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Incense smoke(IS)inhalation exposure system:Physicochemical characterization,IS particle deposition and clearance in human airway using MPPD model

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Particuology 2024年第4期87卷 271-285页

作者： Vyas Kumar Hafsa Hashmi Anshita Nasreen Ghazi Ansari Jyotsna Singh Inhalation toxicology Facility Regulatory Toxicology GroupCSR-Indian Institute of Toxicology ResearchLucknow22001UPIndi Academy of Scientific and Innovative Research(AcsSIR) Ghaziabad201002UPIndia Analytical Chemistry Regulatory Toxicology GroupCSIR-Indian Institute of Toxicology ResearchLucknow226001UPIndia

Incense smoke(IS)is source of indoor air pollution and key risk for diverse human *** in-formation is available regarding controlled IS rodent inhalation exposure system and IS particulate matter(PM)deposition in human *** aimed to demonstrate stable ISPM physicochemical parameters of 10 incense products inside the customized whole body inhalation exposure chamber(without animal)connected to smoke generation unit via aerosol mixing *** analyzed for size segregated PM emission,ISPM in vitro aerodynamics(MMAD and GSD determination),fine and ultrafine particle's SEM,SEM-EDX and PAH *** real life exposure scenario by utilizing MMAD,GSD and PM concentration after Tier 1 exposure assessment as key input parameters,ISPM dosimetry in infant(3 months)and adult(21 years male and female)human airways was calculated using multiple-path particle dosimetry(MPPD 3.04)*** median aerodynamic diameter(MMAD)and geo-metric standard deviation(GSD)ranged between 0.55 and 2.10μm and 1.22 to 1.77(polydisperse)***1.0 and PM0.1 showed multiple morphology and presence of heavy and trace *** like acenaphthylene,anthracene,fluorene,naphthalene and phenanthrene were detected(0.84-143.17μg/g).MPPD results showed higher ISPM deposition in pulmonary region and lowest in trachea bronchial *** deposition in tissue was higher in lower,peripheral lung as compared to upper and central lung *** body inhalation exposure system showed stable IS atmosphere(physi-cochemical parameters)indicating the device suitability in future inhalation *** ISPM deposition fraction and clearance data showed deep lung penetrating and retention behavior with higher risk in infant followed by female and then *** modeled particle deposition and clearance data may be useful in risk assessment analysis of IS.

关键词： Inhalation Incense smoke Multiple-path particle dosimetry(MPPD) Particle deposition Particulate matter(PM) Mass median aerodynamic diameter (MMAD) Human airway

Virus-like nanoparticle vaccines for inducing long-lasting immunity against infectious diseases

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National Science Review 2024年第4期11卷 13-15页

作者： Yi-Nan Zhang Sarah Auclair Jiang Zhu Department of integrative Structural and Computational Biology The Scripps Research Institute Department of Immunology and Microbiology The Scripps Research Institute

Prophylactic vaccines that can generate long-lasting protective immune responses are needed for many infectious diseases. Efficient vaccination requires vaccine antigens to be retained and presented to B cells in lymp...

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Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

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Neural Regeneration Research 2024年第3期19卷 629-635页

作者： Jingzhou Liu Xin Xin Jiejie Sun Yueyue Fan Xun Zhou Wei Gong Meiyan Yang Zhiping Li Yuli Wang Yang Yang Chunsheng Gao State Key Laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijingChina Academy of Medical Engineering and Translational Medicine Medical CollegeTianjin UniversityTianjinChina

Traumatic brain injury results in neuronal loss and glial scar *** neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain *** reprogramming is a promising strategy to convert glial scars to neural ***,previous studies have reported inconsistent *** this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target *** results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive ***,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain *** summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

关键词： AAV9P1 astrocytes astrocyte-to-neuron conversion GFAP promoter glial scar induced neurons neuronal reprogramming P1 peptide PTBP1 traumatic brain injury

Targeting NRP1 axis as a strategy for treating energy metabolism impairment induced by SARS-CoV-2 spike

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Science China(Life Sciences) 2024年第10期67卷 2277-2279页

作者： Lihui Zhang Wanting Hu Jingxuan Li Yuehan Li Feng Liu Wenyi Xiao Ning Jiang Zhiyong Xiao Lu Han Wenxia Zhou Beijing institute of Pharmacology&toxicology Beijing 100850China State Key Laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology&ToxicologyBeijing 100850China School of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China

Dear Editor,Free spike protein of SARS-CoV-2 alone can cause abnormal energy metabolism(Table S1 in Supporting Information),and limited research suggested a potential correlation between spike-induced mitochondrial da... 详细信息

关键词： metabolism ACE2

SIRT2 as a potential new therapeutic target for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 124-131页

作者： Noemi Sola-Sevilla Elena Puerta Department of Pharmacology and toxicology Faculty of PharmacyUniversity of NavarraNavarra Institute for Health Research(IdiSNA)PamplonaSpain

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective *** this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative *** review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative *** role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's ***,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific *** studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological *** will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.

