Publications by authors named "Lili Guo"

260 Publications

MiRNA-202-5p promotes Colorectal Carcinogenesis through suppression of PTEN.

J Cancer 2021 31;12(11):3154-3163. Epub 2021 Mar 31.

Department of Immunology, the school of Basic Medical Sciences, Anhui Medical University, Hefei, China, 230032.

Colorectal cancer (CRC) is still one of the leading causes of cancer-associated death in the modern society. The biological function of miR-202-5p for CRC development remains controversial, largely due to the fact that miR-202-5p can be tumor-suppressive or oncogenic in different contexts. Obtained results indicated that aberrant expression of miR-202-5p was observed in majority of human CRC samples and miR-202-5p was transcriptionally up-regulated by c-Myc. In addition, miR-202-5p functions to promote the activation of PI3K/Akt signaling pathway by directly suppressing PTEN. Silencing or enforced expression of miR-202-5p resulted in CRC cell proliferation inhibition and enhancement, respectively. Importantly, decreased PTEN level and increased phosphorylation of Akt were frequently associated with elevated miR-202-5p expression in colorectal cancer tissues. Increased miR-202-5p expression may serve as a tumor promoter by directly targeting PTEN in colorectal cancer.
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http://dx.doi.org/10.7150/jca.56186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100819PMC
March 2021

A Prognostic Risk Stratification Model to Identify Potential Population Benefiting From Postmastectomy Radiotherapy in T1-2 Breast Cancer With 1-3 Positive Axillary Lymph Nodes.

Front Oncol 2021 19;11:640268. Epub 2021 Apr 19.

Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Background And Objectives: To establish a prognostic stratification nomogram for T1-2 breast cancer with 1-3 positive lymph nodes to determine which patients can benefit from postmastectomy radiotherapy (PMRT).

Methods: A population-based study was conducted utilizing data collected from the Surveillance, Epidemiology, and End Results database. Chi-square test or Fisher exact test was used to compare the distribution of characteristics. Cox analysis identified significant prognostic factors for survival. A prognostic stratification model was constructed by R software. Propensity score matching was applied to balance characteristics between PMRT cohort and control cohort. Kaplan-Meier method was performed to evaluate the performance of stratification and the benefits of PMRT in the total population and three risk groups.

Results: The overall performance of the nomogram was good (3-year, 5-year, 10-year AUC were 0.75, 0.72 and 0.67, respectively). The nomogram was performed to excellently distinguish low-risk, moderate-risk, and high-risk groups with 10-year overall survival (OS) of 86.9%, 73.7%, and 62.7%, respectively (P<0.001). In the high-risk group, PMRT can significantly better OS with 10-year all-cause mortality reduced by 6.7% (P = 0.027). However, there was no significant survival difference between PMRT cohort and control cohort in low-risk (P=0.49) and moderate-risk groups (P = 0.35).

Conclusion: The current study developed the first prognostic stratification nomogram for T1-2 breast cancer with 1-3 positive axillary lymph nodes and found that patients in the high-risk group may be easier to benefit from PMRT.
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http://dx.doi.org/10.3389/fonc.2021.640268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089395PMC
April 2021

A rare cutis verticis gyrata secondary to cerebriform intradermal nevus: case report and literature review.

BMC Surg 2021 May 4;21(1):234. Epub 2021 May 4.

Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.

Background: Cutis verticis gyrate (CVG) is a rare morphologic syndrome that presents with hypertrophy and folding of the scalp. CVG can be classified into three forms: primary essential, primary non-essential, and secondary. Cerebriform intradermal nevus (CIN) is a rare cause of secondary CVG. We are here to report a rare case of CVG with an underlying CIN and discuss the clinical course, treatment options, and critical screening guidelines for these patients.

Case Presentation: A 25 year-old male patient presented with a chief complaint of generalized hair loss in the scalp parietaloccipital region for a duration of 1 year and the hair loss area was occasionally accompanied by mild itching. The hair loss started gradually and worsened over time. In addition, he had scalp skin folds resembling the ridge and furrow of the cerebral cortex in the parietaloccipital region since birth. Physical examination revealed hypertrophy and formation of folds in the parietal-occipital area, forming 5 to 6 furrows and ridges. The size of the cerebriform mass was about 12.0 cm × 8.5 cm, without other skin lesions. Diffuse non-scarring hair loss was distributed on the posterior-parietal scalp, mid-parietal scalp and superior-occipital scalp. The diseased tissue of the patient's parietaloccipital area was excised under general anesthesia. The postoperative pathological examination of the tissue excised showed that there were dense intradermal melanocytic nevus, so the patient was diagnosed with secondary CVG caused by CIN. At the 2 year follow-up, there were no obvious changes in the lesions.

Conclusions: CIN must be differentiated from other conditions that manifest as CVG, including primary essential or non-essential CVG and secondary CVG caused by other reasons. Each CIN patient requires a specific decision of whether to excise the lesion surgically or follow a wait-and-see policy, depending on the patient's will and specific condition. Surgical treatment may be performed when there is an aesthetic demand. However, clinical observation and close follow-up is also a good treatment choice for patients with stable disease or mild symptoms.
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http://dx.doi.org/10.1186/s12893-021-01229-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094459PMC
May 2021

Biochar Improves Soil-Tomato Plant, Tomato Production, and Economic Benefits under Reduced Nitrogen Application in Northwestern China.

Plants (Basel) 2021 Apr 13;10(4). Epub 2021 Apr 13.

College of Water Resources and Architectural Engineering, Northwest A&F University, Weihui Road 23, Yangling 712100, China.

