neuroscience research.Due to its electrochemical activity,DA is commonly detected using electrochemical methods,which are favored for their simplicity,fast response time,and suitability for in vivo analysis.In this work,a highly sensitive DA electrochemical sensor was developed using an Au@MoS_(2)composite,created by modifying molybdenum disulfide(MoS_(2))nanosheets with gold nanoparticles through HAuCl_(4) reduction,and it was aimed at enhancing DA adsorption and improving detection performance.Scanning Electron Microscopy(SEM),transmission electron microscopy(TEM),Energy Dispersive Spectroscopy(EDS),X-ray photoelectron spectroscopy(XPS)and X-ray Diffraction(XRD)confirmed the suc-cessful synthesis of Au@MoS_(2)and the uniform distribution of gold nanoparticles across the MoS_(2)nanosheets.Then,the electrochemical characterization demonstrated that the Au@MoS_(2)/GCE exhibited distinct oxidation peaks in a 10μmol·L^(-1)DA solution,with significantly enhanced electrochemical activity compared to both unmodified GCE and pristine MoS_(2).Furthermore,differential pulse voltammetry(DPV)further revealed a strong linear relationship between DA concentration and the current response in the range of 800 nmol·L^(-1)to 10μmol·L^(-1),with a low detection limit(LOD)of 78.9 nmol·L^(-1)(S/N=3).Additionally,the sensor showed excellent selectivity against other interfering substances.Moreover,the laser-induced Au@MoS_(2)(LIAu@MoS_(2)),with its abundance of negatively charged surface defects,enabled the ultra-sensitive detection of the ultra-low concentrations of DA.In conclusion,the successfully fabricated Au@MoS_(2)based sensor offers advantages such as low cost,ease of operation,and scalability,making it a promising candidate for biosensing applications due to its enhanced DA detection capabilities.展开更多
BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as th...BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as the arms,abdomen,face,neck,head,and genital area.There are only a few reports of the RLS variant affecting the head.AIM To assess the epidemiological,clinical,and other aspects of the RLS variant affecting the head.METHODS We conducted a retrospective study of 17 adult patients(>18 years)who met the RLS criteria and simultaneously experienced RLS-like symptoms in the head.RESULTS The median age at which symptoms appeared was 41.6 years.Males and females were equally affected(1.1:1).All 17 patients had uncomfortable sensations in the lower legs.Insomnia or disturbed sleep was the most common comorbidity(n=16,88.2%).However,headache was the most common presenting or primary symptom(n=10,70.5%).Dizziness or an abnormal sensation in the head was the second most common presenting symptom(5 patients,29.4%).Other presenting features were leg pain,backache,and generalized body pain.All patients responded favorably to dopaminergic medications.CONCLUSION If RLS-related unpleasant sensations and pain are felt in the head,they may be misinterpreted as headache,dizziness,or psychosomatic symptoms.RLS and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.展开更多
Understanding the cellular mechanisms of drug addiction remains a key task in current brain research.While neuron-based mechanisms have been extensively explored over the past three decades,recent evidence indicates a...Understanding the cellular mechanisms of drug addiction remains a key task in current brain research.While neuron-based mechanisms have been extensively explored over the past three decades,recent evidence indicates a critical involvement of astrocytes,the main type of non-neuronal cells in the brain.In response to extracellular stimuli,astrocytes modulate the activity of neurons,synaptic transmission,and neural network properties,collectively influencing brain function.G protein-coupled receptors(GPCRs)expressed on astrocyte surfaces respond to neuron-and environment-derived ligands by activating or inhibiting astrocytic signaling,which in turn regulates adjacent neurons and their circuitry.In this review,we focus on the dopamine D1 receptors(D1R)and metabotropic glutamate receptor 5(mGLUR5 or GRM5)—two GPCRs that have been critically implicated in the acquisition and maintenance of addiction-related behaviors.Positioned as an introductory-level review,this article briefly discusses astrocyte biology,outlines earlier discoveries about the role of astrocytes in substance-use disorders(SUDs),and provides detailed discussion about astrocytic D1Rs and mGLUR5s in regulating synapse and network functions in the nucleus accumbens(NAc)—a brain region that mediates addictionrelated emotional and motivational responses.This review serves as a stepping stone for readers of Engineering to explore links between astrocytic GPCRs and drug addiction and other psychiatric disorders.展开更多
Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While sympto...Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief,they do not halt disease progression.In recent years,significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease,including alpha-synuclein aggregation,mitochondrial dysfunction,neuroinflammation,and lysosomal impairment.These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression.This review comprehensively explores emerging approaches such as gene and cell therapies,LRRK2 inhibitors,alpha-synuclein immunotherapy,and gut microbiota modulation.We also discuss the therapeutic potential of mitophagy activators,digital biomarkers,and neuromodulation techniques.Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms.Special attention is given to recent clinical trials(2023–2025),translational gaps,and the potential of personalized medicine in Parkinson’s disease management.Furthermore,we examine the integration of multi-omics data and digital tools in advancing precision therapeutics.Overall,this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.展开更多
OBJECTIVE:To evaluate the therapeutic effect of a selfformulated Traditional Chinese Medicine(TCM),Shugan Jieyu San(疏肝解郁散),on improvement of liver function and depression alleviation in the patients with triple n...OBJECTIVE:To evaluate the therapeutic effect of a selfformulated Traditional Chinese Medicine(TCM),Shugan Jieyu San(疏肝解郁散),on improvement of liver function and depression alleviation in the patients with triple negative breast cancer(TNBC).METHODS:A total of 60 patients diagnosed with TNBC and depression were enrolled and randomly assigned to either the control group(receiving routine tumor treatment and duloxetine)or the treatment group(receiving the TCM in addition to routine treatment).RESULTS:Both treatment and control groups showed a reduction in depressive symptoms and improved daily living abilities after treatment.However,the treatment group demonstrated significantly better outcomes compared to the control group.Furthermore,the levels of dopamine and serotonin in the serum increased in both groups after 8 weeks of treatment,while the treatment group exhibited superior results.CONCLUSIONS:This TCM showed promising results in reducing depressive symptoms and improving daily abilities in patients with TNBC and comorbid depression,which was verified by the increase in serum levels of dopamine and serotonin,suggesting the potential involvement of these neurotransmitters in the therapeutic effects of this TCM.展开更多
With the rapid development of flexible wearable electronic products,their application fields and demands are increasing,posing new challenges to flexible conductive materials.This paper selected flexible polydimethyls...With the rapid development of flexible wearable electronic products,their application fields and demands are increasing,posing new challenges to flexible conductive materials.This paper selected flexible polydimethylsiloxane(PDMS)as the substrate.In order to enhance the adhesion between the substrate and the metal coating,dopamine and silanization were used to co-modify its surface.A conductive layer of metallic copper is deposited on its surface using an inexpensive,easy-to-use electroless plating technique.By optimizing the process conditions,it is found that a uniform copper layer of about 0.6μm can be formed on the surface of the substrate by electroless plating at a constant temperature of 45℃ for 30 min with a conductivity of 5556 S/cm.The relative resistance changes under different deformation conditions,and the I-V curve of the LED circuit is not very different.Therefore,this paper prepared a flexible conductor with excellent electrical conductivity,high coating adhesion,and good electrical stability under large-scale deformation.展开更多
