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1.
BMC Med ; 22(1): 18, 2024 01 08.
Article in English | MEDLINE | ID: mdl-38185665

ABSTRACT

BACKGROUND: Methadone maintenance treatment (MMT) has been implemented in China for nearly two decades, with a significant decrease in the number of participants in recent years. However, there is a lack of comprehensive research focusing on the long-term effectiveness in the context of this decline, especially from the perspectives of MMT participants themselves. This study aims to address this gap by examining the benefits and challenges experienced by long-term MMT participants in China, to uncover potential causes of the decrease in participant numbers and to improve the effectiveness of the program. METHODS: We conducted semi-structured interviews with 21 long-term MMT participants (treatment duration ≥ 5 years) recruited through purposive sampling from 6 MMT clinics in the Guangdong Province, China, between December 2021 and August 2022. Thematic analysis was employed to analyze the transcribed interviews. Two analysts independently coded the data, and a third researcher double-coded 20% of transcripts to ensure intercoder reliability. RESULTS: Overall, participants corroborated the notable decline in MMT participants during their long-term MMT, citing death, arrest, and self-perceived abstinence from heroin, as their perceived driving factors. They reported positive changes in their health, family relationships, and social functioning. However, they identified economic hardship as their greatest challenge associated with MMT, further exacerbated by other barriers including the conflict of clinic opening hours and working schedules, discrimination from employers, and COVID-19-related restrictions. Additionally, participants identified issues with dose adjustment and emergency treatment continuation. CONCLUSIONS: This study outlines the overall improvement in the quality of life of long-term MMT participants. However, it highlights the need for official guidelines for dose adjustment and emergency treatment continuation as well as the provision of health education, job referrals, and flexibility of clinic opening times to facilitate the return to society receiving participants. Establishing a follow-up mechanism for those receiving MMT is also recommended to prevent relapses to heroin and other illicit substances.


Subject(s)
Heroin , Quality of Life , Humans , Reproducibility of Results , China , Methadone/therapeutic use
2.
BMC Med Inform Decis Mak ; 22(1): 278, 2022 10 25.
Article in English | MEDLINE | ID: mdl-36284327

ABSTRACT

BACKGROUND: Outliers and class imbalance in medical data could affect the accuracy of machine learning models. For physicians who want to apply predictive models, how to use the data at hand to build a model and what model to choose are very thorny problems. Therefore, it is necessary to consider outliers, imbalanced data, model selection, and parameter tuning when modeling. METHODS: This study used a joint modeling strategy consisting of: outlier detection and removal, data balancing, model fitting and prediction, performance evaluation. We collected medical record data for all ICH patients with admissions in 2017-2019 from Sichuan Province. Clinical and radiological variables were used to construct models to predict mortality outcomes 90 days after discharge. We used stacking ensemble learning to combine logistic regression (LR), random forest (RF), artificial neural network (ANN), support vector machine (SVM), and k-nearest neighbors (KNN) models. Accuracy, sensitivity, specificity, AUC, precision, and F1 score were used to evaluate model performance. Finally, we compared all 84 combinations of the joint modeling strategy, including training set with and without cross-validated committees filter (CVCF), five resampling techniques (random under-sampling (RUS), random over-sampling (ROS), adaptive synthetic sampling (ADASYN), Borderline synthetic minority oversampling technique (Borderline SMOTE), synthetic minority oversampling technique and edited nearest neighbor (SMOTEENN)) and no resampling, seven models (LR, RF, ANN, SVM, KNN, Stacking, AdaBoost). RESULTS: Among 4207 patients with ICH, 2909 (69.15%) survived 90 days after discharge, and 1298 (30.85%) died within 90 days after discharge. The performance of all models improved with removing outliers by CVCF except sensitivity. For data balancing processing, the performance of training set without resampling was better than that of training set with resampling in terms of accuracy, specificity, and precision. And the AUC of ROS was the best. For seven models, the average accuracy, specificity, AUC, and precision of RF were the highest. Stacking performed best in F1 score. Among all 84 combinations of joint modeling strategy, eight combinations performed best in terms of accuracy (0.816). For sensitivity, the best performance was SMOTEENN + Stacking (0.662). For specificity, the best performance was CVCF + KNN (0.987). Stacking and AdaBoost had the best performances in AUC (0.756) and F1 score (0.602), respectively. For precision, the best performance was CVCF + SVM (0.938). CONCLUSION: This study proposed a joint modeling strategy including outlier detection and removal, data balancing, model fitting and prediction, performance evaluation, in order to provide a reference for physicians and researchers who want to build their own models. This study illustrated the importance of outlier detection and removal for machine learning and showed that ensemble learning might be a good modeling strategy. Due to the low imbalanced ratio (IR, the ratio of majority class and minority class) in this study, we did not find any improvement in models with resampling in terms of accuracy, specificity, and precision, while ROS performed best on AUC.


