Publications by authors named "Zhao Zhang"

796 Publications

Identification of Apple Leaf Diseases by Improved Deep Convolutional Neural Networks With an Attention Mechanism.

Front Plant Sci 2021 28;12:723294. Epub 2021 Sep 28.

College of Mechanical and Electronic Engineering, Northwest A&F University, Xianyang, China.

The accurate identification of apple leaf diseases is of great significance for controlling the spread of diseases and ensuring the healthy and stable development of the apple industry. In order to improve detection accuracy and efficiency, a deep learning model, which is called the Coordination Attention EfficientNet (CA-ENet), is proposed to identify different apple diseases. First, a coordinate attention block is integrated into the EfficientNet-B4 network, which embedded the spatial location information of the feature by channel attention to ensure that the model can learn both the channel and spatial location information of important features. Then, a depth-wise separable convolution is applied to the convolution module to reduce the number of parameters, and the h-swish activation function is introduced to achieve the fast and easy to quantify the process. Afterward, 5,170 images are collected in the field environment at the apple planting base of the Northwest A&F University, while 3,000 images are acquired from the PlantVillage public data set. Also, image augmentation techniques are used to generate an Apple Leaf Disease Identification Data set (ALDID), which contains 81,700 images. The experimental results show that the accuracy of the CA-ENet is 98.92% on the ALDID, and the average F1-score reaches .988, which is better than those of common models such as the ResNet-152, DenseNet-264, and ResNeXt-101. The generated test dataset is used to test the anti-interference ability of the model. The results show that the proposed method can achieve competitive performance on the apple disease identification task.
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http://dx.doi.org/10.3389/fpls.2021.723294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505739PMC
September 2021

Obstructive Sleep Apnea Syndrome Treated Using a Positive Pressure Ventilator Based on Artificial Intelligence Processor.

J Healthc Eng 2021 23;2021:5683433. Epub 2021 Sep 23.

Hubei No. 3 People's Hospital of Jianghan University, Wuhan 430033, Hubei, China.

With the acceleration of people's life rhythm, obstructive sleep apnea syndrome appears more and more frequently. This research mainly discusses the treatment of obstructive sleep apnea syndrome with a positive pressure ventilator based on artificial intelligence processor. The information storage function of the smart positive pressure ventilator is included in the local medical terminal, presented after logging in with the user authority. It is mainly composed of data collection, data processing, and medical interface design, which embeds data request, data transmission, data analysis, and detailed tasks such as data compression and storage, and functions such as data display, image drawing, and alarm notification are realized by the medical interface. When the CPAP ventilator transmits respiratory data to the local medical terminal, it sends real-time respiratory information data packets. The data packet is collected and sent in real time in a fixed period and then received and analyzed by the local medical terminal. In the CPAP ventilator telemedicine system, the function of alarm message processing is mainly used to detect the patient's breathing status in real time, extract the alarm-related information, and generate an alarm. This function specifically includes several tasks such as alarm detection, alarm prompt, alarm storage, and remote transmission of alarm messages. The confirmed OSAS patients were pressure-titrated with a smart CPAP ventilator and then treated for 5 hours a day, followed by echocardiography after 5 months of continuous treatment. During the study, the average BMI was (28.9 ± 7.2) kg/m and the average AHI index was (53.1 ± 37.8) times/h. This study may help improve the quality of life of patients with obstructive sleep apnea syndrome.
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http://dx.doi.org/10.1155/2021/5683433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486548PMC
September 2021

Lineage tracing and single-cell analysis reveal proliferative Prom1+ tumour-propagating cells and their dynamic cellular transition during liver cancer progression.

Gut 2021 Sep 29. Epub 2021 Sep 29.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

Objective: Hepatocellular carcinoma (HCC) has high intratumoral heterogeneity, which contributes to therapeutic resistance and tumour recurrence. We previously identified Prominin-1 (PROM1)/CD133 as an important liver cancer stem cell (CSC) marker in human HCC. The aim of this study was to investigate the heterogeneity and properties of Prom1+ cells in HCC in intact mouse models.

