RESUMO
The anterior cingulate cortex (ACC) is a key cortical region for pain perception and emotion. Different forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), have been reported in the ACC. Synaptic tagging of LTP plays an important role in hippocampus-related associative memory. In this study, we demonstrate that synaptic tagging of LTD is detected in the ACC of adult male and female mice. This form of tagged LTD requires the activation of metabotropic glutamate receptor subtype 1 (mGluR1). The induction of tagged LTD is time-related with the strongest tagged LTD appearing when the interval between two independent stimuli is 30 min. Inhibitors of mGluR1 blocked the induction of tagged LTD, however, blocking N-methyl-d-aspartate (NMDA) receptors did not affect the induction of tagged LTD. Nimodipine, an inhibitor of L-type voltage-gated calcium channels (VGCCs), also blocked tagged LTD. In an animal model of amputation, we found that tagged LTD was either reduced or completely blocked. Together with our previous report of tagged LTP in the ACC, this study strongly suggests that excitatory synapses in the adult ACC are highly plastic. The biphasic tagging of synaptic transmission provides a new form of heterosynaptic plasticity in the ACC which has functional and pathophysiological significance in phantom pain.Significance Statement The anterior cingulate cortex (ACC) is a key cortical region for pain perception and chronic pain. Previous studies have reported a novel form of long-term heterosynaptic potentiation in the ACC. In this study, we discovered a long-term depression (LTD) form of synaptic tagging in the ACC of adult male and female mice. This form of tagged LTD requires the activation of metabotropic glutamate receptors (mGluRs). In an animal model of amputation, tagged LTD is reduced or completely blocked. Our results strongly suggest that brain cortices of adult mice are highly plastic and show biphasic tagging of plasticity. These findings of tagged LTD may provide a new direction for future treatment of phantom pain and amputation-related emotional disorders.
RESUMO
In this work, a novel polyaniline-modified magnetic microporous organic network (MMON-PANI) composite was fabricated for effective magnetic solid phase extraction (MSPE) of five typical nonsteroidal anti-inflammatory drugs (NSAIDs) from animal-derived food samples before high performance liquid chromatography (HPLC) detection. The core-shell sea urchin shaped MMON-PANI integrates the merits of Fe3O4, MON, and PANI, exhibiting large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites to NSAIDs. Convenient and effective extraction of trace NSAIDs from chicken, beef and pork samples is realized on MMON-PANI via the synergetic π-π, hydrogen bonding, hydrophobic, and electrostatic interactions. Under optimal conditions, the MMON-PANI-MSPE-HPLC-UV method exhibits wide linear ranges (0.2-1000 µg L-1), low limits of detection (0.07-1.7 µg L-1), good precisions (intraday and inter-day RSDs < 5.4 %, n = 3), large enrichment factors (98.6-99.9), and less adsorbent consumption (3 mg). The extraction mechanism and selectivity of MMON-PANI are also evaluated in detail. This work proves the incorporation of PANI onto MMON is an efficient way to promote NSAIDs enrichment and provides a new strategy to synthesize multifunctional MON-based composites in sample pretreatment.
