Publications by authors named "Dong Liang"

1,246 Publications

  • Page 1 of 1

Age-and Region-Dependent Disposition of Raloxifene in Rats.

Pharm Res 2021 Jul 28. Epub 2021 Jul 28.

Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St, Houston, Texas, 77004, USA.

Purpose: Raloxifene undergoes extensive glucuronidation in the gastrointestinal (GI) tract and the liver. However, the impact of age on raloxifene disposition has never been studied. The purpose of this paper is to determine glucuronidation and Pharmacokinetics (PK) profiles of raloxifene in rats at different ages.

Methods: Raloxifene glucuronidation was characterized using S9 fractions prepared from different intestinal segments and the liver of F344 rats at 4-, 11-, and 28-week. PK studies were conducted to determine raloxifene oral bioavailability at different ages. Raloxifene and its glucuronides were quantified using LC-MS/MS.

Results: Raloxifene-6-glucuronide and raloxifene-4'-glucuronide were detected as the major metabolites and the ratio of these two glucuronides were different ranging from 2.1 to 4.9 folds in the ileum, jejunum, liver, and duodenum, and from 14.5 to 50 folds in the colon. The clearances in the duodenum at 4-week for both two glucuronides were significantly lower than those at the other two ages. PK studies showed that the oral bioavailability of raloxifene is age dependent. The absolute oral bioavailability of raloxifene was 3.5-folds higher at 4-week compared to that at 11-weeks. When raloxifene was administered through IV bolus, its half-life was 5.9 ± 1.16 h and 3.7 ± 0.68 h at 11-and 4-week, respectively.

Conclusion: These findings suggested that raloxifene metabolism in the duodenum was significantly slower at young age in rats, which increased the oral bioavailability of raloxifene. At 11-week, enterohepatic recycling efficiency was higher than that of 4-week. Raloxifene's dose at different ages should be carefully considered.
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http://dx.doi.org/10.1007/s11095-021-03084-yDOI Listing
July 2021

Analysis of microbial differences in amniotic fluid between advanced and normal age pregnant women.

J Transl Med 2021 Jul 27;19(1):320. Epub 2021 Jul 27.

Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, China.

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http://dx.doi.org/10.1186/s12967-021-02996-yDOI Listing
July 2021

A Magneto-Heated Ferrimagnetic Sponge for Continuous Recovery of Viscous Crude Oil.

Adv Mater 2021 Jul 23:e2100074. Epub 2021 Jul 23.

Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, CAS Center for Excellence in Nanoscience, Hefei Science Center of CAS, University of Science and Technology of China, Hefei, 230026, China.

The high viscosity and low fluidity of heavy crude oil hinder its sorption by conventional porous sorbents, so the efficient clean-up of such heavy crude oil spills is challenging. Recently, Joule heating has been emerging as a new tool to reduce the viscosity of heavy crude oil dramatically. However, this direct-contact heating approach presents a potential risk due to the high voltage applied. To develop a non-contact recovery of viscous crude oil, here, a new approach for the fabrication of a series of ferrimagnetic sponges (FMSs) with hydrophobic porous channels is reported, whose surface can be remotely heated to 120 °C within 10 s under an alternating magnetic field (f = 274 kHz, H = 30 kA m ). Compared with the solar-driven superficial heating, the integral magnetic heating in FMSs can result in a higher internal temperature of the sponges because of the confinement of thermal transport in the porous channels, which contributes to a dramatic decrease in oil viscosity and a significant increase in oil flow into the pores of FMSs. Furthermore, FMSs assembled with a self-priming pump can achieve continuous recovery of viscous crude oil (33.05 g h cm ) via remotely magnetic heating.
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http://dx.doi.org/10.1002/adma.202100074DOI Listing
July 2021

SuperDTI: Ultrafast DTI and fiber tractography with deep learning.

Magn Reson Med 2021 Jul 26. Epub 2021 Jul 26.

Electrical Engineering, University at Buffalo, State University of New York, Buffalo, New York, USA.

Purpose: To develop a deep learning-based reconstruction framework for ultrafast and robust diffusion tensor imaging and fiber tractography.

Methods: SuperDTI was developed to learn the nonlinear relationship between DWIs and the corresponding diffusion tensor parameter maps. It bypasses the tensor fitting procedure, which is highly susceptible to noises and motions in DWIs. The network was trained and tested using data sets from the Human Connectome Project and patients with ischemic stroke. Results from SuperDTI were compared against widely used methods for tensor parameter estimation and fiber tracking.

Results: Using training and testing data acquired using the same protocol and scanner, SuperDTI was shown to generate fractional anisotropy and mean diffusivity maps, as well as fiber tractography, from as few as six raw DWIs, with a quantification error of less than 5% in all white-matter and gray-matter regions of interest. It was robust to noises and motions in the testing data. Furthermore, the network trained using healthy volunteer data showed no apparent reduction in lesion detectability when directly applied to stroke patient data.

Conclusions: Our results demonstrate the feasibility of superfast DTI and fiber tractography using deep learning with as few as six DWIs directly, bypassing tensor fitting. Such a significant reduction in scan time may allow the inclusion of DTI into the clinical routine for many potential applications.
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http://dx.doi.org/10.1002/mrm.28937DOI Listing
July 2021

[Modification and accuracy of the STOP-Bang questionnaire for screening obstructive sleep apnea in adults].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Aug;35(8):733-740

Operation Room,Affiliated Hospital of Guizhou Medical University.