Subject(s)
Electronic Health Records , Machine Learning , Humans , Reactive Oxygen Species , Support Vector Machine , Cerebral Hemorrhage/diagnosis
3.
Opt Express ; 30(10): 17008-17025, 2022 May 09.
Article in English | MEDLINE | ID: mdl-36221533

ABSTRACT

Aiming at the problems that most of the existing electromagnetic metasurfaces have single function and narrow application scope, a highly integrated lightning-type metasurface is proposed in this study. It can realize the functions of circular dichroism (CD), absorption of electromagnetic waves, broadband x-to-y cross polarization conversion (CPC) function, linear-to-circular polarization conversion (LTC-PC) function and asymmetric transmission (AT), and its functions are also analyzed and verified. The designed metasurface consists of the bottom grating structure, the lower SiO2, the middle lightning-type graphene, the upper SiO2, the top graphene and photosensitive silicon. Through numerical calculations, the CD of design can reach more than 85% at 4.22 THz. The function of bimodal absorption is achieved at 4.09 and 8.69 THz. At 7.41∼8.21 THz, the polarization conversion ratio (PCR) of the metasurface reaches more than 99%. Simultaneously, the function of LTC-PC can be formed when PCR is 50%. Finally, when the designed metasurface is in the transmissive state, the AT of design is close to 60% at 7.84 THz. This design provides a new design idea and method for biomedical detection, image processing, modulators, smart switches, optical diodes and other fields.

4.
Opt Express ; 30(6): 9284-9297, 2022 Mar 14.
Article in English | MEDLINE | ID: mdl-35299360

ABSTRACT

We report a demonstration of an ultrafast all-optical switching with unique light control effects. The all-optical switching consists of a gold film with asymmetric split rings and a silica substrate. The device effectively controls the transmission and absorption of continuous pulses in the communication band (1200-1800 nm) and short pulses with a pulse duration of 80 fs by using the interaction of two coherent beams on nano-metamaterials with a thickness of only 50 nm. The metamaterial can achieve more than 90 % output control under continuous light irradiation. When the pulse duration is 80 fs, the switching contrast ratio is greater than 3 : 1 and the modulation bandwidth is greater than 12.5 THz. Switching time can be on the order of femtosecond. This paper provides a new structure for ultra-high speed optical data processing components in coherent networks.