Assuntos
Compostos de Anilina , Anti-Inflamatórios não Esteroides , Extração em Fase Sólida , Compostos de Anilina/química , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Suínos , Galinhas , Bovinos , Adsorção , Carne/análise , Porosidade , Reprodutibilidade dos TestesRESUMO
Synaptic plasticity is a key cellular model for learning, memory and chronic pain. Most previous studies were carried out in rats and mice, and less is known about synaptic plasticity in non-human primates. In the present study, we used integrative experimental approaches to study long-term potentiation (LTP) in the anterior cingulate cortex (ACC) of adult tree shrews. We found that glutamate is the major excitatory transmitter and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid (AMPA) receptors mediate postsynaptic responses. LTP in tree shrews was greater than that in adult mice and lasted for at least 5 h. N-methyl-d-aspartic acid (NMDA) receptors, Ca2+ influx and adenylyl cyclase 1 (AC1) contributed to tree shrew LTP. Our results suggest that LTP is a major form of synaptic plasticity in the ACC of primate-like animals. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
Assuntos
Giro do Cíngulo , Potenciação de Longa Duração , Receptores de AMPA , Receptores de N-Metil-D-Aspartato , Tupaiidae , Animais , Potenciação de Longa Duração/fisiologia , Giro do Cíngulo/fisiologia , Tupaiidae/fisiologia , Camundongos , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de AMPA/metabolismo , Adenilil Ciclases/metabolismo , Ácido Glutâmico/metabolismo , MasculinoRESUMO
Precipitation in the plum rain period accounts for 40%-50% of annual precipitation in the monsoon region. To clarify the temporal variability of the isotopic composition of precipitation during the plum rain period from event to interannual time scale and identify the influencing factors, we analyzed the isotopic composition of precipitation and its influencing factors in Nanjing from 2015 to 2022. By using the Hybrid Single-particle Lagran-gian Integrated Trajectory (HYSPLIT) model with specific humidity analysis, we investigated the water vapor source and influencing factors. The results showed that 1) the isotopic abundance of atmospheric precipitation was depleted in the summer and enriched in winter. dx was lower in summer and higher in winter. The isotopic abundance of precipitation from the plum rain was depleted compared to mean value of the whole-year. 2) There was no significant correlation between δ2H and δ18O of the plum rain (precipitation) with local meteorological factors. However, dx was lower in light rain, reflecting the effect of sub-cloud evaporation. The average dx was higher during plum rain period in years with more total plum rain precipitation. 3) The low-latitude South China Sea and the western Pacific Ocean source area provided water vapor for the plum rain. The shift of moisture source region led to abrupt changes in precipitation isotopes. Our results could provide data support for studies on precipitation isotopes in the monsoon region, as well as a reference point for further understanding the precipitation mechanism of the plum rain and stu-dying the seasonal variability of atmospheric circulation in the East Asian monsoon region.
Assuntos
Chuva , Estações do Ano , Chuva/química , China , Isótopos de Oxigênio/análise , Monitoramento Ambiental/métodos , Deutério/análise , Isótopos/análise , Prunus domestica/química , Prunus domestica/crescimento & desenvolvimentoRESUMO
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits and repetitive behaviors. A study of autistic human subjects has identified RFWD2 as a susceptibility gene for autism, and autistic patients have 3 copies of the RFWD2 gene. The role of RFWD2 as an E3 ligase in neuronal functions, and its contribution to the pathophysiology of ASD, remain unknown. We generated RFWD2 knockin mice to model the human autistic condition of high gene dosage of RFWD2. We found that heterozygous knockin (Rfwd2+/-) male mice exhibited the core symptoms of autism. Rfwd2+/- male mice showed deficits in social interaction and communication, increased repetitive and anxiety-like behavior, and spatial memory deficits, whereas Rfwd2+/- female mice showed subtle deficits in social communication and spatial memory but were normal in anxiety-like, repetitive, and social behaviors. These autistic-like behaviors in males were accompanied by a reduction in dendritic spine density and abnormal synaptic function on layer II/III pyramidal neurons in the prelimbic area of the medial prefrontal cortex (mPFC), as well as decreased expression of synaptic proteins. Impaired social behaviors in Rfwd2+/- male mice were rescued by the expression of ETV5, one of the major substrates of RFWD2, in the mPFC. These findings indicate an important role of RFWD2 in the pathogenesis of autism.
RESUMO
Adenylyl cyclase 1 (AC1) is a selective subtype of ACs, which is selectively expressed in neurons. The activation of AC1 is activity-dependent, and AC1 plays an important role in cortical excitation that contributes to chronic pain and related emotional disorders. Previous studies have reported that human-used NB001 (hNB001, a selective AC1 inhibitor) produced analgesic effects in different animal models of chronic pain. However, the potential effects of hNB001 on learning and memory have been less investigated. In the present study, we found that hNB001 affected neither the induction nor the expression of trace fear, but selectively enhanced the relearning ability during the extinction in aged mice. By contrast, the same application of hNB001 did not affect recent, remote auditory fear memory, or remote fear extinction in either adult or aged mice. Furthermore, a single or consecutive 30-day oral administration of hNB001 did not affect acute nociceptive response, motor function, or anxiety-like behavior in either adult or aged mice. Our results are consistent with previous findings that inhibition of AC1 did not affect general sensory, emotional, and motor functions in adult mice, and provide strong evidence that inhibiting the activity of AC1 may be beneficial for certain forms of learning and memory in aged mice.
