AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other t...AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other than thyroid disease. METHODS: This retrospective study involved review of intravascular contrast-enhanced MDCT scans of the chest from 3077 consecutive adult outpatients, to identify unsuspected thyroid nodules. Exclusion criteria included history of thyroid cancer, known thyroid nodules or thyroid disease and risk factors for thyroid cancer, as evidenced by their medical records. One of 9 radiologists recorded number of nodules, location and bidirectional measurement of largest nodule, as well as amount of thyroid visualized on the chest computed tomography (CT). Presence of nodule was correlated with age, gender, race and percentage of thyroid imaged. RESULTS: A total of 2510 (2510/3077 or 81.6%) study subjects were included in the data analysis; among them,one or more nodules were identified in 629 subjects (629/2510 or 25.1%), with 242 (242/629 or 38.5%) having multiple nodules. Patients with nodule(s) were significantly older than those without (64 ± 13 years vs 58 ± 14 years, P < 0.0001), and female gender was associated with presence of nodule(s) (373/1222 or 30.5% vs 256/1288 or 19.9%, P < 0.0001). Women were also more likely having multiple nodules (167/373 or 44.8%) compared to men (75/256 or 29.3%, P < 0.0001). The majority of nodules (427/629 or 67.9%) were less than 1 cm. CONCLUSION: This retrospective review revealed a prevalence of 25.1% for unsuspected thyroid nodules on contrast-enhanced chest CT.展开更多
Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral f...Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral function study.However,NIRS-based cerebral function detection accuracy can be signi¯cantly in°uenced by the physiological activities such as cardic cycle,respiration,spontaneous low-frequency oscillation and ultra-low frequency oscillation.The distribution difference of the capillary,artery and vein leads to the heterogeneity feature of the cerebral tissues.In the case that the heterogeneity is not serious,good detection accuracy and stable performance can be achieved through the regression analysis as the reference signal can well represent the interference in the measurement signal when conducting the multi-distance measurement approach.The direct use of the reference signal to estimate the interference is not able to achieve good performance in the case that the heterogeneity is serious.In this study,the cerebral function activity signal is extracted using recursive least square(RLS)method based on the multi-distance measurement method in which the reference signal is processed by ensemble empirical mode decomposition(EEMD)algorithm.The temporal and dimensional correlation of the neighboring sampling values are applied to estimate the interference in the measurement signal.Monte Carlo simulation based on a heterogeneous model is adopted here to investigate the effectiveness of this methodology.The results show that this methodology can effectively suppress the physiological interference and improve the detection accuracy of cerebral activity signal.展开更多
DNA profiling is an established method for cancer treatment selection,while RNA profiling remains investigational.We explored associations between DNA and RNA alterations and between the number of genes with altered e...DNA profiling is an established method for cancer treatment selection,while RNA profiling remains investigational.We explored associations between DNA and RNA alterations and between the number of genes with altered expression and overall survival(OS)using patient data from IMPACT2(NCT02152254),a randomized study evaluating molecular profiling for guiding cancer therapy across tumor types.Molecular profiling,including DNA next-generation sequencing,was performed on all 829 patients in the IMPACT2 study.RNA profiling was performed by Tempus for 253 of 829 patients.We evaluated the concordance between DNA and RNA profiling,analyzed OS in 217 treated patients with RNA profiling,and assessed PD-L1 status and number of genes with altered expression.Fifty patients exhibited 58 concordant events,i.e.,genomic and expression alteration(s)in the same gene,including 38 copy number events,and 41 patients had statistically significant concordance.We identified 123 gene pairs with significant associations between genomic and expression alterations(p<0.05),including TP53 alterations with VEGFA overexpression.The median OS for patients with 0-2,3-5,and≥6 genes with altered expression was 9.8,11.9,and 6.7 months,respectively(p=0.03).These results underscore RNA profiling’s potential actionability,and altered expression in≥6 genes was associated with shorter OS.Significant concordance of TP53 alterations with VEGFA overexpression may partially explain tumor response to bevacizumab in TP53-mutant patients.展开更多
