Fundamental Research最新文献

{"title":"Advances in synaptic PET imaging and intervention with synapse-targeted small-molecular drugs for dementia diagnosis and therapy","authors":"Xiuhong Lu ,&nbsp;Bin Ji ,&nbsp;Gang Huang ,&nbsp;Hong Ding","doi":"10.1016/j.fmre.2024.04.013","DOIUrl":"10.1016/j.fmre.2024.04.013","url":null,"abstract":"<div><div>Dementia is characterized by synaptic and neuronal dysfunction in disease-specific brain regions. Repeated failure of dementia clinical trials with therapeutic drugs targeting abnormal protein aggregates has caused researchers to shift their focus to synaptic functions and increased the importance of clinically available imaging for synaptic density and the development of synapse-targeted intervention. Synaptic density imaging with positron emission tomography (PET) tracer enables non-invasive detection of synaptic loss and hence investigates the association with other neuropathological events exemplified by disease-specific abnormal protein accumulation. Many studies have reviewed the progress of synaptic density imaging; however, to our knowledge, there is no article yet that summarizes the research progress of multimodal imaging of synaptic density tracers combined with other dementia biomarkers. Moreover, synaptic function intervention for dementia therapy has not yet been summarized. In this review, first we detail the progress of synaptic density imaging including tracer development and preclinical/clinical application, followed by a discussion of multimodal imaging of synaptic density tracers combined with classic dementia biomarkers in the clinical research stage. Finally, we briefly summarize the synapse-targeted drugs for dementia therapy.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 63-71"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140772233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mannan-decorated STING-activating vaccine carrier for spatial coordinative stimulating antigen-specific immune responses","authors":"Liping Liu ,&nbsp;Jiayu Zhao ,&nbsp;Zichao Huang ,&nbsp;Yudi Xu ,&nbsp;Hongyu Chen ,&nbsp;Ruirui Qiao ,&nbsp;Wantong Song ,&nbsp;Zhaohui Tang ,&nbsp;Thomas P. Davis ,&nbsp;Xuesi Chen","doi":"10.1016/j.fmre.2023.03.018","DOIUrl":"10.1016/j.fmre.2023.03.018","url":null,"abstract":"<div><div>In recent years, the use of nanotechnologies to improve immunotherapy efficiency has attracted increasing interest in preventive and therapeutic cancer vaccine design. However, current nanocarriers are restricted by difficulties in the systematic spatial coordinative transport of antigens, which greatly hampers the immune response efficacy of nanovaccines. Herein, we designed a mannan-decorated stimulator of the interferon genes (STING)-activating vaccine carrier for spatial coordinative stimulation of antigen-specific immune responses and elicitation of robust antitumor immunity. Mannan-decoration as the shell could significantly enhance the lymph node draining ability of the nanovaccines, especially in CD8⁺ dendritic cells (DCs). Azole molecule end-capped polylactic acid-polyethylenimine (PLA-PEI-4BImi) with innate stimulating activity was applied as the inner core for coordinating antigen-presenting cell activation and antigen cross-presentation. In the in vivo therapy study, single usage of this nanovaccine could achieve a 93% tumor suppression rate in the B16-OVA tumor model, which is superior to the commercialized aluminum adjuvant. This study demonstrates that a rational design of vaccine carriers for solving spatial transmission issues could greatly improve cancer vaccine efficiencies.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 183-191"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43808465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetics disruptions enabled by porphyrin-derived metal-organic frameworks disarm resistances to sonocatalytic ROS anti-tumor actions","authors":"Yan Zhang ,&nbsp;Dou Du ,&nbsp;Chao Fang ,&nbsp;Xin Yu ,&nbsp;Yujia Fang ,&nbsp;Xinyu Liu ,&nbsp;Di Ou ,&nbsp;Haohao Yin ,&nbsp;Hui Liu ,&nbsp;Taixia Wang ,&nbsp;Lu Lu ,&nbsp;Xiaolong Li ,&nbsp;Kun Zhang","doi":"10.1016/j.fmre.2022.06.020","DOIUrl":"10.1016/j.fmre.2022.06.020","url":null,"abstract":"<div><div>Post-transcriptional epigenetic modifications provide numerous implications for tumor progression, metastasis and recurrence, which also pose resistances to reactive oxygen species (ROS)-based anti-tumor. Herein, we proposed an epigenetic deubiquitination disruption strategy to disarm the ubiquitination-deubiquitination balance-induced resistances to ROS production and ROS-based anti-tumor action for potentiating sonodynamic treatment (SDT) efficiency. To end it, porphyrin-derived metal-organic framework (MOF) sonocatalytic nanoplatforms were developed to load deubiquitination inhibitors (i.e., Auranofin). Ultrasound-triggered Auranofin release from PCN224@Au has been validated to blockade the deubiquitinating process and drive proteasome-mediated target protein degradation. The epigenetic deubiquitination disruption not only synergized with MOF-mediated sonocatalytic ROS production, but also inactivate deubiquitinating enzymes, blockade the deubiquitination process and further remove these resistances, both of which mutually behaved as reciprocal impetuses to significantly magnify SDT outcomes against liver cancers. Such a deubiquitination-engineered disruption approach finds an unprecedented pathway to disarm deubiquitination-induced resistances to SDT and other ROS-based anti-tumor means, which also enlightens us to establish other post-transcriptional epigenetic modification disruption strategies to re-program the tumor microenvironment and elevate the anti-tumor efficiency of various treatment methods (e.g., immunotherapy).</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 296-306"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43920929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of steel slag-based carbon sequestration","authors":"Qing Zhao ,&nbsp;Chengjun Liu ,&nbsp;Xiaohui Mei ,&nbsp;Henrik Saxén ,&nbsp;Ron Zevenhoven","doi":"10.1016/j.fmre.2022.09.023","DOIUrl":"10.1016/j.fmre.2022.09.023","url":null,"abstract":"<div><div>Large amounts of steel slag (SS) and CO₂ are produced globally each year during steel production. An SS-based carbon capture and utilization (SS-CCU) process for CO₂ mineralization is suitable specifically for steel-making industries for simultaneous mitigation of CO₂ emissions and valorization of wastes. However, the SS-CCU process is currently in the stage of laboratory research and far away from industrial application. In this review, some SS-CCU processes, including direct and indirect carbonation processes, were explored and summarized. Herein, the key factors and mechanisms of the SS-based CO₂ sequestration process were identified. The carbonation process efficacy and its environmental impact (including global warming, energy use, water use, and metallic pollutants) were evaluated. Furthermore, the challenges and prospects of the further development of the SS-CCU process were discussed.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 282-287"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44661587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polarization variable terahertz metasurface along the propagation path","authors":"Jitao Li ,&nbsp;Jingyu Liu ,&nbsp;Zhen Yue ,&nbsp;Jie Li ,&nbsp;Chenglong Zheng ,&nbsp;Fan Yang ,&nbsp;Hui Li ,&nbsp;Yating Zhang ,&nbsp;Yan Zhang ,&nbsp;Jianquan Yao","doi":"10.1016/j.fmre.2023.03.017","DOIUrl":"10.1016/j.fmre.2023.03.017","url":null,"abstract":"<div><div>Conventional metasurfaces for terahertz polarization are limited to performing lateral (in the <em>x-y</em> plane) polarization control of the output wave. In such cases, the polarization state remains unchanged in each output plane along the propagation path. Herein, we propose a terahertz polarization metasurface that operates longitudinally (i.e., along the <em>z</em>-axis direction of propagation), which modifies the polarization state of each output plane throughout the propagation path. Our designed metasurface can control the phase delays of the left-handed and right-handed circularly polarized (LCP and RCP) components of the incident terahertz wave. This enables the LCP beam and RCP beam to converge to the <em>z</em>-axis through distinct paths, creating a Bessel beam. The proposed design achieved a linearly polarized terahertz wave including both LCP and RCP components with a precise phase difference Δ<em>φ</em> at each point within a certain range along the <em>z</em>-axis. The Δ<em>φ</em> varies as the propagation distance, resulting in a rotated linearly polarized output wave along the propagation path, while the rotation angle ranges from 0 to π. Based on the variable property of longitudinal polarization, we propose an application concept of dielectric refractive index sensing, in which an additional medium is placed in the terahertz propagation path and the unknown refractive index is determined by detecting the rotation angle of the output polarization state. Theoretically, the device might find potential applications in variable media excitation, terahertz communication, and terahertz radar ranging.