The tomato is an important economic crop that is a main ingredient of some prepared food as well as a focus of the agricultural industry. Optimizing nitrogen (N) fertilizers is essential for sustainable agricultural development, while the excessive use of N fertilizers leads to environmental and food production problems. As a soil amendment, biochar has been widely used to improve soil quality and crop yield. However, little information is available on the effects of biochar and N fertilizer reduction on tomato plant, soil characteristics in tomato cultivation and tomato production. In this study, a greenhouse experiment was carried out in Yangling, Shaanxi province, China, including four biochar levels (0, 30, 50, and 70 t ha) under drip irrigation and four N application rates (170, 190, 210, and 250 kg ha). The results showed that adding too much biochar (e.g., 70 t ha) and reducing N fertilizer too far (e.g., by 32%) will not lead to satisfactory results in terms of tomato growth, tomato yield and quality, and economic benefits. Biochar addition could significantly enhance microbial abundance, enzyme activity, and tomato growth compared with non‒biochar treatments when reducing the amount of applied N fertilizer by 16% or 24% (N2 and N3). From the perspectives of tomato yield, tomato quality (sugar‒acid ratio and vitamin C (VC) content), and economic benefits, optimal application rate of biochar and N fertilizer based on the silty clay loam soil of northwest China under drip irrigation is proposed, respectively. The proposal is based on both multidimensional nonlinear regression models and a comparison with experimental treatments. For example, biochar addition at 50 t ha and reducing N fertilizer by 24% achieved the greatest tomato yield. Compared with non-biochar treatment under the corresponding N fertilizer level, soil enzyme activity (urease, phosphatase, and catalase), microbial abundance (bacteria, fungi, and actinomycetes), leaf gas exchange parameters (gs, Pn, and Tr), and biomass increased on average by 88.76%, 7.49%, 43.23%, and 39.67%, respectively. Based on a comprehensive consideration of tomato yield, VC content, sugar‒acid ratio, and economic benefits, 35 t ha biochar and 200 kg ha N fertilizer is the recommended combination of biochar and nitrogen fertilizer for local farmers.
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http://dx.doi.org/10.3390/plants10040759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070344PMC
April 2021

Multi-Way Analysis Coupled with Near-Infrared Spectroscopy in Food Industry: Models and Applications.

Foods 2021 Apr 8;10(4). Epub 2021 Apr 8.

School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen 518172, China.

Near-infrared spectroscopy (NIRS) is a fast and powerful analytical tool in the food industry. As an advanced chemometrics tool, multi-way analysis shows great potential for solving a wide range of food problems and analyzing complex spectroscopic data. This paper describes the representative multi-way models which were used for analyzing NIRS data, as well as the advances, advantages and limitations of different multi-way models. The applications of multi-way analysis in NIRS for the food industry in terms of food process control, quality evaluation and fraud, identification and classification, prediction and quantification, and image analysis are also reviewed. It is evident from this report that multi-way analysis is presently an attractive tool for modeling complex NIRS data in the food industry while its full potential is far from reached. The combination of multi-way analysis with NIRS will be a promising practice for turning food data information into operational knowledge, conducting reliable food analyses and improving our understanding about food systems and food processes. To the best of our knowledge, this is the first paper that systematically reports the advances on models and applications of multi-way analysis in NIRS for the food industry.
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http://dx.doi.org/10.3390/foods10040802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068357PMC
April 2021

Approximate back-projection method for improving lateral resolution in circular-scanning-based photoacoustic tomography.

Med Phys 2021 Apr 10. Epub 2021 Apr 10.

Department of Biomedical Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410083, China.

Purpose: In circular-scanning-based photoacoustic tomography (PAT), the effect of finite transducer aperture has not been effectively resolved. The goal of this paper is to propose a practical reconstruction method that accounts for the finite transducer aperture to improve the lateral resolution.

Methods: We for the first time propose to calculate the spatial-temporal response (STR) of the employed finite-sized transducer in a forward model, and then compensate the time delay and the directional sensitivity of the transducer in the framework of the back-projection method. Both simulation and phantom experiments were carried out to evaluate the lateral resolution improvement with the proposed method. The performance of this new method for imaging complicated targets was also assessed by calculating the mean image gradient.

Results: Simulation results showed that with this new method the lateral resolution for off-center targets can be as good as that for the center targets. Phantom experimental results showed that this new method can improve the lateral resolution more than two times for a point target about 5 mm far from the rotation center. Phantom experimental results also showed that many blurred fine structures of a piece of leaf veins at the off-center regions were well restored with the new method, and the mean image gradient improved about 1.3 times.

Conclusion: The proposed new method can effectively account for the effect of finite transducer aperture for circular-scanning-based PAT in homogenous acoustic media. This new method also features its robustness and computational efficiency, so that it is a worthy replacement to the conventional back-projection algorithm in circular-scanning-based PAT. This new method can be of great importance to the design of circular-scanning or spherical-scanning-based PAT systems.
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http://dx.doi.org/10.1002/mp.14880DOI Listing
April 2021

Detection of EGFR Mutations in Cerebrospinal Fluid of EGFR-Mutant Lung Adenocarcinoma With Brain Metastases.

Front Oncol 2021 22;11:622142. Epub 2021 Mar 22.

Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

Background: We aimed to investigate the feasibility of detecting epidermal growth factor receptor (EGFR) mutations in cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and plasma of advanced lung adenocarcinoma (LADC) with brain metastases (BMs) by droplet digital polymerase chain reaction (ddPCR).

Methods: Thirty advanced LADC patients with BMs were enrolled, and their matched CSF and plasma samples were collected. Droplet digital PCR was used to test cfDNA in CSF and plasma for EGFR mutation status. The clinical response and prognosis were evaluated.

Results: Out of 30 patients, there were 21 females and 9 males, aged 34-75 years. In all of the cases, CSF cytology were negative. In ddPCR assays, 10 patients (33.3%) had EGFR mutation in CSF, including 3 cases of EGFR T790M mutation, and 16 patients (53.3%) had EGFR mutation in plasma, including 6 cases of EGFR T790M mutation. Five patients with activating EGFR mutations in CSF achieved an intracranial partial response (iPR) after combination treatment with the first-generation EGFR-tyrosine kinase inhibitors. Three patients with EGFR T790M mutations in CSF achieved iPR after second-line osimertinib treatment. The median overall survival and intracranial progression-free survival were 17.0 months and 11.0 months, respectively.

Conclusion: It was feasible to test EGFR mutation in cerebrospinal fluid and plasma. In LADC patients with brain metastasis, cerebrospinal fluid can be used as a liquid biopsy specimen to guide treatment strategy by monitoring EGFR mutation status.
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http://dx.doi.org/10.3389/fonc.2021.622142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019917PMC
March 2021

Dipeptidyl-peptidase 3 protects oxygen-glucose deprivation/reoxygenation-injured hippocampal neurons by suppressing apoptosis, oxidative stress and inflammation via modulation of Keap1/Nrf2 signaling.