Mdm2 and Mdm4 are negative regulators of the tumour suppressor p53; hence, this relationship is the focus of many cancerrelated studies. A multitude of experiments across various developmental stages have been conduct...Mdm2 and Mdm4 are negative regulators of the tumour suppressor p53; hence, this relationship is the focus of many cancerrelated studies. A multitude of experiments across various developmental stages have been conducted to explore the tissuespecific roles of these proteins in the mouse. When Mdm2 or Mdm4 are deleted in the germiine or specific tissues, they display different phenotypic defects, some of which lead to embryonic lethaLity. Mdm2 loss is often more deleterious than toss of its homotogue Mdm4. ALL tissues experience activation of p53 target genes upon toss of Mdm2 or Mdm4; however, the degree to which the p53 pathway is perturbed is highly tissue-specific and does not correlate to the severity of the morphological pheno- types. Therefore, a need for further understanding of how these proteins regulate p53 activity is warranted, as therapeutic targeting of the p53 pathway is rapidly evoLving and gaining attention in the field of cancer research. In this review, we discuss the tissue-specificity of Mdm proteins in regulating p53 and expose the need for investigation at the celt-specific level.展开更多
随着医学的发展,精准医疗逐渐成为现代医疗的发展方向.为了给患者制定有效的个体化治疗方案,临床医师对病理诊断的精准性提出了更高的要求.规范化的取材是精准病理诊断的基础,也是精准治疗的前提[1].近几年来,随着乳腺B超引导下粗针穿...随着医学的发展,精准医疗逐渐成为现代医疗的发展方向.为了给患者制定有效的个体化治疗方案,临床医师对病理诊断的精准性提出了更高的要求.规范化的取材是精准病理诊断的基础,也是精准治疗的前提[1].近几年来,随着乳腺B超引导下粗针穿刺活检已经逐渐取代手术活检,多数患者在手术切除时已经有了明确诊断.为了更精准测量肿瘤的位置,客观地评判手术范围,准确地评估肿瘤分期和治疗反应,乳腺标本的大体取材受到临床与病理的共同重视,取材方法也在逐渐改进[1-5].准确的大体检查往往依赖于病理医师、放射医师及外科医师的合作.我们旨在介绍乳腺癌手术切除标本和前哨淋巴结的大体取材方法,其主要内容来自于美国MD安德森癌症中心(MD Anderson Cancer Center,MDACC) 行之有效的多年实践.展开更多
We investigate and compare the performance of four optical transport schemes for distributing Local Multipoint Distribution Service (LMDS) signals using an optical fiber backbone.
Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53 in vitro and in vivo,representing a viable therapeutic strategy for cancer treatment....Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53 in vitro and in vivo,representing a viable therapeutic strategy for cancer treatment.Using phage display techniques,we previously identified a potent peptide activator of P53,termed PMI(TSFAEYWNLLSP),with binding affinities for both MDM2 and MDMX in the low nanomolar concentration range.Here we report an ultrahigh affinity,dual-specificity peptide antagonist of MDM2 and MDMX obtained through systematic mutational analysis and additivitybased molecular design.Functional assays of over 100 peptide analogs of PMI using surface plasmon resonance and fluorescence polarization techniques yielded a dodecameric peptide termed PMI-M3(LTFLEYWAQLMQ)that bound to MDM2 and MDMX with K_(d)values in the low picomolar concentration range as verified by isothermal titration calorimetry.Co-crystal structures of MDM2 and of MDMX in complex with PMI-M3 were solved at 1.65 and 3.0 A resolution,respectively.Similar to PMI,PMI-M3 occupied the P53-binding pocket of MDM2/MDMX,which was dominated energetically by intermolecular interactions involving Phe3,Tyr6,Trp7,and Leu 10.Notable differences in binding between PMI-M3 and PMI were observed at other positions such as Leu4 and Met11 with MDM2,and Leu1 and Met11 with MDMX,collectively contributing to a significantly enhanced binding affinity of PMI-M3 for both proteins.By adding lysine residues to both ends of PMI and PMI-M3 to improve their cellular uptake,we obtained modified peptides termed PMI-2K(KTSFAEYWNLLSPK)and M3-2K(KLTFLEYWAQLMQK).Compared with PMI-2K,M3-2K exhibited significantly improved antitumor activities in vitro and in vivo in a P53-dependent manner.This super-strong peptide inhibitor of the P53-MDM2/MDMX interactions may become,in its own right,a powerful lead compound for anticancer drug development,and can aid molecular design of other classes of P53 activators as well for anticancer therapy.展开更多
During aging,the spine undergoes degenerative changes,particularly with vertebral endplate bone expansion and sclerosis,that are associated with nonspecific low back pain.We report that parathyroid hormone(PTH)treatme...During aging,the spine undergoes degenerative changes,particularly with vertebral endplate bone expansion and sclerosis,that are associated with nonspecific low back pain.We report that parathyroid hormone(PTH)treatment reduced vertebral endplate sclerosis and improved pain behaviors in three mouse models of spinal degeneration(aged,SM/J,and young lumbar spine instability mice).Aberrant innervation in the vertebral body and endplate during spinal degeneration was decreased with PTH treatment as quantified by PGP9.5^(+)and CGRP^(+)nerve fibers,as well as CGRP expression in dorsal root ganglia.The neuronal repulsion factor Slit3 significantly increased in response to PTH treatment mediated by transcriptional factor FoxA2.PTH type 1 receptor and Slit3 deletion in osteocalcin-expressing cells prevented PTH-reduction of endplate porosity and improvement in behavior tests.Altogether,PTH stimulated osteoblast production of Slit3,decreased aberrant sensory nerve innervation,and provided symptomatic relief of LBP associated with mouse spinal degeneration.展开更多
Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patien...Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.展开更多
Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this com...Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this complex problem.One such model,the Oncopig,has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation.However,the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.Methods:Herein,we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and re-placed in the tissue.The study consisted of 3 animals in 3 cohorts(total of 9 animals)that were evaluated at 14,21,and 28 days.CT imaging,immunohistochemistry,multiplex immunofluorescence,and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation.Results:The tumors were hypovascular on CT and predominantly composed of CD45+cells with a strong lymphohistiocytic component,with no carcinomas identified.Ki-67 staining showed proliferation of CD45+immune cells but no neoplastic component.To provide further insight,the results are evaluated in the context of tumor growth kinetics.Conclusion:While progress has been made in generating targetable lesions,achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.展开更多
In vivo imaging of neurodegenerative diseases provides valuable insights into disease mechanisms and potential therapeutic interventions.Many ocular diseases are closely linked to neurodegenerative conditions affectin...In vivo imaging of neurodegenerative diseases provides valuable insights into disease mechanisms and potential therapeutic interventions.Many ocular diseases are closely linked to neurodegenerative conditions affecting the brain,making the eye a unique and accessible model for studying these disorders.The transparency of eyes allows researchers to monitor disease progression non-invasively,offering a window into neural health.展开更多
Structural variations(SVs≥50 bp)are a critical but underexplored source of genetic diversity in cattle,shaping traits vital for productivity,adaptability,and health.Advances in long-read sequencing,pangenome graph co...Structural variations(SVs≥50 bp)are a critical but underexplored source of genetic diversity in cattle,shaping traits vital for productivity,adaptability,and health.Advances in long-read sequencing,pangenome graph construction,and near-complete genome assemblies now allow accurate SV detection and genotyping.These innovations overcome the limitations of single-reference genomes,enabling the discovery of complex SVs,including nested and overlapping variants,and providing access to previously inaccessible genomic regions such as centromeres and telomeres.This review highlights the current landscape of cattle SV research,with emphasis on integrating longread sequencing and pangenome frameworks to uncover breed-specific and population-level variation.While many SVs are linked to economically important traits such as feed efficiency and disease resistance,their broader regulatory impacts remain an active area of investigation.Emerging functional genomics approaches,including transcriptomics,epigenomics,and genome editing,will clarify how SVs influence gene regulation and phenotype.Looking forward,the integration of SV catalogs with multi-omics data,imputation resources,and artificial intelligence-driven models will be essential for translating discoveries into breeding and conservation applications.Integrating structural variants into breeding pipelines promises to revolutionize livestock genomics,enabling precision selection and sustainable agriculture despite challenges in cost,data sharing,and functional validation.展开更多
文摘AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other than thyroid disease. METHODS: This retrospective study involved review of intravascular contrast-enhanced MDCT scans of the chest from 3077 consecutive adult outpatients, to identify unsuspected thyroid nodules. Exclusion criteria included history of thyroid cancer, known thyroid nodules or thyroid disease and risk factors for thyroid cancer, as evidenced by their medical records. One of 9 radiologists recorded number of nodules, location and bidirectional measurement of largest nodule, as well as amount of thyroid visualized on the chest computed tomography (CT). Presence of nodule was correlated with age, gender, race and percentage of thyroid imaged. RESULTS: A total of 2510 (2510/3077 or 81.6%) study subjects were included in the data analysis; among them,one or more nodules were identified in 629 subjects (629/2510 or 25.1%), with 242 (242/629 or 38.5%) having multiple nodules. Patients with nodule(s) were significantly older than those without (64 ± 13 years vs 58 ± 14 years, P < 0.0001), and female gender was associated with presence of nodule(s) (373/1222 or 30.5% vs 256/1288 or 19.9%, P < 0.0001). Women were also more likely having multiple nodules (167/373 or 44.8%) compared to men (75/256 or 29.3%, P < 0.0001). The majority of nodules (427/629 or 67.9%) were less than 1 cm. CONCLUSION: This retrospective review revealed a prevalence of 25.1% for unsuspected thyroid nodules on contrast-enhanced chest CT.
