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1.
Nat Chem Biol ; 20(5): 615-623, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38167916

RESUMO

Cellular context is crucial for understanding the complex and dynamic kinase functions in health and disease. Systematic dissection of kinase-mediated cellular processes requires rapid and precise stimulation ('pulse') of a kinase of interest, as well as global and in-depth characterization ('chase') of the perturbed proteome under living conditions. Here we developed an optogenetic 'pulse-chase' strategy, termed decaging kinase coupled proteomics (DeKinomics), for proteome-wide profiling of kinase-driven phosphorylation at second-timescale in living cells. We took advantage of the 'gain-of-function' feature of DeKinomics to identify direct kinase substrates and further portrayed the global phosphorylation of understudied receptor tyrosine kinases under native cellular settings. DeKinomics offered a general activation-based strategy to study kinase functions with high specificity and temporal resolution under living conditions.


Assuntos
Proteômica , Humanos , Fosforilação , Proteômica/métodos , Proteoma/metabolismo , Optogenética/métodos , Células HEK293
2.
Chemistry ; 30(2): e202302934, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37842799

RESUMO

It is highly challenging to activate the basal plane and minimize the π-π stacking of MoS2 sheets, thus enhancing its catalytic performance. Here, we display an approach for making well-dispersed MoS2 . By using the N-doped multi-walled carbon nanotubes (NMWCNTs) as an isolation unit, the aggregation of MoS2 sheets was effectively reduced, favoring the dispersion of Pt nanoparticles (noted as Pt/NMWCNTs-isolated-MoS2 ). Excellent bifunctional catalytic performance for methanol oxidation and oxygen reduction reaction (MOR/ORR) were demonstrated by the produced Pt/NMWCNTs-isolated-MoS2 . In comparison to Pt nanoparticles supported on MoS2 (Pt/MoS2 ), the MOR activity (2314.14 mA mgpt -1 ) and stability (317.69 mA mgpt -1 after 2 h of operation) on Pt/NMWCNTs-isolatedMoS2 were 24 and 232 times higher, respectively. As for ORR, Pt/NMWCNTs-isolated-MoS2 holds large half-wave potential (0.88 V) and high stability (92.71 % after 22 h of operation). This work presents a tactic for activating the basal planes and reducing the π-π stacking of 2D materials to satisfy their applications in electrocatalysis. In addition, the proposed sheet-isolation method can be used for fabricating other 2D materials to promote the dispersion of nanoparticles, which assist its application in other fields of energy as well as the environment.

3.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34135121

RESUMO

Proteome-wide profiling of protein phosphorylation has been widely used to reveal the underlying mechanism of diverse cellular signaling events. Yet, characterizing subcellular phosphoproteome with high spatial-temporal resolution has remained challenging. Herein, we developed a subcellular-specific uncaging-assisted biotinylation and mapping of phosphoproteome (SubMAPP) strategy to monitor the phosphorylation dynamics of subcellular proteome in living cells and animals. Our method capitalizes on the genetically encoded bioorthogonal decaging strategy, which enables the rapid activation of subcellular localized proximity labeling biotin ligase through either light illumination or small-molecule triggers. By further adopting an integrated orthogonal pull-down strategy with quantitative mass spectrometry, SubMAPP allowed for the investigation of subcellular phosphoproteome dynamics, revealing the altered phosphorylation patterns of endoplasmic reticulum (ER) luminal proteins under ER stress. Finally, we further expanded the scope of the SubMAPP strategy to primary neuron culture and living mice.


Assuntos
Fosfoproteínas/metabolismo , Proteômica , Sequência de Aminoácidos , Animais , Retículo Endoplasmático/metabolismo , Células HEK293 , Humanos , Camundongos , Neurônios/metabolismo , Fosfoproteínas/química , Proteoma/metabolismo , Frações Subcelulares/metabolismo , Fatores de Tempo
4.
J Am Chem Soc ; 145(40): 21752-21759, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37768553

RESUMO

Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, and its derivatives have been extensively used as key synthons in organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched cyclobutane derivatives. The reaction proceeds in a cascade fashion involving Ir-catalyzed asymmetric allylic etherification and visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates and cinnamyl alcohols are directly used as the substrates under mild reaction conditions, providing a broad range of chiral cyclobutanes in good yields with excellent diastereo- and enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all substrates and catalysts were simultaneously added without any separated step in this approach. The gram-scale reaction and diverse transformations of product further enhance the potential utility of this method.

