JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
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2024
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IF 11.4
Haiman Xu,Lianxia Guo,Tingying Hao,Xiaocao Guo,Meiping Huang,Haobin Cen,Min Chen,Jiaxian Weng,Meixia Huang,Zicong Wu,Zifei Qin,Jing Yang,Baojian Wu
Background While the daily rhythm of allergic rhinitis (AR) has long been recognized, the molecular mechanism underlying this phenomenon remains enigmatic. Objective We aim to investigate the role of circadian clock in AR development and to clarify the mechanism by which the daily rhythm of AR is generated. Methods AR was induced in mice using the ovalbumin method. Toluidine blue staining, LC-MS/MS analysis, qPCR, and immunoblotting were performed with AR and control mice. Results Ovalbumin-induced AR is diurnally rhythmic and associated with clock gene disruption in nasal mucosa. In particular, Rev-erbα is generally down-regulated, and its rhythm retained but with a near 12-h phase shift. Furthermore, global knockout of the core clock gene Bmal1 or Rev-erbα increases the susceptibility of mice to AR and blunts AR rhythmicity. Importantly, nasal SCCs (solitary chemosensory cells) are rhythmically activated, and inhibition of the SCC pathway leads to attenuated AR and a loss of its rhythm. Moreover, rhythmic activation of SCCs is accounted for by diurnal expression of ChAT (an enzyme responsible for the synthesis of acetylcholine) and temporal generation of the neurotransmitter acetylcholine. Mechanistically, REV-ERBα trans-represses Chat through direct binding to a specific response element, generating a diurnal oscillation in this target gene. Conclusion These findings identify SCCs, under the control of REV-ERBα, as a driver of AR rhythmicity, and suggest targeting SCCs as a new avenue for AR management.
研究领域:
免疫学
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时间生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2026
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IF 3.1
Jiuhong Zhang,Chenyang Yue,Luling Nie,Wanqi Fu,Qingsong Xie,Zhuyi Jiang,Chao Wang,Jie Jiang,Yan Wu,Jianjun Liu,Xiao Chen
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used halogen-containing organophosphate flame retardant with potential neurotoxicity, but its effects on cardiac autonomic function remain largely unexplored. This study investigated TDCIPP's impact on heart rate variability (HRV) and the underlying molecular mechanisms. Young adult male rats were treated with TDCIPP (0, 13.3, 40, 120, or 360 mg/kg/day) by gavage for 114 days. TDCIPP exposure significantly reduced multiple HRV parameters including SDRR (by 58%–62%, p < 0.005), CVRR (by 57%–64%, p < 0.01), RMSSD (by 55%–63%, p < 0.05), and SD 2 (by 59%–65%, p < 0.01) across all dose groups, indicating impaired cardiac autonomic function with a possible threshold-like pattern instead of a typical dose-dependent response. Further analyses revealed that TDCIPP decreased choline acetyltransferase (ChAT) activity (by 28%–53%, p < 0.001) and mRNA expression (by 22%–48%, p < 0.05 to p < 0.001) dose-dependently without affecting protein levels, while acetylcholinesterase (AChE) activity remained unchanged. Acetylcholine levels were significantly reduced in the 40 and 360 mg/kg/day groups (by 31% and 42%, respectively, p < 0.05). Molecular docking analysis demonstrated that TDCIPP binds to the choline binding site of ChAT, forming a hydrogen bond with His334, the same residue critical for choline binding. This suggests TDCIPP impairs cardiac autonomic function by disrupting cholinergic neurotransmission through putative competitive inhibition of ChAT activity. This novel mechanism differs from that of chlorpyrifos and provides new insights into how environmental flame retardants may impact cardiovascular health.
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DOI
PubMed
高影响因子
Early Education and Development
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2023
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IF 2.9
Wenwei Luo,Huihua He,Jin Liu,Ilene R. Berson,Michael J. Berson,Yisu Zhou,Hui Li
Research Findings: This study aims to explore the optimal roles, pressing challenges, and future developments of ChatGPT in early childhood education (ECE) by interviewing six expert professors from China and the United States. A content analysis approach that combined inductive and deductive coding was employed to analyze the transcribed interviews. The findings of this study revealed two primary roles of ChatGPT in ECE: (1) conversational agent for young children and (2) on-call facilitator for educators and caregivers. The challenges and risks associated with ChatGPT were categorized using the ”3A2S” framework, which includes Accessibility, Affordability, Accountability, Sustainability, and Social Justice. The participants suggest that as knowledge, information retrieval, and integration skills become less critical, human agency and inquiry ability become more important. As a result, they predict that ChatGPT's future trajectory should be as a resource for Intelligence Augmentation (IA) rather than as a replacement for the actions of educators and caregivers. Furthermore, AI opens new domains in ECE, such as AI literacy and AI social interaction, paving the way for novel opportunities and challenges in the field. Practice or Policy: This study contributes to the ongoing discourse on integrating AI technologies in ECE and offers valuable suggestions for policymakers, educators, and caregivers.