Assuntos
Dor Crônica , Medo , Humanos , Camundongos , Animais , Medo/fisiologia , Extinção Psicológica , Adenilil Ciclases/metabolismo , Neurônios/metabolismoRESUMO
Cephalosporins (CEFs) are a class of widely used toxic antibiotics. Development of a rapid and sensitive method for detecting trace CEF residues in food samples is still challenging. Herein, we report preparation of an amide and carboxyl groups dual-functionalized core-shelled magnetic microporous organic network MMON-COOH-2CONH for efficient magnetic solid-phase extraction (MSPE) of CEFs from milk powder samples. Under optimal conditions, the established MMON-COOH-2CONH-MSPE-HPLC-UV method owns wide linear range (3-10000 µg kg-1), low limits of detection (1-3 µg kg-1), large enrichment factors (93.9-99.4), low adsorbent consumption (3 mg), and short extraction time (6 min). Synergistic extraction mechanisms of ionic bonding, hydrogen bonding, π-π, and hydrophobic interactions were elucidated by both theoretical density functional theory calculations and experimental data. This study confirms that preparation of dual-functionalized MMONs and introduction of ionic groups are feasible to promote MMONs application in sample pretreatment.
Assuntos
Amidas , Cefalosporinas , Magnetismo , Fenômenos Físicos , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão , Fenômenos Magnéticos , Limite de DetecçãoRESUMO
Human brain microvascular endothelial cells (HBMVECs) and microglia play critical roles in regulating cerebral homeostasis during ischemic stroke. However, the role of HBMVECs-derived exosomes in microglia polarization after stroke remains unknown. We isolated exosomes (Exos) from oxygen glucose deprivation (OGD)-exposed HBMVECs, before added them into microglia. Microglia polarization markers were tested using RT-qPCR or flow cytometry. Inflammatory cytokines were measured with ELISA. Endothelial cell damage was assessed by cell viability, apoptosis, apoptosis-related proteins, oxidative stress, and angiogenic activity using CCK-8, flow cytometry, western blot, ELISA, and endothelial tube formation assay, respectively. We also established middle cerebral artery occlusion (MCAO) mice model to examine the function of circ_0000495 on stroke in vivo. Our study found that HBMVECs-Exos reduced M2 markers (IL-10, CD163, and CD206), increased M1 markers (TNF-α, IL-1ß, and IL-12), CD86-positive cells, and inflammatory cytokines (TNF-α and IL-1ß), indicating the promotion of microglial M1-polarization. Microglial M1-polarization induced by HBMVECs-Exos reduced viability and promoted apoptosis and oxidative stress, revealing the aggravation of endothelial cell damage. However, circ_0000495 silencing inhibited HBMVECs-Exos-induced alterations. Mechanistically, circ_0000495 adsorbed miR-579-3p to upregulate toll-like receptor 4 (TLR4) in microglia; miR-579-3p suppressed HBMVECs-Exos-induced alterations via declining TLR4; furthermore, Yin Yang 1 (YY1) transcriptionally activated circ_0000495 in HBMVECs. Importantly, circ_0000495 aggravated ischemic brain injury in vivo via activating TLR4/nuclear factor-κB (NF-κB) pathway. Collectively, OGD-treated HBMVECs-Exos transmitted circ_0000495 to regulate miR-579-3p/TLR4/NF-κB axis in microglia, thereby facilitating microglial M1-polarization and endothelial cell damage.