5.
Int J Cancer ; 153(6): 1172-1181, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37260277

RESUMO

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒2 = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒2 = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒2 = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒2 = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒2 = 74.674, P < .001) and 12 days in July-December 2020 (𝜒2 = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.


Assuntos
COVID-19 , Neoplasias do Colo do Útero , Feminino , Humanos , COVID-19/epidemiologia , Pandemias , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapia , China/epidemiologia , Hospitais Universitários
6.
Brain Behav Immun ; 107: 419-431, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35907582

RESUMO

Adolescent alcohol use can permanently alter brain function and lead to poor health outcomes in adulthood. Emerging evidence suggests that alcohol use can predispose individuals to pain disorders or exacerbate existing pain conditions, but the underlying neural mechanisms are currently unknown. Here we report that mice exposed to adolescent intermittent access to ethanol (AIE) exhibit increased pain sensitivity and depressive-like behaviors that persist for several weeks after alcohol cessation and are accompanied by elevated CD68 expression in microglia and reduced numbers of serotonin (5-HT)-expressing neurons in the dorsal raphe nucleus (DRN). 5-HT expression was also reduced in the thalamus, anterior cingulate cortex (ACC) and amygdala as well as the lumbar dorsal horn of the spinal cord. We further demonstrate that chronic minocycline administration after AIE alleviated hyperalgesia and social deficits, while chemogenetic activation of microglia in the DRN of ethanol-naïve mice reproduced the effects of AIE on pain and social behavior. Chemogenetic activation of microglia also reduced tryptophan hydroxylase 2 (Tph2) expression and was negatively correlated with the number of 5-HT-immunoreactive cells in the DRN. Taken together, these results indicate that microglial activation in the DRN may be a primary driver of pain, negative affect, and 5-HT depletion after AIE.


Assuntos
Consumo de Álcool por Menores , Camundongos , Animais , Etanol , Serotonina , Dor
7.
Molecules ; 28(22)2023 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-38005387

RESUMO

Environmental pollution caused by the use of fossil fuels is becoming increasingly serious, necessitating the adoption of clean energy solutions. Lithium-ion batteries (LIBs) have attracted great attention due to their high energy density and currently occupy a dominant commercial position. Metal oxide materials have emerged as promising anode materials for the next generation of LIBs, thanks to their high theoretical capacity. However, the practical application of these materials is hindered by their substantial volume expansion during lithium storage and poor electrical conductivity. In this work, a zinc/iron bimetallic hybrid oxide composite, ZnO/ZnFe2O4/NC, is prepared using ZIF-8 as a precursor (ZIF-8, one of the metal organic frameworks). The N-doped porous carbon composite improves the volume change and optimizes the lithium-ion and electron transport. Meanwhile, the ZnFe2O4 and ZnO synergistically enhance the electrochemical activity of the anode through the built-in heterojunction to promote the reaction kinetics at the interface. As a result, the material delivers an excellent cycling performance of 604.7 mAh g-1 even after 300 cycles of 1000 mA g-1. This study may provide a rational design for the heterostructure and doping engineering of anodes for high-performance lithium-ion batteries.