关键词： Alzheimer's disease amyloid autophagy memory neurodegenerative diseases neuroinflammation sirtuin 2 tau

Chrononutrition in traditional European medicine-Ideal meal timing for cardiometabolic health promotion

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Journal of integrative Medicine 2024年第2期22卷 115-125页

作者： Nora Selena Eberli Ludivine Colas Anne Gimalac Department of Traditional European Medicine Navi Institute of Research in Integrative HealthEcole Professionnelle Superieure de NaturopathieCentre Andre Henzelin1066 EpalingesSwitzerland

Meal timing plays a crucial role for cardiometabolic health,given the circadian regulation of cardiometabolic ***,to the best of our knowledge,no concept of meal timing exists in traditional European medicine(TEM).Therefore,in this narrative review,we aim to define the optimal time slot for energy intake and optimal energy distribution throughout the day in a context of TEM and explore further *** reviewing literature published between 2002 and 2022,we found that optimal timing for energy intake may be between 06:00 and 09:00,12:00 and 14:00,and between 15:00 and18:00,with high energy breakfast,medium energy lunch and low energy dinner and possibly further adjustments according to one’s chronotype and ***,timing and distribution of energy intake may serve as a novel therapeutic strategy to optimize coction,a concept describing digestion and metabolism in TEM.

关键词： Circadian rhythm Chrononutrition Naturopathy Traditional European medicine Metabolic syndrome Meal timing

Effects of acupuncture on hypothalamic–pituitary–adrenal axis:Current status and future perspectives

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Journal of integrative Medicine 2024年第4期22卷 445-458页

作者： Jia-yuan Zheng Jing Zhu Yu Wang Zhan-zhuang Tian Department of integrative Medicine and Neurobiology School of Basic Medical SciencesState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceInstitutes of Brain ScienceInstitute of Acupuncture ResearchAcademy of Integrative MedicineShanghai Key Laboratory for Acupuncture Mechanism and Acupoint FunctionShanghai Medical CollegeFudan UniversityShanghai 200032China Department of Human Anatomy School of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghai 201203China

The hypothalamic–pituitary–adrenal(HPA) axis is a critical component of the neuroendocrine system,playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus,hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA *** review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture.

关键词： Acupuncture Electroacupuncture Hypothalamic-pituitary-adrenal axis Mechanism Neurotransmitter microRNA

Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation:A case report

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World Journal of Clinical Cases 2024年第2期12卷 399-404页

作者： Saeko Kohara Yoshito Kamijo Ryoko Kyan Ichiro Okada Eiju Hasegawa Soichiro Yamada Koichi Imai Asuka Kaizaki-Mitsumoto Satoshi Numazawa Department of Critical Care Medicine and Trauma National Hospital Organization Disaster Medical CenterTokyo 1900014Japan Department of Clinical toxicology Saitama Medical UniversitySaitama 3500495Japan Saitama Prefectural institute of Public Health Saitama Prefectural Institute of Public HealthSaitama 3550133Japan Division of toxicology Department of PharmacologyToxicology and TherapeuticsShowa University School of PharmacyTokyo 1428555Japan

BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular *** describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and *** hours after arrival,an electrocardiogram revealed a return to sinus *** patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,*** hospital day 15,he was transferred to a psychiatric *** other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the *** on admission contained 1.50 ng/mL of *** hospital day 2,neither were *** on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day *** The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

关键词： Aconite poisoning Fatal arrhythmia Veno-arterial extracorporeal membrane oxygenation Aconitine Mesaconitine Case report

Phomaketals A and B,pentacyclic meroterpenoids from a eupC overexpressed mutant strain of Phoma sp.

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Chinese Chemical Letters 2024年第7期35卷 350-354页

作者： Chuan Li Yangyang Han Yanan Zhai Ke Li Xingzhong Liu Zhuan Zhang Cai Jia Yongsheng Che NHC Key Laboratory of Biotechnology of Antibiotics Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of toxicology&Medical Countermeasures Beijing Institute of Pharmacology&ToxicologyBeijing 100850China Department of Microbiology College of Life SciencesNankai UniversityTianjin 300071China

Phomaketals A(1)and B(2),two tropolonic meroterpenoids with the unprecedented pentacyclic skeletons,were isolated from the solid-substrate fermentation cultures of a eupC overexpressed mutant strain of the fungus Phoma sp.,together with a biogenetically related secondary metabolite pughiinin B(3),and the known one noreupenifeldin B(4).The structures of 1–3 were elucidated primarily by nuclear magnetic resonance(NMR)*** absolute configurations of 1 and 2 were assigned by electronic circular dichroism calculations and the calculated NMR with DP4+analysis,while that of 3 was established by single-crystal X-ray diffraction analysis using Cu Kα***,phomaketals A(1)and B(2)could be derived from the hypothetical tropolonic sesquiterpene intermediates neosetophomone B(6)and 9-R-neosetophomone B(6),respectively,via different reactions *** 1 showed antiproliferative effect only against the SUPB15 cells,with an 50%inhibitory concentration(IC50)value of 4.85μmol/L,while the co-isolated known meroterpenoid 4 displayed potent effects against three tumor cell lines,SUPB15,EL4,and H9,showing IC50values of 0.36–27.08μmol/L.

关键词： Phoma sp. Tropolonic sesquiterpenes Biosynthetic pathways Hetero-Diels–Alder Cytotoxicity