To assess the accuracy of the STOP-Bang questionnaire(SBQ) about screening for obstructive sleep apnea(OSA) in adults, and to establish appropriate cutoffs for body mass index(BMI), neck circumference(NC), age, and SBQ score for this population in combination with the body size characteristics of the study subjects, and to evaluate the accuracy of the SBQ for combined screening with waist to height ratio(WHtR). The data were collected from October, 2019 to November, 2020 at the Affiliated Hospital of Guizhou Medical University, and 218 patients with suspicious OSA were included in this study, all of them completed the SBQ and underwent overnight PSG. SBQ screening and PSG were tested in a blinded concurrent manner. Using the PSG results as the gold standard, the subjects were divided into a diseased group with moderate to severe OSA and a non-diseased group based on apnea hypopnea index. According to SBQ screening results, the subjects were divided into a positive group with moderate severe OSA and negative group. And calculated in the form of four-fold table, the optimal cutoffs were determined by adjusting age, BMI, NC, and SBQ score cutoffs, and calculating the sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV), Youden index, and area under the receiver operating characteristic curve(ROC). And the modified version of SBQ was combined with WHtR for joint diagnosis to evaluate the accuracy of combined screening. With all 218 patients completing the experiment, 159(72.94%) patients were in the moderate-severe group. The original SBQ had a sensitivity of 93.71%, specificity of 47.46%, PPV of 82.80%, NPV of 73.70%, Youden index of 0.41, and area under the ROC curve(AUC) of 0.71 for predicting moderate to severe OSA. When adjusting the BMI cutoff to 30 kg/m², NC cutoff to 40 cm, and age cutoff to 50 years, the modified SBQ had a sensitivity of 95.60%, specificity of 47.46%, PPV of 83.10%, NPV of 80.00%, Youden index of 0.43, and AUC of 0.72 for predicting moderate to severe OSA. When the modified SBQ score was 4 or more as the cutoff value, the highest Youden index and AUC were 0.54, 0.77 respectively. When the modified SBQ≥3 points were combined with WHtR>0.55, the highest Youden index and AUC were 0.58, 0.79 respectively. SBQ is effective in screening for moderate to severe OSA and better screening accuracy can be achieved by using a modified version of the SBQ(BMI>30 kg/m², NC>40 cm, age>50 years). The maximum diagnostic accuracy can be achieved when the modified SBQ total score was 4 or more as the cutoff. Those with the modified SBQ total score=3 and WHtR>0.55 can be classified as high risk for moderate to severe OSA, and the modified version of SBQ can be a screening tool to identify moderate to severe OSA.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.08.013DOI Listing
August 2021

Development & validation of LC-MS/MS assay for 5-amino-1-methyl quinolinium in rat plasma: Application to pharmacokinetic and oral bioavailability studies.

J Pharm Biomed Anal 2021 Jul 8;204:114255. Epub 2021 Jul 8.

Department of Pharmaceutical Sciences, Texas Southern University, Houston, TX, 77004, United States. Electronic address:

5-Amino-1-methyl quinolinium (5-AMQ) is a potent Nicotinamide N-methyl transferase (NNMT) inhibitor. NNMT is an enzyme that catalyzes the N-methylation of the endogenous substrate nicotinamide, as well as exogenous xenobiotics. NNMT is fundamental to cellular metabolism; NNMT is overexpressed in select tissues (e.g., adipose tissue, skeletal muscle, etc.) in pathophysiological conditions, making it a clinically relevant target for drug development in several chronic diseases including obesity and diabetes. The objective of this study was to develop and validate a simple, sensitive, and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of 5-AMQ in rat plasma and urine samples. 5-AMQ was extracted from plasma and urine by protein precipitation. Chromatographic separation was achieved using an ACE® Excel™ C column (2 μm, 50 × 2.1 mm) with a binary gradient solvent system comprising of water (A) and acetonitrile (B) containing 0.1 % formic acid as the mobile phase. Analysis was performed using an API 4000 QTRAP hybrid triple quadruple mass spectrometer and multiple reaction monitoring (MRM) in positive mode at m/z transitions of 159.100 → 90.00 and 162.200 → 117.200 for 5-AMQ and the internal standard, respectively. The standard curves of 5-AMQ in rat urine and plasma samples were linear in the concentration range of 10-2500 ng/mL. The intra-day and inter-day precisions and accuracies for 5-AMQ at four concentration levels in rat plasma and urine samples were found to be within the 15 % FDA acceptance range. Similarly, the accuracy and precision of 5-AMQ quantification in samples diluted up to 20-fold using blank plasma were within the 15 % acceptable range. Furthermore, the extraction recoveries and matrix effects at three concentration levels of rat plasma samples ranged from 99.5 %-110.6 % and -6.1 %-14.1 %, respectively. 5-AMQ was stable in rat plasma samples subjected to standard storage, preparation, and handling conditions, with less than 15 % variation noted at two concentration levels. The validated, sensitive, and reproducible LC-MS/MS method for 5-AMQ in rat plasma and urine samples was effectively applied to a pharmacokinetic study in rats with IV and oral administration of 5-AMQ. 5-AMQ displayed substantial plasma exposures via IV and oral route, with a mean maximum plasma concentration of 2252 ng/mL after oral administration, mean area under the curve (AUC) of 3708 h.ng/mL and 14431 h.ng/mL for the IV and oral groups, respectively, mean terminal elimination half-life of 3.80 ± 1.10 h and 6.90 ± 1.20 h respectively after intravenous and oral dose, and a good oral bioavailability (F % = 38.4).
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http://dx.doi.org/10.1016/j.jpba.2021.114255DOI Listing
July 2021

Pyricularia sp. jiangsuensis, a new cryptic rice panicle blast pathogen from rice fields in Jiangsu Province, China.

Environ Microbiol 2021 Jul 20. Epub 2021 Jul 20.

Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, China.

Pyricularia oryzae is a multi-host pathogen causing cereal disease, including the devastating rice blast. Panicle blast is a serious stage, leading to severe yield loss. Thirty-one isolates (average 4.1%) were collected from the rice panicle lesions at nine locations covering Jiangsu province from 2010 to 2017. These isolates were characterized as Pyricularia sp. jiangsuensis distinct from known Pyricularia species. The representative strain 18-2 can infect rice panicle, root and five kinds of grasses. Intriguingly, strain 18-2 can co-infect rice leaf with P. oryzae Guy11. The whole genome of P. sp. jiangsuensis 18-2 was sequenced. Nine effectors were distributed in translocation or inversion region, which may link to the rapid evolution of effectors. Twenty-one homologues of known blast-effectors were identified in strain 18-2, seven effectors including the homologues of SLP1, BAS2, BAS113, CDIP2/3, MoHEG16 and Avr-Pi54, were upregulated in the sample of inoculated panicle with strain 18-2 at 24 hpi compared with inoculation at 8 hpi. Our results provide evidences that P. sp. jiangsuensis represents an addition to the mycobiota of blast disease. This study advances our understanding of the pathogenicity of P. sp. jiangsuensis to hosts, which sheds new light on the adaptability in the co-evolution of pathogen and host.
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http://dx.doi.org/10.1111/1462-2920.15678DOI Listing
July 2021

Towards nanovesicle-based disease diagnostics: a rapid single-step exosome assay within one hour through immunomagnetic extraction and nanophotonic label-free detection.