5.
Theor Appl Genet ; 135(5): 1467-1476, 2022 May.
Article in English | MEDLINE | ID: mdl-35165745

ABSTRACT

KEY MESSAGES: Gray leaf spot (GLS) resistance in tomato is controlled by one major dominant locus, Sm. Sm was fine mapped, and the nucleotide-binding site-leucine-rich repeat (NBS-LRR) gene Solyc11g020100 was identified as a candidate gene for Sm. Further functional analysis indicated that this gene confers high resistance to Stemphylium lycopersici in tomato. Tomato (Solanum Lycopersicum) is widely consumed and cultivated in the world. Gray leaf spot (GLS), caused by Stemphylium lycopersici (S. lycopersici), is one of the most devastating diseases in tomato production. To date, only one resistance gene, Sm, which confers high resistance against GLS disease, has been identified in the wild tomato species Solanum pimpinellifolium. This resistance locus (comprising the Sm gene) has been transferred into the cultivated variety 'Motelle'. Although several studies have reported the mapping of the Sm gene, it has not been cloned, limiting the utilization in tomato breeding. Here, we cloned Sm using a map-based cloning strategy. The Sm gene was mapped in a region of 160 kb at chromosome 11 between two markers, namely, M390 and M410, by using an F2 population from a cross between the resistant cultivar 'Motelle' (Mt) and susceptible line 'Moneymaker' (Mm). Three clustered NBS-LRR (nucleotide-binding site-leucine-rich repeat) resistance genes, namely, Solyc11g020080 (R1), Solyc11g020090 (R2), and Solyc11g020100 (R3) were identified in this interval. Nonsynonymous SNPs were identified in only the open reading frame (ORF) of R3, suggesting it as a strong candidate for the Sm gene. Furthermore, gene silencing of R3 abolished the high resistance to S. lycopersici in Motelle, demonstrating that this gene confers high resistance to S. lycopersici. The cloning of Sm may speed up its utilization for breeding resistant tomato varieties and represents an important step forward in our understanding of the mechanism underlying the resistance to GLS.


Subject(s)
Solanum lycopersicum , Solanum , Ascomycota , Binding Sites , Disease Resistance/genetics , Leucine , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Nucleotides , Plant Breeding , Plant Diseases/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Solanum/genetics
6.
BMC Plant Biol ; 22(1): 13, 2022 Jan 03.
Article in English | MEDLINE | ID: mdl-34979927

ABSTRACT

BACKGROUND: Leaves, which are the most important organs of plants, can not only fix carbon sources through photosynthesis, but also absorb nutrients through transpiration. Leaf development directly determines the growth, flowering and fruiting of plants. There are many factors that affect leaf development, such as the growth environment, gene expression, and hormone synthesis. In this study, tomatoes were used to study the role of the transcription factor Solanum lycopersicum salt-related MYB1-like (SlSRM1-like) in the development of tomato leaves. RESULTS: Loss-of-function of the SlSRM1-like gene mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) resulted in abnormal tomato leaf morphology, including thinner leaves, wrinkled edges, raised veins, disordered edge veins, and left and right asymmetry. An analysis of the transcription levels of genes related to leaf development revealed that the expression of these genes was significantly altered in the SlSRM1-like mutants (SlSRM1-like-Ms). Moreover, the SlSRM1-like gene was expressed at higher transcription levels in young tissues than in old tissues, and its expression was also induced in response to auxin. In addition, the transcription levels of genes related to the auxin pathway, which regulates tomato growth and development, were severely affected in the SlSRM1-like-Ms. Therefore, it is hypothesized that the SlSRM1-like gene functions in the regulation of tomato leaf development through the auxin-related pathway. CONCLUSIONS: In this study, we successfully knocked out the SlSRM1-like gene in the tomato variety Ailsa Craig using CRISPR technology and found that knockout of the SlSRM1-like gene resulted in abnormal development of tomato leaves. Further research indicated that SlSRM1-like regulated tomato leaf development through auxin-related pathways. The results provide an important reference for the functional study of other SRM1-like genes in plants and provide new insights into the regulation of leaf development in tomato and other plants.


