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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

Pleistocene glaciation advances the cryptic speciation of Stellera chamaejasme L.in a major biodiversity hotspot

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Journal of Integrative Plant Biology 2024年第6期66卷 1192-1205页

作者： Santosh Kumar Rana Hum Kala Rana Jacob BLandis Tianhui Kuang Juntong Chen Hengchang Wang Tao Deng Charles C.Davis Hang Sun CAS Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China Arkansas Biosciences Institute Arkansas State UniversityJonesboroArkansas 72401USA School of Integrative Plant Science Section of Plant Biology and the L.H.Bailey HortoriumCornell UniversityIthacaNew York 14853USA BTI computational Biology Center Boyce Thompson InstituteIthacaNew York 14853USA CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Chinese Academy of SciencesWuhan Botanical GardenWuhan 430074China Department of Organismic and Evolutionary Biology HerbariaHarvard UniversityCambridgeMassachusetts 02138USA

The mountains of Southwest China comprise a significant large mountain range and biodiversity hotspot imperiled by global climate change.The high species diversity in this mountain system has long been attributed to a complex set of factors,and recent large-scale macroevolutionary investigations have placed a broad timeline on plant diversification that stretches from 10 million years ago(Mya)to the present.Despite our increasing understanding of the temporal mode of speciation,finer-scale populationlevel investigations are lacking to better refine these temporal trends and illuminate the abiotic and biotic influences of cryptic speciation.This is largely due to the dearth of organismal sampling among closely related species and populations,spanning the incredible size and topological heterogeneity of this region.Our study dives into these evolutionary dynamics of speciation using genomic and ecomorphological data of Stellera chamaejasme L.We identified four previously unrecognized cryptic species having indistinct morphological traits and large metapopulation of evolving lineages,suggesting a more recent diversification(~2.67-0.90 Mya),largely influenced by Pleistocene glaciation and biotic factors.These factors likely influenced allopatric speciation and advocated cyclical warming–cooling episodes along elevational gradients during the Pleistocene.The study refines the evolutionary timeline to be much younger than previously implicated and raises the concern that projected future warming may influence the alpine species diversity,necessitating increased conservation efforts.

关键词： cryptic speciation glacial-interglacial Hengduan Mountains north-south migration Stellera chamaejasme

Elastic scattering and total reaction cross sections of^(6)Li examined via a microscopic continuum discretized coupled-channels model

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Chinese Physics C 2024年第1期48卷 71-81页

作者：陈文棣庞丹阳郭海瑞叶涛孙伟力应阳君 School of Physics Beihang UniversityBeijing 100191China Institute of Applied Physics and computational Mathematics Beijing 100094China

We present a systematic study of 6Li elastic scattering and total reaction cross sections at incident energies around the Coulomb barrier within the continuum discretized coupled-channels(CDCC)framework,where 6Li is treated in anα+d two-body model.Collisions with 27Al,64Zn,138Ba,and 208Pa are analyzed.The microscopic optical potentials(MOP)based on Skyrme nucleon-nucleon interaction forαand d are adopted in CDCC calculations and satisfactory agreement with the experimental data is obtained without any adjustment on MOPs.For comparison,αand d global phenomenological optical potentials(GOP)are also used in CDCC analysis and a reduction of no less than 50%on the surface imaginary part of deuteron GOP is required for describing the data.In all cases,the 6Li breakup effect is significant and provides repulsive correction to the folding model potential.The reduction on the surface imaginary part of GOP of deuteron reveals a strong suppression of the reaction probability of deuteron as a component of 6Li when compared with that of a free deuteron.Further investigation is performed by considering the d breakup process equivalently within the dynamic polarization potential approach,and the results show that d behaves in a manner similar to a tightly bound nucleus in 6Li induced reactions.