8.
J Environ Sci (China) ; 126: 644-655, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36503790

RESUMO

The catalytic oxidation effect of MnSO4 on As(III) by air in an alkaline solution was investigated. According to the X-ray diffraction (XRD), scanning electron microscope-energy dispersive spectrometer (SEM-EDS) and X-ray photoelectron spectroscopy (XPS) analysis results of the product, it was shown that the introduction of MnSO4 in the form of solution would generate Na0.55Mn2O4·1.5H2O with strong catalytic oxidation ability in the aerobic alkaline solution, whereas the catalytic effect of the other product MnOOH is not satisfactory. Under the optimal reaction conditions of temperature 90°C, As/Mn molar ratio 12.74:1, air flow rate 1.0 L/min, and stirring speed 300 r/min, As(III) can be completely oxidized after 2 hr reaction. The excellent catalytic oxidation ability of MnSO4 on As(III) was mainly attributed to the indirect oxidation of As(III) by the product Na0.55Mn2O4·1.5H2O. This study shows a convenient and efficient process for the oxidation of As(III) in alkali solutions, which has potential application value for the pre-oxidation of arsenic-containing solution or the detoxification of As(III).


Assuntos
Álcalis , Arsênio , Catálise , Oxirredução , Espectroscopia Fotoeletrônica
9.
Alcohol Clin Exp Res ; 46(5): 891-906, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35347730

RESUMO

BACKGROUND: Individuals with fetal alcohol spectrum disorders (FASD) often show processing deficits in all sensory modalities. Using an operant light reinforcement model, we tested whether prenatal ethanol exposure (PE) alters operant responding to elicit a contingent sensory stimulus-light onset (turning on the light) and habituation to this behavior in rats. We also explored whether postnatal environmental enrichment could ameliorate PE-induced deficits. METHODS: Pregnant Sprague Dawley rats were gavaged twice/day with 0 or 3 g/kg/treatment ethanol (15% w/v) during gestational days 8-20, mimicking second-trimester heavy PE in humans. The offspring were reared in a standard housing condition or an enriched condition. Adult male and female offspring underwent an operant light reinforcement experiment with either a short-access or a long-access procedure. A dishabituation test was also conducted to characterize the habituation process. RESULTS: In the short-access procedure, PE led to increased operant responding to the contingent light onset in both sexes reared in the standard housing condition. Such an effect was not observed in rats reared in enriched conditions due to an overall decrease in responding. Moreover, rats reared in enriched conditions showed greater short-term habituation. In the long access procedure, PE rats showed increased responding and impaired long-term habituation. The long-access procedure facilitated both short-term and long-term habituation in control and PE rats. CONCLUSION: Prenatal ethanol exposure increases responding to contingent light onset and impairs the long-term habituation process. The PE-induced deficits were ameliorated by rearing in the enriched environment and increasing the duration and frequency of exposure to light onset. The PE-induced effects are like increased sensation-seeking, a subtype of sensory-processing deficit that is often observed in individuals with FASD. Our findings could inform a suitable animal model for investigating the underlying mechanisms and possible intervention strategies for sensory deficits in FASD.


Assuntos
Transtornos do Espectro Alcoólico Fetal , Animais , Etanol/toxicidade , Feminino , Habituação Psicofisiológica , Humanos , Masculino , Percepção , Gravidez , Ratos , Ratos Sprague-Dawley , Sensação
10.
J Environ Manage ; 317: 115380, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35636115

RESUMO

The oxidization of As(III) to As(V) is necessary for both the detoxification of arsenic and the removal of arsenic by solidification. In order to achieve high efficiency and low cost As(III) oxidation, a novel process of catalytic aerial oxidation of As(III) is proposed, using air as oxidant and Mn-loaded diatomite as a catalyst. Through systematic characterization of the reaction products, the catalytic oxidation reaction law of Mn-loaded diatomite for As(III) was found out, and its reaction mechanism was revealed. Results show that Mn-loaded diatomite achieved a good catalytic effect for aerial oxidation of As(III) and maintained high performance over multiple cycles of reuse, which was directly related to the structure of diatomite and the behavior of manganese. Under the conditions of a catalyst concentration of 20 g/L, an air flow rate of 0.3 m3/h, a reaction temperature of 50 °C and an initial pH of 12.6, 96.04% As(III) oxidation was achieved after 3 h. Furthermore, the efficiency of As(III) oxidation did not change significantly after ten cycles of reuse. XPS analysis of the reaction products confirmed that the surface of the catalyst was rich in Mn(III), Mn(IV) and adsorbed oxygen(O-H), which was the fundamental reason for the excellent performance of Mn-loaded diatomite in the catalytic oxidation of As(III).