Assuntos
Exossomos , MicroRNAs , Acidente Vascular Cerebral , Animais , Camundongos , Humanos , Células Endoteliais , Microglia , Receptor 4 Toll-Like/genética , NF-kappa B , Fator de Necrose Tumoral alfa , Encéfalo , Hipóxia , Oxigênio , Citocinas , MicroRNAs/genéticaRESUMO
The ventrolateral orbital cortex (VLO) is identified as an integral component of the endogenous analgesic system comprising a spinal cord - thalamic nucleus submedius - VLO - periaqueductal gray (PAG) - spinal cord loop. The present study investigates the effects of 5-HT5A receptor activation in the VLO on allodynia induced by spared nerve injury and formalin-evoked flinching behavior and spinal c-Fos expression in male SD rats, and further examines whether GABAergic modulation is involved in the effects evoked by VLO 5-HT5A receptor activation. We found an upregulation of 5-HT5A receptor expression in the VLO during neuropathic and inflammatory pain states. Microinjection of the non-selective 5-HT5A receptor agonist 5-CT into the VLO dose dependently alleviated allodynia, and flinching behavior and spinal c-Fos expression, which were blocked by the selective 5-HT5A receptor antagonist SB-699551. Moreover, application of the GABAA receptor antagonist bicuculline in the VLO augmented the analgesic effects induced by 5-CT in neuropathic and inflammatory pain states, whereas the GABAA receptor agonist muscimol attenuated these analgesic effects. Additionally, the 5-HT5A receptors were found to be colocalized with GABAergic neurons in the VLO. These results provide new evidence for the involvement of central 5-HT5A receptors in the VLO in modulation of neuropathic and inflammatory pain and support the hypothesis that activation of 5-HT5A receptors may inhibit the inhibitory effect of GABAergic interneurons on output neurons projecting to the PAG (GABAergic disinhibitory mechanisms), consequently activating the brainstem descending inhibitory system that depresses nociceptive transmission at the spinal cord level.
Assuntos
Hiperalgesia , Doenças do Sistema Nervoso Periférico , Ratos , Masculino , Animais , Hiperalgesia/metabolismo , Serotonina/metabolismo , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Medição da Dor , Dor/tratamento farmacológico , Dor/metabolismo , Analgésicos/farmacologia , Doenças do Sistema Nervoso Periférico/metabolismo , Córtex Pré-FrontalRESUMO
The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this cortical-cortical connection and its functional importance. Here we investigate the cortical-cortical connection between the bilateral anterior cingulate cortex (ACC) by using the classic electrophysiological and optogenetic approach. We find that there is a direct synaptic projection from one side ACC to the contralateral ACC. Glutamate is the major excitatory transmitter for bilateral ACC connection, including projections to pyramidal cells in superficial (II/III) and deep (V/VI) layers of the ACC. Both AMPA and kainate receptors contribute to synaptic transmission. Repetitive stimulation of the projection also evoked postsynaptic Ca2+ influx in contralateral ACC pyramidal neurons. Behaviorally, light activation of the ACC-ACC connection facilitated behavioral withdrawal responses to mechanical stimuli and noxious heat. In an animal model of neuropathic pain, light inhibitory of ACC-ACC connection reduces both primary and secondary hyperalgesia. Our findings provide strong direct evidence for the excitatory or facilitatory contribution of ACC-ACC connection to pain perception, and this mechanism may provide therapeutic targets for future treatment of chronic pain and related emotional disorders.