Int Immunopharmacol 2021 Mar 31;96:107595. Epub 2021 Mar 31.

Anesthesiology Department, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. Electronic address:

Dipeptidyl-peptidase 3 (DPP3) plays a key role in regulating apoptosis, oxidative stress and inflammation under various pathological conditions, however, whether DPP3 regulates apoptosis and oxidative stress in neurons undergoing cerebral ischemia/reperfusion injury has not yet been well studied. The goals of this work were to evaluate the role of DPP3 in the regulation of oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis, oxidative stress and inflammation in HT22 hippocampal neurons. Here, we showed that DPP3 expression was elevated in response to OGD/R in neurons. Knockdown of DPP3 exacerbated OGD/R-induced apoptosis, oxidative stress and inflammation, whilst up-regulation of DPP3 alleviated OGD/R-induced apoptosis, oxidative stress and inflammation in HT22 neurons. Further results revealed that DPP3 enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and promoted transcriptional activity of the anti-oxidant response element (ARE). Additionally, DPP3 was shown to regulate Nrf2/ARE activation in a kelch-like ECH-associated protein 1 (Keap1)-dependent manner. Notably, inhibition of Nrf2 markedly reversed the DPP3-mediated neuroprotective effects against OGD/R injury. Taken together, these findings demonstrate that DPP3 exerts a neuroprotective role in OGD/R-injured neurons by suppressing neuronal apoptosis, oxidative stress and inflammation via modulation of Keap1/Nrf2 signaling. This work suggests DPP3 as a potential target for providing neuroprotective effects during cerebral ischemia/reperfusion injury.
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http://dx.doi.org/10.1016/j.intimp.2021.107595DOI Listing
March 2021

Efficient drug delivery and anticancer effect of micelles based on vitamin E succinate and chitosan derivatives.

Bioact Mater 2021 Oct 9;6(10):3025-3035. Epub 2021 Mar 9.

College of Marine Life Science, Ocean University of China, Qingdao, 266003, PR China.

Nanocarriers have emerged as a promising cancer drug delivery strategy. Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy. Vitamin E derivatives have many essential functions for drug delivery applications, such as biological components that are hydrophobic, stable, water-soluble enhancing compounds, and anticancer activity. In addition, vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins. Here, we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system (-CMCTS-VES). The synthesized polymers were characterized by Fourier Transform IR, and H NMR spectra. The mean sizes of -CMCTS-VES and DOX-loaded nanoparticles were around 177 nm and 208 nm. The drug loading contents were 6.1%, 13.0% and 10.6% with the weight ratio of DOX to -CMCTS-VES corresponding 1:10, 2:10 and 3:10, and the corresponding EEs were 64.3%, 74.5% and 39.7%. Cytotoxicity test, hemolysis test and histocompatibility test showed that it had good biocompatibility and . Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/-CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%. In the study by using H22 cells implanted Balb/C mice, DOX/-CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%. The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors.
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http://dx.doi.org/10.1016/j.bioactmat.2021.02.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960945PMC
October 2021

Discovery of a Novel Series of Pyridone-Based EP3 Antagonists for the Treatment of Type 2 Diabetes.

ACS Med Chem Lett 2021 Mar 26;12(3):451-458. Epub 2021 Feb 26.

Discovery Chemistry, Cardiovascular and Metabolic Research, Janssen Research & Development, LLC, 1400 McKean Roads, Box 776, Spring House, Pennsylvania 19477, United States.

A novel series of pyridones were discovered as potent EP3 antagonists. Optimization guided by EP3 binding and functional assays as well as by eADME and PK profiling led to multiple compounds with good physical properties, excellent oral bioavailability, and a clean in vitro safety profile. Compound was identified as a lead compound as evidenced by the reversal of sulprostone-induced suppression of glucose-stimulated insulin secretion in INS 1E β-cells in vitro and in a rat ivGTT model in vivo. A glutathione adduction liability was eliminated by replacing the naphthalene of structure with the indazole ring of structure .
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http://dx.doi.org/10.1021/acsmedchemlett.0c00667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957929PMC
March 2021

Comparative Study of Anthropometric Nasal Anslysis Based on Han Nationality Young Female Adults in Central China.

J Craniofac Surg 2021 Mar 10. Epub 2021 Mar 10.

Department of Plastic Surgery, the First Affiliated Hospital of Zhengzhou University Department of Plastic Surgery, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.

Background: The data of nasal anthropometric measurements could help surgeons perform preoperative or postoperative assessments and decide surgical strategies of the nose plastic surgery and related cosmetic rhinoplasty. The aim of the study was to describe the average values of the nasal anthropometric measurements in Han Nationality young female population in Central China.

Methods: All 430 Han Chinese young females were obtained for this study, and their anthropometric features were measured including weight, height, 11 items of linear distance and 4 angles. Seven proportion indices of the soft tissue of the external nose were determined. Related results were compared with the result of other available literature about nasal anthropometry in Han Nationality young females from different regions of China and the other racial/ethnic nasal anthropometry in the world populations.

Results: The means of the linear measurements of the external nose in this study were as follows: nasal height (48.9 mm), nasal bridge length (43.3 mm), morphological facial height (110.4 mm), facial width (125.1 mm), intercanthal width (35.9 mm), nasal tip protrusion (21.1 mm), nasal width (35.5 mm), nasal ala length (27.9 mm), nasal ala thickness (4.1 mm), columella height (8.9 mm), columella width (6.0 mm). The means of the angular measurements of the nose were as follows: nasofrontal angle (143.3 degree), nasofacial angle (34.1 degree), nasal tip angle (80.4 degree), nasolabial angle (97.3 degree).

Conclusions: There were regional differences of the external nasal anthropometric of the Han Nationality young female adults in China and the racial/ethnic differences of that compared with the some races/ethnic around the world. This study could provide credible and objective reference material for plastic and maxillofacial surgeons for the external nasal soft tissue evaluation and planning of the cosmetic nasal surgery in the Han Nationality young female adults in Central China.
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http://dx.doi.org/10.1097/SCS.0000000000007282DOI Listing
March 2021

Few-shot pulse wave contour classification based on multi-scale feature extraction.