Lab Chip 2021 Jul 21. Epub 2021 Jul 21.

Department of Electrical and Computer Engineering, Iowa State University, Ames, Iowa 50011, USA. and Microelectronics Research Centre, Iowa State University, Ames, Iowa 50011, USA and Department of Mechanical Engineering, Iowa State University, Ames, Iowa 50011, USA.

Exosomes have been considered as high-quality biomarkers for disease diagnosis, as they are secreted by cells into extracellular environments as nanovesicles with rich and unique molecular information, and can be isolated and enriched from clinical samples. However, most existing exosome assays, to date, require time-consuming isolation and purification procedures; the detection specificity and sensitivity are also in need of improvement for the realization of exosome-based disease diagnostics. This paper reports a unique exosome assay technology that enables completing both magnetic nanoparticle (MNP)-based exosome extraction and high-sensitivity photonic crystal (PC)-based label-free exosome detection in a single miniature vessel within one hour, while providing an improved sensitivity and selectivity. High specificity of the assay to membrane antigens is realized by functionalizing both the MNPs and the PC with specific antibodies. A low limit of detection on the order of 107 exosome particles per milliliter (volume) is achieved because the conjugated MNP-exosome nanocomplexes offer a larger index change on the PC surface, compared to the exosomes alone without using MNPs. Briefly, the single-step exosome assay involves (i) forming specific MNP-exosome nanocomplexes to enrich exosomes from complex samples directly on the PC surface at the bottom of the vessel, with a >500 enrichment factor, and (ii) subsequently, performing in situ quantification of the nanocomplexes using the PC biosensor. The present exosome assay method is validated in analyzing multiple membrane proteins of exosomes derived from murine macrophage cells with high selectivity and sensitivity, while requiring only about one hour. This assay technology will provide great potential for exosome-based disease diagnostics.
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http://dx.doi.org/10.1039/d1lc00446hDOI Listing
July 2021

The PHU-NET: A robust phase unwrapping method for MRI based on deep learning.

Magn Reson Med 2021 Jul 17. Epub 2021 Jul 17.

Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Purpose: This work was aimed at designing a deep-learning-based approach for MR image phase unwrapping to improve the robustness and efficiency of traditional methods.

Methods: A deep learning network called PHU-NET was designed for MR phase unwrapping. In this network, a novel training data generation method was proposed to simulate the wrapping patterns in MR phase images. The wrapping boundary and wrapping counts were explicitly estimated and used for network training. The proposed method was quantitatively evaluated and compared to other methods using a number of simulated datasets with varying signal-to-noise ratio (SNR) and MR phase images from various parts of the human body.

Results: The results showed that our method performed better in the simulated data even under an extremely low SNR. The proposed method had less residual wrapping in the images from various parts of human body and worked well in the presence of severe anatomical discontinuity. Our method was also advantageous in terms of computational efficiency compared to the traditional methods.

Conclusion: This work proposed a robust and computationally efficient MR phase unwrapping method based on a deep learning network, which has promising performance in applications using MR phase information.
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http://dx.doi.org/10.1002/mrm.28927DOI Listing
July 2021

Mortality prediction for patients with acute respiratory distress syndrome based on machine learning: a population-based study.

Ann Transl Med 2021 May;9(9):794

Department of Intensive Care Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China.

Background: Traditional scoring systems for patients' outcome prediction in intensive care units such as Oxygenation Saturation Index (OSI) and Oxygenation Index (OI) may not reliably predict the clinical prognosis of patients with acute respiratory distress syndrome (ARDS). Thus, none of them have been widely accepted for mortality prediction in ARDS. This study aimed to develop and validate a mortality prediction method for patients with ARDS based on machine learning using the Medical Information Mart for Intensive Care (MIMIC-III) and Telehealth Intensive Care Unit (eICU) Collaborative Research Database (eICU-CRD) databases.

Methods: Patients with ARDS were selected based on the Berlin definition in MIMIC-III and eICU-CRD databases. The APPS score (using age, PaO/FiO, and plateau pressure), Simplified Acute Physiology Score II (SAPS-II), Sepsis-related Organ Failure Assessment (SOFA), OSI, and OI were calculated. With MIMIC-III data, a mortality prediction model was built based on the random forest (RF) algorithm, and the performance was compared to those of existing scoring systems based on logistic regression. The performance of the proposed RF method was also validated with the combined MIMIC-III and eICU-CRD data. The performance of mortality prediction was evaluated by using the area under the receiver operating characteristics curve (AUROC) and performing calibration using the Hosmer-Lemeshow test.

Results: With the MIMIC-III dataset (308 patients, for comparisons with the existing scoring systems), the RF model predicted the in-hospital mortality, 30-day mortality, and 1-year mortality with an AUROC of 0.891, 0.883, and 0.892, respectively, which were significantly higher than those of the SAPS-II, APPS, OSI, and OI (all P<0.001). In the multi-source validation (the combined dataset of 2,235 patients in MIMIC-III and 331 patients in eICU-CRD), the RF model achieved an AUROC of 0.905 and 0.736 for predicting in-hospital mortality for the MIMIC-III and eICU-CRD datasets, respectively. The calibration plots suggested good fits for our RF model and these scoring systems for predicting mortality. The platelet count and lactate level were the strongest predictive variables for predicting in-hospital mortality.

Conclusions: Compared to the existing scoring systems, machine learning significantly improved performance for predicting ARDS mortality. Validation with multi-source datasets showed a relatively robust generalisation ability of our prediction model.
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http://dx.doi.org/10.21037/atm-20-6624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246239PMC
May 2021

[Clinical effect and mechanism of 's three-needle combined with acupuncture for intellectual disability in children].

Zhongguo Zhen Jiu 2021 Jul;41(7):751-5

Department of Rehabilitation, Second Affiliated Hospital of Anhui University of CM, Hefei 230061.

