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Simple and robust 3D MINFLUX excitation with a variable phase plate

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Light(Science & Applications) 2024年第7期13卷 1354-1363页

作者： Takahiro Deguchi Jonas Ries European molecular biology laboratory Cell Biology and BiophysicsHeidelbergGermany. Max Perutz Labs Vienna Biocenter Campus(VBC)ViennaAustria. University of Vienna Center for Molecular BiologyDepartment of Structural and Computational BiologyViennaAustria. University of Vienna Faculty of PhysicsViennaAustria

MINFLUX has achieved extraordinary resolution in superresolution imaging and single fluorophore *** is based on localizing single fluorophores by rapid probing with a patterned beam that features a local intensity *** implementations,however,are complex and expensive and are limited in speed and ***,we show that a combination of an electro-optical modulator with a segmented birefringent element such as a spatial light modulator produces a variable phase plate for which the phase can be scanned on the MHz *** or top-hat phase patterns generate high-contrast compact excitation point-spread functions for MINFLUX localization in the x,y,and z-direction,respectively,which can be scanned across a fluorophore within a microsecond,switched within 60 microseconds and alternated among different excitation *** discuss how to compensate for non-optimal performance of the components and present a robust 3D and multi-color MINFLUX excitation module,which we envision as an integral component of a high-performance and cost-effective open-source MINFLUX.

关键词： excitation phase switched

Classifying hepatitis B therapies with insights from covalently closed circular DNA dynamics

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Virologica Sinica 2024年第1期39卷 9-23页

作者： Jie-Li Hu Ai-Long Huang Key laboratory of molecular biology on Infectious Diseases Ministry of EducationChongqing Medical UniversityChongqing400016China

The achievement of a functional cure for chronic hepatitis B(CHB)remains limited to a minority of patients treated with currently approved *** primary objective in developing new anti-HBV drugs is to enhance the functional cure rates for CHB.A critical prerequisite for the functional cure of CHB is a substantial reduction,or even eradication of covalently closed circular DNA(cccDNA).Within this context,the changes in cccDNA levels during treatment become as a pivotal *** have previously analyzed the factors influencing cccDNA dynamics and introduced a preliminary classification of hepatitis B treatment strategies based on these *** this review,we employ a systems thinking perspective to elucidate the fundamental aspects of the HBV replication cycle and to rationalize the classification of treatment strategies according to their impact on the dynamic equilibrium of *** upon this foundation,we categorize current anti-HBV strategies into two distinct groups and advocate for their combined use to significantly reduce cccDNA levels within a well-defined timeframe.

关键词： Hepatitis B cccDNA Functional cure Dynamics Treatment Strategy

Mitogenome-based phylogeny of mosquitoes(Diptera:Culicidae)

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Insect Science 2024年第2期31卷 599-612页

作者： De-Hong Chen Shu-Lin He Wen-Bo Fu Zhen-Tian Yan Yun-Jian Hu Huan Yuan Ming-Bin Wang Bin Chen Chongqing Key laboratory of Vector Insects Institute of Entomology and Molecular BiologyChongqing Normal UniversityChongqingChina

Mosquitoes are of great medical significance as vectors of many deadly *** have been widely used in phylogenetic studies,but mitogenome knowledge within the family Culicidae is limited,and Culicidae phylogeny is far from *** this study,we surveyed the mitogenomes of 149 Culicidae species,including 7 newly sequenced *** analysis of 149 mosquito mitogenomes shows gene composition and order to be identical to that of an ancestral insect,and the AT bias,length variation,and codon usage are all consistent with that of other reported Dipteran *** analyses based on the DNA sequences of the 13 protein-coding genes from the 149 species robustly support the monophyly of the subfamily Anophelinae and the tribes Aedini,Culicini,Mansonini,Sabethini,and *** resolve ambiguous relationships between clades within the subfamily Culicinae,we performed topological tests and show that Aedini is a sister to Culicini and that Uranotaenini is a sister to(Mansonini)+(Toxorhynchitini+Sabethini).In addition,we estimated divergence times using a Bayesian relaxation clock based on the sequence data and 3 fossil calibration *** results show mosquitoes diverged during the Early Jurassic with massive Culicinae radiations during the Cretaceous,coincident with the emergence of angiosperms and the burst of mammals and ***,this study,which uses the largest number of Culicidae mitogenomes sequenced to date,comprehensively reveals the mitogenome characteristics and mitogenome-based phylogeny and divergence times of Culicidae,providing information for further studies on the mitogenome,phylogeny,evolution,and taxonomic revision of Culicidae.

关键词： characterization Culicidae evolution mitogenomes mosquitoes phylogeny

“Three-in-one” strategy of trifluoromethyl regulated blood-brain barrier permeable fluorescent probe for peroxynitrite and antiepileptic evaluation of edaravone

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Chinese Chemical Letters 2024年第10期35卷 360-363页

作者： Lei Shen Hongmei Liu Ming Jin Jinchao Zhang Caixia Yin Shuxiang Wang Yutao Yang Key laboratory of Medicinal Chemistry and molecular Diagnosis of the Ministry of Education Chemical Biology Key Laboratory of Hebei ProvinceState Key Laboratory of New Pharmaceutical Preparations and ExcipientsCollege of Chemistry and Materials ScienceHebei UniversityBaoding 071002China Key laboratory of Chemical biology and molecular Engineering of Ministry of Education Institute of Molecular ScienceShanxi UniversityTaiyuan 030006China

