Publications by authors named "Hui Mao"

314 Publications

Tannin foam immobilized with ferric ions for efficient removal of ciprofloxacin at low concentrations.

J Hazard Mater 2021 07 6;414:125567. Epub 2021 Mar 6.

College of Biomedical Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address:

The presence of ciprofloxacin (CIP) in natural water may cause potential threats to the environment. Adsorption is a convenient and efficient method to remove CIP from aqueous solution. Bayberry tannin (BT), a natural polyphenol, has been utilized in the synthesis of tannin foam (TF) due to its abundant polyphenolic hydroxyls to chelate with metal ions. The obtained TF was subsequently immobilized with Fe via a facile chelative adsorption to fabricate functional tannin foam (TF-Fe), which was highly porous, with a porosity of 78.93%. The Fe species in the TF-Fe featured good dispersity, which were active for chelative adsorption of CIP. The adsorption of CIP on the TF-Fe was a pH-dependent process. At the optimized pH of 7.0, the TF-Fe provided the adsorption capacity of 91.8 mg g. When applied in removal of CIP at the low concentration of 2.0 µg mL, a high removal efficiency of 96.60% was still obtained, which was superior to commercial activated carbon (28.78%). The adsorption kinetics were well fitted by the pseudo-second-order rate model while the adsorption isotherms were well described by the Langmuir model. The TF-Fe was capable of recycling, which still maintained a high removal efficiency of 92.25% in the 5th cycle.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125567DOI Listing
July 2021

Divergent Synthesis of Aziridine and Imidazolidine Frameworks under Blue LED Irradiation.

Org Lett 2021 Jun 14;23(11):4109-4114. Epub 2021 May 14.

Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials, College of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui 230601, People's Republic of China.

We develop a visible light-promoted divergent cycloaddition of α-diazo esters with hexahydro-1,3,5-triazines, leading to a series of aziridine and imidazolidine frameworks in average good yield, by simply changing the reaction media used. It is noteworthy that the reaction occurs under sole visible light irradiation without the need for exogenous photoredox catalysts. More significantly, a reasonable reaction mechanism was proposed on the basis of the control experiments and density functional theory calculation results.
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http://dx.doi.org/10.1021/acs.orglett.1c00979DOI Listing
June 2021

Land Tenure and Green Production Behavior: Empirical Analysis Based on Fertilizer Use by Cotton Farmers in China.

Int J Environ Res Public Health 2021 04 28;18(9). Epub 2021 Apr 28.

Northwest Institute of Historical Environment and Socio-Economic Development, Shaanxi Normal University, Xi'an 710119, China.

Stable land rights can increase farmers' expectations regarding the future and encourage their adoption of green production methods, which is an important guarantee for promoting the development of green agriculture development. This paper takes the fertilizer use as an example and systematically investigated the impact of land tenure stability on the green production behavior of heterogeneous farmers based on a field survey data of 349 cotton-planting farmers from Xinjiang, China. Furthermore, this research aims to assess the differential impact of land tenure stability on different risk preferences, organizational forms and ethnic groups. This study is a continuation of previous studies on factors influencing green production behavior. The results show that land transfers have an inhibiting effect on farmers' green production behavior and this effect is more significant among risk-averse farmers, local farmers and minority nationalities farmers. The land tenure period can promote the green production of farmers and alleviate the restraining effect of land transfers on farmers' green production behavior. Additionally, farmers of Xinjiang Production and Construction Corps (XPCC) and large-scale households are more inclined to green production. The Chinese Government needs to further promote land transfer to large-scale households, improve the stability of land rights and adopt differentiated policies for heterogeneous farmers to encourage their green production.
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http://dx.doi.org/10.3390/ijerph18094677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124971PMC
April 2021

Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery.

Nat Commun 2021 04 22;12(1):2390. Epub 2021 Apr 22.

MOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.

The mitochondrion is an important sub-cellular organelle responsible for the cellular energetic source and processes. Owing to its unique sensitivity to heat and reactive oxygen species, the mitochondrion is an appropriate target for photothermal and photodynamic treatment for cancer. However, targeted delivery of therapeutics to mitochondria remains a great challenge due to their location in the sub-cellular compartment and complexity of the intracellular environment. Herein, we report a class of the mitochondrion-targeted liposomal delivery platform consisting of a guanidinium-based dendritic peptide moiety mimicking mitochondrion protein transmembrane signaling to exert mitochondrion-targeted delivery with pH sensitive and charge-reversible functions to enhance tumor accumulation and cell penetration. Compared to the current triphenylphosphonium (TPP)-based mitochondrion targeting system, this dendritic lipopeptide (DLP) liposomal delivery platform exhibits about 3.7-fold higher mitochondrion-targeted delivery efficacy. Complete tumor eradication is demonstrated in mice bearing 4T1 mammary tumors after combined photothermal and photodynamic therapies delivered by the reported DLP platform.
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http://dx.doi.org/10.1038/s41467-021-22594-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062597PMC
April 2021

Irisin induces white adipose tissue browning in mice as assessed by magnetic resonance imaging.

Exp Biol Med (Maywood) 2021 Apr 22:15353702211006049. Epub 2021 Apr 22.

Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, P. R. China.

This study aimed to track and evaluate the effect of low-dose irisin on the browning of white adipose tissue (WAT) in mice using magnetic resonance imaging (MRI) noninvasively . Mature white adipocytes extracted from mice were cultured, induced and characterized before being treated by irisin. The volume and fat fraction of WAT were quantified using MRI in normal chow diet and high fat mice after injection of irisin. The browning of cultured white adipocytes and WAT in mice were validated by immunohistochemistry and western blotting for uncoupling protein 1 (UCP1) and deiodinase type II (DIO2). The serum indexes were examined with high fat diet after irisin intervention. UCP1 and DIO2 in adipocytes showed increases responding to the irisin treatment. The size of white adipocytes in mice receiving irisin intervention was reduced. MRI measured volumes and fat fraction of WAT were significantly lower after Irisin treatment. Blood glucose and cholesterol levels were reduced in high fat diet mice after irisin treatment. Irisin intervention exerted browning of WAT, resulting reduction of volume and fat fraction of WAT as measured by MRI. Furthermore, it improved the condition of mice with diet-induced obesity and related metabolic disorders.
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http://dx.doi.org/10.1177/15353702211006049DOI Listing
April 2021

Prolonged Duration of Blood Pressure Drops During General Anesthesia Is Associated With Worse Outcomes After Mechanical Thrombectomy.