基金the support from the National Science Foundation of China(Grants Nos.61401117 and 61201017)the Fundamental Research Funds for the Central Universities(Grants Nos.HIT.IBRSEM.201303 and HIT.IBRSEM.B.201401).
文摘Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral function study.However,NIRS-based cerebral function detection accuracy can be signi¯cantly in°uenced by the physiological activities such as cardic cycle,respiration,spontaneous low-frequency oscillation and ultra-low frequency oscillation.The distribution difference of the capillary,artery and vein leads to the heterogeneity feature of the cerebral tissues.In the case that the heterogeneity is not serious,good detection accuracy and stable performance can be achieved through the regression analysis as the reference signal can well represent the interference in the measurement signal when conducting the multi-distance measurement approach.The direct use of the reference signal to estimate the interference is not able to achieve good performance in the case that the heterogeneity is serious.In this study,the cerebral function activity signal is extracted using recursive least square(RLS)method based on the multi-distance measurement method in which the reference signal is processed by ensemble empirical mode decomposition(EEMD)algorithm.The temporal and dimensional correlation of the neighboring sampling values are applied to estimate the interference in the measurement signal.Monte Carlo simulation based on a heterogeneous model is adopted here to investigate the effectiveness of this methodology.The results show that this methodology can effectively suppress the physiological interference and improve the detection accuracy of cerebral activity signal.
基金supported in part by Mr.and Mrs.Steven McKenzie’s EndowmentKatherine Russell Dixie’s Distinguished Professorship Endowment+1 种基金donor funds from Jamie’s Hope and Mrs.and Mr.James Ritter for Dr.Tsimberidou’s Personalized Medicine Programin part also supported by the National Institutes of Health/National Cancer Institute award number P30 CA016672(University of Texas MD Anderson Cancer Center).
文摘DNA profiling is an established method for cancer treatment selection,while RNA profiling remains investigational.We explored associations between DNA and RNA alterations and between the number of genes with altered expression and overall survival(OS)using patient data from IMPACT2(NCT02152254),a randomized study evaluating molecular profiling for guiding cancer therapy across tumor types.Molecular profiling,including DNA next-generation sequencing,was performed on all 829 patients in the IMPACT2 study.RNA profiling was performed by Tempus for 253 of 829 patients.We evaluated the concordance between DNA and RNA profiling,analyzed OS in 217 treated patients with RNA profiling,and assessed PD-L1 status and number of genes with altered expression.Fifty patients exhibited 58 concordant events,i.e.,genomic and expression alteration(s)in the same gene,including 38 copy number events,and 41 patients had statistically significant concordance.We identified 123 gene pairs with significant associations between genomic and expression alterations(p<0.05),including TP53 alterations with VEGFA overexpression.The median OS for patients with 0-2,3-5,and≥6 genes with altered expression was 9.8,11.9,and 6.7 months,respectively(p=0.03).These results underscore RNA profiling’s potential actionability,and altered expression in≥6 genes was associated with shorter OS.Significant concordance of TP53 alterations with VEGFA overexpression may partially explain tumor response to bevacizumab in TP53-mutant patients.
