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CRISPR,CAR-T,and NK:Current applications and future perspectives

Genes & Diseases 2024年第4期11卷 246-257页

作者： Mohadeseh Khoshandam Hossein Soltaninejad Amir Ali Hamidieh Saman Hosseinkhani department of Reproductive Biology Academic Center for EducationCultureand Research(ACECR)Qom branch***Iran National Institute of Genetic engineering and biotechnology(NIGEB) Tehran 14965/161Iran department of stem cells technology and Tissue Regeneration Faculty of Interdisciplinary Science and TechnologiesTarbiat Modares UniversityTehran 15614Iran Pediatric Cell Therapy and Gene Therapy Research Center GeneCell&Tissue Research InstituteTehran University of Medical SciencesTehran ***Iran department of Biochemistry Faculty of Biological SciencesTarbiat Modares UniversityTehran 15614Iran

Chimeric antigen receptor T(CAR-T)cell therapy represents a breakthrough in personalized cancer treatments.In this regard,synthetic receptors comprised of antigen recognition domains,signaling,and stimulatory domains are used to reprogram T-cells to target tum or cells and destroy them.Despite the success of this approach in refractory B-cell malignancies,the optimal potency of CAR T-cell therapy for many other cancers,particularly solid tumors,has not been validated.Natural killer cells are powerful cytotoxic lymphocytes specialized in recognizing and dispensing the tumor cells in coordination with other anti-tumor immunity cells.Based on these studies,many investigations are focused on the accurate designing of CAR T-cells with clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system or other novel gene editing tools that can induce hereditary changes with or without the presence of a double-stranded break into the genome.These methodologies can be specifically focused on negative controllers of T-cells,induce modifications to a particular gene,and produce reproducible,safe,and powerful allogeneic CAR T-cells for on-demand cancer immunotherapy.The improvement of the CRISPR/Cas9 innovation offers an adaptable and proficient gene-editing capability in activating different pathways to help natural killer cells interact with novel CARs to particularly target tumor cells.Novel achievements and future challenges of combining next-generation CRISPR-Cas9 gene editing tools to optimize CAR T-cell and natural killer cell treatment for future clinical trials toward the foundation of modern cancer treatments have been assessed inthis review.

关键词： Cancer CAR T-cell CRISPR Gene editing Immunotherapy NK cell

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Non-invasive imaging of pathological scars using a portable handheld two-photon microscope

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Chinese medical Journal 2024年第3期137卷 329-337页

作者： Yang Han Yuxuan Sun Feili Yang Qingwu Liu Wenmin Fei Wenzhuo Qiu Junjie Wang Linshuang Li Xuejun Zhang Aimin Wang Yong Cui Graduate School Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China department of Dermatology China-Japan Friendship HospitalBeijing 100029China College of engineering Peking UniversityBeijing 100871China School of Chemical Biology and biotechnology State Key Laboratory of Chemical OncogenomicsPeking University Shenzhen Graduate SchoolShenzhenGuangdong 518055China department of Dermatology The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China College of Future Technology Peking UniversityBeijing 100871China Beijing Transcend Vivoscope Biotech Beijing 100085China department of Dermatology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230001China Institute of Dermatology Anhui Medical UniversityHefeiAnhui 230001China School of Electronics Peking UniversityBeijing 100871China

Background:Pathological scars are a disorder that can lead to various cosmetic,psychological,and functional problems,and no effective assessment methods are currently available.Assessment and treatment of pathological scars are based on cutaneous manifestations.A two-photon microscope(TPM)with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo.This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients.Methods:Fifteen patients with pathological scars and three healthy controls were recruited.Imaging was performed using a portable handheld TPM.Five indexes were extracted from two dimensional(2D)and three dimensional(3D)perspectives,including collagen depth,dermo-epidermal junction(DEJ)contour ratio,thickness,orientation,and occupation(proportion of collagen fibers in the field of view)of collagen.Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images.We assessed index differences between scar and normal skin and changes before and after treatment.Results:Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers.Five indexes were employed to distinguish between normal skin and scar tissue.Statistically significant differences were found in average depth(t=9.917,P<0.001),thickness(t=4.037,P<0.001),occupation(t=2.169,P<0.050),orientation of collagen(t=3.669,P<0.001),and the DEJ contour ratio(t=5.105,P<0.001).Conclusions:Use of portable handheld TPM can distinguish collagen from skin tissues;thus,it is more suitable for scar imaging than reflectance confocal microscopy.Thus,a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