BACKGROUND Schizophrenia is a complex psychiatric disorder with significant functional impairment.Although olanzapine is effective in treating positive symptoms,its efficacy against negative symptoms and cognitive def...BACKGROUND Schizophrenia is a complex psychiatric disorder with significant functional impairment.Although olanzapine is effective in treating positive symptoms,its efficacy against negative symptoms and cognitive deficits is limited.Yueju pill,a traditional Chinese herbal formula,has shown potential in improving these domains,but its mechanisms remain largely unexplored.AIM To evaluate the therapeutic efficacy and underlying mechanisms of Yueju pill combined with olanzapine in treating schizophrenia.METHODS Ninety-seven patients with schizophrenia were randomly assigned to an intervention group(n=48)receiving olanzapine and Yueju pill,or a control group(n=49)receiving olanzapine and a placebo for 8 weeks.Symptom severity was assessed using the positive and negative syndrome scale,the scale for the assessment of negative symptoms,and cognitive and social function scales.Serum levels of brain-derived neurotrophic factor(BDNF),dopamine(DA),and serotonin(5-HT)were measured.Network pharmacology analysis identified key chemical components and target genes involved in the treatment response.RESULTS The intervention group demonstrated a significantly higher overall efficacy rate(93.75%)compared to the control group(73.47%,P<0.05).Improvements in psychiatric symptoms,cognitive function,and social performance were more pronounced in the intervention group.Additionally,serum levels of BDNF,DA,and 5-HT were significantly higher in the intervention group(P<0.05).Network pharmacology analysis revealed quercetin as a key component,modulating genes such as CHRM1,GSK3B,and KCNH2,crucial in DA signaling.CONCLUSION Yueju pill,when combined with olanzapine,significantly improves clinical outcomes in schizophrenia patients,with safety comparable to olanzapine alone.展开更多
The complexity of living environment system demands higher requirements for the sensitivity and selectivity of the probe.Therefore,it is of great importance to develop a universal strategy for highperformance probe op...The complexity of living environment system demands higher requirements for the sensitivity and selectivity of the probe.Therefore,it is of great importance to develop a universal strategy for highperformance probe optimization.Herein,we propose a novel“Enrichment-enhanced Detection”strategy and use carbon dots-dopamine detection system as a representative model to evaluate its feasibility.The composite probe carbon dots (CDs)-encapsulated in glycol-chitosan (GC)(i.e.,CDs@GC) was obtained by simply mixing GC and CDs through noncovalent interactions,including electrostatic interactions and hydrogen bonding.Dopamine (DA) could be detected through internal filter effect (IFE)-induced quenching of CDs.In the case of CDs@GC,noncovalent interactions (electrostatic interactions) between GC and the formed quinone (oxide of DA) could selectively extract and enrich the local concentration of DA,thus effectively improving the sensitivity and selectivity of the sensing system.The nanosensor had a low detection limit of 3.7 nmol/L,which was a 12-fold sensitivity improvement compared to the bare CDs probes with similar fluorescent profiles,proving the feasibility of the“Enrichment-enhanced Detection”strategy.Further,to examine this theory in real case,we designed a highly portable sensing platform to realize visual determination of DA.Overall,our work introduces a new strategy for accurately detecting DA and provides valuable insights for the universal design and optimization of superior nanoprobes.展开更多
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
基金supported by the DGIST start-up funds from the Ministry of Science and ICT(2024010330)a National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)(No.RS-2024-00351442)(to TWK).
文摘Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
基金supported by the National Natural Science Foundation of China,Nos.82304990(to NY),81973748(to JC),82174278(to JC)the National Key R&D Program of China,No.2023YFE0209500(to JC)+4 种基金China Postdoctoral Science Foundation,No.2023M732380(to NY)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,No.202102010014(to JC)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University,No.201911(to JC)National Innovation and Entrepreneurship Training Program for Undergraduates in China,No.202310559128(to NY and QM)Innovation and Entrepreneurship Training Program for Undergraduates at Jinan University,Nos.CX24380,CX24381(both to NY and QM)。
文摘Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.
文摘Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by an under-40 grant from the Italian Association for Alzheimer’s Research [AIRALZH AGYR2021]the Strategic University Projects–Young Researcher Independence grant [YRG2021] from the Università Campus Bio-Medico di Roma (Rome, Italy)(to LLB)+1 种基金Italian Ministry of Health [Research Grant:GR-2019-12370446]the American Alzheimer’s Association [AARG-22-922961](to PK)。
文摘Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.