Front Neurol 2021 29;12:640841. Epub 2021 Mar 29.

Department of Neurology, Zhejiang Provincial People's Hospital, Hangzhou, China.

Optimal periprocedural management of blood pressure during mechanical thrombectomy (MT) remains controversial. This study aimed to investigate the relationship between the duration of blood pressure drops during general anesthesia and the outcomes in large vessel occlusion (LVO) patients treated with MT. We retrospectively reviewed our prospectively collected data for LVO patients treated with MT between January 2018 and July 2020. Intraprocedural mean arterial pressure (MAP) was recorded every 5 min throughout the procedure. Baseline MAP minus each MAP value recorded during general anesthesia was defined ΔMAP. Cumulated time (in min) and longest continuous episode (in min) with ΔMAP more than 10, 15, 20, 25, and 30 mmHg were calculated, respectively. Poor outcome was defined as 90-day modified Rankin score (mRS) 3-6. Associations between cumulated time of different ΔMAP thresholds and poor outcome were determined using binary logistic regression models. A total of 131 patients were finally included in the study. After controlling for age, atrial fibrillation, baseline NIHSS, baseline ASPECTS, procedure duration of MT, and times of retrieval attempts, the results indicated that cumulated time of MAP drop more than 10 mmHg (OR 1.013; 95% CI 1.004-1.023; = 0.007) and 15 mmHg (OR 1.011; 95% CI 1.002-1.020; = 0.017) were independently associated with poor outcomes. Prolonged episodes of intraprocedural MAP lowering were more likely to have poor outcomes in LVO patients following MT with general anesthesia, which might be helpful in guiding intraprocedural hemodynamic management of patients under general anesthesia.
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http://dx.doi.org/10.3389/fneur.2021.640841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039315PMC
March 2021

Establishment of deep eutectic solvent assisted matrix solid-phase dispersion extraction for the determination of four flavonoids in Scutellariae Radix based on the concept of quality by design.

J AOAC Int 2021 Mar 28. Epub 2021 Mar 28.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, P. R. China.

Background: Sample preparation is the most crucial step in the whole analytical schemes. Micro matrix solid-phase dispersion, as a method for microextraction of analytes, has prevailed recently for its low sample and extraction solvent consumption. However, small amount of adsorbent, sample or short extraction time always brings uncertainty on the result when using this method.

Objective: To develop a simple and reliable method by deep eutectic solvents assisted ultrasonic-synchronized matrix solid-phase dispersion microextraction for the analysis of four flavonoids in Scutellariae Radix based on the concept of quality by design.

Methods: Molecular sieve ZSM-5 was used as new adsorbent in MSPD process. Single factor and Box-Behnken design were used to construct the design space.

Results: Verification of experiment demonstrated that the design space is robust. Under the optimal conditions, all analytes showed good linearity (R2 > 0.999), high reproducibility (RSD < 2.24%) and stability (RSD < 2.87%), satisfactory recoveries (95.90∼102.31%), which indicated that the established method is reliable and reproducible. Moreover, it has been successfully applied to determine the flavonoids in nine batches of Scutellariae Radix.

Conclusion: The result indicated a great potential on analyzing precious complicated samples and helps to promote the quality control of the sample preparation process of traditional Chinese medicines.

Highlights: A systematic approach by using a facile DES assisted ultrasonic-synchronized matrix solid-phase dispersion extraction coupled with HPLC for the analysis of flavonoids in Scutellariae Radix has been developed based on the concept of quality by design.
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http://dx.doi.org/10.1093/jaoacint/qsab043DOI Listing
March 2021

Spectral Wavelet-feature Analysis and Classification Assisted Denoising for enhancing magnetic resonance spectroscopy.

NMR Biomed 2021 Jun 9;34(6):e4497. Epub 2021 Mar 9.

Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.

Magnetic resonance spectroscopy (MRS) is capable of revealing important biochemical and metabolic information of tissues noninvasively. However, the low concentrations of metabolites often lead to poor signal-to-noise ratio (SNR) and a long acquisition time. Therefore, the applications of MRS in detection and quantitative measurements of metabolites in vivo remain limited. Reducing or even eliminating noise can improve SNR sufficiently to obtain high quality spectra in addition to increasing the number of signal averaging (NSA) or the field strength, both of which are limited in clinical applications. We present a Spectral Wavelet-feature ANalysis and Classification Assisted Denoising (SWANCAD) approach to differentiate signal and noise peaks in magnetic resonance spectra based on their respective wavelet features, followed by removing the identified noise components to improve SNR. The performance of this new denoising approach was evaluated by measuring and comparing SNRs and quantified metabolite levels of low NSA spectra (e.g. NSA = 8) before and after denoising using the SWANCAD approach or by conventional spectral fitting and denoising methods, such as LCModel and wavelet threshold methods, as well as the high NSA spectra (e.g. NSA = 192) recorded in the same sampling volumes. The results demonstrated that SWANCAD offers a more effective way to detect the signals and improve SNR by removing noise from the noisy spectra collected with low NSA or in the subminute scan time (e.g. NSA = 8 or 16 s). The potential applications of SWANCAD include using low NSA to accelerate MRS acquisition while maintaining adequate spectroscopic information for detection and quantification of the metabolites of interest when a limited time is available for an MRS examination in the clinical setting.
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http://dx.doi.org/10.1002/nbm.4497DOI Listing
June 2021

Targeting signal pathways triggered by cyclic peptides in cancer: Current trends and future challenges.

Arch Biochem Biophys 2021 04 27;701:108776. Epub 2021 Jan 27.

Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China. Electronic address:

Cancer is a global health issue that origins thousands of deaths annually worldwide. Cyclic peptides are polypeptide chains which are formed by cyclic sequence of amide bonds between proteinogenic or non-proteinogenic amino acids. Numerous evidences indicate that cyclic peptides are implicated with the occurrence and development of cancer. This review presents the current knowledge about the role of cyclic peptides in cancer, such as liver cancer, colorectal cancer, ovarian cancer, breast cancer as well as prostate cancer. Specifically, the precise molecular mechanisms between cyclic peptides and cancer are elaborated. Some cyclic peptides from nature and synthesis prevent the occurrence and development of cancer. However, some other cyclic peptides including endothelin-1, urotensinⅡand melanin-concentrating hormone deteriorate the pathogenesis of cancer. Given the pleiotropic actions of cyclic peptides, the identification and development of cyclic peptides and their derivates as drug may be a potent therapeutic strategy for cancer.
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http://dx.doi.org/10.1016/j.abb.2021.108776DOI Listing
April 2021

A dual preconcentration method by combining micro matrix solid-phase dispersion extraction with field-enhanced sample injection and micelle to cyclodextrin stacking for sensitive analysis of neutral coumarins.