文摘Mdm2 and Mdm4 are negative regulators of the tumour suppressor p53; hence, this relationship is the focus of many cancerrelated studies. A multitude of experiments across various developmental stages have been conducted to explore the tissuespecific roles of these proteins in the mouse. When Mdm2 or Mdm4 are deleted in the germiine or specific tissues, they display different phenotypic defects, some of which lead to embryonic lethaLity. Mdm2 loss is often more deleterious than toss of its homotogue Mdm4. ALL tissues experience activation of p53 target genes upon toss of Mdm2 or Mdm4; however, the degree to which the p53 pathway is perturbed is highly tissue-specific and does not correlate to the severity of the morphological pheno- types. Therefore, a need for further understanding of how these proteins regulate p53 activity is warranted, as therapeutic targeting of the p53 pathway is rapidly evoLving and gaining attention in the field of cancer research. In this review, we discuss the tissue-specificity of Mdm proteins in regulating p53 and expose the need for investigation at the celt-specific level.
文摘随着医学的发展,精准医疗逐渐成为现代医疗的发展方向.为了给患者制定有效的个体化治疗方案,临床医师对病理诊断的精准性提出了更高的要求.规范化的取材是精准病理诊断的基础,也是精准治疗的前提[1].近几年来,随着乳腺B超引导下粗针穿刺活检已经逐渐取代手术活检,多数患者在手术切除时已经有了明确诊断.为了更精准测量肿瘤的位置,客观地评判手术范围,准确地评估肿瘤分期和治疗反应,乳腺标本的大体取材受到临床与病理的共同重视,取材方法也在逐渐改进[1-5].准确的大体检查往往依赖于病理医师、放射医师及外科医师的合作.我们旨在介绍乳腺癌手术切除标本和前哨淋巴结的大体取材方法,其主要内容来自于美国MD安德森癌症中心(MD Anderson Cancer Center,MDACC) 行之有效的多年实践.
文摘We investigate and compare the performance of four optical transport schemes for distributing Local Multipoint Distribution Service (LMDS) signals using an optical fiber backbone.
基金supported by grants from the National Natural Science Foundation of China,No.21807112(to Xiang Li),No.82030062(to Wuyuan Lu),Nos.91849129 and 22077078(to Honggang Hu)Shanghai Rising-Star Program(to Xiang Li,China)+1 种基金supported by the U.S.Department of Energy,Office of Science,Office of Basic Energy Sciences under Contract No.DE-AC02-76SF00515supported by the DOE Office of Biological and Environmental Research,and by the National Institutes of Health,National Institute of General Medical Sciences
文摘Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53 in vitro and in vivo,representing a viable therapeutic strategy for cancer treatment.Using phage display techniques,we previously identified a potent peptide activator of P53,termed PMI(TSFAEYWNLLSP),with binding affinities for both MDM2 and MDMX in the low nanomolar concentration range.Here we report an ultrahigh affinity,dual-specificity peptide antagonist of MDM2 and MDMX obtained through systematic mutational analysis and additivitybased molecular design.Functional assays of over 100 peptide analogs of PMI using surface plasmon resonance and fluorescence polarization techniques yielded a dodecameric peptide termed PMI-M3(LTFLEYWAQLMQ)that bound to MDM2 and MDMX with K_(d)values in the low picomolar concentration range as verified by isothermal titration calorimetry.Co-crystal structures of MDM2 and of MDMX in complex with PMI-M3 were solved at 1.65 and 3.0 A resolution,respectively.Similar to PMI,PMI-M3 occupied the P53-binding pocket of MDM2/MDMX,which was dominated energetically by intermolecular interactions involving Phe3,Tyr6,Trp7,and Leu 10.Notable differences in binding between PMI-M3 and PMI were observed at other positions such as Leu4 and Met11 with MDM2,and Leu1 and Met11 with MDMX,collectively contributing to a significantly enhanced binding affinity of PMI-M3 for both proteins.By adding lysine residues to both ends of PMI and PMI-M3 to improve their cellular uptake,we obtained modified peptides termed PMI-2K(KTSFAEYWNLLSPK)and M3-2K(KLTFLEYWAQLMQK).Compared with PMI-2K,M3-2K exhibited significantly improved antitumor activities in vitro and in vivo in a P53-dependent manner.This super-strong peptide inhibitor of the P53-MDM2/MDMX interactions may become,in its own right,a powerful lead compound for anticancer drug development,and can aid molecular design of other classes of P53 activators as well for anticancer therapy.