Subject(s)
Plant Leaves/growth & development , Plant Proteins/genetics , CRISPR-Cas Systems , Solanum lycopersicum , Mutagenesis , Plant Leaves/genetics , Plant Proteins/metabolism
7.
J Microbiol Methods ; 193: 106417, 2022 02.
Article in English | MEDLINE | ID: mdl-35033634

ABSTRACT

Many factors affecting satellitism tests are unclear, and it is difficult to avoid misidentification, even if the medium is properly selected. We investigated the factors causing false-positive results for Haemophilus influenzae and false-negative results for Haemophilus parainfluenzae in the satellitism tests using Staphylococcus aureus as the source of nicotinamide adenine dinucleotide (NAD). H. influenzae (four reference strains and 47 clinical isolates), H. parainfluenzae (two reference strains and 67 clinical isolates), four different media, and two strains of S. aureus revived on two different media were used in this study. The type of medium used to revive S. aureus was the most common factor causing false-positive results for H. influenzae, followed by different strains of S. aureus and the type of medium used for the experiment. The production of false-negative results for H. parainfluenzae was only related to the medium used in the experiment. To improve the accuracy of the tests in routine laboratories, using S. aureus as the source of NAD, tryptic soy agar, and S. aureus (ATCC 25923) revived on nutrient agar should be adopted.


Subject(s)
Haemophilus Infections , Haemophilus influenzae , Agar , Culture Media , Haemophilus , Haemophilus parainfluenzae , Humans , Indicators and Reagents , NAD , Staphylococcus aureus
8.
Int J Mol Sci ; 22(15)2021 Jul 29.
Article in English | MEDLINE | ID: mdl-34360893

ABSTRACT

Flowering is a morphogenetic process in which angiosperms shift from vegetative growth to reproductive growth. Flowering time has a strong influence on fruit growth, which is closely related to productivity. Therefore, research on crop flowering time is particularly important. To better understand the flowering period of the tomato, we performed transcriptome sequencing of early flower buds and flowers during the extension period in the later-flowering "Moneymaker" material and the earlier-flowering "20965" homozygous inbred line, and we analyzed the obtained data. At least 43.92 million clean reads were obtained from 12 datasets, and the similarity with the tomato internal reference genome was 92.86-94.57%. Based on gene expression and background annotations, 49 candidate genes related to flowering time and flower development were initially screened, among which the greatest number belong to the photoperiod pathway. According to the expression pattern of candidate genes, the cause of early flowering of "20965" is predicted. The modes of action of the differentially expressed genes were classified, and the results show that they are closely related to hormone regulation and participated in a variety of life activities in crops. The candidate genes we screened and the analysis of their expression patterns provide a basis for future functional verification, helping to explore the molecular mechanism of tomato flowering time more comprehensively.


Subject(s)
Crops, Agricultural/growth & development , Crops, Agricultural/genetics , Flowers/growth & development , Flowers/genetics , Genes, Plant , Solanum lycopersicum/growth & development , Solanum lycopersicum/genetics , Transcriptome , Crops, Agricultural/metabolism , Flowers/metabolism , Gene Expression Regulation, Plant , Gene Regulatory Networks , Genetic Association Studies/methods , Solanum lycopersicum/metabolism , Photoperiod , Plant Proteins/genetics , RNA-Seq/methods , Signal Transduction/genetics
9.
BMC Plant Biol ; 21(1): 72, 2021 Feb 02.
Article in English | MEDLINE | ID: mdl-33530947

ABSTRACT

BACKGROUND: APETALA2/ethylene responsive factor (AP2/ERF) transcription factors are a plant-specific family of transcription factors and one of the largest families of transcription factors. Ethylene response factors (ERF) regulate plant growth, development, and responses to biotic and abiotic stress. In a previous study, the ERF2 gene was significantly upregulated in both resistant and susceptible tomato cultivars in response to Stemphylium lycopersici. The main purpose of this study was to systematically analyze the ERF family and to explore the mechanism of ERF2 in tomato plants resisting pathogen infection by the Virus-induced Gene Silencing technique. RESULTS: In this experiment, 134 ERF genes were explored and subjected to bioinformatic analysis and divided into twelve groups. The spatiotemporal expression characteristics of ERF transcription factor gene family in tomato were diverse. Combined with RNA-seq, we found that the expression of 18 ERF transcription factors increased after inoculation with S. lycopersici. In ERF2-silenced plants, the susceptible phenotype was observed after inoculation with S. lycopersici. The hypersensitive response and ROS production were decreased in the ERF2-silenced plants. Physiological analyses showed that the superoxide dismutase, peroxidase and catalase activities were lower in ERF2-silenced plants than in control plants, and the SA and JA contents were lower in ERF2-silenced plants than in control plants after inoculation with S. lycopersici. Furthermore, the results indicated that ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance. CONCLUSIONS: In this study, we identified and analyzed members of the tomato ERF family by bioinformatics methods and classified, described and analyzed these genes. Subsequently, we used VIGS technology to significantly reduce the expression of ERF2 in tomatoes. The results showed that ERF2 had a positive effect on tomato resistance to S. lycopersici. Interestingly, ERF2 played a key role in multiple SA, JA and ROS signaling pathways to confer resistance to invasion by S. lycopersici. In addition, ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance to S. lycopersici. In summary, this study provides gene resources for breeding for disease resistance in tomato.