Assuntos
Giro do Cíngulo , Neuralgia , Camundongos , Animais , Giro do Cíngulo/fisiologia , Transmissão Sináptica/fisiologia , Células Piramidais , Ácido GlutâmicoRESUMO
Implementation of clinical practice guidelines (CPG) is a complex and challenging task. Computer technology, including artificial intelligence (AI), has been explored to promote the CPG implementation. This study has reviewed the main domains where computer technology and AI has been applied to CPG implementation. PubMed, Embase, Web of science, the Cochrane Library, China National Knowledge Infrastructure database, WanFang DATA, VIP database, and China Biology Medicine disc database were searched from inception to December 2021. Studies involving the utilization of computer technology and AI to promote the implementation of CPGs were eligible for review. A total of 10429 published articles were identified, 117 met the inclusion criteria. 21 (17.9%) focused on the utilization of AI techniques to classify or extract the relative content of CPGs, such as recommendation sentence, condition-action sentences. 47 (40.2%) focused on the utilization of computer technology to represent guideline knowledge to make it understandable by computer. 15 (12.8%) focused on the utilization of AI techniques to verify the relative content of CPGs, such as conciliation of multiple single-disease guidelines for comorbid patients. 34 (29.1%) focused on the utilization of AI techniques to integrate guideline knowledge into different resources, such as clinical decision support systems. We conclude that the application of computer technology and AI to CPG implementation mainly concentrated on the guideline content classification and extraction, guideline knowledge representation, guideline knowledge verification, and guideline knowledge integration. The AI methods used for guideline content classification and extraction were pattern-based algorithm and machine learning. In guideline knowledge representation, guideline knowledge verification, and guideline knowledge integration, computer techniques of knowledge representation were the most used.
Assuntos
Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Humanos , Algoritmos , Computadores , TecnologiaRESUMO
With the implementation of ecological protection and a high-quality development strategy in the Yellow River Basin, the environmental conditions around the Yellow River have attracted wide attention from scholars. In this study, the soil of drinking water sources(Heichi and Liuchi) in the typical suspended reach of the lower reaches of the Yellow River was selected as the research object. The geo-accumulation index and pollution load index were used to analyze the pollution characteristics of seven heavy metals(Cr, Ni, Cu, Zn, Cd, Pb, and As), and correlation analysis, principal component analysis, and absolute factor score-multiple linear regression(APCS-MLR) were employed to reveal the sources of soil heavy metals from both qualitative and quantitative perspectives. The health risk assessment model recommended by the United States Environmental Protection Agency(USEPA) was used to analyze the impact of soil heavy metals on human health, and the contribution rate of pollution sources to health risks was analyzed by combining the APCS-MLR model. The results showed that the average values of ω(Cr), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the soil around the water source were 60.27, 30.00, 35.14, 77.75, 0.38, 21.74, and 9.70 mg·kg-1, respectively. Except for As, the contents of Cr, Ni, Cu, Zn, Cd, and Pb were higher than the background values of soil elements in the fluvo-aquic soil area of the lower Yellow River, whereas the contents of Cu and Zn in the soil around Liuchi were significantly higher than those in Heichi. Both the geo-accumulation index and the single-factor index showed that the black pond and the willow pond were slightly polluted by heavy metals, and Cd was the main pollution factor. The pollution load index model showed that the number of non-polluted and mildly polluted samples in the study area accounted for 5% and 95% of the total samples, respectively, indicating that the study area was at a mild pollution level. The source apportionment showed that Cr, Ni, Cu, and As were mainly affected by parent materials. The analysis results of the APCS-MLR model showed that the soil pollutants in the study area were mainly from natural sources, traffic sources, agricultural sources, and unknown sources, and their contribution rates were 42.95%, 23.39%, 16.95%, and 16.71%, respectively. The health risk assessment showed that As was the main non-carcinogenic factor, and Ni was the main carcinogenic factor. The non-carcinogenic risk of heavy metals to adults and children was negligible, and there was a tolerable carcinogenic risk to the human body. For both adults and children, the non-carcinogenic and carcinogenic risk contribution rates of the four pollution sources were:natural sources>unknown sources>traffic sources>agricultural sources, among which natural sources contributed the most to non-carcinogenic and carcinogenic risks. Therefore, it is of great significance to study the characteristics, sources, and effects of soil pollution on human health around the water source area of the suspended reach of the lower reaches of the Yellow River, which is of great significance for the protection of water sources and provides theoretical support for the high-quality development of the ecological environment along the Yellow River.