Assuntos
Arsênio , Compostos de Manganês , Arsênio/química , Terra de Diatomáceas/química , Compostos de Manganês/química , Oxirredução , Óxidos/química
11.
Angew Chem Int Ed Engl ; 61(48): e202213520, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36178409

RESUMO

An iridium-catalyzed asymmetric allylic benzylation of aryl vinyl carbinols under light irradiation is described. 2-Methylbenzophenone derivatives are employed and activated to hydroxy-o-quinodimethanes by an ultraviolet (UV) light. This approach enables asymmetric allylic benzylation with high enantioselectivity (up to 99 % ee) from readily available 2-methylbenzophenones without the utilization of strong bases, and pre-activation or pre-functionalization of the substrates. Moreover, deuterium experiments reveal the generation of nucleophilic benzyl species from 2-methylbenzophenone under UV irradiation.


Assuntos
Irídio , Estereoisomerismo , Catálise
12.
Alcohol Clin Exp Res ; 45(5): 1122-1135, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33730380

RESUMO

BACKGROUND: Attention deficits caused by prenatal ethanol (EtOH) exposure (PE) are a prevalent condition in fetal alcohol spectrum disorders (FASDs). Importantly, the deficits are observed in individuals with FASD who have normal IQs and show no dysmorphic facial features caused by heavy PE. These observations suggest that even moderate PE could lead to attention deficits. This possibility was investigated in the present study using a rat model. METHODS: Pregnant Sprague Dawley rats were administered EtOH (3 g/kg/day) or vehicle via intragastric gavage on gestational days 8 to 20. The blood EtOH concentration (BEC) in EtOH-treated rats was 87.7 ± 1.2 mg/dl (1 h after the gavage), similar to the BECs reported in other moderate PE studies in rodents. Moderate PE did not produce teratogenic effects on birthweight or litter size. The adult offspring underwent a 2-choice reaction time task. RESULTS: Moderate PE led to augmented action impulsivity in both sexes, indicated by more rapid response initiation and more premature responses. Deficits were more marked in males than in females. No greater lapses of attention, assessed by incorrect or relatively slow responses, were observed in rats of either sex with moderate PE. In addition, no deficits in learning or motor function were detected after moderate PE. Interestingly, rats with moderate PE completed more trials than controls. CONCLUSIONS: Our results confirm that moderate PE leads to attention deficits in both sexes, which is demonstrated by greater action impulsivity, but not more lapses of attention. This effect differs from that of heavy PE, as shown in our previous study, which is manifested as impaired action impulsivity and lapses of attention in both sexes.


Assuntos
Atenção/fisiologia , Depressores do Sistema Nervoso Central , Etanol , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Feminino , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Masculino , Gravidez , Ratos , Tempo de Reação/fisiologia
13.
Eur J Neurosci ; 52(11): 4517-4524, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32959420

RESUMO

Drugs of abuse, including cocaine, alter the mechanisms underpinning synaptic plasticity, including long-term potentiation of glutamatergic synapses in the mesolimbic system. These effects are thought to underlie addictive behaviors. In the ventral tegmental area (VTA), glutamatergic synapses also exhibit long-term depression (LTD), a type of plasticity that weakens synaptic strength. This form of synaptic plasticity is induced by low-frequency stimulation and mediated by endocannabinoid (eCB) signaling, which also modulates addictive behaviors. However, it remains unknown whether eCB-LTD in the VTA could be altered by cocaine use. Therefore, the goal of the present study was to examine the impact of cocaine self-administration on eCB-LTD of glutamatergic synapses onto VTA dopaminergic (DA) neurons. To that end, male rats underwent cocaine (0.75 mg/kg/infusion) or saline self-administration under the fixed ratio 1 schedule for 6-9 days. One day after the last self-administration session, the magnitude of eCB-LTD was examined using ex vivo whole-cell recordings of putative VTA DA neurons from naïve rats and rats with saline or cocaine self-administration. The results revealed that cocaine self-administration abolished eCB-LTD. The cocaine-induced blockade of eCB-LTD in the VTA was mediated by an impaired function of presynaptic CB1 receptors. Collectively, these findings indicate that cocaine exposure blunts eCB-mediated synaptic plasticity in midbrain DA neurons. This effect could be one of the cellular mechanisms that mediate, at least in part, addictive behaviors.