Subject(s)
Ascomycota/physiology , Disease Resistance/genetics , Genome, Plant , Multigene Family , Plant Diseases/genetics , Plant Proteins/genetics , Solanum lycopersicum/genetics , Solanum lycopersicum/microbiology , Amino Acid Motifs , Catalase/metabolism , Chromosomes, Plant/genetics , Conserved Sequence , Cyclopentanes/metabolism , Gene Expression Regulation, Plant , Hydrogen Peroxide/metabolism , Organ Specificity/genetics , Oxylipins/metabolism , Peroxidase/metabolism , Phylogeny , Plant Diseases/microbiology , Plant Proteins/chemistry , Plant Proteins/metabolism , Salicylic Acid/metabolism , Signal Transduction , Superoxide Dismutase/metabolism , Superoxides/metabolism , Transcription Factors/metabolism
10.
BMC Plant Biol ; 20(1): 376, 2020 Aug 15.
Article in English | MEDLINE | ID: mdl-32799800

ABSTRACT

BACKGROUND: Tomato gray leaf spot caused by Stemphylium lycopersici (S. lycopersici) is a serious disease that can severely hinder tomato production. To date, only Sm has been reported to provide resistance against this disease, and the molecular mechanism underlying resistance to this disease in tomato remains unclear. To better understand the mechanism of tomato resistance to S. lycopersici, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR)-based analysis, physiological indexes, microscopy observations and transgenic technology were used in this study. RESULTS: Our results showed that the expression of SlERF01 was strongly induced by S. lycopersici and by exogenous applications of the hormones salicylic acid (SA) and jasmonic acid (JA). Furthermore, overexpression of SlERF01 enhanced the hypersensitive response (HR) to S. lycopersici and elevated the expression of defense genes in tomato. Furthermore, the accumulation of lignin, callose and hydrogen peroxide (H2O2) increased in the transgenic lines after inoculation with S. lycopersici. Taken together, our results showed that SlERF01 played an indispensable role in multiple SA, JA and reactive oxygen species (ROS) signaling pathways to provide resistance to S. lycopersici invasion. Our findings also indicated that SlERF01 could activate the expression of the PR1 gene and enhance resistance to S. lycopersici. CONCLUSIONS: We identified the SlERF01 gene, which encodes a novel tomato AP2/ERF transcription factor (TF). Functional analysis revealed that SlERF01 positively regulates tomato resistance to S. lycopersici. Our findings indicate that SlERF01 plays a key role in multiple SA, JA and ROS signaling pathways to provide resistance to invasion by S. lycopersici. The findings of this study not only help to better understand the mechanisms of response to pathogens but also enable targeted breeding strategies for tomato resistance to S. lycopersici.