Design: We established two mouse models representing chronic fibrotic HCC and rapid steatosis-related HCC. We performed lineage tracing post-HCC induction using Prom1; Rosa26 mice, and targeted depletion using Prom1; Rosa26 mice. Single-cell RNA sequencing (scRNA-seq) was carried out to analyse the transcriptomic profile of traced Prom1+ cells.

Results: Prom1 in HCC tumours marks proliferative tumour-propagating cells with CSC-like properties. Lineage tracing demonstrated that these cells display clonal expansion in situ in primary tumours. Labelled Prom1+ cells exhibit increasing tumourigenicity in 3D culture and allotransplantation, as well as potential to form cancers of differential lineages on transplantation. Depletion of Prom1+ cells impedes tumour growth and reduces malignant cancer hallmarks in both HCC models. scRNA-seq analysis highlighted the heterogeneity of Prom1+ HCC cells, which follow a trajectory to the dedifferentiated status with high proliferation and stem cells traits. Conserved gene signature of Prom1 linage predicts poor prognosis in human HCC. The activated oxidant detoxification underlies the protective mechanism of dedifferentiated transition and lineage propagation.

Conclusion: Our study combines in vivo lineage tracing and scRNA-seq to reveal the heterogeneity and dynamics of Prom1+ HCC cells, providing insights into the mechanistic role of malignant CSC-like cells in HCC progression.
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http://dx.doi.org/10.1136/gutjnl-2021-324321DOI Listing
September 2021

Management of adrenoleukodystrophy: From pre-clinical studies to the development of new therapies.

Biomed Pharmacother 2021 Nov 21;143:112214. Epub 2021 Sep 21.

HKUMed Laboratory of Cellular Therapeutics, the University of Hong Kong, Hong Kong; State Key Laboratory of Pharmaceutical Biotechnology, the University of Hong Kong, Hong Kong; Prenatal Diagnostic Centre and Cord Blood Bank, China. Electronic address:

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder associated with mutations of the ABCD1 gene that encodes a peroxisomal transmembrane protein. It results in accumulation of very long chain fatty acids in tissues and body fluid. Along with other factors such as epigenetic and environmental involvement, ABCD1 mutation-provoked disorders can present different phenotypes including cerebral adrenoleukodystrophy (cALD), adrenomyeloneuropathy (AMN), and peripheral neuropathy. cALD is the most severe form that causes death in young childhood. Bone marrow transplantation and hematopoietic stem cell gene therapy are only effective when performed at an early stage of onsets in cALD. Nonetheless, current research and development of novel therapies are hampered by a lack of in-depth understanding disease pathophysiology and a lack of reliable cALD models. The Abcd1 and Abcd1/Abcd2 knock-out mouse models as well as the deficiency of Abcd1 rabbit models created in our lab, do not develop cALD phenotypes observed in human beings. In this review, we summarize the clinical and biochemical features of X-ALD, the progress of pre-clinical and clinical studies. Challenges and perspectives for future X-ALD studies are also discussed.
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http://dx.doi.org/10.1016/j.biopha.2021.112214DOI Listing
November 2021

Animal-eRNAdb: a comprehensive animal enhancer RNA database.

Nucleic Acids Res 2021 Sep 22. Epub 2021 Sep 22.

Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P.R. China.

Enhancer RNAs (eRNAs) are a class of non-coding RNAs transcribed from enhancers. As the markers of active enhancers, eRNAs play important roles in gene regulation and are associated with various complex traits and characteristics. With increasing attention to eRNAs, numerous eRNAs have been identified in different human tissues. However, the expression landscape, regulatory network and potential functions of eRNAs in animals have not been fully elucidated. Here, we systematically characterized 185 177 eRNAs from 5085 samples across 10 species by mapping the RNA sequencing data to the regions of known enhancers. To explore their potential functions based on evolutionary conservation, we investigated the sequence similarity of eRNAs among multiple species. In addition, we identified the possible associations between eRNAs and transcription factors (TFs) or nearby genes to decipher their possible regulators and target genes, as well as characterized trait-related eRNAs to explore their potential functions in biological processes. Based on these findings, we further developed Animal-eRNAdb (http://gong_lab.hzau.edu.cn/Animal-eRNAdb/), a user-friendly database for data searching, browsing and downloading. With the comprehensive characterization of eRNAs in various tissues of different species, Animal-eRNAdb may greatly facilitate the exploration of functions and mechanisms of eRNAs.
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http://dx.doi.org/10.1093/nar/gkab832DOI Listing
September 2021

Multiview Learning With Robust Double-Sided Twin SVM.