Sci Rep 2021 Feb 12;11(1):3762. Epub 2021 Feb 12.

The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, China.

The annotation procedure of pulse wave contour (PWC) is expensive and time-consuming, thereby hindering the formation of large-scale datasets to match the requirements of deep learning. To obtain better results under the condition of few-shot PWC, a small-parameter unit structure and a multi-scale feature-extraction model are proposed. In the small-parameter unit structure, information of adjacent cells is transmitted through state variables. Simultaneously, a forgetting gate is used to update the information and retain long-term dependence of PWC in the form of unit series. The multi-scale feature-extraction model is an integrated model containing three parts. Convolution neural networks are used to extract spatial features of single-period PWC and rhythm features of multi-period PWC. Recursive neural networks are used to retain the long-term dependence features of PWC. Finally, an inference layer is used for classification through extracted features. Classification experiments of cardiovascular diseases are performed on photoplethysmography dataset and continuous non-invasive blood pressure dataset. Results show that the classification accuracy of the multi-scale feature-extraction model on the two datasets respectively can reach 80% and 96%, respectively.
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http://dx.doi.org/10.1038/s41598-021-83134-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881007PMC
February 2021

Induced neural stem cell grafts exert neuroprotection through an interaction between Crry and Akt in a mouse model of closed head injury.

Stem Cell Res Ther 2021 Feb 12;12(1):128. Epub 2021 Feb 12.

Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.

Background: Recently, growing evidence has indicated an important role of the complement system, a crucial component of immunity, in mediating neuroinflammation and promoting neuronal apoptosis following closed head injury (CHI). We previously reported that transplanted induced neural stem cells (iNSCs) pre-treated with CHI mouse serum could enhance complement receptor type 1-related protein y (Crry) expression and ameliorate complement-mediated damage in mouse CHI models. However, the mechanism underlying the elevated levels of Crry expression remains elusive.

Methods: CHI models were established using a standardized weight-drop device. We collected CHI mouse serum at 12 h post-trauma. RT-QPCR assay, western blot analysis, complement deposition assay, Akt inhibition assay, flow cytometry, cell transplantation, and functional assay were utilized to clarify the mechanism of Crry expression in iNSCs receiving CHI mouse serum treatment.

Results: We observed dramatic increases in the levels of Crry expression and Akt activation in iNSCs receiving CHI mouse serum treatment. Remarkably, Akt inhibition led to the reduction of Crry expression in iNSCs. Intriguingly, the treatment of iNSC-derived neurons with recombinant complement receptor 2-conjugated Crry (CR2-Crry), which inhibits all complement pathways, substantially enhanced Crry expression and Akt activation in neurons after CHI mouse serum treatment. In subsequent in vitro experiments of pre-treatment of iNSCs with CR2-Crry, we observed significant increases in the levels of Crry expression and Akt activation in iNSCs and iNSC-derived astrocytes and neurons post-treatment with CHI mouse serum. Additionally, an in vivo study showed that intracerebral-transplanted iNSCs pre-treated with CR2-Crry markedly enhanced Crry expression in neurons and protected neurons from complement-dependent damage in the brains of CHI mice.

Conclusion: INSCs receiving CR2-Crry pre-treatment increased the levels of Crry expression in iNSCs and iNSC-derived astrocytes and neurons and attenuated complement-mediated injury following CHI.
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http://dx.doi.org/10.1186/s13287-021-02186-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881465PMC
February 2021

Predictive value of baseline F-FDG PET/CT and interim treatment response for the prognosis of patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy.

Oncol Lett 2021 Feb 18;21(2):132. Epub 2020 Dec 18.

The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

The present study aimed to investigate the prognostic value of baseline F-FDG PET/CT quantitative parameters and interim treatment response, and to assess whether the combination of these could improve the predictive efficacy in patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. PET/CT images and clinical data of 64 patients with DLBCL who had undergone F-FDG PET/CT scan before and after 3 or 4 cycles of R-CHOP chemotherapy were retrospectively reviewed. The quantitative parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter of the maximum lesion (Dmax) were measured on baseline PET/CT images. Cox proportional hazards model was used to evaluate the influence of baseline PET/CT parameters, clinical indicators and interim treatment response on prognosis. Survival analysis was performed using Kaplan-Meier method. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive efficacy of the combination of baseline PET/CT parameters and interim treatment response. Ann Arbor stage, International Prognostic Index (IPI), lactate dehydrogenase (LDH), necrosis, MTVmax, TLGmax, Dmax and interim treatment response showed association with 2-year progression-free survival (PFS, P<0.05). LDH, necrosis, MTVmax, MTVsum, TLGmax, TLGsum, Dmax and interim treatment response showed association with 2-year overall survival (OS, P<0.05). Ann Arbor stage, Dmax and interim treatment response were found to be independent predictors of 2-year PFS (P<0.05), while Dmax and interim treatment response were found to be independent predictors of 2-year OS (P<0.05). The PFS and OS curves of Dmax <5.7 cm group and Dmax ≥5.7 cm group, complete response (CR) group and non-CR group were significantly different, respectively (P<0.05). The baseline F-FDG PET/CT parameters and interim treatment response have important prognostic values in DLBCL patients who received R-CHOP chemotherapy. Combined application of Dmax and interim treatment response improved the predictive efficacy of 2-year PFS. It may be helpful to identify patients who are at high-risk of relapse and to guide early clinical intervention of these patients.
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http://dx.doi.org/10.3892/ol.2020.12393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798034PMC
February 2021

3D acoustic resolution-based photoacoustic endoscopy with dynamic focusing.

Quant Imaging Med Surg 2021 Feb;11(2):685-696

Department of Biomedical Engineering, Central South University, Changsha, China.

Background: Acoustic resolution-based photoacoustic endoscopy (ARPAE) is a non-invasive potential tool for imaging gastrointestinal and urogenital tracts. However, current ARPAE systems usually only provide 2D sectorial B-mode images, and have the limitation of the image quality significantly deteriorating out-of-focus regions due to transducers with fixed focus in these systems. To overcome these limitations, we put forward a modified back-projection method that can provide 3D images with dynamic focusing in ARPAE.