Subject(s)
Ascomycota/physiology , Plant Diseases/genetics , Plant Proteins/metabolism , Solanum lycopersicum/genetics , Transcription Factors/metabolism , Cloning, Molecular , Cyclopentanes/metabolism , Disease Resistance/genetics , Gene Expression Regulation, Plant , Gene Silencing , Genes, Plant , Solanum lycopersicum/microbiology , Oxylipins/metabolism , Phylogeny , Plant Diseases/microbiology , Plant Proteins/genetics , Salicylic Acid , Signal Transduction , Transcription Factors/genetics
11.
IEEE Trans Biomed Eng ; 67(9): 2490-2496, 2020 09.
Article in English | MEDLINE | ID: mdl-31902753

ABSTRACT

OBJECTIVE: Tumor stiffening in pancreatic adenocarcinoma (PDAC) has been linked to cancer progression and lack of therapy response, yet current elastography tools cannot map stiffness in a whole tumor field-of-view with biologically relevant spatial resolution. Therefore, this study was developed to assess stiffness heterogeneity and geometrical patterns across whole PDAC xenograft ex vivo tumors. METHODS: The ex vivo elastography (EVE) mapping system was capable of creating stiffness map at 300-micron spatial resolution under a 5-20 mm field of view relevant to whole tumor assessment. The stiffness value at each location was determined by compression testing and an absolute tumor Young's modulus map was calculated based on the calibration between the system and ultrasound elastography (R2 = 0.95). RESULTS: Two PDAC tumor lines AsPC-1 and BxPC-3 implanted in xenograft models were assessed to show tumor stiffness and its linear relationship to collagen content (R2 = 0.59). EVE was able to capture stiffness heterogeneity ranging between 5 and 100 kPa in pancreatic tumors with collagen content up to 25%. More importantly, data shows the inverse relationship of local stiffness to local drug distribution (R2 = 0.66) and vessel patency (R2 = 0.61) in both PDAC tumor lines. CONCLUSION: The results suggested that elastography could be utilized to predict drug penetration in PDAC tumors or assess response to biological modifying adjunct therapies. SIGNIFICANCE: This study presents the first attempt to map out stiffness on a biologically relevant spatial scale across whole PDAC tumor slices with spatial resolution in the hundreds of microns.


Subject(s)
Adenocarcinoma , Elasticity Imaging Techniques , Pancreatic Neoplasms , Adenocarcinoma/diagnostic imaging , Animals , Elastic Modulus , Mice , Pancreatic Neoplasms/diagnostic imaging , Ultrasonography
12.
Ultrasound Med Biol ; 46(2): 393-404, 2020 02.
Article in English | MEDLINE | ID: mdl-31727378

ABSTRACT

Neither contrast-enhanced computed tomography nor magnetic resonance imaging can monitor changes in the pancreatic ductal adenocarcinoma microenvironment during therapy. We hypothesized that shear wave elastography could overcome this limitation. To test this hypothesis, we measured the shear modulus of two groups of murine pancreatic tumors (KCKO, n = 30; PAN02, n = 30) treated with stereotactic body radiation therapy (SBRT). The mean shear modulus of KCKO tumors was 7.651 kPa higher than that of PAN02 tumors (p < 0.001). SBRT reduced the shear modulus in KCKO tumors by 8.914 kPa (p < 0.001). No significant difference in the shear modulus of SBRT-treated PAN02 tumors was observed. Additionally, necrotic and collagen densities were reduced only in the SBRT-treated KCKO tumors. Shear modulus was dependent on collagen distribution and histological texture parameters (i.e., entropy and fractional dimension). Shear wave elastography imaging differentiates between SBRT-responsive (KCKO) and non-responsive (PAN02) tumors.


Subject(s)
Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/radiotherapy , Elasticity Imaging Techniques , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/radiotherapy , Animals , Diagnosis, Differential , Disease Models, Animal , Female , Mice , Mice, Inbred C57BL , Treatment Outcome
13.
Sci Rep ; 9(1): 19619, 2019 12 23.
Article in English | MEDLINE | ID: mdl-31873114