IEEE Trans Cybern 2021 Sep 21;PP. Epub 2021 Sep 21.

Multiview learning (MVL), which enhances the learners' performance by coordinating complementarity and consistency among different views, has attracted much attention. The multiview generalized eigenvalue proximal support vector machine (MvGSVM) is a recently proposed effective binary classification method, which introduces the concept of MVL into the classical generalized eigenvalue proximal support vector machine (GEPSVM). However, this approach cannot guarantee good classification performance and robustness yet. In this article, we develop multiview robust double-sided twin SVM (MvRDTSVM) with SVM-type problems, which introduces a set of double-sided constraints into the proposed model to promote classification performance. To improve the robustness of MvRDTSVM against outliers, we take L1-norm as the distance metric. Also, a fast version of MvRDTSVM (called MvFRDTSVM) is further presented. The reformulated problems are complex, and solving them are very challenging. As one of the main contributions of this article, we design two effective iterative algorithms to optimize the proposed nonconvex problems and then conduct theoretical analysis on the algorithms. The experimental results verify the effectiveness of our proposed methods.
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http://dx.doi.org/10.1109/TCYB.2021.3088519DOI Listing
September 2021

Disturbance of functional and effective connectivity of the salience network involved in attention deficits in right temporal lobe epilepsy.

Epilepsy Behav 2021 Sep 15;124:108308. Epub 2021 Sep 15.

Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. Electronic address:

The salience network (SN) acts as a switch that generates transient control signals to regulate the executive control network (ECN) and the default mode network (DMN) and has been implicated in cognitive processes. Temporal lobe epilepsy (TLE) is usually accompanied by different types of cognitive deficits, but whether it is associated with dysfunctional connectivity of the SN remains unknown. To address this, thirty-six patients with right TLE (rTLE) and thirty-six healthy controls (HCs) were recruited for the present study. All of the participants were subjected to attention network test (ANT) and resting-state functional resonance imaging (rs-fMRI) scanning. The patient group showed deficits in attention performance. Moreover, the functional connectivity (FC) and effective connectivity (EC) were analyzed based on key SN hubs (the anterior cingulate cortex (ACC) and the bilateral anterior insula (AI)). When compared with those in the HC group, the ACC showed increased FC with the left middle frontal gyrus and the left precentral gyrus, and the right AI showed decreased FC with the right precuneus and the right superior occipital gyrus in the patient group. The EC analysis revealed an increased inflow of information from the left middle temporal gyrus to the ACC and the right AI and an increased outflow of information from the bilateral AI to the left middle frontal gyrus. Furthermore, in the correlation analysis, the abnormal EC from the right AI to the left middle temporal gyrus was positively correlated with the executive control effect. These findings demonstrated aberrant modulation of the SN in rTLE, which was particularly characterized by dysfunctional connectivity between the SN and key brain regions in the DMN and ECN. Elucidation of this effect may further contribute to the comprehensive understanding of the neural mechanisms of the SN in regard to attention deficits in patients with TLE.
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http://dx.doi.org/10.1016/j.yebeh.2021.108308DOI Listing
September 2021

Incremental multi-view spectral clustering with sparse and connected graph learning.

Neural Netw 2021 Sep 5;144:260-270. Epub 2021 Sep 5.

School of Information Engineering, Huzhou University, Hu'zhou 313000, China; Zhejiang Province Key Laboratory of Smart Management & Application of Modern Agricultural Resources, Huzhou University, Hu'zhou 313000, China.