Objective: To observe the effect of 's three-needle combined with acupuncture on development level and activity of daily living in children with intellectual disability, and explore its mechanism.

Methods: A total of 60 children with intellectual disability were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off). In the control group, rehabilitation training and routine acupuncture were adopted, 30 min each time, once a day, 6 times a week for 3 months. On the base of the treatment as the control group, 's three-needle combined with acupuncture were adopted in the observation group. 's three-needle was applied at , , and for 1 h, and for 30 min. acupuncture was applied at Baihui (GV 20), Shenting (GV 24), Shuigou (GV 26), etc. for 30 min, once a day, 6 times a week for 3 months. Before and after treatment,the scores of developmental quotient (DQ) and activity of daily living (ADL) were recorded, and the serum levels of neuron-specific enolase (NSE) and monoamine neurotransmitters (dopamine [DA], norepinephrine [NE] and 5-hydroxytryptamine [5-HT]) were detected in the two groups.

Results: Compared before treatment, the scores of DQ and ADL and the serum levels of DA, NE, 5-HT after treatment were increased (<0.05), the serum levels of NSE were decreased (<0.05) in the two groups. After treatment, the scores of DQ and ADL and the serum levels of DA, NE, 5-HT in the observation group were higher than the control group (<0.05), while the serum level of NSE was lower than the control group (<0.05).

Conclusion: On the base of rehabilitation training and routine acupuncture, 's three-needle combined with acupuncture can significantly improve development level and activity of daily living in children with intellectual disability, and its mechanism may be related to the regulation of serum levels of NSE and monoamine neurotransmitter.
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http://dx.doi.org/10.13703/j.0255-2930.20201101-0003DOI Listing
July 2021

Unveiling Crystal Orientation in Quasi-2D Perovskite Films by In Situ GIWAXS for High-Performance Photovoltaics.

Small 2021 Jul 12:e2100972. Epub 2021 Jul 12.

Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, P. R. China.

Quasi-2D perovskites are enchanting alternative materials for solar cells due to their intrinsic stability. The manipulation of crystal orientation of quasi-2D perovskites is indispensable to target efficient devices, however, the origin of orientation during the film fabrication process still lacks in-depth understanding and convincing evidence yet, which hinders further boosting the performance of photovoltaic devices. Herein, the crystallizing processes during spin-coating and annealing are probed by in situ grazing-incidence wide-angle X-ray scattering (GIWAXS), and the incident-angle-dependent GIWAXS is conducted to unveil the phase distribution in the films. It is found that undesirable lead iodide sol-gel formed intermediate phase would disturb oriented crystalline growth, resulting in random crystal orientation in poor quasi-2D films. A general strategy is developed via simple additive agent incorporation to suppress the formation of the intermediate phase. Accordingly, highly oriented perovskite films with reduced trap density and higher carrier mobility are obtained, which enables the demonstration of optimized quasi-2D perovskite solar cells with a power conversion efficiency of 15.2% as well as improved stability. This work paves a promising way to manipulate the quasi-2D perovskites nucleation and crystallization processes via tuning nucleation stage.
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http://dx.doi.org/10.1002/smll.202100972DOI Listing
July 2021

Technical note: A preliminary study of dual-tracer PET image reconstruction guided by FDG and/or MR kernels.

Med Phys 2021 Jul 12. Epub 2021 Jul 12.

Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Purpose: Clinically, single radiotracer positron emission tomography (PET) imaging is a commonly used examination method; however, since each radioactive tracer reflects the information of only one kind of cell, it easily causes false negatives or false positives in disease diagnosis. Therefore, reasonably combining two or more radiotracers is recommended to improve the accuracy of diagnosis and the sensitivity and specificity of the disease when conditions permit.

Methods: This paper proposes incorporating F-fluorodeoxyglucose (FDG) as a higher-quality PET image to guide the reconstruction of other lower-count C-methionine (MET) PET datasets to compensate for the lower image quality by a popular kernel algorithm. Specifically, the FDG prior is needed to extract kernel features, and these features were used to build a kernel matrix using a k-nearest-neighbor (kNN) search for MET image reconstruction. We created a 2-D brain phantom to validate the proposed method by simulating sinogram data containing Poisson random noise and quantitatively compared the performance of the proposed FDG-guided kernelized expectation maximization (KEM) method with the performance of Gaussian and non-local means (NLM) smoothed maximum likelihood expectation maximization (MLEM), MR-guided KEM, and multi-guided-S KEM algorithms. Mismatch experiments between FDG/MR and MET data were also carried out to investigate the outcomes of possible clinical situations.

Results: In the simulation study, the proposed method outperformed the other algorithms by at least 3.11% in the signal-to-noise ratio (SNR) and 0.68% in the contrast recovery coefficient (CRC), and it reduced the mean absolute error (MAE) by 8.07%. Regarding the tumor in the reconstructed image, the proposed method contained more pathological information. Furthermore, the proposed method was still superior to the MR-guided KEM method in the mismatch experiments.

Conclusions: The proposed FDG-guided KEM algorithm can effectively utilize and compensate for the tissue metabolism information obtained from dual-tracer PET to maximize the advantages of PET imaging.
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http://dx.doi.org/10.1002/mp.15089DOI Listing
July 2021

Learning data consistency and its application to dynamic MR imaging.

IEEE Trans Med Imaging 2021 Jul 12;PP. Epub 2021 Jul 12.

Magnetic resonance (MR) image reconstruction from undersampled k-space data can be formulated as a minimization problem involving data consistency and image prior. Existing deep learning (DL)-based methods for MR reconstruction employ deep networks to exploit the prior information and integrate the prior knowledge into the reconstruction under the explicit constraint of data consistency, without considering the real distribution of the noise. In this work, we propose a new DL-based approach termed Learned DC that implicitly learns the data consistency with deep networks, corresponding to the actual probability distribution of system noise. The data consistency term and the prior knowledge are both embedded in the weights of the networks, which provides an utterly implicit manner of learning reconstruction model. We evaluated the proposed approach with highly undersampled dynamic data, including the dynamic cardiac cine data with up to 24-fold acceleration and dynamic rectum data with the acceleration factor equal to the number of phases. Experimental results demonstrate the superior performance of the Learned DC both quantitatively and qualitatively than the state-of-the-art.
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http://dx.doi.org/10.1109/TMI.2021.3096232DOI Listing
July 2021

Learned Low-rank Priors in Dynamic MR Imaging.