文摘Dopamine,often termed the"feel-good"neurotransmitter,plays a crucial role in myriad physiological and psychological brain processes.While dopamine is primarily associated with pleasure,reward,and motivation,its effects can be quite complex;and this complexity is further compounded when examining how dopamine functions in typical versus disease-affected neural circuits.In pa rticula r,epilepsy,characte rized by heightened brain excitability,is linked to cognitive dysfunction,and dopamine is implicated in elements of both its pathology and treatment.Neuroscience has been successful in describing the synaptic abnormalities believed to contribute to memory issues in epilepsy,aiding in the search for effective therapies for what persists as a major medical issue.
基金supported by the National Research Foundation of Korea(RS-2023-00245298)the Korea Healthcare Technology R&D(HI21C1795)grants,funded by the Korean government(to SRK).
文摘A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.
基金supported by the National Natural Science Foundation of China,No.82071254(to WZ).
文摘Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
基金supported by the Young Talent Innovation Team Support Project from Zhengzhou University(No.32213280)the scientific research program of innovation platform in State Tobacco Monopoly Administrationthe State Key Program of National Natural Science Foundation of China(Grant No.32130083).
文摘Dopamine(DA)is a vital neurotransmitter,and accurate detection of its concentration is critical for both clinical diagnos-tics and neuroscience research.Due to its electrochemical activity,DA is commonly detected using electrochemical methods,which are favored for their simplicity,fast response time,and suitability for in vivo analysis.In this work,a highly sensitive DA electrochemical sensor was developed using an Au@MoS_(2)composite,created by modifying molybdenum disulfide(MoS_(2))nanosheets with gold nanoparticles through HAuCl_(4) reduction,and it was aimed at enhancing DA adsorption and improving detection performance.Scanning Electron Microscopy(SEM),transmission electron microscopy(TEM),Energy Dispersive Spectroscopy(EDS),X-ray photoelectron spectroscopy(XPS)and X-ray Diffraction(XRD)confirmed the suc-cessful synthesis of Au@MoS_(2)and the uniform distribution of gold nanoparticles across the MoS_(2)nanosheets.Then,the electrochemical characterization demonstrated that the Au@MoS_(2)/GCE exhibited distinct oxidation peaks in a 10μmol·L^(-1)DA solution,with significantly enhanced electrochemical activity compared to both unmodified GCE and pristine MoS_(2).Furthermore,differential pulse voltammetry(DPV)further revealed a strong linear relationship between DA concentration and the current response in the range of 800 nmol·L^(-1)to 10μmol·L^(-1),with a low detection limit(LOD)of 78.9 nmol·L^(-1)(S/N=3).Additionally,the sensor showed excellent selectivity against other interfering substances.Moreover,the laser-induced Au@MoS_(2)(LIAu@MoS_(2)),with its abundance of negatively charged surface defects,enabled the ultra-sensitive detection of the ultra-low concentrations of DA.In conclusion,the successfully fabricated Au@MoS_(2)based sensor offers advantages such as low cost,ease of operation,and scalability,making it a promising candidate for biosensing applications due to its enhanced DA detection capabilities.
文摘BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as the arms,abdomen,face,neck,head,and genital area.There are only a few reports of the RLS variant affecting the head.AIM To assess the epidemiological,clinical,and other aspects of the RLS variant affecting the head.METHODS We conducted a retrospective study of 17 adult patients(>18 years)who met the RLS criteria and simultaneously experienced RLS-like symptoms in the head.RESULTS The median age at which symptoms appeared was 41.6 years.Males and females were equally affected(1.1:1).All 17 patients had uncomfortable sensations in the lower legs.Insomnia or disturbed sleep was the most common comorbidity(n=16,88.2%).However,headache was the most common presenting or primary symptom(n=10,70.5%).Dizziness or an abnormal sensation in the head was the second most common presenting symptom(5 patients,29.4%).Other presenting features were leg pain,backache,and generalized body pain.All patients responded favorably to dopaminergic medications.CONCLUSION If RLS-related unpleasant sensations and pain are felt in the head,they may be misinterpreted as headache,dizziness,or psychosomatic symptoms.RLS and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.