Methods: A graphics processing unit (GPU)-based parallel computation technique was adopted for efficient computation. Both simulated and phantom/ex-vivo experiments were conducted to validate our method.

Results: The findings indicated that our proposed method can effectively improve the lateral resolution and signal-to-noise ratio (SNR) in the out-of-focus regions. For a target 3 mm from the transducer focus, the new method can improve 11 times in the lateral resolution, along with an improvement of up to 37 dB in the SNR.

Conclusions: 3D ARPAE provides high-quality imaging in both focus and out-of-focus regions.
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http://dx.doi.org/10.21037/qims-20-625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779925PMC
February 2021

Biodegradable JDBM coating stent has potential to be used in the treatment of benign biliary strictures.

Biomed Mater 2021 Feb 18;16(2):025010. Epub 2021 Feb 18.

Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, People's Republic of China. Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road No. 650, Shanghai 201620, People's Republic of China.

In our previous study, to find out the optimal alloy suitable for biliary surgery, magnesium alloy Jiao Da Bio-magnesium (denoted as JDBM) alloy, Zn-3Cu alloys, and their respective coating (MgF-PDLLA) products were produced for our research. We found that JDBM seems to be a potential material for clinical biliary stent application due to its uniform degradation and good compatibility. In order to apply the JDBM alloy to treat benign bile duct stricture, our group prepared the bare JDBM and its coating product into finished stents by mesh weaving carving technology and conducted the mechanical property tests, degradation tests and biocompatibility tests. During the mechanical property tests, we found the bare JDBM stent was more suitable than titanium alloy stent when applies to the bile duct, and the coating of the JDBM coating stent has no effect on its mechanical properties. Our in vitro and in vivo experiments revealed that the degradation rate of the JDBM coating stent is lower than that of the JDBM stent, and both stents were biosafe. Thus, there is promise for JDBM coating stents for the treatment of benign biliary strictures.
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http://dx.doi.org/10.1088/1748-605X/abda88DOI Listing
February 2021

Quantitative selenium speciation in feed by enzymatic probe sonication and ion chromatography-inductively coupled plasma mass spectrometry.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2021 Feb 6;38(2):268-279. Epub 2021 Jan 6.

Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences , Beijing, China.

A rapid, sensitive and species preservative analytical method for the simultaneous determination of six selenium (Se) species has been developed. Enzymatic probe sonication (EPS) was investigated as a novel and alternative technology for the extraction of Se species from feed matrices and the results were compared with the conventional hot water extraction, enzymatic hydrolysis and sequential extraction. The critical parameters of EPS such as enzyme types, extraction time, temperature, ultrasonic power and sample/enzyme ratio were varied with control. The Se species were separated and quantitatively determined by ion chromatography-inductively coupled plasma mass spectrometry (IC-ICP-MS). Under current optimised conditions, six inorganic and organic Se species were completely separated within 15 min in a single chromatographic run. The spectral interferences from the argon plasma Ar, ArCl or HBr were effectively removed by employing the kinetic energy discrimination (KED) mode. Quantitative extraction for total Se (>94.8%) and more than 89.0% for the sum of different Se chemical forms without species transformation were obtained in only 60 s by applying the EPS treatment using aqueous protease XIV. The limits of detection (LODs) and quantification (LOQs) for Se species were in the ranges of 0.21-0.56 µg kg and 0.69-1.87 µg kg, respectively. The proposed method was successfully applied to the speciation of Se in several reference materials and feed samples collected from the markets and local farms.
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http://dx.doi.org/10.1080/19440049.2020.1849820DOI Listing
February 2021

ResGNet-C: A graph convolutional neural network for detection of COVID-19.

Neurocomputing 2020 Dec 30. Epub 2020 Dec 30.

School of Informatics, University of Leicester, Leicester LE1 7RH, UK.

The widely spreading COVID-19 has caused thousands of hundreds of mortalities over the world in the past few months. Early diagnosis of the virus is of great significance for both of infected patients and doctors providing treatments. Chest Computerized tomography (CT) screening is one of the most straightforward techniques to detect pneumonia which was caused by the virus and thus to make the diagnosis. To facilitate the process of diagnosing COVID-19, we therefore developed a graph convolutional neural network ResGNet-C under ResGNet framework to automatically classify lung CT images into normal and confirmed pneumonia caused by COVID-19. In ResGNet-C, two by-products named NNet-C, ResNet101-C that showed high performance on detection of COVID-19 are simultaneously generated as well. Our best model ResGNet-C achieved an averaged accuracy at 0.9662 with an averaged sensitivity at 0.9733 and an averaged specificity at 0.9591 using five cross-validations on the dataset, which is comprised of 296 CT images. To our best knowledge, this is the first attempt at integrating graph knowledge into the COVID-19 classification task. Graphs are constructed according to the Euclidean distance between features extracted by our proposed ResNet101-C and then are encoded with the features to give the prediction results of CT images. Besides the high-performance system, which surpassed all state-of-the-art methods, our proposed graph construction method is simple, transferrable yet quite helpful for improving the performance of classifiers, as can be justified by the experimental results.
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http://dx.doi.org/10.1016/j.neucom.2020.07.144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772101PMC
December 2020

Comprehensive evaluation of corneas from normal, forme fruste keratoconus and clinical keratoconus patients using morphological and biomechanical properties.

Int Ophthalmol 2021 Apr 3;41(4):1247-1259. Epub 2021 Jan 3.

School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China.

Objective: To more comprehensively evaluate the ability of the parameters reflecting the morphological and biomechanical properties of the cornea to distinguish clinical keratoconus (CKC) and forme fruste keratoconus (FFKC) from normal.

Methods: Normal eyes (n = 50), CKC (n = 45) and FFKC (n = 15) were analyzed using Pentacam, Corvis ST and ORA. Stepwise logistic regression of all parameters was performed to obtain the optimal combination model capable of distinguishing CKC, FFKC from normal, named SLR1 and SLR2, respectively. Receiver operating characteristic (ROC) curves were applied to determine the predictive accuracy of the parameters and the two combination models, as described by the area under the curve (AUC). AUCs were compared using the DeLong method.