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高影响因子
NEUROTOXICOLOGY
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2023
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IF 3.4
Tong Zhang,Chunmei Zhang,Yuyou Luo,Shuping Liu,Siyuan Li,Lixia Li,Yuxin Ma,Jing Liu
The present study aimed to investigate the protective effect of rutin on the injury of spinal motor neuron in rats exposed to acrylamide (ACR) the underlying mechanism. Fifty male Sprague-Dawley rats, aged 7–8 weeks, were randomly divided into control group, ACR group (20 mg/kg), low dose(100 mg/kg), medium dose (200 mg/kg) and high dose(400 mg/kg) rutin groups, ten rats in each group. The rats were given intragastric administration for 21 days. Every week, a neurobehavioral test was conducted. Nissl staining was used to observe the morphological changes in motor neurons in the L4-L6 segment of the spinal cord . Immunohistochemistry was used to identify AChE and ChAT in the rat spinal cord. Western blot was used to identify the expression of AChE, ChAT, P-ERK, ERK, and Nrf2 proteins in the rat spinal cord. The commercial kits were used to detect the presence of SOD, GSH, and LDH in the rat spinal cord. At the start of the second week, the medium and high dosage rutin group's rats' gait scores significantly decreased as compared to those of the ACR group. When rutin dosage was increased, the Nissl staining revealed that Nissl bodies was staining intensified compared to the ACR group. Immunohistochemistry and Western blot analysis revealed that AChE and ChAT expression changed when rutin dose was raised, but P-ERK and Nrf2 expression steadily increased in the spinal cord of rats in the medium and high dose groups compared to the ACR group. In the spinal cord of rats in each dosage group compared to the ACR group, the findings of the oxidative stress indices demonstrated that the expression levels of SOD and GSH rose with the increase of rutin dose, while the expression of LDH reduced with the rise of rutin dose. Rutin has an anti-oxidative impact through up-regulating the expression of P-ERK and Nrf2 proteins in the ERK/Nrf2 pathway, which may be connected to its protective action on motor neurons in the spinal cord of rats exposed to ACR.
研究领域:
神经科学
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药理学
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毒理学
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DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Zhiqiang Lu,Yuan Gao,Zhijie Bao,Songyi Lin
The peptide Ser-Phe-Gly-Asp-Ile (SFGDI), derived from sea cucumber, has demonstrated neuroprotective effects in cell models; however, the in vivo neuroprotective efficacy of SFGDI remains unexplored. In this study, we utilized a cognitive disorder mouse model induced by scopolamine and observed that daily oral administration of SFGDI at a dosage of 40 mg/kg resulted in improved behavioral performance in the Passive avoidance test, the Channel-type water maze test, and the Novel object recognition test (P < 0.05). Furthermore, our investigation into the underlying neuroprotective mechanisms of SFGDI revealed that it reduced oxidative stress levels through the activation of the Sirt3/SOD/ROS pathway, thereby balancing hippocampal unsaturated lipids (P < 0.05) in the mouse hippocampus. Moreover, SFGDI significantly decreased hippocampal neuroinflammation by modulating the activation of microglia and hypertrophy of astrocytes. Additionally, SFGDI was found to enhance synaptic plasticity in the mouse hippocampus by activating the ChAT/p-CaMKⅡ/BDNF pathway and increasing spine density in neuron cells (P < 0.05), particularly mushroom spines (P < 0.05). These experiments demonstrate that SFGDI exhibits neuroprotective effects by regulating hippocampal oxidative stress through the Sirt3/SOD/ROS pathway and synaptic plasticity via the ChAT/p-CaMKⅡ/BDNF pathway in the mouse hippocampus, thus emerging as a potential neuro-nutraceutical agent for alleviating memory impairment.
研究领域:
神经科学
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药理学
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分子生物学
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高影响因子
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