关键词： Scars Two-photon microscope Two-photon excitation fluorescence Second harmonic generation microscopy

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MXene-Based Elastomer Mimetic StretchableSensors: Design, Properties, and Applications

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Nano-Micro Letters 2024年第7期16卷 295-342页

作者： Poushali Das Parham Khoshbakht Marvi Sayan Ganguly Xiaowu(Shirley)Tang Bo Wang Seshasai Srinivasan Amin Reza Rajabzadeh Andreas Rosenkranz School of Biomedical engineering McMaster University1280 Main Street WestHamiltonON L8S 4L8Canada department of Chemistry and Waterloo Institute for Nanotechnology(WIN) University of Waterloo200 University Ave WestWaterlooONCanada Centre for Eye and Vision Research(CEVR) 17W Hong Kong Science ParkShatinHong KongPeople’s Republic of China Chair of Functional Materials Department of Materials Science and EngineeringSaarland UniversitySaarbruckenGermany W Booth School of engineering Practice and Technology McMaster University1280 Main Street WestHamiltonON L8S 4L7Canada department for Chemical engineering Biotechnology and MaterialsUniversity of ChileSantiagoChile

Flexible sensors based on MXene-polymer composites are highly prospective for next-generation wearable electronics used in human-machine interfaces.One of the motivating factors behind the progress of flexible sensors is the steady arrival of new conductive materials.MXenes,a new family of 2D nanomaterials,have been draw-ing attention since the last decade due to their high electronic conduc-tivity,processability,mechanical robustness and chemical tunability.In this review,we encompass the fabrication of MXene-based polymeric nanocomposites,their structure-property relationship,and applications in the flexible sensor domain.Moreover,our discussion is not only lim-ited to sensor design,their mechanism,and various modes of sensing platform,but also their future perspective and market throughout the world.With our article,we intend to fortify the bond between flexible matrices and MXenes thus promoting the swift advancement of flexible MXene-sensors for wearable technologies.

关键词： Flexible sensor 2D nanomaterials MXene Wearable and conductive Applications

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Generative pretrained transformer 4:an innovative approach to facilitate value-based healthcare

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Intelligent Medicine 2024年第1期4卷 10-15页

作者： Han Lyu Zhixiang Wang Jia Li Jing Sun Xinghao Wang Pengling Ren Linkun Cai Zhenchang Wang Max Wintermark department of Radiology Capital Medical University Affiliated Beijing Friendship HospitalBeijing 100050China department of medical Imaging Capital Medical University Affiliated Beijing Friendship HospitalBeijing 100050China School of Biological Science and medical engineering Beihang UniversityBeijing 100191China department of Neuroradiology University of Texas MD Anderson CenterHoustonTX 77030USA

Objective Appropriate medical imaging is important for value-based care.We aim to evaluate the performance of generative pretrained transformer 4(GPT-4),an innovative natural language processing model,providing appropriate medical imaging automatically in different clinical scenarios.Methods Institutional Review Boards(IRB)approval was not required due to the use of nonidentifiable data.Instead,we used 112 questions from the American College of Radiology(ACR)Radiology-TEACHES Program as prompts,which is an open-sourced question and answer program to guide appropriate medical imaging.We included 69 free-text case vignettes and 43 simplified cases.For the performance evaluation of GPT-4 and GPT-3.5,we considered the recommendations of ACR guidelines as the gold standard,and then three radiologists analyzed the consistency of the responses from the GPT models with those of the ACR.We set a five-score criterion for the evaluation of the consistency.A paired t-test was applied to assess the statistical significance of the findings.Results For the performance of the GPT models in free-text case vignettes,the accuracy of GPT-4 was 92.9%,whereas the accuracy of GPT-3.5 was just 78.3%.GPT-4 can provide more appropriate suggestions to reduce the overutilization of medical imaging than GPT-3.5(t=3.429,P=0.001).For the performance of the GPT models in simplified scenarios,the accuracy of GPT-4 and GPT-3.5 was 66.5%and 60.0%,respectively.The differences were not statistically significant(t=1.858,P=0.070).GPT-4 was characterized by longer reaction times(27.1 s in average)and extensive responses(137.1 words on average)than GPT-3.5.Conclusion As an advanced tool for improving value-based healthcare in clinics,GPT-4 may guide appropriate medical imaging accurately and efficiently。