Epilepsy,as a chronic neurological disease of the brain,is closely related to oxidative stress,and the peroxynitrite(ONOO-)significantly rise up in this ***,ONOO-is considered as a potential biomarker for early prediction of ***,some potential diagnostic reagents for epilepsy are hindered by the blood-brain barrier(BBB).Meanwhile,“drug repurposing”is attracting a growing ***(EDA),as a first-line drug in the clinical treatment of cerebral ischemia,plays antioxidant roles in scavenging free radicals,promising potential antiepileptic ***,it is imperative to develop fluorescent probes for monitoring ONOO-fluctuations in the epileptic ***,we proposed a novel fluorescent probe with the thiocarbonate as the promising recognition unit for ONOO-and dicyanoisophorone derivative as the ***,by the“three-in-one”strategy,the introduction of trifluoromethyl into DCI-ONOO-3 can extend the emission wavelength of the fluorophore,shorten the response and increase ***,DCI-ONOO-3 was used for monitoring ONOO-fluxes in brain of epileptic mice and evaluating the antiepileptic efficacy of *** opens up a new way for the design of BBB permeable fluorescent probes,and provides a convincing new method for the diagnosis and treatment of epilepsy.

关键词： Fluorescent probe Blood-brain barrier Peroxynitrite Epilepsy Drug repurposing

Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai Key laboratory of Reproductive Medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key laboratory of molecular biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental *** a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and *** gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ *** maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)*** addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization *** conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

Refining biome labeling for large-scale microbial community samples:Leveraging neural networks and transfer learning

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Environmental Science and Ecotechnology 2024年第1期17卷 128-137页

作者： Nan Wang Teng Wang Kang Ning Key laboratory of molecular Biophysics of the Ministry of Education Hubei Key Laboratory of Bioinformatics and Molecular-imagingCenter of AI BiologyDepartment of Bioinformatics and Systems BiologyCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074HubeiChina

Microbiome research has generated an extensive amount of data,resulting in a wealth of publicly accessible *** annotation of these samples is crucial for effectively utilizing microbiome data across scientific ***,a notable challenge arises from the lack of essential annotations,particularly regarding collection location and sample biome information,which significantly hinders environmental microbiome *** this study,we introduce Meta-Sorter,a novel approach utilizing neural networks and transfer learning,to enhance biome labeling for thousands of microbiome samples in the MGnify database that have incomplete *** findings demonstrate that Meta-Sorter achieved a remarkable accuracy rate of 96.7%in classifying samples among the 16,507 lacking detailed biome ***,Meta-Sorter provides precise classifications for representative environmental samples that were previously ambiguously labeled as“Marine”in MGnify,thereby elucidating their specific origins in benthic and water column ***,Meta-Sorter effectively distinguishes samples derived from human-environment interactions,enabling clear differentiation between environmental and human-related *** improving the completeness of biome label information for numerous microbial community samples,our research facilitates more accurate knowledge discovery across diverse disciplines,with particular implications for environmental research.

关键词： Microbial community Transfer learning Sample classification Environmental scientific research Novel knowledge discovery

The piRNA size matters

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National Science Review 2024年第2期11卷 96-98页

作者： Jingwen Liu Falong Lu State Key laboratory of molecular Developmental biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences

Small RNAs, including small interfering RNAs(siRNAs), microRNAs(miRNAs) and PIWI-interacting RNAs(piRNAs), serve as pivotal agents in the post-transcriptional regulation of gene expression [1–3]. Among these,piRNAs t... 详细信息

关键词： PIWI

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis laboratory of Developmental biology Department of BiologyUniversity of PatrasPatrasGreece laboratory of Cellular and molecular Neurobiology-Stem Cells Hellenic Pasteur InstituteAthensGreece Department of Physiology School of MedicineUniversity of PatrasPatrasGreece

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal ***,we extended our investigation in two clinically-relevant ***,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian ***,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of *** found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian *** agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver ***,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin *** results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by ***,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells(iPSCs) neurotrophic factors Parkinson's disease substantia

Heat Shock Factor A1s are required for phytochrome-interacting factor 4-mediated thermomorphogenesis in Arabidopsis

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Journal of Integrative Plant biology 2024年第1期66卷 20-35页

作者： Bingjie Li Shimeng Jiang Liang Gao Wenhui Wang Haozheng Luo Yining Dong Zhihua Gao Shuzhi Zheng Xinye Liu Wenqiang Tang Key laboratory of molecular and Cellular biology of Ministry of Education Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell SignalingHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China School of Information Technology Hebei University of Economics and BusinessShijiazhuang 050061China

Thermomorphogenesis and the heat shock(HS)response are distinct thermal responses in plants that are regulated by PHYTOCHROME-INTERACTING FACTOR 4(PIF4)and HEAT SHOCK FACTOR A1s(HSFA1s),*** is known about whether these responses are interconnected and whether they are activated by similar *** analysis of transcriptome dynamics in response to warm temperature(28℃)treatment revealed that 30 min of exposure activated the expression of a subset of HSFA1 target genes in Arabidopsis ***,a loss-of-function HSFA1 quadruple mutant(hsfa1-cq)was insensitive to warm temperature-induced hypocotyl *** hsfa1-cq plants grown at 28℃,the protein and transcript levels of PIF4 were greatly reduced,and the circadian rhythm of many thermomorphogenesis-related genes(including PIF4)was ***,the nuclear localization of HSFA1s and the binding of HSFA1d to the PIF4 promoter increased following warm temperature exposure,whereas PIF4 overexpression in hsfa1-cq partially rescued the altered warm temperature-induced hypocotyl growth of the *** together,these results suggest that HSFA1s are required for PIF4 accumulation at a warm temperature,and they establish a central role for HSFA1s in regulating both thermomorphogenesis and HS responses in Arabidopsis.

关键词： HSFA1 PIF4 thermomorphogenesis