基金partially supported by the National Institutes of Health(NIH)grants DA056213(to Alexander K.Zinsmaier),DA053388(to Eric J.Nestler),DA023206(to Yan Dong),DA060868(to Yan Dong),and DA040620(to Eric J.Nestler and Yan Dong)。
文摘Understanding the cellular mechanisms of drug addiction remains a key task in current brain research.While neuron-based mechanisms have been extensively explored over the past three decades,recent evidence indicates a critical involvement of astrocytes,the main type of non-neuronal cells in the brain.In response to extracellular stimuli,astrocytes modulate the activity of neurons,synaptic transmission,and neural network properties,collectively influencing brain function.G protein-coupled receptors(GPCRs)expressed on astrocyte surfaces respond to neuron-and environment-derived ligands by activating or inhibiting astrocytic signaling,which in turn regulates adjacent neurons and their circuitry.In this review,we focus on the dopamine D1 receptors(D1R)and metabotropic glutamate receptor 5(mGLUR5 or GRM5)—two GPCRs that have been critically implicated in the acquisition and maintenance of addiction-related behaviors.Positioned as an introductory-level review,this article briefly discusses astrocyte biology,outlines earlier discoveries about the role of astrocytes in substance-use disorders(SUDs),and provides detailed discussion about astrocytic D1Rs and mGLUR5s in regulating synapse and network functions in the nucleus accumbens(NAc)—a brain region that mediates addictionrelated emotional and motivational responses.This review serves as a stepping stone for readers of Engineering to explore links between astrocytic GPCRs and drug addiction and other psychiatric disorders.
文摘Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief,they do not halt disease progression.In recent years,significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease,including alpha-synuclein aggregation,mitochondrial dysfunction,neuroinflammation,and lysosomal impairment.These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression.This review comprehensively explores emerging approaches such as gene and cell therapies,LRRK2 inhibitors,alpha-synuclein immunotherapy,and gut microbiota modulation.We also discuss the therapeutic potential of mitophagy activators,digital biomarkers,and neuromodulation techniques.Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms.Special attention is given to recent clinical trials(2023–2025),translational gaps,and the potential of personalized medicine in Parkinson’s disease management.Furthermore,we examine the integration of multi-omics data and digital tools in advancing precision therapeutics.Overall,this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.
文摘OBJECTIVE:To evaluate the therapeutic effect of a selfformulated Traditional Chinese Medicine(TCM),Shugan Jieyu San(疏肝解郁散),on improvement of liver function and depression alleviation in the patients with triple negative breast cancer(TNBC).METHODS:A total of 60 patients diagnosed with TNBC and depression were enrolled and randomly assigned to either the control group(receiving routine tumor treatment and duloxetine)or the treatment group(receiving the TCM in addition to routine treatment).RESULTS:Both treatment and control groups showed a reduction in depressive symptoms and improved daily living abilities after treatment.However,the treatment group demonstrated significantly better outcomes compared to the control group.Furthermore,the levels of dopamine and serotonin in the serum increased in both groups after 8 weeks of treatment,while the treatment group exhibited superior results.CONCLUSIONS:This TCM showed promising results in reducing depressive symptoms and improving daily abilities in patients with TNBC and comorbid depression,which was verified by the increase in serum levels of dopamine and serotonin,suggesting the potential involvement of these neurotransmitters in the therapeutic effects of this TCM.
基金supported by the Natural Science Foundation of Hunan Province(Grant No.2021JJ40463).