Electrophoresis 2021 May 1;42(9-10):1102-1107. Epub 2021 Feb 1.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, P. R. China.

A rapid, sensitive, environmental friendly dual preconcentration method by combining micro matrix solid-phase dispersion extraction with field-enhanced sample injection and micelle to cyclodextrin stacking has been developed for the determination of furocoumarins. Molecular sieve, KIT-6, was used as an adsorbent in micro matrix solid-phase dispersion process. The important parameters affecting off-line and online CE preconcentration efficiency were optimized. Under the optimal experimental conditions, all analytes showed good linearity (R > 0.999). The LODs of notopterol, isoimperatorin, and imperatorin were 0.1 μg/mL, 1.2 mg/kg, and 1.0 mg/kg, respectively. Compared with the normal CE method, the enrichment times were up to 300. Moreover, Angelicae Dahuricae Radix was used as the mode of complex solid sample matrix to demonstrate the prospect of application of this methodology. The results showed the proposed strategy is promising for determining trace furocoumarins in complex matrix samples, which might be applied as a powerful and economic tool in monitoring illegal cosmetic adding.
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http://dx.doi.org/10.1002/elps.202000273DOI Listing
May 2021

Transcriptomic Analyses and Potential Therapeutic Targets of Pancreatic Cancer With Concomitant Diabetes.

Front Oncol 2020 4;10:563527. Epub 2020 Nov 4.

Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.

Background: Type 2 diabetes mellitus (T2DM) known as non-insulin-dependent diabetes mellitus, which is increasingly acknowledged as being associated with an increased risk for a series of cancers. Pancreatic cancer is currently the fourth most common cause of cancer-related mortality, which has been proved to be worsened by internal diabetic condition. However, the underlying molecular mechanisms are less addressed. Furthermore, current knowledge revealed that therapeutic strategy by anti-diabetes for pancreatic cancer under diabetes condition have no satisfactory efficacy, and nor by chemotherapy in our study.

Methods: To clarify these mysteries and widen our knowledge, both obesity-associated and non-obese-associated T2DM mouse models were generated by chemical induction with streptozotocin (STZ) and leptin receptor knockout () in mice. Then, the process of tumor progression was researched, and the gene expression profiling of pancreatic cancer in mice was performed using RNA-seq.

Results: Our results showed that pancreatic cancer malignancy was increased with notable proliferation and metastatic potential in two diabetic mice model. Totally, 136 and 64 significantly differentially expressed genes (DEGs) were identified in STZ and / mice by transcriptomic analysis. The results also suggested that different carcinogenesis-related genes and potential molecular mechanisms contribute to the malignancy of pancreatic cancer in obesity-associated and non-obesity-associated T2DM. In obesity-associated / mice, the GO subcategories associated with most of the genes with downregulated expression are involved in the immune response. However, in non-obesity-associated STZ mice, in addition to the immune response category, the enriched subcategories also included angiogenesis and the extracellular matrix. While, two genes respectively encoding MMP-2 and MMP-9 were simultaneously abnormal up-regulated in pancreatic cancer tissue from diabetic mice of both STZ and /, that could act as potential therapeutic targets for significantly suppressing the malignant progression. Furthermore, an optimizing therapeutic strategy was further proposed that combining MMP-2/9 inhibitor with gemcitabine significantly enhanced anti-tumor effects on pancreatic cancer under diabetic condition, providing a theoretical basis for clinical applications.

Conclusions: Generally, this study provides a comprehensive insight into diabetes as a risk factor for pancreatic cancer and has the potential to guide the development of enhanced treatment strategies.
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http://dx.doi.org/10.3389/fonc.2020.563527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672183PMC
November 2020

Biomechanically constrained non-rigid MR-TRUS prostate registration using deep learning based 3D point cloud matching.

Med Image Anal 2021 01 7;67:101845. Epub 2020 Oct 7.

Department of Radiation Oncology, Emory University, 1365 Clifton Road NE, Atlanta, GA 30322, United States; Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States. Electronic address:

A non-rigid MR-TRUS image registration framework is proposed for prostate interventions. The registration framework consists of a convolutional neural networks (CNN) for MR prostate segmentation, a CNN for TRUS prostate segmentation and a point-cloud based network for rapid 3D point cloud matching. Volumetric prostate point clouds were generated from the segmented prostate masks using tetrahedron meshing. The point cloud matching network was trained using deformation field that was generated by finite element analysis. Therefore, the network implicitly models the underlying biomechanical constraint when performing point cloud matching. A total of 50 patients' datasets were used for the network training and testing. Alignment of prostate shapes after registration was evaluated using three metrics including Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD). Internal point-to-point registration accuracy was assessed using target registration error (TRE). Jacobian determinant and strain tensors of the predicted deformation field were calculated to analyze the physical fidelity of the deformation field. On average, the mean and standard deviation were 0.94±0.02, 0.90±0.23 mm, 2.96±1.00 mm and 1.57±0.77 mm for DSC, MSD, HD and TRE, respectively. Robustness of our method to point cloud noise was evaluated by adding different levels of noise to the query point clouds. Our results demonstrated that the proposed method could rapidly perform MR-TRUS image registration with good registration accuracy and robustness.
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http://dx.doi.org/10.1016/j.media.2020.101845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725979PMC
January 2021

Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma.

J Hematol Oncol 2020 10 21;13(1):141. Epub 2020 Oct 21.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Background: Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation.

Methods: High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo.

Results: We identified a small molecular inhibitor, "MNPC," that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo.

Conclusions: Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.
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http://dx.doi.org/10.1186/s13045-020-00979-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579906PMC
October 2020

Multimodal MRI synthesis using unified generative adversarial networks.

Med Phys 2020 Dec 27;47(12):6343-6354. Epub 2020 Oct 27.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Purpose: Complementary information obtained from multiple contrasts of tissue facilitates physicians assessing, diagnosing and planning treatment of a variety of diseases. However, acquiring multiple contrasts magnetic resonance images (MRI) for every patient using multiple pulse sequences is time-consuming and expensive, where, medical image synthesis has been demonstrated as an effective alternative. The purpose of this study is to develop a unified framework for multimodal MR image synthesis.

