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Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： peter h.King Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham Veterans Affairs Medical Center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SO

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

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Immunological Exploration of helicobacter pylori Serotype O_(2) O-Antigen by Using a Synthetic Glycan Library

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Chinese Journal of Chemistry 2024年第3期42卷 243-251页

作者： Ming Zhao Guangzong Tian Chunjun Qin Xiaopeng Zou peter h. Seeberger Jing hu Jian Yin Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationSchool of Biotechnology & School of Life Sciences and Health EngineeringJiangnan UniversityLihu Avenue 1800WuxiJiangsu214122 China Biomolecular Systems Department Max Planck Institute of Colloids and InterfacesAm Mühlenberg 1Potsdam14476 Germany Wuxi School of Medicine Jiangnan UniversityLihu Avenue 1800WuxiJiangsu214122 China

helicobacter pylori(h.pylori)infection is a threat to human health.The lipopolysaccharide(LPS)O-antigen holds promise for developing vaccines.It is meaningful to explore the immunological activity of oligosaccharides with different lengths and frameshifts for antigen development.herein,a glycan library of h.pylori O2 O-antigen containing eight fragments is constructed.After screening with anti-h.pylori O2 LPS sera and patients’sera by glycan microarray,the disaccharide hPO2G-2b and trisaccharide hPO2G-3a show strong antigenicity and then are separately conjugated with carrier protein CRM197.Both glycoconjugates elicit a robust immunoglobulin G(IgG)immune response in rabbits.The anti-hPO2G-3a IgG antibodies possess a much stronger binding affinity with the LPS and bacteria of h.pylori O2 than the anti-hPO2G-2b IgG antibodies.There is no cross-reaction between both sera IgG antibodies with LPS and bacteria of h.pylori O1,O6,and E.coli.The results demonstrate the trisaccharide hPO2G-3a is a promising candidate for h.pylori vaccine development.

关键词： Glycoconjugates helicobacter pylori Immunology Microarrays O-antigen Oligosaccharides

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Net effect of air pollution controls on health risk in the Beijing-Tianjin-hebei region during the 2022 winter Olympics and Paralympics

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Journal of Environmental Sciences 2024年第1期135卷 560-569页

作者： Changqing Lin peter K.K.Louie Alexis K.h.Lau Jimmy C.h.Fung Zibing Yuan Minghui Tao Xuguo Zhang Md.Shakhaoat hossain Chengcai Li Xiang Qian Lao Division of Environment and Sustainability The Hong Kong University of Science and TechnologyHong KongChina Environmental Protection Department Hong Kong Government SARHong KongChina Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyHong KongChina Guangdong-hongkong-Macao Joint Laboratory of Collaborative Innovation for Environmental Quality The Hong Kong University of Science and TechnologyHong KongChina Department of Mathematics The Hong Kong University of Science and TechnologyHong KongChina School of Environment and Energy South China University of TechnologyGuangzhou 510006China hubei Key Laboratory of Critical Zone Evolution School of Geography and Information EngineeringChina University of GeosciencesWuhan 430074China Department of Public health and Informatics Jahangirnagar UniversityDhaka 1342Bangladesh Department of Atmospheric and Oceanic Sciences School of PhysicsPeking UniversityBeijing 100871China Jockey Club School of Public health and Primary Care The Chinese University of Hong KongHong KongChina

Due to the non-linearity in ozone(O_(3))formation,reducing the emission of nitrogen oxides(NO_(x))may increase O_(3) concentration.Given the counteractive O_(3) response to NO_(x) reduction,overall impact of air pollution controls can be ambiguous when the assessments focus on the changes in pollutant concentrations.In this study,a risk-based method was used to gauge the net effect of air pollution controls on mortality risk in the Beijing–Tianjin–hebei(BTh)region during the 2022 Winter Olympics and Paralympics(WOP).This mega-event presents a unique opportunity to investigate the efficacy of deep cuts in pollutant emissions.Results show that O_(3) concentrations greatly increased as nitrogen dioxide(NO_(2))concentrations decreased in the BTh.Due to the active photochemical formations,O_(3) became the dominant pollutant that affected human health during the WOP.Despite the substantial O_(3) increases,the health benefits of NO_(2) reductions overwhelmed the adverse health effects of O_(3) increases in most regions of the BTh(at 81 out of 112 stations).After considering the impacts of particulate matter,the integrated health risk of air pollution mixtures declined almost everywhere in the BTh.Our results underscore the great necessity of changing the assessment paradigm of pollution control from using concentration-based methods to using risk-based methods.Together with the carbon neutrality policy,stringent control of NO_(x)emission from combustion sources is a promising way to achieve synergistic control solutions for air pollution and climate change.