基金supported by the U.S.Department of Health&Human Services NIH National Institute on Aging under Award Number P01AG066603(to J.C.)。
文摘During aging,the spine undergoes degenerative changes,particularly with vertebral endplate bone expansion and sclerosis,that are associated with nonspecific low back pain.We report that parathyroid hormone(PTH)treatment reduced vertebral endplate sclerosis and improved pain behaviors in three mouse models of spinal degeneration(aged,SM/J,and young lumbar spine instability mice).Aberrant innervation in the vertebral body and endplate during spinal degeneration was decreased with PTH treatment as quantified by PGP9.5^(+)and CGRP^(+)nerve fibers,as well as CGRP expression in dorsal root ganglia.The neuronal repulsion factor Slit3 significantly increased in response to PTH treatment mediated by transcriptional factor FoxA2.PTH type 1 receptor and Slit3 deletion in osteocalcin-expressing cells prevented PTH-reduction of endplate porosity and improvement in behavior tests.Altogether,PTH stimulated osteoblast production of Slit3,decreased aberrant sensory nerve innervation,and provided symptomatic relief of LBP associated with mouse spinal degeneration.
基金supported by the Canadian Institutes of Health Research(DFD-181599)the National Institutes of Health(T32AG058527)to RJB and R0190106435 to VM.
文摘Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.
基金Institutional Research Grant,MD Anderson Cancer CenterUPWARDS Training Program(Undergraduate Students Working Towards Research in Science),Grant/Award Number:1R25CA240137-01A1the CPRIT Research Training Award CPRIT Training Program,Grant/Award Number:RP210028。
文摘Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this complex problem.One such model,the Oncopig,has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation.However,the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.Methods:Herein,we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and re-placed in the tissue.The study consisted of 3 animals in 3 cohorts(total of 9 animals)that were evaluated at 14,21,and 28 days.CT imaging,immunohistochemistry,multiplex immunofluorescence,and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation.Results:The tumors were hypovascular on CT and predominantly composed of CD45+cells with a strong lymphohistiocytic component,with no carcinomas identified.Ki-67 staining showed proliferation of CD45+immune cells but no neoplastic component.To provide further insight,the results are evaluated in the context of tumor growth kinetics.Conclusion:While progress has been made in generating targetable lesions,achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.
基金supported[in part]by the IntramuralResearch Program of the National Institutes ofHealth(NIH)(to KJM),and also supported by theOffice by the Office of the Assistant Secretary ofDefense for Health Affairs and the Defense HealthAgency J9,Research and Development Directorate,through the Vision Research Program under AwardNo.(CDMRPL-18-0-VR180205 to KJM and FMN-N).
文摘In vivo imaging of neurodegenerative diseases provides valuable insights into disease mechanisms and potential therapeutic interventions.Many ocular diseases are closely linked to neurodegenerative conditions affecting the brain,making the eye a unique and accessible model for studying these disorders.The transparency of eyes allows researchers to monitor disease progression non-invasively,offering a window into neural health.
基金supported in part by AFRI grant numbers 2019-7015-29321 and 2021-67015-33409 from the USDA National Institute of Food and Agriculture(NIFA)the SCINet project of the USDA ARS project number 0500-00093-001-00-D。
文摘Structural variations(SVs≥50 bp)are a critical but underexplored source of genetic diversity in cattle,shaping traits vital for productivity,adaptability,and health.Advances in long-read sequencing,pangenome graph construction,and near-complete genome assemblies now allow accurate SV detection and genotyping.These innovations overcome the limitations of single-reference genomes,enabling the discovery of complex SVs,including nested and overlapping variants,and providing access to previously inaccessible genomic regions such as centromeres and telomeres.This review highlights the current landscape of cattle SV research,with emphasis on integrating longread sequencing and pangenome frameworks to uncover breed-specific and population-level variation.While many SVs are linked to economically important traits such as feed efficiency and disease resistance,their broader regulatory impacts remain an active area of investigation.Emerging functional genomics approaches,including transcriptomics,epigenomics,and genome editing,will clarify how SVs influence gene regulation and phenotype.Looking forward,the integration of SV catalogs with multi-omics data,imputation resources,and artificial intelligence-driven models will be essential for translating discoveries into breeding and conservation applications.Integrating structural variants into breeding pipelines promises to revolutionize livestock genomics,enabling precision selection and sustainable agriculture despite challenges in cost,data sharing,and functional validation.