关键词： continuum discretized coupled channels method microscopic optical potential 6Li induced reaction elastic scattering total reaction cross section

Impacts of Climate Change on Seawater Temperature and Total Dissolved Solids: Challenges and Sustainable Solutions for Reverse Osmosis Desalination in the Arabian Gulf Region

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computational Water, Energy, and Environmental Engineering 2024年第1期13卷 86-93页

作者： Ahmed Al Kubaish Jamal Salama Water Quality section Saline Water Conversion Corporation Al-Khobar Saudi Arabia

This article examines the influence of seawater temperature and total dissolved solids (TDS) on reverse osmosis (RO) desalination in the Arabian Gulf region, with a focus on the impact of climate change. The study highlights the changes in seawater temperature and TDS levels over the years and discusses their effects on the efficiency and productivity of RO desalination plants. It emphasizes the importance of monitoring TDS levels and controlling seawater temperature to optimize water production. The article also suggests various solutions, including intensive pre-treatment, development of high-performance membranes, exploration of alternative water sources, and regulation of discharges into the Gulf, to ensure sustainable water supply in the face of rising TDS levels and seawater temperature. Further research and comprehensive monitoring are recommended to understand the implications of these findings and develop effective strategies for the management of marine resources in the Arabian Gulf.

关键词： Climate Change Temperature Reverse Osmosis Seawater Total Dissolved Solids Desalination

Sensitivity Analysis of Electromagnetic Scattering from Dielectric Targets with Polynomial Chaos Expansion and Method of Moments

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 2079-2102页

作者： Yujing Ma Zhongwang Wang Jieyuan Zhang Ruijin Huo Xiaohui Yuan College of Architecture and Civil Engineering Xinyang Normal UniversityXinyang464000China Henan International Joint Laboratory of Structural Mechanics and computational Simulation College of Architecture and Civil EngineeringHuanghuai UniversityZhumadian463000China Academy of Military Sciences Beijing100091China Henan New Environmentally-Friendly Civil Engineering Materials Engineering Research Center Xinyang Normal UniversityXinyang464000China

In this paper,an adaptive polynomial chaos expansion method(PCE)based on the method of moments(MoM)is proposed to construct surrogate models for electromagnetic scattering and further sensitivity analysis.The MoM is applied to accurately solve the electric field integral equation(EFIE)of electromagnetic scattering from homogeneous dielectric targets.Within the bistatic radar cross section(RCS)as the research object,the adaptive PCE algorithm is devoted to selecting the appropriate order to construct the multivariate surrogate model.The corresponding sensitivity results are given by the further derivative operation,which is compared with those of the finite difference method(FDM).Several examples are provided to demonstrate the effectiveness of the proposed algorithm for sensitivity analysis of electromagnetic scattering from homogeneous dielectric targets.

关键词： Adaptive polynomial chaos expansion method method of moments radar cross section electromagnetic scattering

Study of Total Dissolved Solids (TDS) Concentrations Factor of SWCC Al-Khobar Plant Seawater Intakes

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computational Water, Energy, and Environmental Engineering 2024年第1期13卷 1-12页

作者： Ahmed Al-Kubaish Jamal Salama Waleed Al-Jurayan Water Quality section Al-Khobar Production System Saline Water Conversion Corporation Al-Khobar Saudi Arabia

This study presents a significant contribution to the field of water quality assessment and sustainable water management practices. By evaluating the levels of total dissolved solids (TDS) in seawater intakes within Al-Khobar desalination production system, the study addresses a crucial aspect of water treatment and environmental impact assessment. The findings provide valuable insights into the variations and trends of TDS levels across different phases of the system, highlighting the importance of monitoring and management strategies. The study provided both gravimetric total dissolved solids (TDS) and electrical conductivity (EC) measurements to analyze TDS calculation factor and evaluate measurement accuracy. Results revealed significant variations in TDS levels across the sampling locations, with phase-2 exhibiting higher levels and greater fluctuations. Phase-3 displayed similar trends but with lower TDS levels, while phase-4 showed slightly different behavior with higher average TDS levels. EC measurements demonstrated a strong correlation with TDS, providing a reliable estimation. However, additional methods such as gravimetric analysis should be employed to confirm TDS measurements. The findings contribute to understanding water quality in the Al-Khobar desalination system, aiding in monitoring, management, and decision-making processes for water treatment and environmental impact assessment. The study enhances the credibility of water quality assessments and supports sustainable water management practices.