Results: The SLR1 model included only the TBI output by Pentacam, while the SLR2 model included the morphological parameter F.Ele.Th and two parameters from the Corvis ST, HC DfA and SP-A1. The majority of the parameters had sufficient strength to differentiate the CKC from normal corneas, even the seven separate parameters and the SLR1 model had a discrimination efficiency of 100%. The predictive accuracy of the parameters was moderate for FFKC, and the SLR2 model (0.965) presented an excellent AUC, followed by TBI, F.Ele.Th and BAD-D.

Conclusion: The F.Ele.Th from Pentacam was the most sensitive morphological parameter for FFKC, and the combination of F.Ele.Th, HC DfA and SP-A1 made the diagnosis of FFKC more efficient. The CRF and CH output by ORA did not improve the combined diagnosis, despite the corneal combination of morphological and biomechanical properties that optimized the diagnosis of FFKC.
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http://dx.doi.org/10.1007/s10792-020-01679-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035106PMC
April 2021

Lactate Limits T Cell Proliferation via the NAD(H) Redox State.

Cell Rep 2020 12;33(11):108500

Division of Nephrology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Immune cell function is influenced by metabolic conditions. Low-glucose, high-lactate environments, such as the placenta, gastrointestinal tract, and the tumor microenvironment, are immunosuppressive, especially for glycolysis-dependent effector T cells. We report that nicotinamide adenine dinucleotide (NAD), which is reduced to NADH by lactate dehydrogenase in lactate-rich conditions, is a key point of metabolic control in T cells. Reduced NADH is not available for NAD-dependent enzymatic reactions involving glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and 3-phosphoglycerate dehydrogenase (PGDH). We show that increased lactate leads to a block at GAPDH and PGDH, leading to the depletion of post-GAPDH glycolytic intermediates, as well as the 3-phosphoglycerate derivative serine that is known to be important for T cell proliferation. Supplementing serine rescues the ability of T cells to proliferate in the presence of lactate-induced reductive stress. Directly targeting the redox state may be a useful approach for developing novel immunotherapies in cancer and therapeutic immunosuppression.
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http://dx.doi.org/10.1016/j.celrep.2020.108500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830708PMC
December 2020

TRIM11 Prevents and Reverses Protein Aggregation and Rescues a Mouse Model of Parkinson's Disease.

Cell Rep 2020 12;33(9):108418

Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Neurodegenerative diseases are characterized by the formation and propagation of protein aggregates, especially amyloid fibrils. However, what normally suppresses protein misfolding and aggregation in metazoan cells remains incompletely understood. Here, we show that TRIM11, a member of the metazoan tripartite motif (TRIM) family, both prevents the formation of protein aggregates and dissolves pre-existing protein deposits, including amyloid fibrils. These molecular chaperone and disaggregase activities are ATP independent. They enhance folding and solubility of normal proteins and cooperate with TRIM11 SUMO ligase activity to degrade aberrant proteins. TRIM11 abrogates α-synuclein fibrillization and restores viability in cell models of Parkinson's disease (PD). Intracranial adeno-associated viral delivery of TRIM11 mitigates α-synuclein-mediated pathology, neurodegeneration, and motor impairments in a PD mouse model. Other TRIMs can also function as ATP-independent molecular chaperones and disaggregases. Thus, we define TRIMs as a potent and multifunctional protein quality-control system in metazoa, which might be applied to treat neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.celrep.2020.108418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906527PMC
December 2020

Neurologic Factors in Patients with Vascular Mild Cognitive Impairment Based on fMRI.

World Neurosurg 2021 May 27;149:461-469. Epub 2020 Nov 27.

Department of Medical Imaging, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian City, China. Electronic address:

This study focused on the application of functional magnetic resonance imaging and neuropsychology in diagnosis of vascular mild cognitive impairment (MCI) and the exploration of its relevant factors. The study enrolled 28 patients with vascular MCI in an observation group and 30 healthy individuals in a control group. All patients underwent magnetic resonance imaging. An automatic segmentation algorithm based on graph theory was adopted to process the images. Age, sex, disease course, Montreal Cognitive Assessment score, regional homogeneity, and amplitude of low-frequency fluctuation levels were recorded. There were no significant differences in age, gender, and course of disease between the observation group and the control group (P > 0.05). The level of regional homogeneity in the left posterior cerebellum in the observation group was significantly higher than that in the control group (P < 0.05).The regional homogeneity level of bilateral cingulate cortex was negatively correlated with Montreal Cognitive Assessment score (P < 0.05). The amplitude of low-frequency fluctuation of bilateral inferior parietal lobe, parietal lobe, and prefrontal lobe in the observation group was significantly lower than that in the control group, and the amplitude of low-frequency fluctuation of bilateral anterior cingulate gyrus, superior medial frontal gyrus, orbital frontal gyrus, right middle frontal gyrus, and right auxiliary motor area was higher than that in the control group (P < 0.05). Heart disease, such as myocardial infarction and atrial fibrillation, is a high risk factor for vascular MCI. Functional magnetic resonance imaging combined with an automatic segmentation algorithm can noninvasively observe the changes of a patient's brain tissue, which can be used in the recognition of vascular MCI. The global network attributes of patients with depression tend to be more randomized and have stronger resilience under targeted attacks.
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http://dx.doi.org/10.1016/j.wneu.2020.11.120DOI Listing
May 2021

Environmental virus detection associated with asymptomatic SARS-CoV-2-infected individuals with positive anal swabs.

Sci Total Environ 2021 Jan 9;753:142289. Epub 2020 Sep 9.

