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Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib

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Chinese Chemical Letters 2024年第4期35卷 260-267页

作者： Dexuan Xiao Tianyu Chen Tianxu Zhang Sirong Shi Mei Zhang Xin Qin Yunkun Liu Longjiang Li Yunfeng Lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Sichuan Provincial Engineering research Center of Oral Biomaterials Chengdu 610041China Department of Head and Neck Oncology National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids(tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared t FNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of t FNAs(AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand,AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-t FNAs/vemurafenib could inhibit the growth of human A375melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

关键词： Melanoma Vemurafenib DNA nanostructure Transdermal treatment Side effect

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Cardiac arrest, stony heart, and cardiopulmonary resuscitation: An updated revisit

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World Journal of Cardiology 2024年第3期16卷 126-136页

作者： Ayman El-Menyar Bianca M Wahlen Department of Trauma and Vascular Surgery Clinical ResearchHamad Medical CorporationDoha 3050Qatar Department of clinical Medicine Weill Cornell Medical CollegeDoha 24144Qatar Department of Anesthesiology Hamad Medical CorporationDoha 3050Qatar

The post-resuscitation period is recognized as the main predictor of cardiopul-monary resuscitation(CPR)outcomes.The first description of post-resuscitation syndrome and stony heart was published over 50 years ago.Major manifestations may include but are not limited to,persistent precipitating pathology,systemic ischemia/reperfusion response,post-cardiac arrest brain injury,and finally,post-cardiac arrest myocardial dysfunction(PAMD)after successful resuscitation.Why do some patients initially survive successful resuscitation,and others do not?Also,why does the myocardium response vary after resuscitation?These ques-tions have kept scientists busy for several decades since the first successful resuscitation was described.By modifying the conventional modalities of resu-scitation together with new promising agents,rescuers will be able to salvage the jeopardized post-resuscitation myocardium and prevent its progression to a dismal,stony heart.Community awareness and staff education are crucial for shortening the resuscitation time and improving short-and long-term outcomes.Awareness of these components before and early after the restoration of circulation will enhance the resuscitation outcomes.This review extensively addresses the underlying pathophysiology,management,and outcomes of post-resuscitation syndrome.The pattern,management,and outcome of PAMD and post-cardiac arrest shock are different based on many factors,including in-hospital cardiac arrest vs out-of-hospital cardiac arrest(OHCA),witnessed vs unwitnessed cardiac arrest,the underlying cause of arrest,the duration,and protocol used for CPR.Although restoring spontaneous circulation is a vital sign,it should not be the end of the game or lone primary outcome;it calls for better understanding and aggressive multi-disciplinary interventions and care.The development of stony heart post-CPR and OHCA remain the main challenges in emergency and critical care medicine.

关键词： Cardiac arrest Out-of-hospital cardiac arrest In-hospital cardiac arrest Post-resuscitation Myocardial dysfunction Cardiopulmonary resuscitation Stony heart

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Weathering and accumulation of trace elements in the soils of the Porali Plain, Balochistan: repercussions in agriculture

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Acta Geochimica 2024年第2期43卷 214-234页

作者： Maria Kaleem Erum Bashir Shahid Naseem Tahir Rafique Bushra Shahab Department of Geology University of KarachiKarachi 75270Pakistan Applied Chemistry research centre PCSIR Laboratories ComplexKarachi 75280Pakistan

This study is theﬁrst attempt to assess the nature of the soil,especially on the western side of the Porali Plain in Balochistan;a new emerging agriculture hub,using weathering and pollution indices supplemented by multi-variate analysis based on geochemical data.The outcomes of this study are expected to help farmers in soil manage-ment and selecting suitable crops for the region.Twenty-ﬁve soil samples were collected,mainly from the arable land of the Porali Plain.After drying and coning-quarter-ing,soil samples were analyzed for major and trace ele-ments using the XRF technique;sieving and hydrometric methods were employed for granulometric analysis.Esti-mated data were analyzed using Excel,SPSS,and Surfer software to calculate various indices,correlation matrix,and spatial distribution.The granulometric analysis showed that 76%of the samples belonged to loam types of soil,12%to sand type,and 8%to silt type.Weathering indices:CIA,CIW,PIA,PWI,WIP,CIX,and ICV were calculated to infer the level of alteration.These indices reﬂect mod-erate to intense weathering;supported by K_(2)O/AI_(2)O_(3),Rb/K_(2)O,Rb/Ti,and Rb/Sr ratios.Assessment of the geo-ac-cumulation and Nemerow Pollution indices pinpoint rela-tively high concentrations of Pb,Ni,and Cr concentration in the soils.The correlation matrix and Principal Compo-nent Analysis show that the soil in this study area is mainly derived from the weathering of igneous rocks of Bela Ophiolite(Cretaceous age)and Jurassic sedimentary rocks of Mor Range having SEDEX/MVT type mineralization.Weathering may result in the undesirable accumulation of certain trace elements which adversely affects crops.