Methods: A unified generative adversarial network consisting of only a single generator and a single discriminator was developed to learn the mappings among images of four different modalities. The generator took an image and its modality label as inputs and learned to synthesize the image in the target modality, while the discriminator was trained to distinguish between real and synthesized images and classify them to their corresponding modalities. The network was trained and tested using multimodal brain MRI consisting of four different contrasts which are T1-weighted (T1), T1-weighted and contrast-enhanced (T1c), T2-weighted (T2), and fluid-attenuated inversion recovery (Flair). Quantitative assessments of our proposed method were made through computing normalized mean absolute error (NMAE), peak signal-to-noise ratio (PSNR), structural similarity index measurement (SSIM), visual information fidelity (VIF), and naturalness image quality evaluator (NIQE).

Results: The proposed model was trained and tested on a cohort of 274 glioma patients with well-aligned multi-types of MRI scans. After the model was trained, tests were conducted by using each of T1, T1c, T2, Flair as a single input modality to generate its respective rest modalities. Our proposed method shows high accuracy and robustness for image synthesis with arbitrary MRI modality that is available in the database as input. For example, with T1 as input modality, the NMAEs for the generated T1c, T2, Flair respectively are 0.034 ± 0.005, 0.041 ± 0.006, and 0.041 ± 0.006, the PSNRs respectively are 32.353 ± 2.525 dB, 30.016 ± 2.577 dB, and 29.091 ± 2.795 dB, the SSIMs are 0.974 ± 0.059, 0.969 ± 0.059, and 0.959 ± 0.059, the VIF are 0.750 ± 0.087, 0.706 ± 0.097, and 0.654 ± 0.062, and NIQE are 1.396 ± 0.401, 1.511 ± 0.460, and 1.259 ± 0.358, respectively.

Conclusions: We proposed a novel multimodal MR image synthesis method based on a unified generative adversarial network. The network takes an image and its modality label as inputs and synthesizes multimodal images in a single forward pass. The results demonstrate that the proposed method is able to accurately synthesize multimodal MR images from a single MR image.
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http://dx.doi.org/10.1002/mp.14539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796974PMC
December 2020

[Common variable immune deficiency in adult patients: analysis of 13 cases and literature review].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Aug;40(8):1213-1219

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the clinical and immunological characteristics, treatment and prognosis of common variable immune deficiency (CVID) in adult patients.

Methods: We retrospectively analyzed the clinical data of 13 adult patients hospitalized in our hospital for CVID diagnosed according to the criteria in International Consensus Document (2016), and analyzed their clinical manifestations, laboratory test results, imaging findings, pathological examinations and treatments.

Results: The mean age of onset was 24.46±16.82 years in these patients, who had a mean age of 32.54±14.86 years at diagnosis with a median diagnostic delay of 5 years (IQR: 2-15 years). The main manifestation of the patients was repeated infections, including repeated respiratory tract infection (10 cases; 76.9%) and repeated diarrhea (3 cases; 23.1%). Three (23.1%) of the patients had autoimmune disease and 10 (76.9%) had chronic pulmonary disease. IgG, IgA and IgM were decreased in all the patients. The proportion of CD4+T cells decreased in 10 patients (76.9%), CD8+T cells increased in 11 patients (84.6%), and CD4/ CD8 decreased in 10 patients (76.9%). Complement C3 decreased in 58.3% (7/12) and C4 decreased in 33.3% (4/12) of the patients. Twelve patients (92.3%) were treated with intravenous infusion of gamma globulin with symptomatic treatments. One patient died due to massive gastrointestinal hemorrhage, and the other patients showed improve ments after the treatments and were discharged.

Conclusions: The clinical manifestations of CVID are diverse, and recurrent respiratory tract infection is the most common manifestation. Decreased IgG often accompanied by lowered IgA and IgM levels is a common finding in laboratory tests. The treatment of CVID currently relies on gamma globulin with symptomatic treatments for the complications.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.08.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429157PMC
August 2020

A new fucosylated glycosaminoglycan containing disaccharide branches from Acaudina molpadioides: Unusual structure and anti-intrinsic tenase activity.

Carbohydr Polym 2020 Oct 2;245:116503. Epub 2020 Jun 2.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address:

A fucosylated glycosaminoglycan (AmFG) was extracted from the sea cucumber Acaudina molpadioides. And a series of oligosaccharides were purified from the size-homogeneous fractions, which were prepared from the β-eliminative depolymerized AmFG. According to "bottom-up" strategy, the precise structure of AmFG was elucidated by analyzing the structures of these purified oligosaccharides, combining with NMR analysis of its free-radical depolymerized product. It contained a CS-E-like backbone, and each GlcUA was branched with a mono- or di-sulfated fucose (Fuc) at O-3. Intriguingly, besides two types of monosaccharide branches, Fuc (60 %) and Fuc (25 %), that were common in FG, AmFG also contained an unusual disaccharide branch GalNAc-α1,2-Fuc (15 %); this is the first report of such a structure in a glycosaminoglycan. Biological assays indicated that native AmFG and its oligosaccharides had potent anticoagulant and intrinsic tenase (iXase) inhibitory activities in a chain length-dependent manner. For these oligosaccharides, octasaccharide was the minimum structural fragment for potent anti-iXase activity, and the disaccharide branch might enhance this activity.
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http://dx.doi.org/10.1016/j.carbpol.2020.116503DOI Listing
October 2020

A Network Pharmacology Approach to Investigate the Active Compounds and Mechanisms of Musk for Ischemic Stroke.

Evid Based Complement Alternat Med 2020 3;2020:4063180. Epub 2020 Jul 3.

The Second Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, China.

Objectives: This study aims to study the material basis and effective mechanism of musk for ischemic stroke (IS) based on the network pharmacology approach.

Methods: We collected the chemical components and target gene of musk from the BATMAN-TCM analytical platform and identified ischemic stroke-related targets from the following databases: DisGeNET, NCBI-Gene, HPO, OMIM, DrugBank, and TTD. The targets of musk and IS were uploaded to the String database to construct the protein-protein interaction (PPI) network, and then, the key targets were analyzed by topological methods. At last, the function biological process and signaling pathways of key targets were carried out by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and cluster analysis by using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server and Metascape platform.