Jiangsu Provincial Center for Disease Prevention and Control, 172 Jiangsu Road, Nanjing 210009, China. Electronic address:

In the fight against the outbreak of COVID-19 in China, we treated some asymptomatic infected individuals. This study aimed to detect pathogens in biological and environmental samples of these asymptomatic infected individuals and analyse their association. Using a cross-sectional study design, we collected biological and environmental samples from 19 patients treated in the isolation ward of Nanjing No.2 Hospital. Biological samples included saliva, pharyngeal swabs, blood, anal swabs, and exhaled breath condensate. Swab samples from the ward environment included inside masks, outside masks, palm swabs, bedside handrails, bedside tables, cell phone screens, toilet cell phone shelves, toilet pads and toilet lids. We also obtained some samples from public areas. We used RT-PCR to detect pathogens and colloidal gold to detect antibodies. As results, 19 asymptomatic infected individuals participated in the survey, with 8 positives for pathogens and 11 positives only for antibodies. Three positive samples were detected from among 96 environmental samples, respectively, from a cell phone surface, a cell phone shelf and a bedside handrail. No positive samples were detected in the exhaled breath condensate in this work. All patients identified pathogens in the environment had positive anal swabs. There was a statistical association between positive anal swabs and positive environmental samples. The association of positive samples from the surrounding of asymptomatically infected patients with positive anal swabs suggested that patients might secrete the virus for a more extended period.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480639PMC
January 2021

Remifentanil ameliorates lung injury in neonate rats with acute respiratory distress by down-regulating TIMP1 expression.

Am J Transl Res 2020 15;12(10):6325-6334. Epub 2020 Oct 15.

Department of Anesthesiology, The Eye Hospital of Wenzhou Medical University (WMU) Hangzhou 310014, Zhejiang, China.

Acute respiratory distress syndrome (ARDS) is a critical clinical disease characterized by diffuse inflammation of lung parenchyma and refractory hypoxemia. Remifentanil has been reported to act as an anti-inflammatory antioxidant in a variety of diseases. However, whether Remifentanil has a protective effect in ARDS and its mechanism remains to be further studied. This study was designed to investigate the effects of Remifentanil on ARDS in neonate rats. In this study, we established the model of acute respiratory distress in neonate rats. To study the effects of Remifentanil on ARDS through a series of and experiments. Furthermore, the overexpression vector of recombinant tissue inhibitors of metalloproteinase 1 (TIMP1) was injected into the neonate rat before the operation to explore the effect of TIMP-1 overexpression on acute respiratory distress rats through the above experiments. Remifentanil reduced lung injury in rats with acute respiratory distress, reduced inflammation, oxidative stress and tissue cell apoptosis in rats with acute respiratory distress. Remifentanil inhibited the expression of TIMP-1 in rats with acute respiratory distress, and TIMP-1 overexpression inhibited the protective effect of Remifentanil on rats with acute respiratory distress. Remifentanil can reduce lung injury and inflammatory response in young mice with acute respiratory distress and play a protective role by down-regulating the expression of TIMP-1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653556PMC
October 2020

Upregulation of Antioxidant Capacity and Nucleotide Precursor Availability Suffices for Oncogenic Transformation.

Cell Metab 2021 Jan 6;33(1):94-109.e8. Epub 2020 Nov 6.

Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The emergence of cancer from diverse normal tissues has long been rationalized to represent a common set of fundamental processes. However, these processes are not fully defined. Here, we show that forced expression of glucose-6-phosphate dehydrogenase (G6PD) affords immortalized mouse and human cells anchorage-independent growth in vitro and tumorigenicity in animals. Mechanistically, G6PD augments the NADPH pool by stimulating NAD kinase-mediated NADP biosynthesis in addition to converting NADP to NADPH, bolstering antioxidant defense. G6PD also increases nucleotide precursor levels through the production of ribose and NADPH, promoting cell proliferation. Supplementation of antioxidants or nucleosides suffices to convert immortalized mouse and human cells into a tumorigenic state, and supplementation of both is required when their overlapping metabolic consequences are minimized. These results suggest that normal cells have a limited capacity for redox balance and nucleotide synthesis, and overcoming this limit might represent a key aspect of oncogenic transformation.
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http://dx.doi.org/10.1016/j.cmet.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846267PMC
January 2021

Construction and investigation of a combined hypoxia and stemness index lncRNA-associated ceRNA regulatory network in lung adenocarcinoma.

BMC Med Genomics 2020 11 4;13(1):166. Epub 2020 Nov 4.

Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 1 Beiguandajie, Tongzhou District, Beijing, 101149, China.

Hypoxia and stemness are important factors in tumor progression. We aimed to explore the ncRNA classifier associated with hypoxia and stemness in lung adenocarcinoma (LUAD). We found that the prognosis of LUAD patients with high hypoxia and stemness index was worse than that of patients with low hypoxia and stemness index. RNA expression profiles of these two clusters were analyzed, and 6867 differentially expressed (DE) mRNAs were screened. Functional analysis showed that DE mRNAs were associated with cell cycle and DNA replication. Protein-protein interaction network analysis revealed 20 hub genes, among which CENPF, BUB1, BUB1B, KIF23 and TTK had significant influence on prognosis. In addition, 807 DE lncRNAs and 243 DE miRNAs were identified. CeRNA network analysis indicated that AC079160.1-miR-539-5p-CENPF may be an important regulatory axis that potentially regulates the progression of LUAD. The expression of AC079160.1 and CENPF were positively correlated with hypoxia and stemness index, while miR-539-5p expression level was negatively correlated with hypoxia and stemness index. Overall, we identified CENPF, BUB1, BUB1B, KIF23 and TTK as potentially key genes involved in regulating hypoxia-induced tumor cell stemness, and found that AC079160.1-miR-539-5p-CENPF axis may be involved in regulating hypoxia induced tumor cell stemness in LUAD.
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http://dx.doi.org/10.1186/s12920-020-00816-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643392PMC
November 2020

Mapping abandoned farmland in China using time series MODIS NDVI.

Sci Total Environ 2021 Feb 1;755(Pt 2):142651. Epub 2020 Oct 1.