ABSTRACT

Lung cancer is the leading cause of cancer-related deaths worldwide, with 50-70% of patients suffering from bone metastasis. Accumulating evidence has demonstrated that miRNAs are involved in cell proliferation, migration, and invasion in malignancy, such as lung cancer bone metastasis. In the present study, we demonstrated that reduced miR-192-5p and increased TRIM44 levels were associated with the proliferation, migration and invasion of lung cancer. Furthermore, the potential functions of miR-192-5p were explored in A549 and NCI-H1299 cells. We found that miR-192-5p upregulation suppressed tumour behaviours in lung cancer cells. To further investigate whether miR-192-5p is associated with TRIM44, we used TargetScan software to predict the binding site between miR-192-5p and TRIM44. Luciferase activity assays were performed to verify this prediction. In addition, the significant role of miR-192-5p in negatively regulating TRIM44 expression was manifested by our research group. our results suggest that miR-192-5p inhibited the proliferation, migration and invasion of lung cancer through TRIM44.


Subject(s)
Bone Neoplasms/metabolism , Intracellular Signaling Peptides and Proteins/biosynthesis , Lung Neoplasms/metabolism , MicroRNAs/metabolism , Neoplasm Proteins/biosynthesis , RNA, Neoplasm/metabolism , Tripartite Motif Proteins/biosynthesis , A549 Cells , Animals , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Cell Movement , Female , Gene Expression Regulation, Neoplastic , Humans , Intracellular Signaling Peptides and Proteins/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Proteins/genetics , RNA, Neoplasm/genetics , Tripartite Motif Proteins/genetics
14.
Clin Cancer Res ; 25(7): 2136-2143, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30352906

ABSTRACT

PURPOSE: High tissue pressure prevents chemotherapeutics from reaching the core of pancreatic tumors. Therefore, targeted therapies have been developed to reduce this pressure. While point probes have shown the effectiveness of these pressure-reducing therapies via single-location estimates, ultrasound elastography is now widely available as an imaging technique to provide real-time spatial maps of shear modulus (tissue stiffness). However, the relationship between shear modulus and the underlying tumor microenvironmental causes of high tissue pressure has not been investigated. In this work, elastography was used to investigate how shear modulus influences drug delivery in situ, and how it correlates with collagen density, hyaluronic acid content, and patent vessel density-features of the tumor microenvironment known to influence tissue pressure. EXPERIMENTAL DESIGN: Intravenous injection of verteporfin, an approved human fluorescent drug, was used in two pancreatic cancer xenograft models [AsPC-1 (n = 25) and BxPC-3 (n = 25)]. RESULTS: Fluorescence intensity was higher in AsPC-1 tumors than in BxPC-3 tumors (P < 0.0001). Comparing drug uptake images and shear wave elastographic images with histologic images revealed that: (i) drug delivery and shear modulus were inversely related, (ii) shear modulus increased linearly with increasing collagen density, and (iii) shear modulus was marginally correlated with the local assessment of hyaluronic acid content. CONCLUSIONS: These results demonstrate that elastography could guide targeted therapy and/or identify patients with highly elevated tissue pressure.See related commentary by Nia et al., p. 2024.


Subject(s)
Carcinoma, Pancreatic Ductal , Elasticity Imaging Techniques , Pancreatic Neoplasms , Animals , Disease Models, Animal , Elastic Modulus , Humans , Tumor Microenvironment
15.
Environ Sci Pollut Res Int ; 26(33): 33847-33855, 2019 Nov.
Article in English | MEDLINE | ID: mdl-29936611

ABSTRACT

Atrazine, one of the most widespread herbicides in the world, is considered as an environmental estrogen and has potential carcinogenicity. In this study, atrazine was degraded on boron-fluorine co-doped TiO2 nanotube arrays (B, F-TiO2 NTAs), which had similar morphology with the pristine TiO2 NTAs. The structure and morphology of TiO2 nanotube samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV-visible diffuse reflectance spectroscopy (DRS). It showed that the decoration of fluorine and boron made both the absorption in the visible region enhanced and the band edge absorption shifted. The efficiency of atrazine degradation by B, F-TiO2 NTAs through photoelectrocatalysis was investigated by current, solution pH, and electrolyte concentration, respectively. The atrazine removal rate reached 76% through photoelectrocatalytic reaction by B, F-TiO2 NTAs, which was 46% higher than that under the photocatalysis process. Moreover, the maximum degradation rate was achieved at pH of 6 in 0.01 M of Na2SO4 electrolyte solution under a current of 0.02 A and visible light for 2 h in the presence of B, F-TiO2 NTAs. These results showed that B, F-TiO2 NTAs exhibit remarkable photoelectrocatalytic activity in degradation of atrazine.