关键词： Total Dissolved Solids Conductivity Seawater Desalination

6DOF pose estimation of a 3D rigid object based on edge-enhanced point pair features

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computational Visual Media 2024年第1期10卷 61-77页

作者： Chenyi Liu Fei Chen Lu Deng Renjiao Yi Lintao Zheng Chenyang Zhu Jia Wang Kai Xu College of Computing National University of Defense TechnologyChangsha410073China Department of Spine Surgery the Second Xiangya HospitalCentral South UniversityChangsha410011China Clinical Nursing Teaching and Research section the Second Xiangya HospitalChangsha410011China College of Meteorology and Oceanography National University of Defense TechnologyChangsha410073China Beijing Institute of Tracking and Communication Technology Beijing100094China

The point pair feature(PPF)is widely used for 6D pose estimation.In this paper,we propose an efficient 6D pose estimation method based on the PPF framework.We introduce a well-targeted down-sampling strategy that focuses on edge areas for efficient feature extraction for complex geometry.A pose hypothesis validation approach is proposed to resolve ambiguity due to symmetry by calculating the edge matching degree.We perform evaluations on two challenging datasets and one real-world collected dataset,demonstrating the superiority of our method for pose estimation for geometrically complex,occluded,symmetrical objects.We further validate our method by applying it to simulated punctures.

关键词： point pair feature(PPF) pose estimation object recognition 3D point cloud

Could non-invasive brain-stimulation prevent neuronal degeneration upon ion channel re-distribution and ion accumulation after demyelination?

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Neural Regeneration Research 2020年第11期15卷 1977-1980页

作者： Friederike Pfeiffer Alia Benali Werner Reichardt Centre for Integrative Neuroscience(CIN) University of TubingenTubingenGermany section for computational sensomotorics Department of Cognitive NeurologyHertie-Institute for Clinical Brain Research and Centre for Integrative NeuroscienceUniversity of TubingenTubingenGermany

Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve fibers.In neuronal diseases such as multiple sclerosis,the conduction properties of axons are disturbed by the removal of the myelin sheath,leaving nerve cells at a higher risk of degenerating.In some cases,the protective myelin sheath of axons can be rebuilt by remyelination through oligodendroglial cells.In any case,however,changes in the ion channel organization occur and may help to restore impulse conduction after demyelination.On the other hand,changes in ion channel distribution may increase the energy demand of axons,thereby increasing the probability of axonal degeneration.Many attempts have been made or discussed in recent years to increase remyelination of affected axons in demyelinating diseases such as multiple sclerosis.These approaches range from pharmacological treatments that reduce inflammatory processes or block ion channels to the modulation of neuronal activity through electrical cortical stimulation.However,these treatments either affect the entire organism(pharmacological)or exert a very local effect(electrodes).Current results show that neuronal activity is a strong regulator of oligodendroglial development.To bridge the gap between global and very local treatments,non-invasive transcranial magnetic stimulation could be considered.Transcranial magnetic stimulation is externally applied to brain areas and experiments with repetitive transcranial magnetic stimulation show that the neuronal activity can be modulated depending on the stimulation parameters in both humans and animals.In this review,we discuss the possibilities of influencing ion channel distribution and increasing neuronal activity by transcranial magnetic stimulation as well as the effect of this modulation on oligodendroglial cells and their capacity to remyelinate previously demyelinated axons.Although the physiological mechanisms underlying the effects of transcranial magnetic stimulation clearly need further inv

关键词： ion channel multiple sclerosis neuronal activity oligodendrocyte (re-)myelination repetitive transcranial magnetic stimulation transcranial magnetic stimulation

动态全场光学相干断层扫描结合深度学习在肿瘤患者术中诊断的应用:一项乳腺癌患者的前瞻性队列研究

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Science Bulletin 2024年第11期69卷 1748-1756页

作者：张舒玮杨滨杨后圃赵进张原媛高元绪 Olivia Monteiro 张康刘博王殊 Breast Center Peking University People’s HospitalBeijing 100044China China ESG Institute Capital University of Economics and BusinessBeijing 100070China Faculty of Information Technology Beijing University of TechnologyBeijing 100124China Department of Pathology Peking University People’s HospitalBeijing 100044China Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and TechnologyMacao 999078China College of Future Technology Peking UniversityBeijing 100091China School of Mathematical and computational Sciences Massey UniversityAuckland 0745New Zealand

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin(H&E) histology, such as frozen section, are time-,resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography(D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group(n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma(IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ(DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests(n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%;only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow(approximately 3 min)was significantly shorter than that required for traditional procedures(approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

关键词： Cancer diagnosis Breast neoplasms Dynamic full-field optical coherence tomography Deep learning Image classification