Assuntos
Cocaína , Área Tegmentar Ventral , Animais , Endocanabinoides , Masculino , Plasticidade Neuronal , Ratos , Ratos Sprague-Dawley , Sinapses
14.
Alcohol Clin Exp Res ; 44(2): 435-444, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31872887

RESUMO

BACKGROUND: Prenatal ethanol exposure (PE) impairs midbrain dopaminergic (DA) neuron function, which might contribute to various cognitive and behavioral deficits, including attention deficits and increased addiction risk, often observed in individuals with fetal alcohol spectrum disorders. Currently, the underlying mechanisms for PE-induced deficits are unclear. PE could lead to neuroinflammation by activating microglia, which play an important role in synaptic function. In the present study, we investigated PE effects on microglial activation and DA neuron density and morphology in the ventral tegmental area (VTA). Since postnatal environmental enrichment can reduce neuroinflammation and ameliorate several PE-induced behavioral deficits, we examined if a postnatal environmental intervention strategy using neonatal handling and postweaning complex housing could reverse PE effects on VTA DA neurons and microglia. METHODS: Pregnant rats received 0 or 6 g/kg/d ethanol by 2 intragastric intubations on gestation days 8 to 20. After birth, rats were reared in the standard laboratory or enriched condition. Male adult rats (8 to 12 weeks old) were used for immunocytochemistry. RESULTS: The results showed that PE decreased VTA DA neuron body size in standardly housed rats. Moreover, there was a significant decrease in numbers of VTA microglial branches and junctions in PE rats, suggesting morphological activation of microglia and possible neuroinflammation. The PE effects on microglia were normalized by postnatal environmental intervention, which also decreased the numbers of microglial branches and junctions in control animals, possibly via reduced stress. CONCLUSIONS: Our findings show an association between PE-induced morphological activation of microglia and impaired DA neuron morphology in the VTA. Importantly, postnatal environmental intervention rescues possible PE-induced microglial activation. These data support that environmental intervention can be effective in ameliorating cognitive and behavioral deficits associated with VTA DA neuron dysfunctions, such as attention deficits and increased addiction risk.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Meio Ambiente , Etanol/toxicidade , Microglia/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/terapia , Área Tegmentar Ventral/efeitos dos fármacos , Fatores Etários , Animais , Animais Recém-Nascidos , Neurônios Dopaminérgicos/patologia , Etanol/administração & dosagem , Feminino , Abrigo para Animais , Masculino , Microglia/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Ratos Sprague-Dawley , Área Tegmentar Ventral/patologia
15.
Angew Chem Int Ed Engl ; 59(22): 8421-8424, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32134170

RESUMO

Phase-stable CsSnx Pb1-x I3 perovskite quantum dots (QDs) hold great promise for optoelectronic applications owing to their strong response in the near-infrared region. Unfortunately, optimal utilization of their potential is limited by the severe photoluminescence (PL) quenching, leading to extremely low quantum yields (QYs) of approximately 0.3 %. The ultra-low sodium (Na) doping presented herein is found to be effective in improving PL QYs of these alloyed QDs without alerting their favourable electronic structure. X-ray photoelectron spectroscopy (XPS) studies suggest the formation of a stronger chemical interaction between I- and Sn2+ ions upon Na doping, which potentially helps to stabilize Sn2+ and suppresses the formation of I vacancy defects. The optimized PL QY of the Na-doped QDs reaches up to around 28 %, almost two orders of magnitude enhancement compared with the pristine one.