Assuntos
Água Potável , Metais Pesados , Poluentes do Solo , Criança , Adulto , Humanos , Solo , Água Potável/análise , Monitoramento Ambiental , Rios , Cádmio/análise , Chumbo/análise , Metais Pesados/análise , Medição de Risco , Poluentes do Solo/análise , Carcinógenos/análise , ChinaRESUMO
Ulcerative colitis (UC) is the most common inflammatory bowel disease (IBD); it is incurable, and the treatment is expensive. Trans-anethole (TA), the main component of fennel, exhibits various biological activities. An increasing number of studies have demonstrated the efficacy of herbal active ingredients in the treatment of UC. This study aimed to investigate the effect and mechanism of TA in UC. In this study, we have experimented on mice with dextran sulfate sodium salt (DSS)-induced UC. The TA group was gavaged with 62.5 mg/kg TA by gavage once daily on days 8-14. To observe the effect of TA on the colon tissue, various investigations were performed, including western blot and immunohistochemistry for intestinal barrier protein expression, TUNEL staining for apoptosis, western blot, and ELISA for inflammation level, flow cytometry for Th17/Treg, LC-MS for blood bile acid content, GC-MS for blood fatty acid content, and 16s RNA for intestinal contents. TA alleviated weight loss in mice with UC; increased colon length; alleviated intestinal mucosal damage; upregulated claudin-1, occludin, and ZO-1 protein expression levels; reduced inflammatory factors in the colon and serum; and alleviated apoptosis. TA reduced fatty acid and bile acid levels by inhibiting colony abundance and reducing Th17/Treg cell differentiation in the colon. We found that TA alleviates DSS-induced UC by remodeling the intestinal flora to regulate immunity and bile acid metabolism.
Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo/metabolismo , Ácidos e Sais Biliares/metabolismo , Ácidos Graxos/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colite/metabolismoRESUMO
With open spaces and good ecological environments, urban parks have become the first choice for the leisure and entertainment of many people. Therefore, the quality of park soil environments has gradually attracted the extensive attention of scholars. In this study, we take the Yellow River Cultural Park, a typical human disturbance area in the lower reaches of the Yellow River, as the research area to discuss the characteristics and sources of heavy metal pollution in the soil. Thirty-three soil surface samples were collected from the Yellow River Cultural Park, and the contents of seven heavy metals (Cr, Ni, Cu, Zn, Cd, Pb, and As) were determined using an inductively coupled plasma emission spectrometer (ICP-AES) and an inductively coupled plasma mass spectrometer (ICP-MS). The geo-accumulation index and geo-statistics method were used. Meanwhile, the absolute factor analysis-multiple linear regression (APCS-MLR) receptor model and positive matrix factorization (PMF) analysis model were employed to reveal the sources of soil heavy metals. The results showed that the average contents of heavy metals (Cd, Zn, Cu, Pb, and As) in the surface soil of the study area were 4.62, 1.78, 1.41, 1.08, and 1.03 times higher than the background values of soil elements in the tidal soil area of the lower reaches of the Yellow River, respectively. Except for Zn, the contents of other elements were lower than the corresponding values of soil elements in different regions along the Yellow River Basin. Among the seven heavy metal elements, the coefficients of variation of Cd and As were greater than 50%, showing obvious spatial variability. The decreasing trend of the accumulation index of the seven elements was Cd>Zn>Cu>Ni>Pb>As=Cr, and the element Cd belonged to the middle pollution category, which was obviously accumulated in the surface soil. The spatial distribution of heavy metals in the soil differed:the high contents of Cr, Cu, and Ni were distributed in the southwest and northeast, and the high-value areas of Cd and Pb were consistent with the areas of human activity intensity. The high-value areas of Zn and As were located in the center of lacustrine sediments. The combined results of the APCS-MLR and PMF models suggested that the first pollution source of soil heavy metal elements in the Yellow River Cultural Park could have been a natural source, the second pollution source may have been a transportation source, and the third source of pollution was judged as a mixed source. Human activities such as transportation sources and mixed sources were the main sources of heavy metal soil pollution, and Cr, Cu, and Ni were affected by natural factors. The contribution rates of APCS-MLR were 46.67%, 24.11%, 16.12%, and 13.10%, respectively, and the contribution rates of PMF were 35.50%, 35.48%, and 29.02%, respectively. This research can provide a basis for improving the ecological environment quality of the park and improving the health level of the population and can also provide support for the ecological environment risk management and comprehensive management along the Yellow River.