IEEE Trans Med Imaging 2021 Jul 12;PP. Epub 2021 Jul 12.

Deep learning methods have achieved attractive performance in dynamic MR cine imaging. However, most of these methods are driven only by the sparse prior of MR images, while the important low-rank (LR) prior of dynamic MR cine images is not explored, which may limit further improvements in dynamic MR reconstruction. In this paper, a learned singular value thresholding (Learned-SVT) operator is proposed to explore low-rank priors in dynamic MR imaging to obtain improved reconstruction results. In particular, we put forward a model-based unrolling sparse and low-rank network for dynamic MR imaging, dubbed as SLR-Net. SLR-Net is defined over a deep network flow graph, which is unrolled from the iterative procedures in the iterative shrinkage-thresholding algorithm (ISTA) for optimizing a sparse and LR-based dynamic MRI model. Experimental results on a single-coil scenario show that the proposed SLR-Net can further improve the state-of-the-art compressed sensing (CS) methods and sparsity-driven deep learning-based methods with strong robustness to different undersampling patterns, both qualitatively and quantitatively. Besides, SLR-Net has been extended to a multi-coil scenario, and achieved excellent reconstruction results compared with a sparsity-driven multi-coil deep learning-based method under a high acceleration. Prospective reconstruction results on an open real-time dataset further demonstrate the capability and flexibility of the proposed method on real-time scenarios.
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http://dx.doi.org/10.1109/TMI.2021.3096218DOI Listing
July 2021

T-Weighted Whole-Brain Intracranial Vessel Wall Imaging at 3 Tesla With Cerebrospinal Fluid Suppression.

Front Neurosci 2021 25;15:665076. Epub 2021 Jun 25.

Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Background: T-weighted (Tw) intracranial vessel wall imaging (IVWI) provides good contrast to differentiate intracranial vasculopathies and discriminate various important plaque components. However, the strong cerebrospinal fluid (CSF) signal in Tw images interferes with depicting the intracranial vessel wall. In this study, we propose a T-prepared sequence for whole-brain IVWI at 3T with CSF suppression.

Methods: A preparation module that combines T preparation and inversion recovery (TIR) was used to suppress the CSF signal and was incorporated into the commercial three-dimensional (3D) turbo spin echo sequence-Sampling Perfection with Application optimized Contrast using different flip angle Evolution (SPACE). This new technique (hereafter called TIR-SPACE) was evaluated on nine healthy volunteers and compared with two other commonly used 3D T-weighted sequences: Tw-SPACE and FLAIR-SPACE (FLAIR: fluid-attenuated inversion recovery). The signal-to-noise ratios (SNRs) of the vessel wall (VW) and CSF and contrast-to-noise ratios (CNRs) between them were measured and compared among these three T-weighted sequences. Subjective wall visualization of the three T-weighted sequences was scored blindly and independently by two radiologists using a four-point scale followed by inter-rater reproducibility analysis. A pilot study of four stroke patients was performed to preliminarily evaluate the diagnostic value of this new sequence, which was compared with two conventional T-weighted sequences.

Results: TIR-SPACE had the highest CNR (11.01 ± 6.75) compared with FLAIR-SPACE (4.49 ± 3.15; < 0.001) and Tw-SPACE (-56.16 ± 18.58; < 0.001). The subjective wall visualization score of TIR-SPACE was higher than those of FLAIR-SPACE and Tw-SPACE (TIR-SPACE: 2.35 ± 0.59; FLAIR-SPACE: 0.52 ± 0.54; Tw-SPACE: 1.67 ± 0.58); the two radiologists' scores showed excellent agreement (ICC = 0.883).

Conclusion: The TIR preparation module markedly suppressed the CSF signal without much SNR loss of the other tissues (i.e., vessel wall, white matter, and gray matter) compared with the IR pulse. Our results suggest that TIR-SPACE is a potential alternative T-weighted sequence for assessing intracranial vascular diseases.
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http://dx.doi.org/10.3389/fnins.2021.665076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267868PMC
June 2021

A positive-negative switching LC-MS/MS method for quantification of fenoldopam and its phase II metabolites: Applications to a pharmacokinetic study in rats.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jul 5;1179:122854. Epub 2021 Jul 5.

Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA. Electronic address:

Fenoldopam is an approved drug used to treat hypotension. The purpose of this study is to develop and validate an LC-MS method to quantify fenoldopam and its major metabolites fenoldopam-glucuronide and fenoldopam-sulfate in plasma and apply the method to a pharmacokinetic study in rats. A Waters C column was used with 0.1% formic acid in acetonitrile and 0.1% formic acid in water as the mobile phases to elute the analytes. A positive-negative switching method was performed in a triple quadrupole mass spectrometer using Multiple Reaction Monitoring (MRM) mode. A one-step protein precipitation using methanol and ethyl acetate was successfully applied for plasma sample preparation. The method was validated following the FDA guidance. The results show that the LLOQ of fenoldopam, fenoldopam-glucuronide and fenoldopam-sulfate is 0.98, 9.75 and 0.98 nM, respectively. The intraday and interday variance is less than 8.4% and the accuracy is between 82.5 and 116.0 %. The extraction recovery for these three analytes ranged from 81.3 ± 4.1% to 113.9 ± 13.2%. There was no significant matrix effect and no significant degradation under the experimental conditions. PK studies showed that fenoldopam was rapidly eliminated (t = 0.63 ± 0.24 h) from the plasma and glucuronide is the major metabolite. This method was suitably selective and sensitive for pharmacokinetic and phase II metabolism studies.
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http://dx.doi.org/10.1016/j.jchromb.2021.122854DOI Listing
July 2021

Nomogram for predicting survival of patients with metastatic nonfunctioning pancreatic neuroendocrine tumors: A SEER based study.

Medicine (Baltimore) 2021 Jul;100(27):e26347

Department of Oncology, Shaoxing Central Hospital, Shaoxing, Zhejiang, China.