Results: A total of 29 active compounds involving 1081 predicted targets were identified in musk and there were 1104 IS-related targets. And 88 key targets of musk for IS were obtained including AKT1, MAPK1/3, TP53, TNF, SRC, FOS, CASP3, JUN, NOS3, and IL1B. The GO and KEGG enrichment analysis suggested that these key targets are mainly involved in multiple pathways which participated in TNF signaling pathway, estrogen signaling pathway, prolactin signaling pathway, neurotrophin signaling pathway, T-cell receptor signaling pathway, cAMP signaling pathway, FoxO signaling pathway, and HIF1 signaling pathway.

Conclusion: This study revealed that the effective mechanisms of musk against IS would be associated with the regulation of apoptosis, inflammatory response, and gene transcription.
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http://dx.doi.org/10.1155/2020/4063180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354650PMC
July 2020

Brain tumor segmentation using 3D Mask R-CNN for dynamic susceptibility contrast enhanced perfusion imaging.

Phys Med Biol 2020 09 18;65(18):185009. Epub 2020 Sep 18.

Department of Radiation Oncology, Emory University, Atlanta, GA 30322, United States of America. Department of Biomedical Informatics, Emory University, Atlanta, GA 30322, United States of America.

The segmentation of neoplasms is an important part of radiotherapy treatment planning, monitoring disease progression, and predicting patient outcome. In the brain, functional magnetic resonance imaging (MRI) like dynamic susceptibility contrast enhanced (DSCE) or T1-weighted dynamic contrast enhanced (DCE) perfusion MRI are important tools for diagnosis. They play a crucial role in providing pre-operative assessment of tumor histology, grading, and biopsy guidance. However, the manual contouring of these neoplasms is tedious, expensive, time-consuming, and vulnerable to inter-observer variability. In this work, we propose a 3D mask region-based convolutional neural network (R-CNN) method to automatically segment brain tumors in DSCE MRI perfusion images. As our goal is to simultaneously localize and segment the tumor, our training process contained both a region-of-interest (ROI) localization and regression with voxel-wise segmentation. The combination of classification loss, ROI location and size regression loss, and segmentation loss were used to supervise the proposed network. We retrospectively investigated 21 patients' perfusion images, with between 50 and 70 perfusion time point volumes, a total of 1260 3D volumes. Tumor contours were automatically segmented by our proposed method and compared against other state-of-the-art methods and those delineated by physicians as the ground truth. The results of our method demonstrated good agreement with the ground truth contours. The average DSC, precision, recall, Hausdorff distance, mean surface distance (MSD), root MSD, and center of mass distance were 0.90 ± 0.04, 0.91 ± 0.04, 0.90 ± 0.06, 7.16 ± 5.78 mm, 0.45 ± 0.34 mm, 1.03 ± 0.72 mm, and 0.86 ± 0.91 mm, respectively. These results support the feasibility of our method in accurately localizing and segmenting brain tumors in DSCE perfusion MRI. Our 3D Mask R-CNN segmentation method in DSCE perfusion imaging has great promise for future clinical use.
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http://dx.doi.org/10.1088/1361-6560/aba6d4DOI Listing
September 2020

Identification of plasma miR-106a-5p and miR-30a-5p as potential biomarkers for mesangial proliferative glomerulonephritis.

Clin Biochem 2020 Oct 13;84:79-86. Epub 2020 Jul 13.

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China; College of Pharmacy, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Background: Although stable microRNAs (miRNAs) are present in human peripheral blood and have been considered as novel biomarkers for various diseases. But there is little research about miRNAs as biomarkers of mesangial proliferative glomerulonephritis (MsPGN). This study aimed to identify whether there exist disordered circulating miRNAs that can function as biomarkers for MsPGN disease activity.

Methods: The candidate miRNAs were validated in 70 MsPGN patients and 70 healthy controls by quantitative real-time PCR (RT-qPCR). The specificity and sensitivity of the miRNA panel was assessed by receiver operating characteristic (ROC) curves. In addition, the candidate miRNA levels were measured in the different MsPGN progression and in the membranous nephropathy (MN) patients and the hypothetical role of the candidate miRNA on mesangial cell proliferation was analysed. Situ hybridization was performed to examine the candidate miRNA levels in the glomerulus.

Results: These results showed that miR-106a-5p and miR-30a-5p were highly expressed in MsPGN patients compared with healthy controls and could discriminate MsPGN from healthy controls with an area under the ROC curve (AUC) of 0.93. In addition, the two miRNAs were not only higher in moderate and severe MsPGN patients, but could distinguish MsPGN from MN. We also observed a decreased expression in MsPGN regression group after treatment. Plasma miR-106a-5p level was positively correlated with estimated glomerular filtration rate (eGFR). Furthermore, the two miRNAs were highly expressed in MsPGN glomerulus and their overexpression could prompt mesangial cell proliferation.

Conclusion: Plasma miR-30a-5p and miR-106a-5p can serve as novel and potential diagnostic biomarkers for MsPGN.
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http://dx.doi.org/10.1016/j.clinbiochem.2020.07.001DOI Listing
October 2020

Fraction of Exhaled Nitric Oxide Is Elevated in Patients With Stable Chronic Obstructive Pulmonary Disease: A Meta-analysis.

Am J Med Sci 2020 08 7;360(2):166-175. Epub 2020 May 7.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address:

Background: Fraction of exhaled nitric oxide (FeNO) is a noninvasive indicator of eosinophilic airway inflammation and has been used for the diagnosis and treatment of asthma. The levels of FeNO are controversial in patients with stable chronic obstructive pulmonary disease (COPD). Accordingly, this study aimed to assess FeNO levels in patients with stable COPD.

Materials And Methods: A search of the Medline, Embase, Web of Science, ClinicalTrials.gov and The Cochrane Library databases was performed in August 2019. The literature search was restricted to articles published in English. Studies were included if they reported data addressing FeNO levels in patients with stable COPD and healthy controls. Review Manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used for meta-analysis.

Results: A total of 19 studies were included. Analysis revealed that FeNO levels in patients with stable COPD were higher than those in the healthy control group (mean difference [MD] 2.49 [95% confidence interval {CI} 0.99-4.00]; P < 0.05), those in nonsmoking patients with stable COPD were higher than those in the healthy control group (MD 5.04 [95% CI 2.19-7.89]; P < 0.05) and those in smoking patients with stable COPD were not higher than those in the healthy control group (MD 0.30 [95% CI -2.81 to 3.41]; P = 0.85). FeNO measured using a chemiluminescence analyzer in nonsmoking patients with stable COPD was higher than those in the healthy control group (MD 4.84 [95% CI 1.83-7.86]; P < 0.05).