文摘With the rapid development of flexible wearable electronic products,their application fields and demands are increasing,posing new challenges to flexible conductive materials.This paper selected flexible polydimethylsiloxane(PDMS)as the substrate.In order to enhance the adhesion between the substrate and the metal coating,dopamine and silanization were used to co-modify its surface.A conductive layer of metallic copper is deposited on its surface using an inexpensive,easy-to-use electroless plating technique.By optimizing the process conditions,it is found that a uniform copper layer of about 0.6μm can be formed on the surface of the substrate by electroless plating at a constant temperature of 45℃ for 30 min with a conductivity of 5556 S/cm.The relative resistance changes under different deformation conditions,and the I-V curve of the LED circuit is not very different.Therefore,this paper prepared a flexible conductor with excellent electrical conductivity,high coating adhesion,and good electrical stability under large-scale deformation.
文摘BACKGROUND Schizophrenia is a complex psychiatric disorder with significant functional impairment.Although olanzapine is effective in treating positive symptoms,its efficacy against negative symptoms and cognitive deficits is limited.Yueju pill,a traditional Chinese herbal formula,has shown potential in improving these domains,but its mechanisms remain largely unexplored.AIM To evaluate the therapeutic efficacy and underlying mechanisms of Yueju pill combined with olanzapine in treating schizophrenia.METHODS Ninety-seven patients with schizophrenia were randomly assigned to an intervention group(n=48)receiving olanzapine and Yueju pill,or a control group(n=49)receiving olanzapine and a placebo for 8 weeks.Symptom severity was assessed using the positive and negative syndrome scale,the scale for the assessment of negative symptoms,and cognitive and social function scales.Serum levels of brain-derived neurotrophic factor(BDNF),dopamine(DA),and serotonin(5-HT)were measured.Network pharmacology analysis identified key chemical components and target genes involved in the treatment response.RESULTS The intervention group demonstrated a significantly higher overall efficacy rate(93.75%)compared to the control group(73.47%,P<0.05).Improvements in psychiatric symptoms,cognitive function,and social performance were more pronounced in the intervention group.Additionally,serum levels of BDNF,DA,and 5-HT were significantly higher in the intervention group(P<0.05).Network pharmacology analysis revealed quercetin as a key component,modulating genes such as CHRM1,GSK3B,and KCNH2,crucial in DA signaling.CONCLUSION Yueju pill,when combined with olanzapine,significantly improves clinical outcomes in schizophrenia patients,with safety comparable to olanzapine alone.
基金the financial support from the National Natural Science Foundation of China(No.21904007)the Fundamental Research Funds for the Central Universities(China,No.2412022QD008)+1 种基金the Jilin Provincial Department of Education(China),the Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province(China)the Analysis and Testing Center of Northeast Normal University(China)。
文摘The complexity of living environment system demands higher requirements for the sensitivity and selectivity of the probe.Therefore,it is of great importance to develop a universal strategy for highperformance probe optimization.Herein,we propose a novel“Enrichment-enhanced Detection”strategy and use carbon dots-dopamine detection system as a representative model to evaluate its feasibility.The composite probe carbon dots (CDs)-encapsulated in glycol-chitosan (GC)(i.e.,CDs@GC) was obtained by simply mixing GC and CDs through noncovalent interactions,including electrostatic interactions and hydrogen bonding.Dopamine (DA) could be detected through internal filter effect (IFE)-induced quenching of CDs.In the case of CDs@GC,noncovalent interactions (electrostatic interactions) between GC and the formed quinone (oxide of DA) could selectively extract and enrich the local concentration of DA,thus effectively improving the sensitivity and selectivity of the sensing system.The nanosensor had a low detection limit of 3.7 nmol/L,which was a 12-fold sensitivity improvement compared to the bare CDs probes with similar fluorescent profiles,proving the feasibility of the“Enrichment-enhanced Detection”strategy.Further,to examine this theory in real case,we designed a highly portable sensing platform to realize visual determination of DA.Overall,our work introduces a new strategy for accurately detecting DA and provides valuable insights for the universal design and optimization of superior nanoprobes.