Abstract: More attention has been placed on nonfunctioning pancreatic neuroendocrine tumors due to the increase in its incidence in recent years. Whether tumor resection at the primary site of metastatic NFpNET is effective remains controversial. Moreover, clinicians need a more precise prognostic tool to estimate the survival of these patients.Patients with metastatic NFpNET were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were identified using a multivariate Cox regression model and included in the nomogram. Coarsened exact matching analysis was used to balance the clinical variables between the non-surgical and surgical groups in our study.A total of 1464 patients with metastatic nonfunctioning pancreatic neuroendocrine tumors (NFpNETs) were included in our cohort. Multivariate analysis identified age, sex, tumor size, differentiated grade, lymph node metastases, resection of primary tumors, and marital status as independent predictors of metastatic NFpNET. The nomogram showed excellent accuracy in predicting 1-, 3-, and 5-year overall survival, with a C-index of 0.812. The calibration curve revealed good consistency between the predicted and actual survival.Coarsened exact matching analysis using SEER data indicated the survival advantages of resection of primary tumors. Our study is the first to build a nomogram model for patients with metastatic NFpNETs. This predictive tool can help clinicians identify high-risk patients and more accurately assess patient survival times.
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http://dx.doi.org/10.1097/MD.0000000000026347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270631PMC
July 2021

Effectiveness of omalizumab in patients with severe allergic asthma: A retrospective study in China.

Respir Med 2021 Jun 29;186:106522. Epub 2021 Jun 29.

Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: We conducted the first real-world study of treatment with omalizumab, a humanized monoclonal anti-immunoglobulin E antibody, in Chinese patients with severe allergic asthma.

Objective: The primary objective was the steroid-sparing effect of omalizumab after 12 and 16 weeks of treatment. Characteristics of the patient population, treatment patterns, response rate, and other measures of therapeutic effectiveness were also reported.

Methods: This nationwide, retrospective, real-world study was conducted in patients with severe allergic asthma who were treated with omalizumab in China. Data, including demographics, Asthma Control Test (ACT) and laboratory and lung function test results, and omalizumab use information, were extracted from patient records collected as part of a previously conducted real-world survey (Asthma Group of the Respiratory Disease Society of the Chinese Medical Association).

Results: In total, 139 patient records were included; 131 and 118 patients remained on treatment at the ≥12- and ≥16-week time points, respectively. The mean ± standard deviation age and median asthma duration (interquartile range) were 47.4 ± 14.3 and 7 (4, 15) years, respectively; 75.6% of patients had a history of allergic disease. Reductions (versus baseline) in inhaled corticosteroid/long-acting β2 agonists or oral corticosteroids were reported in 61.1% and 63.6% of patients at ≥12 and ≥ 16 weeks, respectively. There were significant improvements in ACT scores (6.08, P < .001) and nitric oxide fraction in exhaled air (-13.0, P = .01) from baseline. Multivariate analysis revealed that age and allergic medical history were predictors of omalizumab treatment response. No serious adverse events were reported.

Conclusion: Real-world omalizumab treatment was efficacious and well-tolerated in Chinese patients with severe allergic asthma.
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http://dx.doi.org/10.1016/j.rmed.2021.106522DOI Listing
June 2021

Study of chondroitin sulfate E oligosaccharide as a promising complement C5 inhibitor for osteoarthritis alleviation.

Mater Sci Eng C Mater Biol Appl 2021 Aug 8;127:112234. Epub 2021 Jun 8.

Key Laboratory of Chemical Biology (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address:

Osteoarthritis (OA) is a degenerative joint disease which is highly prevalent worldwide. However, no therapy for blocking OA pathogenesis is available currently. In this study, chondroitin sulfate (CS) E oligosaccharides were prepared and we identified disaccharide as the functional unit showing the strongest anti-complement activity and screened out complement C5 as its target in the complement system. We determined that CS-E disaccharide produced anti-inflammatory effects to treat OA by regulating the complement system: it inhibited the formation of complement-dependent complexes such as the membrane-attack complex (MAC) by targeting C5 and suppressed MAC-induced protein expression and the activation of downstream MAPK and NF-κB signaling pathways accordingly. By identifying CS-E disaccharide which could be regarded as a complement regulator or inhibitor exhibiting high anti-complement activity and revealing its OA-alleviating mechanism, this study not only provides a new strategy for OA treatment and drug development, but also potentially offers a promising C5 target therapy for other associated diseases.
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http://dx.doi.org/10.1016/j.msec.2021.112234DOI Listing
August 2021

Anti-PD-1 antibodies as a salvage therapy for patients with diffuse large B cell lymphoma who progressed/relapsed after CART19/20 therapy.

J Hematol Oncol 2021 Jul 5;14(1):106. Epub 2021 Jul 5.

Department of Bio-Therapeutic, the First Medical Centre in Chinese PLA General Hospital, Beijing, China.

CD19-directed chimeric antigen receptor T cell (CART19) therapy is efficient and approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL). To increase durable antitumor response, we previously designed tandem CART19/20 cells and shown longer progression-free survival. However, a proportion of CART19/20-treated patients will finally progress and require salvage therapies. In this study, we analyzed data from five patients with relapsed/refractory DLBCL who had disease progression or relapse following CART19/20 therapy and then treated with PD-1-blocking antibodies as salvage therapy. Two of five patients acquired complete remissions after anti-PD-1 therapy, including one patient remained ongoing remission for more than 21 months. One patient achieved a partial remission, and the other two had progressive diseases. No ≥ grade 3 treatment-related adverse events or cytokine release syndrome was observed. Immunohistochemistry of tumor specimens revealed higher PD-1/PD-L1 expression in responsive patients with anti-PD-1 therapy as compared to that in non-responders. After anti-PD-1 treatment, circulating T cells were activated in responders, and no significant expansion of CART19/20 cells was detected. Our data suggest that PD-1 blockade therapy can be active in patients with relapsed/refractory DLBCL after failure of CAR T cell therapy who had PD-L1 expression in tumor cells and high PD-1 level in tumor-infiltrated T cells.
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http://dx.doi.org/10.1186/s13045-021-01120-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259370PMC
July 2021

Evaluation of vertical transmission of SARS-CoV-2 in utero: Nine pregnant women and their newborns.