Conclusions: Findings suggested that FeNO levels in patients with stable COPD were elevated, and that smokers exhibited decreased levels.
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http://dx.doi.org/10.1016/j.amjms.2020.04.038DOI Listing
August 2020

KDELR2 is an unfavorable prognostic biomarker and regulates CCND1 to promote tumor progression in glioma.

Pathol Res Pract 2020 Jul 19;216(7):152996. Epub 2020 May 19.

Department of Neurosurgery, First Affiliated Hospital of Jishou University, Jishou 416000, Hunan, China. Electronic address:

Background: The KDEL receptor is a seven-transmembrane-domain protein, which plays a key role in ER quality control and in the ER stress response, KDELR2 involved in regulation of cellular functions, including cell proliferation, survival, promotes glioblastoma tumorigenesis. The aim of this study was to investigate the clinicpathological value and biological role of KDELR2 in glioma.

Methods: We studied the expression of KEDLR2 and its association with the prognosis through the TCGA, CGGA, and GSE16011 database. To explore the role of KDELR2 in glioma, KDELR2 siRNA was constructed and transfected into U87 glioma cells. CCK-8, colony formation and Transwell assays were used to investigate the roles of KDELR2 on GBM cell proliferation. We further studied the effect of KDELR2 on tumorigenesis in animal model. Additionally, flow cytometry was used to monitor the changes in the cell cycle and apoptosis following transfection with KDELR2 siRNA. We applied GeneChip primeview expression array to analysis the differential gene expression profiling. Ingenuity Pathway Analysis to show that KDELR2 has a significant impact in canonical pathway in cell cycle regulation and participate in multiple pathways. And we detected the cell cycle proteins CCND1 expression by Western blot analysis.

Results: Our results showed that KDELR2 was up-regulated in glioma tissue and cell lines. Knockdown KDELR2 was able to reduce cell viability, promote cell cycle arrest at the G1 phase, and induce apoptotic cell death. Moreover, our results suggested that KDELR2 regulated the cellular functions of U87 cells by targeting CCND1. Therefore, we demonstrated that KDELR2 is a novel biomarker in glioma.

Conclusions: KDELR2 is highly expressed in human glioma tissues and cell lines, a higher expression of KDELR2 is associated with a poor prognosis of glioma patients. Moreover, KDELR2 regulated the cellular functions of U87 cells by targeting CCND1. The KDELR2/CCND1 axis may provide a new therapeutic target for the treatment of glioma and deepen our understanding of glioma mechanisms.
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http://dx.doi.org/10.1016/j.prp.2020.152996DOI Listing
July 2020

Characterization of the Hydrolysis Kinetics of Fucosylated Glycosaminoglycan in Mild Acid and Structures of the Resulting Oligosaccharides.

Mar Drugs 2020 May 29;18(6). Epub 2020 May 29.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China.

Mild acid hydrolysis is a common method for the structure analysis of fucosylated glycosaminoglycan (FG). In this work, the effects of acid hydrolysis on the structure of FG from S. variegatus (SvFG) and the reaction characteristic were systemically studied. The degree of defucosylation (DF) and molecular weights (Mw) of partial fucosylated glycosaminoglycans (pFs) were monitored by H NMR and size-exclusion chromatography, respectively. The kinetic plots of DF, degree of desulfation (DS) from fucose branches, and degree of hydrolysis (DH) of the backbone are exponentially increased with time, indicating that acid hydrolysis of SvFG followed a first-order kinetics. The kinetic rate constants k, k, and k were determined to be 0.0223 h, 0.0041 h, and 0.0005 h, respectively. The structure of the released sulfated fucose branches (FucS) from SvFG and HfFG (FG from ) was characterized by 1D/2D NMR spectroscopy, suggesting the presence of six types of fucose: α/β Fuc2S4S, Fuc3S4S, Fuc3S, Fuc4S, Fuc2S, and Fuc. The Fuc3S4S was more susceptible to acid than Fuc2S4S, and that the sulfate ester in position of O-2 and O-3 than in O-4 of fucose. The structure characteristic of pF18 indicated the cleavage of backbone glycosidic bonds. The APTT prolonged activity reduced with the decrease of the DF and Mw of the pFs, and became insignificant when its DF was 87% with Mw of 3.5 kDa.
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http://dx.doi.org/10.3390/md18060286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345840PMC
May 2020

Going even smaller: Engineering sub-5 nm nanoparticles for improved delivery, biocompatibility, and functionality.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2020 11 20;12(6):e1644. Epub 2020 May 20.

Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia, USA.

The rapid development and advances in nanomaterials and nanotechnology in the past two decades have made profound impact in our approaches to individualized disease diagnosis and treatment. Nanomaterials, mostly in the range of 10-200 nm, developed for biomedical applications provide a wide range of platforms for building and engineering functionalized structures, devices, or systems to fulfill the specific diagnostic and therapeutic needs. Driven by achieving the ultimate goal of clinical translation, sub-5 nm nano-constructs, in particular inorganic nanoparticles such as gold, silver, silica, and iron oxide nanoparticles, have been developed in recent years to improve the biocompatibility, delivery and pharmacokinetics of imaging probes and drug delivery systems, as well as in vivo theranostic applications. The emerging studies have provided new findings that demonstrated the unique size-dependent physical properties, physiological behaviors and biological functions of the nanomaterials in the range of the sub-5 nm scale, including renal clearance, novel imaging contrast, and tissue distribution. This advanced review attempts to introduce the new strategies of rational design for engineering nanoparticles with the core sizes under 5 nm in consideration of the clinical and translational requirements. We will provide readers the update on recent discoveries of chemical, physical, and biological properties of some biocompatible sub-5 nm nanomaterials as well as their demonstrated imaging and theranostic applications, followed by sharing our perspectives on the future development of this class of nanomaterials. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants.
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http://dx.doi.org/10.1002/wnan.1644DOI Listing
November 2020

Ultrathin 1T-MoS Nanoplates Induced by Quaternary Ammonium-Type Ionic Liquids on Polypyrrole/Graphene Oxide Nanosheets and Its Irreversible Crystal Phase Transition During Electrocatalytic Nitrogen Reduction.

ACS Appl Mater Interfaces 2020 Jun 18;12(22):25189-25199. Epub 2020 May 18.

Institute of Clean Energy Chemistry, Key Laboratory for Green Synthesis and Preparative Chemistry of Advanced Materials, College of Chemistry, Liaoning University, Shenyang 110036, China.

