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Photonics Research 2024年第4期12卷 821-832页

作者： WEI SHI YINGCHUAN HE JIANLIN WANG LULU ZHOU JIANWEI CHEN LIWEI ZHOU ZEYU XI ZHEN WANG KE FANG YIMING LI Department of biomedical Engineering Southern University of Science and TechnologyShenzhen 518055China

Single-molecule localization microscopy(SMLM)enables three-dimensional(3D)investigation of nanoscale structures in biological samples,offering unique insights into their organization.However,traditional 3D super-resolution microscopy using high numerical aperture(NA)objectives is limited by imaging depth of field(DOF),restricting their practical application to relatively thin biological samples.Here,we developed a unified solution for thick sample super-resolution imaging using a deformable mirror(DM)which served for fast remote focusing,optimized point spread function(PSF)engineering,and accurate aberration correction.By effectively correcting the system aberrations introduced during remote focusing and sample aberrations at different imaging depths,we achieved high-accuracy,large DOF imaging(~8μm)of the whole-cell organelles[i.e.,nuclear pore complex(NPC),microtubules,and mitochondria]with a nearly uniform resolution of approximately 35 nm across the entire cellular volume.

关键词： enable mirror resolution

Long-term in vivo chimeric cells tracking in non-human primate

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Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang Xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of Primate biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate biomedical Research Kunming 650500China Faculty of Life science and technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

Deep neural network based on multi-level wavelet and attention for structured illumination microscopy

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Journal of Innovative Optical Health sciences 2024年第2期17卷 12-23页

作者： Yanwei Zhang Song Lang Xuan Cao Hanqing Zheng Yan Gong School of biomedical Engineering(Suzhou)division of Life sciencesand Medicine University of science and technology of China Hefei Anhui230026P.R.China Suzhou Institute of biomedical Engineering and technology Chinese Academy of sciences Suzhou Jiangsu 215163P.R.China School of Physical science and technology Suzhou University of science and technology Suzhou Jiangsu 215009P.R.China

Structured illumination microscopy(SIM)is a popular and powerful super-resolution(SR)technique in biomedical research.However,the conventional reconstruction algorithm for SIM heavily relies on the accurate prior knowledge of illumination patterns and signal-to-noise ratio(SNR)of raw images.To obtain high-quality SR images,several raw images need to be captured under high fluorescence level,which further restricts SIM’s temporal resolution and its applications.Deep learning(DL)is a data-driven technology that has been used to expand the limits of optical microscopy.In this study,we propose a deep neural network based on multi-level wavelet and attention mechanism(MWAM)for SIM.Our results show that the MWAM network can extract high-frequency information contained in SIM raw images and accurately integrate it into the output image,resulting in superior SR images compared to those generated using wide-field images as input data.We also demonstrate that the number of SIM raw images can be reduced to three,with one image in each illumination orientation,to achieve the optimal tradeoff between temporal and spatial resolution.Furthermore,our MWAM network exhibits superior reconstruction ability on low-SNR images compared to conventional SIM algorithms.We have also analyzed the adaptability of this network on other biological samples and successfully applied the pretrained model to other SIM systems.

关键词： Super-resolution reconstruction multi-level wavelet packet transform residual channel attention selective kernel attention

Three-dimensional morphological and fluorescent imaging of zebrafish with a continuous-rotational light-sheet microscope

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Journal of Innovative Optical Health sciences 2024年第2期17卷 59-66页

作者： Dongmin Zhang Guang Yang Yao Tan Chong Chen Jie Zhang Hui Li School of biomedical Engineering(Suzhou)division of Life sciences and Medicine University of science and technology of China Hefei 230041 P.R.China Suzhou Institute of biomedical Engineering and technology Chinese A cademy of sciences Suzhou Jiangsu 215163P.R.China

Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scattering cause shading of the light-sheet illumination,preventing the even 3D image of thick samples.Herein,we report a continuous-rotational light-sheet microscope(CR-LSM)that enables simultaneous 3D bright-field and fluorescence imaging.With a high-accuracy rotational stage,CR-LSM records the outline projections and the fluorescent images of the sample at multiple rotation angles.Then,3D morphology and fluorescent structure were reconstructed with a developed algorithm.Using CR-LSM,zebrafish’s whole-fish contour and blood vessel structures were obtained simultaneously.