16.
J Neurosci ; 37(24): 5798-5808, 2017 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-28476947

RESUMO

Prenatal ethanol exposure (PE) leads to increased addiction risk which could be mediated by enhanced excitatory synaptic strength in ventral tegmental area (VTA) dopamine (DA) neurons. Previous studies have shown that PE enhances excitatory synaptic strength by facilitating an anti-Hebbian form of long-term potentiation (LTP). In this study, we investigated the effect of PE on endocannabinoid-mediated long-term depression (eCB-LTD) in VTA DA neurons. Rats were exposed to moderate (3 g/kg/d) or high (6 g/kg/d) levels of ethanol during gestation. Whole-cell recordings were conducted in male offspring between 4 and 10 weeks old.We found that PE led to increased amphetamine self-administration. Both moderate and high levels of PE persistently reduced low-frequency stimulation-induced eCB-LTD. Furthermore, action potential-independent glutamate release was regulated by tonic eCB signaling in PE animals. Mechanistic studies for impaired eCB-LTD revealed that PE downregulated CB1 receptor function. Interestingly, eCB-LTD in PE animals was rescued by metabotropic glutamate receptor I activation, suggesting that PE did not impair the synthesis/release of eCBs. In contrast, eCB-LTD in PE animals was not rescued by increasing presynaptic activity, which actually led to LTP in PE animals, whereas LTD was still observed in controls. This result shows that the regulation of excitatory synaptic plasticity is fundamentally altered in PE animals. Together, PE leads to impaired eCB-LTD at the excitatory synapses of VTA DA neurons primarily due to CB1 receptor downregulation. This effect could contribute to enhanced LTP and the maintenance of augmented excitatory synaptic strength in VTA DA neurons and increased addiction risk after PE.SIGNIFICANCE STATEMENT Prenatal ethanol exposure (PE) is among many adverse developmental factors known to increase drug addiction risk. Increased excitatory synaptic strength in VTA DA neurons is a critical cellular mechanism for addiction risk. Our results show that PE persistently alters eCB signaling and impairs eCB-LTD at the excitatory synapses, an important synaptic plasticity that weakens synaptic strength. These effects combined with PE-induced anti-Hebbian long-term potentiation reported in a previous study could result in the maintenance of enhanced excitatory synaptic strength in VTA DA neurons, which in turn contributes to PE-induced increase in addiction risk. Our findings also suggest that restoring normal eCB signaling in VTA DA neurons could be a useful strategy for treating behavioral symptoms caused by PE.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Endocanabinoides/metabolismo , Etanol/intoxicação , Plasticidade Neuronal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Transmissão Sináptica/efeitos dos fármacos , Área Tegmentar Ventral/fisiopatologia , Animais , Relação Dose-Resposta a Droga , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Feminino , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/patologia
17.
Biochemistry ; 57(26): 3945-3952, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29894168

RESUMO

An abasic (AP) site is a ubiquitous DNA lesion that is produced via several cellular processes. Although AP sites are cytotoxic and mutagenic, cells are protected from them by different DNA damage tolerance and repair pathways, including base excision repair (BER). AP lesions are alkali-labile, but the half-life for strand scission is several weeks in free DNA at around neutral pH. The AP lifetime is reduced ∼100-fold in nucleosome core particles (NCPs) because the histone proteins promote strand scission. The reactivity of other DNA lesions to BER enzymes and exogenous reagents is highly dependent upon rotational positioning within the NCP. We examined strand scission at AP sites as a function of rotational position over approximately one helical turn of DNA. The rate constant for strand scission at AP varies ∼4-fold, a range of reactivity much smaller than that observed for processes that involve reaction with diffusible reagents in solution. In addition, the change in rate constant does not exhibit an obvious pattern with respect to rotational position. The small dependence of reactivity on rotational position is attributed to interactions with histone proteins. A molecular model based upon NCP X-ray crystal structures indicates that histone protein tails access AP sites via the major or minor groove and are therefore not limited to regions where one particular groove is exposed to solvent. Determining the roles of individual proteins is difficult because of the unstructured nature of the histone tails and the chemical mechanism, which involves reversible Schiff base formation, followed by irreversible elimination.