Ultrathin nanoplates of metastable 1T-MoS have been successfully stabilized and uniformly distributed on the surface of -butyl triethyl ammonium bromide functionalized polypyrrole/graphene oxide (BTAB/PPy/GO) by a very simple hydrothermal method. BTAB as a typical kind of quaternary ammonium-type ionic liquids (ILs) played a crucial role in the formation of the obtained 1T-MoS/BTAB/PPy/GO. It was covalently linked with PPy/GO and arranged in a highly ordered order at the solid-liquid interface of PPy/GO and HO due to Coulombic interactions and other intermolecular interactions, which would induce and stabilize ultrathin 1T-MoS nanoplates by morphosynthesis. The good electrocatalytic activity toward nitrogen reduction reaction (NRR) with strong durability and good stability can be achieved by 1T-MoS/BTAB/PPy/GO due to their excellent inorganic/organic hierarchical lamellar micro-/nanostructures. Especially, after the long-term electrocatalysis for NRR at a negative potential, metastable 1T-MoS as the catalytic center undergoes two types of irreversible crystal phase transition, which was converted to 1T'-MoS and MoN, caused by the competitive hydrogen evolution reaction (HER) process and the electrochemical reaction between the electroactive 1T-MoS and N, respectively. The new N-Mo bonding prevents Mo atoms from binding to other N atoms in N, resulting in the deactivation of the electrocatalysts to NRR after being used for 18 h. Even so, quaternary ammonium-type ILs would induce the crystal structures of transition-metal dichalcogenides (TMDCs), which might provide a new thought for the reasonable design of electrocatalysts based on TMDCs for electrocatalysis.
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http://dx.doi.org/10.1021/acsami.0c05204DOI Listing
June 2020

Simultaneous determination of seven compounds in Chinese patent medicines Chenxiangqu by matrix solid-phase dispersion coupled with ultra high performance liquid chromatography and quadrupole time-of-flight mass spectrometry.

J Sep Sci 2020 Jul 25;43(14):2869-2879. Epub 2020 May 25.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, P. R. China.

A simple, efficient, and sensitive strategy by coupling matrix solid-phase dispersion with ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry was proposed to extract and determine three types of components (including seven analytes) in Chinese patent medicines Chenxiangqu. The highly ordered mesoporous material Fe-SBA-15 synthesized under weakly acidic conditions was selected as a dispersant in matrix solid phase dispersion extraction for the first time. Several parameters including the mass ratio of sample to dispersant, the type of dispersant, the grinding time, and the elution condition were investigated in this work. Under the optimized conditions, 20 compounds were identified by quadrupole time-of-flight mass spectrometry and seven analytes were quantified. The results demonstrated that the developed method has good linearity (r > 0.9995), and the limits of detection of the analytes were as low as 0.55 ng/mL. The recoveries of all seven analytes ranged from 97.6 to 104.6% (relative standard deviation < 3.4%). Finally, the improved method was successfully applied to determination of five batches of Chenxiangqu samples, which provided a robust method in quality control of Chinese patent medicines Chenxiangqu. The developed strategy also shows its great potential in analysis of complex matrix samples.
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http://dx.doi.org/10.1002/jssc.201901226DOI Listing
July 2020

Label-driven magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) registration using weakly supervised learning for MRI-guided prostate radiotherapy.

Phys Med Biol 2020 06 26;65(13):135002. Epub 2020 Jun 26.

Department of Radiation Oncology, Emory University, Atlanta, Georgia, United States of America.

Registration and fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) of the prostate can provide guidance for prostate brachytherapy. However, accurate registration remains a challenging task due to the lack of ground truth regarding voxel-level spatial correspondence, limited field of view, low contrast-to-noise ratio, and signal-to-noise ratio in TRUS. In this study, we proposed a fully automated deep learning approach based on a weakly supervised method to address these issues. We employed deep learning techniques to combine image segmentation and registration, including affine and nonrigid registration, to perform an automated deformable MRI-TRUS registration. To start with, we trained two separate fully convolutional neural networks (CNNs) to perform a pixel-wise prediction for MRI and TRUS prostate segmentation. Then, to provide the initialization of the registration, a 2D CNN was used to register MRI-TRUS prostate images using an affine registration. After that, a 3D UNET-like network was applied for nonrigid registration. For both the affine and nonrigid registration, pairs of MRI-TRUS labels were concatenated and fed into the neural networks for training. Due to the unavailability of ground-truth voxel-level correspondences and the lack of accurate intensity-based image similarity measures, we propose to use prostate label-derived volume overlaps and surface agreements as an optimization objective function for weakly supervised network training. Specifically, we proposed a hybrid loss function that integrated a Dice loss, a surface-based loss, and a bending energy regularization loss for the nonrigid registration. The Dice and surface-based losses were used to encourage the alignment of the prostate label between the MRI and the TRUS. The bending energy regularization loss was used to achieve a smooth deformation field. Thirty-six sets of patient data were used to test our registration method. The image registration results showed that the deformed MR image aligned well with the TRUS image, as judged by corresponding cysts and calcifications in the prostate. The quantitative results showed that our method produced a mean target registration error (TRE) of 2.53 ± 1.39 mm and a mean Dice loss of 0.91 ± 0.02. The mean surface distance (MSD) and Hausdorff distance (HD) between the registered MR prostate shape and TRUS prostate shape were 0.88 and 4.41 mm, respectively. This work presents a deep learning-based, weakly supervised network for accurate MRI-TRUS image registration. Our proposed method has achieved promising registration performance in terms of Dice loss, TRE, MSD, and HD.
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http://dx.doi.org/10.1088/1361-6560/ab8cd6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771987PMC
June 2020

Development of ZnO Nanoparticles as an Efficient Zn Fertilizer: Using Synchrotron-Based Techniques and Laser Ablation to Examine Elemental Distribution in Wheat Grain.

J Agric Food Chem 2020 May 21;68(18):5068-5075. Epub 2020 Apr 21.

School of Agriculture and Food Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia.