关键词： Light-sheet microscope zebrafish blood vessels morphology

The Application of Permanent Magnet Synchronous Motor with Small Electrical Time Constant in Fiber Positioner

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Research in Astronomy and Astrophysics 2024年第1期24卷 212-222页

作者： Shaoxiong Guo Yan Yang Yanbin Yin Yihu Tang Yang Tian Chao Zhai Department of Precision Machinery and Precision Instrumentation University of Science and Technology of ChinaHefei 230026China School of biomedical Engineering Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Experiment Center of Engineering and Material science University of Science and Technology of ChinaHefei 230026China

With the development of cutting-edge multi-object spectrographs,fiber positioners located in the focal plane are being scaled down in size,and miniature hollow-cup Permanent Magnet motors are now being considered as a suitable replacement for Faulhaber Precistep stepper motors.However,the small electrical time constant of such coreless motors poses a challenge,as the problem of severe commutation torque ripple in a fiber positioner running a position loop has been tricky.To overcome this challenge,it is advised to increase the Pulse Width Modulation(PWM)frequency as much as possible to mitigate the effects of the current fluctuation.This must be done while ensuring adequate resolution of the PWM generator.By employing a voltage open-loop field-oriented control based on a modulation frequency of 1 MHz,the drive current only costs 25 m A under a 3.3 V power supply.The sine degree of phase current is immaculate,and the repeat positioning accuracy can reach 2μm.Moreover,it is possible to further shrink the bill of devices and the layout area of the Printed Circuit Board,especially in sizesensitive applications.This device has been developed under the new generation of The Large Sky Area MultiObject Fiber Spectroscopic Telescope.

关键词： instrumentation:adaptive optics instrumentation:spectrographs proper motions reference systems

Modified DS np Chart Using Generalized Multiple Dependent State Sampling under Time Truncated Life Test

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Computer Modeling in Engineering & sciences 2024年第3期138卷 2471-2495页

作者： Wimonmas Bamrungsetthapong Pramote Charongrattanasakul division of Applied Statistics Department of Mathematics and Computer ScienceFaculty of Science and TechnologyRajamangala University of Technology ThanyaburiPathum Thani12110Thailand division of Mathematics Department of Mathematics and Computer ScienceFaculty of Science and TechnologyRajamangala University of Technology KrungthepBangkok10120Thailand

This study presents the design of a modified attributed control chart based on a double sampling(DS)np chart applied in combination with generalized multiple dependent state(GMDS)sampling to monitor the mean life of the product based on the time truncated life test employing theWeibull distribution.The control chart developed supports the examination of the mean lifespan variation for a particular product in the process of manufacturing.Three control limit levels are used:the warning control limit,inner control limit,and outer control limit.Together,they enhance the capability for variation detection.A genetic algorithm can be used for optimization during the in-control process,whereby the optimal parameters can be established for the proposed control chart.The control chart performance is assessed using the average run length,while the influence of the model parameters upon the control chart solution is assessed via sensitivity analysis based on an orthogonal experimental design withmultiple linear regression.A comparative study was conducted based on the out-of-control average run length,in which the developed control chart offered greater sensitivity in the detection of process shifts while making use of smaller samples on average than is the case for existing control charts.Finally,to exhibit the utility of the developed control chart,this paper presents its application using simulated data with parameters drawn from the real set of data.

关键词： Modified DS np chart generalizedmultiple dependent state sampling time truncated life test Weibull distribution average run length average sample size

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

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Asian Journal of Pharmaceutical sciences 2024年第1期19卷 69-85页

作者： Noehyun Myung Hyun-Wook Kang Department of biomedical Engineering Ulsan National Institute of Science and Technology(UNIST)Ulju-gun 44919South Korea

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

关键词： Dose-dense chemotherapy Triple-negative breast cancer 3D printing Pulsatile release Local drug delivery systems

Unified deep learning model for predicting fundus fluorescein angiography image from fundus structure image

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Journal of Innovative Optical Health sciences 2024年第3期17卷 105-113页

作者： Yiwei Chen Yi He Hong Ye Lina Xing Xin Zhang Guohua Shi Jiangsu Key Laboratory of Medical Optics Suzhou Institute of Biomedical Engineering and TechnologyChinese Academy of SciencesSuzhou 215163P.R.China School of biomedical Engineering(Suzhou) Division of Life Sciences and MedicineUniversity of Science and Technology of China Hefei 230026P.R.China Center for Excellence in Brain science and Intelligence technology Chinese Academy of SciencesShanghai 200031P.R.China