关键词： Ozone Nitrogen dioxide health risk Carbon neutrality Mega-events

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Ultrafast magneto-optical dynamics in nickel(111)single crystal studied by the integration of ultrafast reflectivity and polarimetry probes

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Chinese Physics B 2024年第3期33卷 65-69页

作者：匡皓余军潇陈洁 h.E.Elsayed-Ali 李润泽 peter M.Rentzepis School of Physical Science and Technology ShanghaiTech UniversityShanghai 201210China Center for Transformative Science ShanghaiTech UniversityShanghai 201210China Center for Ultrafast Science and Technology Key Laboratory for Laser Plasmas (Ministry of Education)Collaborative Innovation Center of IFSA (CICIFSA)School of Physics and AstronomyShanghai Jiao Tong UniversityShanghai 200240China Department of Electrical and Computer Engineering Old Dominion UniversityNorfolkVirginia 23529USA Department of Electrical and Computer Engineering Texas A&M UniversityCollege StationTexas 77843USA

With the integration of ultrafast reflectivity and polarimetry probes,we observed carrier relaxation and spin dynamics induced by ultrafast laser excitation of Ni(111)single crystals.The carrier relaxation time within the linear excitation range reveals that electron-phonon coupling and dissipation of photon energy into the bulk of the crystal take tens of picoseconds.On the other hand,the observed spin dynamics indicate a longer time of about 120 ps.To further understand how the lattice degree of freedom is coupled with these dynamics may require the integration of an ultrafast diffraction probe.

关键词： ultrafast spin dynamics non-equilibrium dynamics multi-probe

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A product version of the hilton-Milner-Frankl theorem

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Science China Mathematics 2024年第2期67卷 455-474页

作者： peter Frankl Jian Wang Alfréd Rényi Institute of Mathematics Hungarian Academy of SciencesBudapest H-1053Hungary Department of Mathematics Taiyuan University of TechnologyTaiyuan 030024China

Two families F and G of k-subsets of {1, 2,..., n} are called non-trivial cross t-intersecting if|F ∩ G|≥t for all F ∈ F, G ∈ G and | ∩ {F : F ∈ F}| < t, | ∩ {G : G ∈ G}| < t. In the present paper,we determine... 详细信息

Two families F and G of k-subsets of {1, 2,..., n} are called non-trivial cross t-intersecting if|F ∩ G|≥t for all F ∈ F, G ∈ G and | ∩ {F : F ∈ F}| he present paper,we determine the maximum product of the sizes of two non-trivial cross t-intersecting families of k-subsets of{1, 2,..., n} for n≥4(t + 2)2k2, k≥5, which is a product version of the hilton-Milner-Frankl theorem.

关键词： extremal set theory cross t-intersecting family product version non-trivial

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Macroalgal deep genomics illuminate multiple paths to aquatic,photosynthetic multicellularity

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Molecular Plant 2024年第5期17卷 747-771页

作者： David R.Nelson Alexandra Mystikou Ashish Jaiswal Cecilia Rad-Menendez Michael J.Preston Frederik De Boever Diana C.El Assal Sarah Daakour Michael W.Lomas Jean-Claude Twizere David h.green William C.Ratcliff Kourosh Salehi-Ashtiani Division of Science and Math New York University Abu DhabiAbu DhabiUAE Center for Genomics and Systems Biology(CGSB) New York University Abu DhabiAbu DhabiUAE Biotechnology Research Center Technology Innovation InstitutePO Box 9639Masdar CityAbu DhabiUAE Culture Collection of Algae and Protozoa Scottish Association for Marine ScienceObanScotlandUK National Center for Marine Algae and Microbiota Bigelow Laboratory for Ocean SciencesEast BoothbayMEUSA Laboratory of Viral Interactomes GIGA InstituteUniversity of LiegeLiegeBelgium School of Biological Sciences Georgia Institute of TechnologyAtlantaGAUSA

Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity phenotypes.however,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized.In this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal relatives.Genes for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular processes.Adhesome genes show phylum-and climate-specific expansions that may facilitate niche adaptation.Collectively,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.

关键词： macroalgae multicellularity comparative genomics evolution adhesome endogenous viral elements

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Simultaneously targeting extracellular vesicle trafficking and TGF-β receptor kinase activity blocks signaling hyperactivation and metastasis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 308-325页

作者： Adilson Fonseca Teixeira Yanhong Wang Josephine Iaria peter ten Dijke hong-Jian Zhu Department of Surgery(The Royal Melbourne hospital) The University of MelbourneParkvilleVICAustralia huagene Institute Kecheng Science and Technology ParkPukou DistrictNanjingJiangsuChina Department of Cell and Chemical Biology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands

Metastasis is the leading cause of cancer-related deaths.Transforming growth factor beta(TGF-β)signaling drives metastasis and is strongly enhanced during cancer progression.Yet,the use of on-target TGF-βsignaling inhibitors in the treatment of cancer patients remains unsuccessful,highlighting a gap in the understanding of TGF-βbiology that limits the establishment of efficient anti-metastatic therapies.here,we show that TGF-βsignaling hyperactivation in breast cancer cells is required for metastasis and relies on increased small extracellular vesicle(sEV)secretion.Demonstrating sEV’s unique role,TGF-βsignaling levels induced by sEVs exceed the activity of matching concentrations of soluble ligand TGF-β.Further,genetic disruption of sEV secretion in highlymetastatic breast cancer cells impairs cancer cell aggressiveness by reducing TGF-βsignaling to nearly-normal levels.Otherwise,TGF-βsignaling activity in non-invasive breast cancer cells is inherently low,but can be amplified by sEVs,enabling invasion and metastasis of poorly-metastatic breast cancer cells.Underscoring the translational potential of inhibiting sEV trafficking in advanced breast cancers,treatment with dimethyl amiloride(DMA)decreases sEV secretion,TGF-βsignaling activity,and breast cancer progression in vivo.Targeting both the sEV trafficking and TGF-βsignaling by combining DMA and SB431542 at suboptimal doses potentiated this effect,normalizing the TGF-βsignaling in primary tumors to potently reduce circulating tumor cells,metastasis,and tumor self-seeding.Collectively,this study establishes sEVs as critical elements in TGF-βbiology,demonstrating the feasibility of inhibiting sEV trafficking as a new therapeutic approach to impair metastasis by normalizing TGF-βsignaling levels in breast cancer cells.

关键词： metastasis doses invasion

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Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients

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World Journal of Gastrointestinal Endoscopy 2016年第18期8卷 653-662页

作者： Edward J Ciaccio Govind Bhagat Suzanne K Lewis peter h green Celiac Disease Center Department of Medicine Columbia University Medical Center Department of Pathology and Cell Biology Columbia University Medical Center

AIM To quantify the presence of villous atrophy in endoscopic images for improved automation.METhODS There are two main categories of quantitative descriptors helpful to detect villous atrophy:(1) Statistical and(2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape.RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished.CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients.

关键词： Celiac disease Endoscopy Small intestine Video capsule Villous atrophy

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Use of shape-from-shading to characterize mucosal topography in celiac disease videocapsule images

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World Journal of Gastrointestinal Endoscopy 2017年第7期9卷 310-318页

作者： Edward J Ciaccio Govind Bhagat Suzanne K Lewis peter h green Department of Medicine Celiac Disease CenterColumbia University Department of Pathology and Cell Biology Columbia University Medical Center

AIM To use a computerized shape-from-shading technique to characterize the topography of the small intestinal mucosa.METhODS Videoclips comprised of 100-200 images each were obtained from the distal duodenum in 8 celiac and 8 control patients.Images with high texture were selected from each videoclip and projected from two to three dimensions by using grayscale pixel brightness as the Z-axis spatial variable.The resulting images for celiac patients were then ordered using the Marsh score to estimate the degree of villous atrophy,and compared with control data.RESULTS Topographic changes in celiac patient three-dimensional constructs were often more variable as compared to controls.The mean absolute derivative in elevation was 2.34 ± 0.35 brightness units for celiacs vs 1.95 ± 0.28 for controls(P = 0.014).The standard deviation of the derivative in elevation was 4.87 ± 0.35 brightness units for celiacs vs 4.47 ± 0.36 for controls(P = 0.023).Celiac patients with Marsh ⅢC villous atrophy tended to have the largest topographic changes.Plotted in two dimensions,celiac data could be separated from controls with 80% sensitivity and specificity.CONCLUSION Use of shape-from-shading to construct three-dimensional projections approximating the actual spatial geometry of the small intestinal substrate is useful to observe features not readily apparent in two-dimensional videocapsule images.This method represents a potentially helpful adjunct to detect areas of pathology during videocapsule analysis.

关键词：腹的疾病十二指肠 Shape-from-shading 小肠 Videocapsule

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Quantitative image analysis of celiac disease

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World Journal of Gastroenterology 2015年第9期21卷 2577-2581页

作者： Edward J Ciaccio Govind Bhagat Suzanne K Lewis peter h green Department of Medicine Celiac Disease CenterColumbia UniversityNew YorkNY 10032United States

We outline the use of quantitative techniques that are currently used for analysis of celiac disease.Image processing techniques can be useful to statistically analyze the pixular data of endoscopic images that is acquired with standard or videocapsule endoscopy.It is shown how current techniques have evolved to become more useful for gastroenterologists who seek to understand celiac disease and to screen for it in suspected patients.New directions for focus in the development of methodology for diagnosis and treatment of this disease are suggested.It is evident that there are yet broad areas where there is potential to expand the use of quantitative techniques for improved analysis in suspected or known celiac disease patients.

关键词： Celiac disease Frequency analysis Motility Videoca

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