关键词： Generative pretrained transformer 4 model Natural language processing medical imaging Appropriateness

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Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

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World Journal of Gastroenterology 2024年第7期30卷 636-643页

作者： Xuan-Yu Hao Kai Zhang Xing-Yong Huang Fei Yang Si-Yu Sun department of Gastroenterology Endoscopic CenterShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina department of Gastroenterology Endoscopic CenterEngineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

关键词： Muscle strength Non-alcoholic fatty liver disease Metabolic-associated fatty liver disease Sarcopenia Insulin resistance Inflammation

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Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key Laboratory of Molecular Virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen Institute of Microbes and Infections College of Life Sciences Nanjing Normal University State Key Laboratory of Virology and department of medical Microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health Research Fudan University Key Laboratory of medical Molecular Virology(MOE/MOH) Shanghai Medical CollegeFudan University Laboratory for Marine Biology and biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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Contrast Normalization Strategies in Brain Tumor Imaging:From Preprocessing to Classification

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Computer Modeling in engineering & Sciences 2024年第8期140卷 1539-1562页

作者： Samar M.Alqhtani Toufique A.Soomro Faisal Bin Ubaid Ahmed Ali Muhammad Irfan Abdullah A.Asiri department of Information Systems College of Computer Science and Information SystemsNajran UniversityNajran61441Saudi Arabia department of Electronic engineering The University of LarkanoLarkanaSindh75660Pakistan Computer Science department Sukkur IBA UniversitySukkurSindh65200Pakistan Eletrical engineering department Sukkur IBA UniversitySukkurSindh65200Pakistan Electrical engineering department College of EngineeringNajran UniversityNajran61441Saudi Arabia Radiological Sciences department College of Applied Medical SciencesNajran UniversityNajran61441Saudi Arabia

Cancer-related to the nervous system and brain tumors is a leading cause of mortality in various countries.Magnetic resonance imaging(MRI)and computed tomography(CT)are utilized to capture brain images.MRI plays a crucial role in the diagnosis of brain tumors and the examination of other brain disorders.Typically,manual assessment of MRI images by radiologists or experts is performed to identify brain tumors and abnormalities in the early stages for timely intervention.However,early diagnosis of brain tumors is intricate,necessitating the use of computerized methods.This research introduces an innovative approach for the automated segmentation of brain tumors and a framework for classifying different regions of brain tumors.The proposed methods consist of a pipeline with several stages:preprocessing of brain images with noise removal based on Wiener Filtering,enhancing the brain using Principal Component Analysis(PCA)to obtain well-enhanced images,and then segmenting the region of interest using the Fuzzy C-Means(FCM)clustering technique in the third step.The final step involves classification using the Support Vector Machine(SVM)classifier.The classifier is applied to various types of brain tumors,such as meningioma and pituitary tumors,utilizing the Contrast-Enhanced Magnetic Resonance Imaging(CE-MRI)database.The proposed method demonstrates significantly improved contrast and validates the effectiveness of the classification framework,achieving an average sensitivity of 0.974,specificity of 0.976,accuracy of 0.979,and a Dice Score(DSC)of 0.957.Additionally,this method exhibits a shorter processing time of 0.44 s compared to existing approaches.The performance of this method emphasizes its significance when compared to state-of-the-art methods in terms of sensitivity,specificity,accuracy,and DSC.To enhance the method further in the future,it is feasible to standardize the approach by incorporating a set of classifiers to increase the robustness of the brain classification method.

关键词： Brain tumor magnetic resonance imaging principal component analysis fuzzy c-clustering support vector machine

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Transient receptor potential vanilloid 1 involved in the analgesic effects of total flavonoids extracted from Longxuejie(Resina Dracaenae Cochinchinensis)

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Journal of Traditional Chinese Medicine 2024年第3期44卷 437-447页

作者： MO Xiaoqiang CHEN Yating YIN Qian CHEN Haibo BAN Qiang LI Jun CHEN Su YAO Jinguang department of Stomatology Affiliated Hospital of Youjiang Medical University for Nationalities College of General Practitioners Youjiang Medical University for Nationalities College of Biomedical engineering South-Central Minzu UniversityKey Laboratory of Cognitive Science of State Ethnic Affairs CommissionHubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment College of Pharmacy South-Central Minzu University

OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloid 1(TRPV1).METHODS: Whole-cell patch clamp technique was used to observe the effects of TFDB on capsaicin-induced TRPV1 currents. Rat experiments in vivo were used to observe the analgesic effects of TFDB. Western blot and immunofluorescence experiments were used to test the change of TRPV1 expression in DRG neurons induced by TFDB.RESULTS: Results showed that TFDB inhibited capsaicin-induced TRPV1 receptor currents in acutely isolated dorsal root ganglion(DRG) neurons of rats and the half inhibitory concentration was(16.7 ± 1.6) mg/L.TFDB(2-20 mg/kg) showed analgesic activity in the phase Ⅱ of formalin test and(0.02-2 mg per paw)reduced capsaicin-induced licking times of rats. TFDB(20 mg/kg) was fully efficacious on complete Freund's adjuvant(CFA)-induced inflammatory thermal hyperalgesia and capsaicin could weaken the analgesic effects. The level of TRPV1 expressions of DRG neurons was also decreased in TFDB-treated CFA-inflammatory pain rats.CONCLUSION: All these results indicated that the analgesic effect of TFDB may contribute to their modulations on both function and expression of TRPV1 channels in DRG neurons.

关键词： Freund's adjuvant Longxuejie () capsaicin flavonoids formaldehyde inflammatory pain transient receptor potential vanilloid 1

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A personalized electronic textile for ultrasensitive pressure sensing enabled by biocompatible MXene/ PEDOT:PSS composite

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Carbon Energy 2024年第3期6卷 224-238页

作者： Yahua Li Wentao Cao Zhi Liu Yue Zhang Ziyan Chen Xianhong Zheng department of Interventional Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina School of Textile and Garment Anhui Polytechnic UniversityWuhuAnhuiChina department of Prosthodontics Shanghai Stomatological Hospital and School of StomatologyFudan UniversityShanghaiChina College of Chemistry Chemical Engineering and BiotechnologyDonghua UniversityShanghaiChina

Flexible,breathable,and highly sensitive pressure sensors have increasingly become a focal point of interest due to their pivotal role in healthcare monitoring,advanced electronic skin applications,and disease diagnosis.However,traditional methods,involving elastomer film-based substrates or encapsulation techniques,often fall short due to mechanical mismatches,discomfort,lack of breathability,and limitations in sensing abilities.Consequently,there is a pressing need,yet it remains a significant challenge to create pressure sensors that are not only highly breathable,flexible,and comfortable but also sensitive,durable,and biocompatible.Herein,we present a biocompatible and breathable fabric-based pressure sensor,using nonwoven fabrics as both the sensing electrode(coated with MXene/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate[PEDOT:PSS])and the interdigitated electrode(printed with MXene pattern)via a scalable spray-coating and screen-coating technique.The resultant device exhibits commendable air permeability,biocompatibility,and pressure sensing performance,including a remarkable sensitivity(754.5 kPa^(−1)),rapid response/recovery time(180/110 ms),and robust cycling stability.Furthermore,the integration of PEDOT:PSS plays a crucial role in protecting the MXene nanosheets from oxidation,significantly enhancing the device's long-term durability.These outstanding features make this sensor highly suitable for applications in fullrange human activities detection and disease diagnosis.Our study underscores the promising future of flexible pressure sensors in the realm of intelligent wearable electronics,setting a new benchmark for the industry.

关键词： biocompatibility MXene pressure sensor screen printing textile

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Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

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Neural Regeneration Research 2024年第10期19卷 2281-2289页

作者： Wang Liao Jiana Wei Chongxu Liu Haoyu Luo Yuting Ruan Yingren Mai Qun Yu Zhiyu Cao Jiaxin Xu Dong Zheng Zonghai Sheng Xianju Zhou Jun Liu department of Neurology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Special medical Service Center Neuroscience CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangdongGuangdong ProvinceChina department of Rehabilitation The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of Neurology The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Biomedical and Health engineering Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

关键词： Alzheimer's disease APP/PS1 double-transgenic Alzheimer's disease mouse model inflammation intestinal barrier dysfunction magnesium-L-threonate microbiome microbiota-gut-brain axis oxidative stress serum metabolites

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