Gansu Institute of Nature Resources Planning and Research, Lanzhou 730000, China. Electronic address:

Farmland abandonment is an important aspect of land cover land use (LCLU) that has both positive and negative effects on the environment. There is limited information regarding the spatial distribution of abandoned farmland in China. In this study, we 1) use a C5.0 decision tree classification based on a 250 m spatial resolution Moderate-resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) time series to develop LCLU maps for the period 2000-2017; 2) produce time series maps of the abandoned farmland during the period 2002-2017 based on LCLU maps; and 3) analyze spatial distribution, intensity, trend, frequency, and recultivation in terms of farmland abandonment. The results show that the overall accuracy of the LCLU maps ranged from 85.45% to 90.56% over the study period (2002-2017). The average national rate of farmland abandonment was 5% over the period 2002-2017, with the lowest rate in 2002 and the highest in 2015. Approximately 60% of the 34 agricultural areas in China showed an increasing trend for abandonment including some of the main grain-producing areas such as the North China Plain and the middle and lower reaches of the Yangtze River. Abandoned farmland areas with an abandonment frequency of ≤ 3 y comprised 58.24% of the total area of abandoned farmland. The first map detailing the distribution of the abandoned farmland across China was produced in this study, providing guidance for the development of a method of identifying abandoned farmland on a large spatial scale.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142651DOI Listing
February 2021

Identification of immune checkpoint inhibitors and biomarkers among STAT family in stomach adenocarcinoma.

Am J Transl Res 2020 15;12(9):4977-4997. Epub 2020 Sep 15.

Department of General Surgery, Shengjing Hospital, China Medical University No. 36 Sanhao St, Heping District, Shenyang 110004, Liaoning, China.

Gastric cancer is the fifth most prevalent malignancy worldwide, and the third leading cause of cancer-related death. Activating mutations of the JAK/STAT pathway on cellular biological process, inflammation, and immunity of cancer cells have made them promising biomarkers for drug exploitation and malignancy treatment. Specific functions of the STAT family in stomach adenocarcinoma (STAD) have not yet been systematically described. Bioinformatics web resources, including UALCAN, The Kaplan Meier plotter, and GSCALite, were used to identify immune checkpoint inhibitors and biomarkers among the STAT family in STAD. STAT1, STAT4, STAT5A, and STAT6 were upregulated in STAD at both the mRNA and protein level. STAT1 and STAT5A may act as potential prognostic and prognostic biomarkers in STAD. Among all members of the STAT family, STAT5B (33%), STAT1 (27%), and STAT5A (18%) were the top three frequently mutated genes, and missense mutations were the most common types of genetic alteration. The STAT family has mainly been associated with the activity of several well-known cancer-associated pathways. Low expression of STAT5A and STAT5B were resistant to most of drugs or small molecules in the Genomics of drug Sensitivity in Cancer (GDSC). The functions and pathways of STAT5A in STAD were mainly associated with immune responses, chemokine signaling pathways, and cell adhesion molecules. In addition, we identified several STAT5A associated-targets (transcription factor, kinase, and miRNA targets). Immuno-infiltration analysis suggested a strong association between the STAT5A level, the abundance of immune cells, and the level of immune biomarkers. We identified the immune checkpoint inhibitor and biomarkers among the STAT family in STAD, thereby providing additional information about the significant role of the STAT family in STAD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540141PMC
September 2020

Extra-mitochondrial mouse frataxin and its implications for mouse models of Friedreich's ataxia.

Sci Rep 2020 09 25;10(1):15788. Epub 2020 Sep 25.

Penn Medicine/CHOP Center of Excellence in Friedreich's Ataxia, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Mature frataxin is essential for the assembly of iron-sulfur cluster proteins including a number of mitochondrial enzymes. Reduced levels of mature frataxin (81-20) in human subjects caused by the genetic disease Friedreich's ataxia results in decreased mitochondrial function, neurodegeneration, and cardiomyopathy. Numerous studies of mitochondrial dysfunction have been conducted using mouse models of frataxin deficiency. However, mouse frataxin that is reduced in these models, is assumed to be mature frataxin (78-207) by analogy with human mature frataxin (81-210). Using immunoaffinity purification coupled with liquid chromatography-high resolution tandem mass spectrometry, we have discovered that mature frataxin in mouse heart (77%), brain (86%), and liver (47%) is predominantly a 129-amino acid truncated mature frataxin (79-207) in which the N-terminal lysine residue has been lost. Mature mouse frataxin (78-207) only contributes 7-15% to the total frataxin protein present in mouse tissues. We have also found that truncated mature frataxin (79-207) is present primarily in the cytosol of mouse liver; whereas, frataxin (78-207) is primarily present in the mitochondria. These findings, which provide support for the role of extra-mitochondrial frataxin in the etiology of Friedreich's ataxia, also have important implications for studies of mitochondrial dysfunction conducted in mouse models of frataxin deficiency.
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http://dx.doi.org/10.1038/s41598-020-72884-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519113PMC
September 2020

Integrative analysis of the common genetic characteristics in ovarian cancer stem cells sorted by multiple approaches.

J Ovarian Res 2020 Sep 25;13(1):116. Epub 2020 Sep 25.

Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv., Wuhan, 430030, Hubei, China.

Background: Ovarian cancer is the second fatal malignancy of the female reproductive system. Based on the cancer stem cell (CSC) theory, its poor prognosis of ovarian cancer attributed to tumor recurrence caused by CSCs. A variety of cell surface-specific markers have been employed to identify ovarian cancer stem cells (OCSCs). In this study, we attempted to explore the common feature in ovarian cancer stem cells sorted by multiple approaches.

Methods: We collected the gene expression profiles of OCSCs were from 5 public cohorts and employed R software and Bioconductor packages to establish differently expressed genes (DEGs) between OCSCs and parental cells. We extracted the integrated DEGs by protein-protein interaction (PPI) network construction and explored potential treatment by the Cellminer database.

Results: We identified and integrated the DEGs of OCSCs sorted by multiple isolation approaches. Besides, we identified OCSCs share characteristics in the lipid metabolism and extracellular matrix changes. Moreover, we obtained 16 co-expressed core genes, such as FOXQ1, MMP7, AQP5, RBM47, ETV4, NPW, SUSD2, SFRP2, IDO1, ANPEP, CXCR4, SCNN1A, SPP1 and IFI27 (upregulated) and SERPINE1, DUSP1, CD40, and IL6 (downregulated). Through correlation analysis, we screened out ten potential drugs to target the core genes.

Conclusion: Based on the comprehensive analysis of the genomic datasets with different sorting methods of OCSCs, we figured out the common driving genes to regulating OCSC and obtained ten new potential therapies for eliminating ovarian cancer stem cells. Hence, the findings of our study might have potential clinical significance.
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http://dx.doi.org/10.1186/s13048-020-00715-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519480PMC
September 2020