Assuntos
DNA/química , Nucleossomos/química , Cristalografia por Raios X , Dano ao DNA , Reparo do DNA , Humanos
18.
Org Biomol Chem ; 16(24): 4501-4508, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29873384

RESUMO

A TBAB-mediated brominative 5-exo-dig oxy-cyclization of 2-alkynylbenzamide is described here for the synthesis of isobenzofuran-1-imines and isobenzofuran derivatives at room temperature with a high efficiency and a broad reaction scope. The resulting isobenzofuran derivatives are also applied for synthesising various substituted isobenzofuran derivatives.

19.
PLoS One ; 19(3): e0300178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512952

RESUMO

Self-healing microcapsules in the asphalt pavement must be kept intact under vehicle load to ensure there is enough rejuvenator in capsules when cracks appear in asphalt pavement. In this paper, the crack resistance of self-healing microcapsules in asphalt pavement was evaluated. Firstly, an expanding multi-scale analysis was conducted based on proposed mesoscopic mechanical models with the aim to determine the mechanical parameters for the following contracting multi-scale analysis. Secondly, the periodic boundary condition was introduced for the contracting multi-scale analysis and the stress field of the capsule wall was obtained. Finally, the effects of the design parameters of the microcapsule on its crack resistance in asphalt pavement were investigated. The results showed that the incorporation of microcapsules has almost no effect on the elastic constants of the asphalt mixture. The core could be simplified as an approximately incompressible solid with the elastic constants determined by the proposed mesoscopic mechanical model. With the increase of the modulus of the capsule wall, the mean maximum tensile stress of the capsule wall increased from 0.372 MPa to 0.465 MPa, while with the decrease of the relative radius of the capsule core, the mean maximum tensile stress of the capsule wall increased from 0.349 MPa to 0.461 MPa. The change in the mean maximum tensile stress of the capsule wall caused by the change of capsule diameter was within 5%. The relative radius of the capsule core and the elastic modulus of capsule wall were two key parameters in capsule design. Besides, the microcapsules with the wall made of resin would not crack under the vehicle load before microcracks occurred in asphalt pavement.


Assuntos
Febre Familiar do Mediterrâneo , Prunella , Cápsulas , Hidrocarbonetos , Módulo de Elasticidade
20.
Traffic Inj Prev ; 25(2): 116-121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38019530

RESUMO

OBJECTIVE: A driver's active emergency response in dangerous traffic scenes consists of two parts, including reaction behavior and physiological state. In dangerous traffic scenes, the driver's active emergency response has an important impact on human collision injury. Clarifying the driver's active emergency response is an important prerequisite for the study of human collision injury under nonstandard posture. Therefore, this study investigates the driver's active emergency response in different inevitable collision scenes using driving simulator. METHODS: A driving simulator with a high-speed camera system and human physiological signal acquisition system was first built. Then, three typical vehicle dangerous collision scenes were developed, including frontal collision, side collision, and rear-end collision. Finally, twenty participants (15 males and 5 females) were recruited for a driving experiment, and their active emergency responses were recorded and analyzed. RESULTS: All subjects would rotate the steering wheel to the left or right in the active emergency state, and the rotation of the hand would also cause the subject's upper body to tilt in the same direction. The maximum angle for male subjects to rotate the steering wheel was 59.98°, while for the female subjects, it was 44.28°. In addition, the maximum grip force between the male subjects and the steering wheel was 280.5 N, compared to 192.5 N for female subjects. Compared to the female participants, the male participants not only have a greater rotation angle and a greater grip force on the steering wheel, but also have greater pressure on the brake pedal, and the foot moves quickly from the accelerator pedal to the brake pedal and presses the brake pedal. CONCLUSIONS: Drivers have different active emergency responses to different vehicle collision scenes. Quantitative statistics of driver's active emergency response will have important guiding significance for the analysis of the impact of human active emergency response on human injury characteristics in subsequent vehicle collision experiments.


Assuntos
Condução de Veículo , Humanos , Masculino , Feminino , Acidentes de Trânsito/prevenção & controle , Tempo de Reação/fisiologia , Extremidade Inferior/fisiologia , Comportamento Perigoso
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