The prediction of fundus fluorescein angiography(FFA)images from fundus structural images is a cutting-edge research topic in ophthalmological image processing.Prediction comprises estimating FFA from fundus camera imaging,single-phase FFA from scanning laser ophthalmoscopy(SLO),and three-phase FFA also from SLO.Although many deep learning models are available,a single model can only perform one or two of these prediction tasks.To accomplish three prediction tasks using a unified method,we propose a unified deep learning model for predicting FFA images from fundus structure images using a supervised generative adversarial network.The three prediction tasks are processed as follows:data preparation,network training under FFA supervision,and FFA image prediction from fundus structure images on a test set.By comparing the FFA images predicted by our model,pix2pix,and CycleGAN,we demonstrate the remarkable progress achieved by our proposal.The high performance of our model is validated in terms of the peak signal-to-noise ratio,structural similarity index,and mean squared error.

关键词： Fundus fluorescein angiography image fundus structure image image translation unified deep learning model generative adversarial networks

Integration of multiple flexible electrodes for realtime detection of barrier formation with spatial resolution in a gut-on-chip system

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Microsystems & Nanoengineering 2024年第1期10卷 105-114页

作者： Mara Lucchetti Gabriel Werr Sofia Johansson Laurent Barbe Léa Grandmougin Paul Wilmes Maria Tenje Luxembourg Centre for Systems Biomedicine(LCSB) University of LuxembourgEsch-sur-Alzette L-4362Luxembourg division of biomedical Engineering Department of Materials Science and EngineeringScience for Life LaboratoryUppsala University75121 UppsalaSweden Department of Life sciences and Medicine Faculty of ScienceTechnology and MedicineUniversity of LuxembourgEsch-sur-Alzette L-4362Luxembourg

In healthy individuals,the intestinal epithelium forms a tight barrier to prevent gut bacteria from reaching blood circulation.To study the effect of probiotics,dietary compounds and drugs on gut barrier formation and disruption,human gut epithelial and bacterial cells can be cocultured in an in vitro model called the human microbial crosstalk(HuMiX)gut-on-a-chip system.Here,we present the design,fabrication and integration of thin-film electrodes into the HuMiX platform to measure transepithelial electrical resistance(TEER)as a direct readout on barrier tightness in realtime.As various aspects of the HuMiX platform have already been set in their design,such as multiple compressible layers,uneven surfaces and nontransparent materials,a novel fabrication method was developed whereby thin-film metal electrodes were first deposited on flexible substrates and sequentially integrated with the HuMiX system via a transfer-tape approach.Moreover,to measure localized TEER along the cell culture chamber,we integrated multiple electrodes that were connected to an impedance analyzer via a multiplexer.We further developed a dynamic normalization method because the active measurement area depends on the measured TEER levels.The fabrication process and system setup can be applicable to other barrier-on-chip systems.As a proof-of-concept,we measured the barrier formation of a cancerous Caco-2 cell line in real-time,which was mapped at four spatially separated positions along the HuMiX culture area.

关键词： barrier system multiple

Fli1 acts in parallel with Pu.1 to control macrophage and neutrophil fate in zebrafish

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Journal of Genetics and Genomics 2024年第3期51卷 359-362页

作者： Ao Zhang Jingao Lu Shachuan Feng Huapeng Yu Tao Yu Shizheng Zhao Kemin Chen Zhibin Huang Jin Xu Jianan Y.Qu Zilong Wen division of Life science Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China Department of Immunology and Microbiology School of Life ScienceSouthern University of Science and TechnologyShenzhenGuangdong 518055China biomedical Research Institute Shenzhen Peking University-Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China Department of Electronic and Computer Engineering Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Greater Bay biomedical Innocenter Shenzhen Bay LaboratoryShenzhenGuangdong 518067China

Macrophages and neutrophils are key components of myeloid cells and play critical roles in innate immune responses,organ formation,and tissue homeostasis.The integrity of their functions heavily relies on the generation of a proper number of mature macrophages and neutrophils through embryonic and adult myelopoiesis.In mammalian adult myelopoiesis,oligopotent common myeloid progenitors(CMPs)are known to be the earliest myeloid progenitors,which give rise to granulocyte-macrophage progenitors(GMPs),subsequently differentiate into unipotent neutrophil and macrophage precursors,and finally,mature macrophages and neutrophils(Orkin and Zon,2008).In contrast,the ontogeny of embryonic myelopoiesis and the mechanism underlying the formation of macrophages and neutrophils remainless understood.

关键词： fish macrophage homeostasis