Zinc (Zn) deficiency is an important problem worldwide, adversely impacting human health. Using a field trial in China, we compared the foliar application of both ZnO nanoparticles (ZnO-NPs) and ZnSO on winter wheat ( L.) for increasing the Zn concentration within the grain. We also used synchrotron-based X-ray fluorescence microscopy and laser ablation inductively coupled plasma mass spectrometry to examine the distribution of Zn within the grain. We found that ZnO-NPs increase the Zn concentration in the wheat grain, increasing from 18 mg·kg in the control up to 40 mg·kg when the ZnO-NPs were applied four times. These grain Zn concentrations in the ZnO-NP-treated grains are similar to those recommended for human consumption. However, the ZnO-NPs were similar in their effectiveness to ZnSO. When examining trace element distribution in the grain, the trace elements were found to accumulate primarily in the aleurone layer and the crease region across all treatments. Importantly, Zn concentrations in the grain endosperm increased by nearly 30-fold relative to the control, with markedly increasing Zn concentrations within the edible portion. These results demonstrate that ZnO-NPs are a suitable fertilizer for increasing Zn within wheat grain and can potentially be used to improve human nutrition.
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http://dx.doi.org/10.1021/acs.jafc.0c00084DOI Listing
May 2020

Optimized truncation to integrate multi-channel MRS data using rank-R singular value decomposition.

NMR Biomed 2020 07 6;33(7):e4297. Epub 2020 Apr 6.

Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia.

Multi-channel phased receive arrays have been widely adopted for magnetic resonance imaging (MRI) and spectroscopy (MRS). An important step in the use of receive arrays for MRS is the combination of spectra collected from individual coil channels. The goal of this work was to implement an improved strategy termed OpTIMUS (i.e., optimized truncation to integrate multi-channel MRS data using rank-R singular value decomposition) for combining data from individual channels. OpTIMUS relies on spectral windowing coupled with a rank-R decomposition to calculate the optimal coil channel weights. MRS data acquired from a brain spectroscopy phantom and 11 healthy volunteers were first processed using a whitening transformation to remove correlated noise. Whitened spectra were then iteratively windowed or truncated, followed by a rank-R singular value decomposition (SVD) to empirically determine the coil channel weights. Spectra combined using the vendor-supplied method, signal/noise weighting, previously reported whitened SVD (rank-1), and OpTIMUS were evaluated using the signal-to-noise ratio (SNR). Significant increases in SNR ranging from 6% to 33% (P ≤ 0.05) were observed for brain MRS data combined with OpTIMUS compared with the three other combination algorithms. The assumption that a rank-1 SVD maximizes SNR was tested empirically, and a higher rank-R decomposition, combined with spectral windowing prior to SVD, resulted in increased SNR.
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http://dx.doi.org/10.1002/nbm.4297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317403PMC
July 2020

Probing and Enhancing Ligand-Mediated Active Targeting of Tumors Using Sub-5 nm Ultrafine Iron Oxide Nanoparticles.

Theranostics 2020 22;10(6):2479-2494. Epub 2020 Jan 22.

Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.

: "Active targeting" based on the ligand-target affinity is a common strategy to precisely deliver nanoparticle (NP) imaging probes or drug carriers to the diseased tissue. However, such ligand-mediated active targeting inevitably takes place with prerequisite "passive targeting", driven by the enhanced permeability and retention (EPR) effect. Thus, the efficiency of active targeting in relation to off-targeted unbound NPs is of great importance in quantitative imaging of tumor biomarkers and delivery. With the notion that easy clearance of off-targeted uIONPs may lead to enhanced active targeting and tumor accumulation, we examined the NP size effect on "active targeting" of the transferrin receptor (TfR) using transferrin (Tf)-conjugated sub-5 nm (3 nm core) ultrafine iron oxide NPs (uIONPs) and larger IONPs (30 nm core). : Green fluorescent dye (FITC)-labeled active targeting uIONPs (FITC-Tf-uIONPs) and red fluorescent dye (TRITC)-labeled passive targeting uIONPs (TRITC-uIONPs) were prepared. FITC-Tf-IONPs and TRITC-IONPs were used as comparison for the NP size effect. Multiphoton imaging, confocal fluorescence imaging, histological staining and computational analysis were applied to track different types of NPs in tumors at 1, 3 and 24 hours after co-injection of equal amounts of paired NPs, e.g., active targeting FITC-Tf-uIONPs and non-targeting TRITC-uIONPs, or FITC-Tf-IONPs and TRITC-IONPs into the same mice bearing 4T1 mouse mammary tumors. : Active targeting uIONPs exhibited an almost 6-fold higher level of tumor retention with deeper penetration comparing to non-targeting uIONPs at 24 hours after co-injection. However, accumulation of active targeting IONPs with a 30-nm core is only about 1.15-fold higher than non-targeting IONPs. The enhanced active targeting by uIONPs can be attributed to the size dependent clearance of unbound off-targeted NPs, as majority off-targeted uIONPs were readily cleared from the tumor by intravasation back into tumor blood vessels likely due to high interstitial pressure, even though they are not favorable for macrophage uptake. : Ligand-mediated active targeting improves the delivery and accumulation of the sub-5 nm NPs. The improvement on active targeting is size-dependent and facilitated by NPs with sub-5 nm core sizes. Thus, sub-5 nm NPs may serve as favorable platforms for development of NP-based molecular imaging probes and targeted drug carriers.
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http://dx.doi.org/10.7150/thno.39560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052897PMC
February 2021

Online preconcentration by electrokinetic supercharging for sensitive determination of berberine and jatrorrhizine in biological samples.

Biomed Chromatogr 2020 Jun 18;34(6):e4824. Epub 2020 Mar 18.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, P.R. China.

Electrokinetic supercharging, a convenient and powerful online preconcentration technique in capillary electrophoresis, was introduced and evaluated for the determination of two alkaloids, berberine and jatrorrhizine, in mice fecal samples for the first time. The method depended on using a bare fused silica capillary (50 cm × 50 μm i.d.) and applying the voltage of 25 kV with UV detection at 205 nm. Parameters that affect the separation and preconcentration efficiency have been optimized. The optimum conditions used were as follows: background electrolyte consisting of 40mM sodium dihydrogenphosphate containing 30% methanol (v/v); hydrodynamic injection of 20mM KCl (50 mbar × 150 s) as the leading electrolyte; electrokinetic injection of the sample (+15 kV, 120 s) followed by the hydrodynamic injection of 30mM dodecyl trimethyl ammonium chloride (50 mbar × 12 s) as the terminating electrolyte. The results showed that the detection sensitivity of berberine and jatrorrhizine was, respectively, improved up 2740- and 2928-fold compared with normal injection, providing limits of detection lower than 3 ng/mL with good repeatability in areas (relative standard deviation < 3%). In summary, the developed method proved its ability in analyzing trace alkaloids in complicated biological samples.
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http://dx.doi.org/10.1002/bmc.4824DOI Listing
June 2020