Placenta 2021 08 16;111:91-96. Epub 2021 Jun 16.

Hunan Engineering Research Center of Gynecology Disease, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Department of Dermatology & Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China. Electronic address:

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly transmitted by droplets and close contact, has caused a pandemic worldwide as of March 2020. According to the current case reports and cohort studies, the symptoms of pregnant women infected with SARS-CoV-2 were similar to normal adults and may cause a series of adverse consequences of pregnancy (placental abruption, fetal distress, epilepsy during pregnancy, etc.). However, whether SARS-CoV-2 can be transmitted to the fetus through the placental barrier is still a focus of debate.

Methods: In this study, in order to find out whether SARS-CoV-2 can infect fetus through the placental barrier, we performed qualitative detection of virus structural protein (spike protein and nucleoprotein) and targeted receptor protein Angiotensin Converting Enzyme 2 (ACE2), Basigin (CD147) and molecular chaperone GRP78 expression on the placental tissue of seven pregnant women diagnosed with COVID-19 through immunohistochemistry. Amniotic fluid, neonatal throat, anal swab and breastmilk samples were collected immediately in the operating room or delivery room for verification after delivery, which were all tested for SARS-CoV-2 by reverse transcriptionpolymerase chain reaction (RT-PCR).

Results/discussion: The result showed that CD147 was expressed on the basal side of the chorionic trophoblast cell membrane and ACE2 was expressed on the maternal side, while GRP78 was strongly expressed in the cell membrane and cytoplasm. The RT-PCR results of Amniotic fluid, neonatal throat, anal swab and breastmilk samples were all negative. On the basis of these findings, we speculated that it may be due to the placental barrier between mother and baby, for example, villous matrix and interstitial blood vessels have low expression of virus-related receptors (ACE2, CD147, GRP78), the probability of vertical transmission of SARS-CoV-2 through the placenta is low.
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http://dx.doi.org/10.1016/j.placenta.2021.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245148PMC
August 2021

Classification of Aflatoxin B1 Concentration of Single Maize Kernel Based on Near-Infrared Hyperspectral Imaging and Feature Selection.

Sensors (Basel) 2021 Jun 22;21(13). Epub 2021 Jun 22.

Beijing Research Center of Intelligent Equipment for Agriculture, Beijing 100097, China.

A rapid and nondestructive method is greatly important for the classification of aflatoxin B1 (AFB1) concentration of single maize kernel to satisfy the ever-growing needs of consumers for food safety. A novel method for classification of AFB1 concentration of single maize kernel was developed on the basis of the near-infrared (NIR) hyperspectral imaging (1100-2000 nm). Four groups of AFB1 samples with different concentrations (10, 20, 50, and 100 ppb) and one group of control samples were prepared, which were preprocessed with Savitzky-Golay (SG) smoothing and first derivative (FD) algorithms for their raw NIR spectra. A key wavelength selection method, combining the variance and order of average spectral intensity, was proposed on the basis of pretreated spectra. Moreover, principal component analysis (PCA) was conducted to reduce the dimensionality of hyperspectral data. Finally, a classification model for AFB1 concentrations was developed through linear discriminant analysis (LDA), combined with five key wavelengths and the first three PCs. The results show that the proposed method achieved an ideal performance for classifying AFB1 concentrations in a single maize kernel with overall accuracy, with an F1-score and Kappa values of 95.56%, 0.9554, and 0.9444, respectively, as well as the test accuracy yield of 88.67% for independent validation samples. The combinations of variance and order of average spectral intensity can be used for key wavelength selection which, combined with PCA, can achieve an ideal dimensionality reduction effect for model development. The findings of this study have positive significance for the classification of AFB1 concentration of maize kernels.
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http://dx.doi.org/10.3390/s21134257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271414PMC
June 2021

Complete Genome Sequence and Function Gene Identify of Prometryne-Degrading Strain sp. DY-1.

Microorganisms 2021 Jun 10;9(6). Epub 2021 Jun 10.

College of Life Science, Northeast Agricultural University, Harbin 150038, China.

The genus is widely recognized for its potential for environmental remediation and plant growth promotion. sp. DY-1 was isolated from the agricultural soil contaminated five years by prometryne, it manifested an outstanding prometryne degradation efficiency and an untapped potential for plant resistance improvement. Thus, it is meaningful to comprehend the genetic background for strain DY-1. The whole genome sequence of this strain revealed a series of environment adaptive and plant beneficial genes which involved in environmental stress response, heavy metal or metalloid resistance, nitrate dissimilatory reduction, riboflavin synthesis, and iron acquisition. Detailed analyses presented the potential of strain DY-1 for degrading various organic compounds via a homogenized pathway or the protocatechuate and catechol branches of the β-ketoadipate pathway. In addition, heterologous expression, and high efficiency liquid chromatography (HPLC) confirmed that prometryne could be oxidized by a Baeyer-Villiger monooxygenase (BVMO) encoded by a gene in the chromosome of strain DY-1. The result of gene knock-out suggested that the sulfate starvation-induced (SSI) genes in this strain might also involve in the process of prometryne degradation. These results would provide the molecular basis for the application of strain DY-1 in various fields and would contribute to the study of prometryne biodegradation mechanism as well.
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http://dx.doi.org/10.3390/microorganisms9061261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230428PMC
June 2021

MRI-aided kernel PET image reconstruction method based on texture features.

Phys Med Biol 2021 Jul 26;66(15). Epub 2021 Jul 26.

Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.

We investigate the reconstruction of low-count positron emission tomography (PET) projection, which is an important, but challenging, task. Using the texture feature extraction method of radiomics, i.e. the gray-level co-occurrence matrix (GLCM), texture features can be extracted from magnetic resonance imaging images with high-spatial resolution. In this work, we propose a kernel reconstruction method combining autocorrelation texture features derived from the GLCM. The new kernel function includes the correlations of both the intensity and texture features from the prior image. By regarding the GLCM as a discrete approximation of a probability density function, the asymptotically gray-level-invariant autocorrelation texture feature is generated, which can maintain the accuracy of texture features extracted from small image regions by reducing the number of quantized image gray levels. A computer simulation shows that the proposed method can effectively reduce the noise in the reconstructed image compared to the maximum likelihood expectation maximum method and improve the image quality and tumor region accuracy compared to the original kernel method for low-count PET reconstruction. A simulation study on clinical patient images also shows that the proposed method can improve the whole image quality and that the reconstruction of a high-uptake lesion is more accurate than that achieved by the original kernel method.
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http://dx.doi.org/10.1088/1361-6560/ac1024DOI Listing
July 2021

An epigenome-wide DNA methylation study of patients with COVID-19.