关键词： Weathering indices Pollution indices Accumulation Repercussions Trace elements Multivariate analyses Porali Plain Balochistan

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Multi-omics:Powerful accelerator for uncovering plant specialized metabolic pathways:The case of leonurine

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Molecular Plant 2024年第1期17卷 13-15页

作者： Priyanka Gupta Anuj Sharma Dinesh A.Nagegowda Molecular Plant Biology and Biotechnology Lab CSIR-Central Institute of Medicinal and Aromatic PlantsResearch CentreBengaluru 560065India Academy of Scientific and Innovative research Ghaziabad 201002India

As sessile organisms,plants employ a unique adaptive strategy to survive harsh terrestrial environments and defend against or interact with coevolving animals and microorganisms.This strategy involves expanding their metabolic systems,resulting in the production of plant specialized metabolites(PSMs)or natural products.Chemically,PSMs constitute a highly diverse group of compounds based on their common core structure,comprising terpenoids,phenylpropanoids,benzenoids,alkaloids and nitrogen-containing compounds,glucosinolates,indoles and sulfur-containing indole compounds,phenolics,and fatty acid derivatives(Garagounis et al.,2021).

关键词： expanding alkaloids sulfur

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Coinfection of SARS-CoV-2 Omicron variant and other respiratory pathogens in children

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World Journal of Pediatrics 2024年第1期20卷 92-96页

作者： Wei Li Bing-Han Wang Bao-Hai Chen Yi Sun Lin Li Wen-Qing Xiang Ahmed Faisal Ali Lin-Xuan Su Hai-Yan Mao Hong-Qiang Shen Qiang Shu Department of clinical Laboratory Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina School of Public Health Zhejiang University School of MedicineHangzhouChina Department of Information Center Children's HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Provincial Center for Disease Control and Prevention HangzhouChina Department of Thoracic&Cardiovascular Surgery Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina

Since the outbreak of coronavirus disease 2019(COVID-19),the entire world has been affected by the epidemic[1,2].On November 9,2021,a variant of the novel coronavirus B.1.1.529 was detected for the first time from case samples in South Africa.The Omicron strain spread and mutated significantly fast.This variant has the characteristics of escape immunity,which can induce relatively extreme disease and reduce the neutralization of antibodies in vaccinators,and is more likely to be reinfected[3,4].The clinical presentation of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)in children has mild symptoms and a lower risk of hospitalization and death.

关键词： respiratory immunity acute

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Predictive active control of building structures using LQR and artificial intelligence

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Earthquake Engineering and Engineering Vibration 2024年第2期23卷 489-502页

作者： Nirmal S.Mehta Vishisht Bhaiya K.A.Patel Ehsan Noroozinejad Farsangi Department of Civil Engineering SVNIT SuratGujarat 395007India Urban Transformations research centre Western Sydney UniversityNSWAustralia

This study presents a neural network-based model for predicting linear quadratic regulator(LQR)weighting matrices for achieving a target response reduction.Based on the expected weighting matrices,the LQR algorithm is used to determine the various responses of the structure.The responses are determined by numerically analyzing the governing equation of motion using the state-space approach.For training a neural network,four input parameters are considered:the time history of the ground motion,the percentage reduction in lateral displacement,lateral velocity,and lateral acceleration,Output parameters are LQR weighting matrices.To study the effectiveness of an LQR-based neural network(LQRNN),the actual percentage reduction in the responses obtained from using LQRNN is compared with the target percentage reductions.Furthermore,to investigate the efficacy of an active control system using LQRNN,the controlled responses of a system are compared to the corresponding uncontrolled responses.The trained neural network effectively predicts weighting parameters that can provide a percentage reduction in displacement,velocity,and acceleration close to the target percentage reduction.Based on the simulation study,it can be concluded that significant response reductions are observed in the active-controlled system using LQRNN.Moreover,the LQRNN algorithm can replace conventional LQR control with the use of an active control system.