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 124-131"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42542580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease prediction by network information gain on a single sample basis","authors":"Jinling Yan ,&nbsp;Peiluan Li ,&nbsp;Ying Li ,&nbsp;Rong Gao ,&nbsp;Cheng Bi ,&nbsp;Luonan Chen","doi":"10.1016/j.fmre.2023.01.009","DOIUrl":"10.1016/j.fmre.2023.01.009","url":null,"abstract":"<div><div>There are critical transition phenomena during the progression of many diseases. Such critical transitions are usually accompanied by catastrophic disease deterioration, and their prediction is of significant importance for disease prevention and treatment. However, predicting disease deterioration solely based on a single sample is a difficult problem. In this study, we presented the network information gain (NIG) method, for predicting the critical transitions or disease state based on network flow entropy from omics data of each individual. NIG can not only efficiently predict disease deteriorations but also detect their dynamic network biomarkers on an individual basis and further identify potential therapeutic targets. The numerical simulation demonstrates the effectiveness of NIG. Moreover, our method was validated by successfully predicting disease deteriorations and identifying their potential therapeutic targets from four real omics datasets, i.e., an influenza dataset and three cancer datasets.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 215-227"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43590705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum dots enhanced stability of in-situ fabricated perovskite nanocrystals based light-emitting diodes: Electrical field distribution effects","authors":"Xulan Xue ,&nbsp;Menglin Li ,&nbsp;Zhenjie Liu ,&nbsp;Chenhui Wang ,&nbsp;Jincheng Xu ,&nbsp;Shuangpeng Wang ,&nbsp;Hanzhuang Zhang ,&nbsp;Haizheng Zhong ,&nbsp;Wenyu Ji","doi":"10.1016/j.fmre.2022.08.004","DOIUrl":"10.1016/j.fmre.2022.08.004","url":null,"abstract":"<div><div>With the development in fabricating efficient perovskite light emitting diodes (PeLEDs), improving the operating stability becomes an urgent task. Here we report quantum dot (QD) enhanced stability of PeLEDs by introducing CdSe/ZnS core-shell QDs in toluene anti-solvent during <em>in</em>-<em>situ</em> fabrication of FAPbBr₃ perovskite nanocrystals (PNCs) films. In comparison with PNC films with pristine toluene as the anti-solvent, the as-prepared FAPbBr₃ PNC films with a QD monolayer on the surface exhibit improved photoluminescence quantum yield, enhanced photostability and better reproducibility. Benefiting from these advantages, the peak luminance and the maximum external quantum efficiency of the PeLED containing QD monolayer are increased from 6807 cd/m² to 86,670 cd/m² and 2.4% to 7.1%, respectively. The <em>T</em>₅₀ lifetime under the initial luminance of 1021 cd/m² approaches 83 minutes. Based on electrical field simulation and transient electroluminescence measurements, the enhanced stability can be mainly attributed to the electrical field redistribution induced by the QD monolayer. This work demonstrates that the combination of QDs and perovskites provides an effective strategy to address the operational stability of PeLEDs. The insights into electrical field distribution effect will make great impact on stability improvement of other perovskite based devices.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 347-353"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44975629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Logarithmic sensitivity ratio elucidates thermal transport physics in multivariate thermoreflectance experiments","authors":"Jing Tu ,&nbsp;Md Azimul Haque ,&nbsp;Derya Baran ,&nbsp;Wee-Liat Ong","doi":"10.1016/j.fmre.2023.01.010","DOIUrl":"10.1016/j.fmre.2023.01.010","url":null,"abstract":"<div><div>We mathematically derived a sensitivity-based method that identifies the thermal transport physics and parameters suitable for multivariate nonlinear fits in a frequency-domain thermoreflectance (FDTR) experiment. Modern electronic devices often consist of heterogeneous nanolayers with multiple unknown thermal transport properties. However, simultaneous fitting in a single experiment for these unknown parameters will produce unreliable results if they are correlated. Current methods to identify such correlations are unreliable. This unreliability has impeded the accuracy and speed of characterizing the unknown thermal properties of such multilayer stacks. Our proposed logarithmic sensitivity ratio (LSR) analysis can evaluate the feasibility of fitting a pair of unknown parameters and clarify the governing thermal transport physics. The effectiveness and convenience of this analysis were studied using Monte Carlo simulations and actual FDTR experiments for fitting up to three unknown parameters. The principle behind this method can be extended to other techniques where multivariate fits are needed.