Subject(s)
Atrazine/chemistry , Herbicides/chemistry , Nanotubes/chemistry , Photochemical Processes , Titanium/chemistry , Boron/chemistry , Fluorides , Fluorine/chemistry , Light , Microscopy, Electron, Scanning , X-Ray Diffraction
16.
Ultrasound Med Biol ; 43(12): 2891-2903, 2017 12.
Article in English | MEDLINE | ID: mdl-28964615

ABSTRACT

High tissue pressures prevent chemotherapeutics from reaching the parenchyma of pancreatic ductal adenocarcinoma, which makes it difficult to treat this aggressive disease. Researchers currently use invasive probes to monitor the effectiveness of pressure-reducing therapies, but this practice introduces additional complications. Here, we hypothesize that Young's modulus is a good surrogate for tissue pressure because collagen density and hyaluoronic acid, the key features of the tumor microenvironment responsible for high tissue pressures, also affect modulus elastograms. To corroborate this hypothesis, we used model-based quasi-static elastography to assess how the Young's modulus of naturally occurring AsPc-1 pancreatic tumors varies with collagen density and hyaluoronic acid concentration. We observed that Young's moduli of orthotopically grown xenograft tumors were 6 kPa (p < 0.05) higher than that of their subcutaneously grown counterparts. We also observed a strong correlation between Young's modulus and regions within the tumors with high collagen (R2 ≈ 0.8) and hyaluoronic acid (R2 ≈ 0.6) densities. These preliminary results indicate that hyaluronic acid and collagen density, features of the pancreatic ductal adenocarcinoma tumor microenvironment responsible for high tissue pressure, influence Young's modulus.


Subject(s)
Carcinoma, Pancreatic Ductal/diagnostic imaging , Elasticity Imaging Techniques/methods , Heterografts/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Animals , Disease Models, Animal , Elastic Modulus , Humans , Mice , Rats
17.
Sci Rep ; 7(1): 12081, 2017 09 21.
Article in English | MEDLINE | ID: mdl-28935983

ABSTRACT

Increased arterial thickness measured with ultrasound correlates with future cardiovascular events, but conventional ultrasound imaging techniques cannot distinguish between intima, media, or atherosclerotic plaque in the carotid artery. In this work, we evaluated how well vascular elastography can detect intimal changes in a mouse model of carotid remodeling. We ligated the left external and internal branches of the carotid artery of male FVB mice and performed sham operations for 2 weeks. High-resolution ultrasound imaging accurately detected lower blood velocities and low blood volume flow in the carotid arteries after ligation in FVB mice. However, ultrasound could not detect differences in the carotid wall even at 2 weeks post-surgery. The Young's modulus was measured based on displacements of the carotid artery wall, and Young's modulus was 2-fold greater in shams at 1 week post ligation, and 3-fold greater 2 weeks after ligation. Finally, the higher Young's modulus was most associated with higher intimal thickness but not medial or adventitial thickness as measured by histology. In conclusion, we developed a robust ultrasound-based elastography method for early detection of intimal changes in small animals.


Subject(s)
Carotid Arteries/physiology , Elastic Modulus/physiology , Elasticity Imaging Techniques/methods , Vascular Remodeling/physiology , Algorithms , Animals , Blood Flow Velocity/physiology , Carotid Arteries/diagnostic imaging , Carotid Arteries/surgery , Carotid Intima-Media Thickness , Ligation , Male , Mice, Inbred Strains , Models, Cardiovascular , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/physiopathology , Ultrasonography/methods
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