Ann Hum Genet 2021 Jun 29. Epub 2021 Jun 29.

Department of Respiratory, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

In the early 2000s, emerging SARS-CoV-2, which is highly pathogenic, posed a great threat to public health. During COVID-19, epigenetic regulation is deemed to be an important part of the pathophysiology and illness severity. Using the Illumina Infinium Methylation EPIC BeadChip (850 K), we investigated genome-wide differences in DNA methylation between healthy subjects and COVID-19 patients with different disease severities. We conducted a combined analysis and selected 35 "marker" genes that could indicate a SARS-CoV-2 infection, including 12 (ATHL1, CHN2, CHST15, CPLX2, CRHR2, DCAKD, GNAI2, HECW1, HYAL1, MIR510, PDE11A, and SMG6) situated in the promoter region. The functions and pathways of differentially methylated genes were enriched in biological processes, signal transduction, and the immune system. In the "Severe versus Mild" group, differentially methylated genes, after eliminating duplicates, were used for PPI analyses. The four hub genes (GNG7, GNAS, PRKCZ, and PRKAG2) that had the highest degree of nodes were identified and among them, GNG7 and GNAS genes expressions were also downregulated in the severe group in sequencing results. Above all, the results suggest that GNG7 and GNAS may play a non-ignorable role in the progression of COVID-19. In conclusion, the identified key genes and related pathways in the current study can be used to study the molecular mechanisms of COVID-19 and may provide possibilities for specific treatments.
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http://dx.doi.org/10.1111/ahg.12440DOI Listing
June 2021

The in vivo dissolution of tricalcium silicate bone cement.

J Biomed Mater Res A 2021 Jun 29. Epub 2021 Jun 29.

School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.

This study aimed to investigate the in vivo dissolution of tricalcium silicate (Ca SiO , C S) bone cement in the rabbit femoral defect. Results indicated that C S paste directly integrated with the bone tissue without the protection of the bone-like apatite. Calcium silicate hydrate gel (C-S-H gel) and Ca(OH) were the main components of C S paste. The dissolution model of C S paste was a mass loss rather than a decrease in volume. The initial dissolution of C S paste (0 ~ 6 weeks) was greatly attributed to the release of Ca(OH) , and the later dissolution (>6 weeks) was attributed to the decalcification of C-S-H gel. Although the mass of C S paste could decrease by more than 19 wt % after 6 weeks of implantation, the created pores (<1 μm) were not large enough for the bone tissue to migrate into C S paste. The loss of Ca ions also resulted in the transformation of SiO tetrahedrons from Q and Q to Q , Q , and Q in C-S-H gel. Because only isolated SiO tetrahedrons (Q ) and Ca ions could be absorbed by the bone tissue, C S paste gradually transformed into a silica-rich gel. The fundamental reason for no decrease in volume of C S paste was that the SiO tetrahedron network still maintained the frame structure of C S paste during the implantation.
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http://dx.doi.org/10.1002/jbm.a.37247DOI Listing
June 2021

The Landscape of Microbial Composition and Associated Factors in Pancreatic Ductal Adenocarcinoma Using RNA-Seq Data.

Front Oncol 2021 31;11:651350. Epub 2021 May 31.

Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.

Recent research studies on interrogation of the tumor microbiome (including bacteria, viruses, and fungi) have yielded important insights into the role of microbes in carcinogenesis, therapeutic responses, and resistance. Once thought to be a sterile organ, a number of studies have showed the presence of microbes within this organ in PDAC status. A microbiome-pancreas axis for PDAC (pancreatic ductal adenocarcinoma) carcinogenesis is proposed. However, the microbial composition of localized PDAC tissue is still unclear. The associations between microbiome and PDAC reported in previous studies were detected in an indirect way, which mostly used samples from stool, oral saliva, and intestinal samples. This study integrated 582 samples derived from PDAC tissues across four datasets and presented a landscape of tumor microbiome at the genus level in PDAC based on remining of RNA-Seq data. On average, there are hundreds of genera distributed in the PDAC tissue, and dozens of core microbiota were identified by PDAC tissue. The pan-microbiome of PDAC tissue was also estimated, which might surpass 2,500 genera. In addition, sampling sites (stroma . epithelium) and tissue source (human tissue . PDX) were found to have great effects on the microbial composition of PDAC tissue, but not the traditional risk factors (sex and age). It is the first study to systematically focus on exploring the microbial composition of PDAC tissue and is helpful to have a deep understanding of tumor microbiome. The identified specific taxa might be potential biomarkers for follow-up research studies.
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http://dx.doi.org/10.3389/fonc.2021.651350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202409PMC
May 2021

Development of photocontrolled BRD4 PROTACs for tongue squamous cell carcinoma (TSCC).

Eur J Med Chem 2021 Jun 5;222:113608. Epub 2021 Jun 5.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. Electronic address:

The catalytic properties of small-molecule proteolysis targeting chimeras (PROTACs) may lead to uncontrolled degradation. Therefore, the main disadvantages of PROTACs are non-cancer specificity and relatively high toxicity, which limit the clinical application of PROTACs. The photocontrolled PROTACs (photoPROTACs) were proposed to overcome this issue, in which they can be triggered by ultraviolet A (UVA) or visible light to induce the degradation of the target protein. Herein, we designed several photoPROTACs to cause the degradation of bromodomain-containing protein 4 (BRD4) on-demand using 365 nm light. The representative compound N2 is proved to induce the degradation of BRD4 upon irradiation. Moreover, compound N2 was successfully applied in vivo to inhibit tumor growth in a zebrafish xenograft model of skin cancer tongue squamous cell carcinoma (TSCC) in a photocontrol manner.
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http://dx.doi.org/10.1016/j.ejmech.2021.113608DOI Listing
June 2021
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