RESUMO
A zwitterionic magnetic microporous organic network (MMON-SO3H-NH2) with numerous amino and sulfonic acid ion-pare binding sites was designed and synthesized for efficient magnetic solid-phase extraction (MSPE) of fluoroquinolones (FQs) from meat samples. The core-shell MMON-SO3H-NH2 offered large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites for FQs. The density functional theory and independent gradient model evaluations confirmed hydrogen bonding, π-π and ion-pair interactions between MMON-SO3H-NH2 and FQs. Under the optimal conditions, the established MMON-SO3H-NH2-MSPE-HPLC-UV method gave wide linear range (0.15-1000 µg L-1), low limits of detection (0.05-4.5 µg L-1) and limits of quantitation (0.15-13 µg L-1), and high enrichment factors (82.1-99.6) using 3 mg of adsorbent. This work demonstrates that the preparation of zwitterionic MONs is an efficient way to promote the extraction performance of MONs for zwitterionic targets and provides an effective sample pretreatment method for enriching and monitoring FQs in complex food matrices.
Assuntos
Fluoroquinolonas , Extração em Fase Sólida , Fluoroquinolonas/análise , Cromatografia Líquida de Alta Pressão , Extração em Fase Sólida/métodos , Antibacterianos , Carne/análise , Fenômenos Magnéticos , Limite de DetecçãoRESUMO
Migraines are a common medical condition. From a basic science point of view, the central mechanism for migraine and headache is largely unknown. In the present study, we demonstrate that cortical excitatory transmission is significantly enhanced in the anterior cingulate cortex (ACC)-a brain region which is critical for pain perception. Biochemical studies found that the phosphorylation levels of both the NMDA receptor GluN2B and AMPA receptor GluA1 were enhanced in ACC of migraine rats. Both the presynaptic release of glutamate and postsynaptic responses of AMPA receptors and NMDA receptors were enhanced. Synaptic long-term potentiation (LTP) was occluded. Furthermore, behavioral anxiety and nociceptive responses were increased, which were reversed by application of AC1 inhibitor NB001 within ACC. Our results provide strong evidence that cortical LTPs contribute to migraine-related pain and anxiety. Drugs that inhibit cortical excitation such as NB001 may serve as potential medicines for treating migraine in the future.
RESUMO
Long-term potentiation (LTP) is a key cellular mechanism for learning and memory, and recent studies in the hippocampus found that LTP was impaired in aged animals. Previous studies of cortical LTP have focused primarily on the homosynaptic plasticity in adult mice, while fewer studies have looked at heterosynaptic plasticity-such as synaptic tagging in aged mice. In the present study, we investigated synaptic tagging in adult and middle-aged mice's anterior cingulate cortex (ACC) using the 64-channel multielectrode dish (MED64) recording system. We found that synaptic tagging was impaired in the ACC of middle-aged male mice as compared to adult mice. Both the network late-phase LTP (L-LTP) and the recruitment of inactive responses were reduced in the ACC of middle-aged male mice. Similar results were found in female middle-aged mice, indicating that there is no gender difference. Furthermore, bath application of brain-derived neurotrophic factor (BDNF) or systemic treatment with newly developed TrkB receptor agonists R13, was shown to rescue both synaptic tagging, and L-LTP, in middle-aged mice. To determine the distribution of synaptic LTP within the ACC, a new visualization method was developed to map the Spatio-temporal variation of LTP in the ACC. Our results provide strong evidence that cortical potentiation and synaptic tagging show an age-dependent reduction, and point to the TrkB receptor as a potential drug target for the treatment of memory decline.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Receptor trkB , Camundongos , Masculino , Feminino , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Receptor trkB/metabolismo , Giro do Cíngulo , Potenciação de Longa Duração/fisiologia , Hipocampo/metabolismoRESUMO
Background: The association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association. Materials and methods: In this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10-8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources. Results: The genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512-1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10-8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676-1.125, p = 0.292). Conclusion: Our MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.
RESUMO
Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.