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 288-295"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47143671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current AAV-mediated gene therapy in sensorineural hearing loss","authors":"Jieyu Qi ,&nbsp;Xiaolong Fu ,&nbsp;Liyan Zhang ,&nbsp;Fangzhi Tan ,&nbsp;Nianci Li ,&nbsp;Qiuhan Sun ,&nbsp;Xiaojie Hu ,&nbsp;Zuhong He ,&nbsp;Ming Xia ,&nbsp;Renjie Chai","doi":"10.1016/j.fmre.2022.08.015","DOIUrl":"10.1016/j.fmre.2022.08.015","url":null,"abstract":"<div><div>The number of patients with hearing loss is on the rise due to congenital abnormalities, degenerative changes in old age, and acquired injuries such as virus or ototoxic drug-induced diseases. Hearing loss is a refractory and disabling disease that has serious negative effects on quality of life. The pathology of hearing loss in the inner ear is characterized by varying degrees of damage to the cochlear sensory epithelium cells (such as hair cells and supporting cells), stria vascularis (including marginal, intermediate and basal cells) and spiral ganglion neurons. Regeneration or direct repair of damaged cells in the inner ear is an effective way to treat sensorineural deafness. It is currently possible to regenerate hair cells to treat sensorineural hearing loss by FX-322, a small molecule drug in clinical trials. With the development of genetic engineering technology, gene therapy has brought a promising treatment strategy for many previously intractable diseases. Gene therapy has been regarded as a promising method in the treatment and rehabilitation of sensorineural hearing loss, and recombinant adeno-associated virus gene therapy has been widely used in fundamental research into hearing loss treatments. At present, gene therapy for hearing loss is transitioning from feasibility studies to explorations of its safety and its therapeutic potential. The present article reviews the concepts, strategies, and applications of gene therapy mediated by recombinant adeno-associated viruses in the field of hearing loss treatment.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 192-202"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49315482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiepileptic activity and potential mechanism of full-spectrum hemp extract","authors":"Zengliang Jin ,&nbsp;Zhuo Huang","doi":"10.1016/j.fmre.2024.11.002","DOIUrl":"10.1016/j.fmre.2024.11.002","url":null,"abstract":"<div><div>Epilepsy is the fourth most common neuropsychiatric disorder. Although the approval of Epidiolex has ignited hope for patients, there is still a large gap in the field of anti-seizure research. The effect and underlying mechanism of full-spectrum hemp extract (HE) remains unclear. Here this study investigated the anti-seizure effect of HE on seizure models. The results showed that HE significantly reduced seizure susceptibility and prolonged seizure latency with better pharmacokinetic performance compared to CBD. This article then further explored the anti-seizure active components and their possible mechanism in HE. The results indicated that cannabichromene (CBC) and cannabinol (CBN) were involved in the anti-seizure process, especially CBC showed a strong allosteric enhancement effects on CBD binding site of the GABAA receptor, which implied that the GABAA receptor seemed to be the primary anti-epileptic target of HE. This article not only presents the great potential of HE as a candidate for new anti-epileptic drugs with less psychoactive, but also provides a valuable contribution to subsequent mechanism research and drug development on epilepsy.Abstract: Epilepsy is the fourth most coneuropsychiatric disorder. Although the approval of Epidiolex has ignited hope for patients, there is still a large gap in the field of anti-seizure research. The effect and underlying mechanism of full-spectrum hemp extract remains unclear. Here this study investigated the anti-seizure effect of HE on seizure models. The results showed that HE significantly reduced seizure susceptibility and prolonged seizure latency with better pharmacokinetic performance compared to CBD. This article then further explored the anti-seizure active components and their possible mechanism in HE. The results indicated that cannabichromene and cannabinol were involved in the anti-seizure process, especially CBC showed a strong allosteric enhancement effects on CBD binding site of the GABAA receptor, which implied that the GABAA receptor seemed to be the primary anti-epileptic target of HE. This article not only presents the great potential of HE as a candidate for new anti-epileptic drugs with less psychoactive, but also provides a valuable contribution to subsequent mechanism research and drug development on epilepsy.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 1","pages":"Pages 379-380"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143175609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}