关键词： active control system linear quadratic regulator artificial neural networks state-space approach response effectiveness factor resilience

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Status of biomarker development for frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration research 2024年第10期19卷 2117-2118页

作者： Yue Yang Qi Cheng Jianqun Gao Woojin Scott Kim Brain and Mind centre&School of Medical Sciences The University of SydneySydneyNSWAustralia Department of Neurology and Neurophysiology Liverpool HospitalSydneyNSWAustralia Stroke and Neurology research Group Ingham Institute for Applied Medical ResearchSydneyNSWAustralia Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation ShanghaiChina clinical research Center for Anesthesiology and Perioperative Medicine ShanghaiChina Translational research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina

Frontotemporal dementia(FTD) and amyotrophic lateral sclerosis(ALS) are neurodegenerative diseases that belong to the same disease spectrum,with overlapping of genetic and pathological features.Genetic mutations in TA... 详细信息

关键词： amyotrophic sclerosis diseases

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Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

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Neural Regeneration research 2024年第1期19卷 161-170页

作者： Guoqiang Zhang Jianan Lu Jingwei Zheng Shuhao Mei Huaming Li Xiaotao Zhang An Ping Shiqi Gao Yuanjian Fang Jun Yu Department of Neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Neurosurgery Huashan Hospital of Fudan University School of MedicineShanghaiChina clinical research Center for Neurological Diseases of Zhejiang Province HangzhouZhejiang ProvinceChina Key Laboratory of Precise Treatment and clinical Translational research of Neurological Diseases HangzhouZhejiang ProvinceChina

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

关键词： intracerebral hemorrhage macrophage microglia neuroinflammation phagocytosis PI3K/AKT/mTOR signaling pathway Spi1 transcriptomics

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Progress of gaseous arsenic removal from flue gas by adsorption:Experimental and theoretical calculations

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Journal of Environmental Sciences 2024年第2期136卷 470-485页

作者： Xuelei Yan Qingzhu Li Xiaowei Huang Bensheng Li Shengtu Li Qingwei Wang School of Metallurgy and Environment Central South UniversityChangsha 410083China National Engineering research centre for Control and Treatment of Heavy Metal Pollution Central South UniversityChangsha 410083China National Engineering research Center for Rare Earth Materials General Research Institute for Non-Ferrous MetalsBeijing 100088China

Because of its high mobility and difficult capture,gaseous arsenic pollution control has become the focus of arsenic pollution control.It mainly exists in the form of highly toxic As_(2)O_(3)in the flue gas.Therefore,removing gaseous As_(2)O_(3)from flue gas is of great practical significance for arsenic pollution control.Stabilizing gaseous As_(2)O_(3)on the surface of adsorbents by physical or chemical adsorption is an effective way to reduce the content of arsenic in the flue gas and alleviate arsenic pollution.Over the past few decades,various adsorbents have been developed to capture gaseous As_(2)O_(3)in the flue gas,and their adsorption mechanisms have been studied in detail.Thus,it is necessary to review the strategies of arsenic removal from flue gas by adsorption,which can inspire further research.Based on summarizing the morphological distribution of gaseous As_(2)O_(3)in the flue gas,this review further summarizes the removal of gaseous As_(2)O_(3)by several adsorbents and the effect of temperature and the main components of the flue gas on arsenic adsorption.In addition,the mechanism of arsenic removal based on adsorption in the flue gas is discussed in depth through theoretical calculations,which is the particular focus of this review.Finally,prospects based on the present research state of arsenic removal by adsorption are proposed to provide ideas for developing effective and stable adsorbents for arsenic removal from flue gas.

关键词： Gaseous arsenic Flue gas Adsorption Theoretical calculation Mechanism

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Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

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Neural Regeneration research 2024年第1期19卷 29-34页

作者： Marta Zagrebelsky Martin Korte Division of Cellular Neurobiology Zoological InstituteTU BraunschweigBraunschweigGermany Helmholtz centre for Infection research AG NINDBraunschweigGermany

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin rec

关键词： Alzheimer's disease brain-derived neurotrophic factor depression Parkinson's disease tropomyosin receptor kinase B receptor

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