In recent years, a lot of excellent multi-view clustering methods have been proposed. Because most of them need to fuse all views at one time, they are infeasible as the number of views increases over time. If the present multi-view clustering methods are employed directly to re-fuse all views at each time, it is too expensive to store all historical views. In this paper, we proposed an efficient incremental multi-view spectral clustering method with sparse and connected graph learning (SCGL). In our method, only one consensus similarity matrix is stored to represent the structural information of all historical views. Once the newly collected view is available, the consensus similarity matrix is reconstructed by learning from its previous version and the current new view. To further improve the incremental multi-view clustering performance, the sparse graph learning and the connected graph learning are integrated into our model, which can not only reduce the noises, but also preserve the correct connections within clusters. Experiments on several multi-view datasets demonstrate that our method is superior to traditional methods in clustering accuracy, and is more suitable to deal with the multi-view clustering with the number of views increasing over time.
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http://dx.doi.org/10.1016/j.neunet.2021.08.031DOI Listing
September 2021

Can nitrogen-based complex hydrides be a hydrogen isotope separation material?

Chem Commun (Camb) 2021 Sep 30;57(78):10063-10066. Epub 2021 Sep 30.

Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. China.

A nitrogen-based complex hydride is investigated for hydrogen isotope separation for the first time. The experimental results show that a lithium amide-lithium hydride composite (Li-N-H) possesses a distinct positive isotope effect with a separation factor of 1.42. The H-D exchange process in this system occurs at 373 K and can be accelerated with the increase of temperature.
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http://dx.doi.org/10.1039/d1cc03825gDOI Listing
September 2021

Dip coating of cylinders with Newtonian fluids.

J Colloid Interface Sci 2021 Sep 1;607(Pt 1):502-513. Epub 2021 Sep 1.

Department of Materials Science and Engineering, Clemson University, Clemson, SC 29634, United States; Center for Optical Materials Science and Engineering Technologies (COMSET),Clemson University, Anderson, SC 29625, United States. Electronic address:

Hypothesis: The Landau-Levich-Derjaguin (LLD) theory is widely applied to predict the film thickness in the dip-coating process. However, the theory was designed only for flat plates and thin fibers. Fifty years ago, White and Tallmadge attempted to generalize the LLD theory to thick rods using a numerical solution for a static meniscus and the LLD theory to forcedly match their numeric solution with the LLD asymptotics. The White-Talmadge solution has been criticized for not being rigorous yet widely used in engineering applications mostly owing to the lack of alternative solutions. A new set of experiments significantly expanding the range of White-Tallmadge conditions showed that their theory cannot explain the experimental results. We then hypothesized that the results of LLD theory can be improved by restoring the non-linear meniscus curvature in the equation. With this modification, the obtained equation should be able to describe static menisci on any cylindrical rods and the film profiles observed at non-zero rod velocity.

Experiment: To test the hypothesis, we distinguished capillary forces from viscous forces by running experiments with different rods and at different withdrawal velocities and video tracking the menisci profiles and measuring the weight of deposited films. The values of film thickness were then fitted with a mathematical model based on the modified LLD equation. We also fitted the meniscus profiles.

Findings: The results show that the derived equation allows one to reproduce the results of the LLD theory and go far beyond those to include rods of different radii. A new set of experimental data together with the White-Tallmadge experimental data are explained with the modified LLD theory. A set of simple formulas approximating numeric results have been derived. These formulas can be used in engineering applications for the prediction of the coating thickness.
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http://dx.doi.org/10.1016/j.jcis.2021.08.181DOI Listing
September 2021

Influence of Sand-Cement Ratio and Polycarboxylate Superplasticizer on the Basic Properties of Mortar Based on Water Film Thickness.

Materials (Basel) 2021 Aug 26;14(17). Epub 2021 Aug 26.

Guangxi Construction Testing Centre, Nanning 530004, China.

Previous studies demonstrated that water film thickness (WFT) is a key factor that affects the fluidity of mortar. Changes in the sand-cement (S/C) ratio and polycarboxylate superplasticizer (PCE) dosage will affect the WFT. In this study, several mortar samples with different S/C ratios and different PCE dosages were prepared, and the basic properties of the mortar were measured. The results show that as the S/C ratio increases, the packing density of the mortar will decrease, the WFT will decrease, and the cohesiveness will increase, resulting in a decrease in the flow spread and strength of the mortar. When the PCE dosage is increased, the packing density of the mortar will increase, the WFT will increase, and the cohesiveness will decrease, which increases the flow spread of the mortar. When the water-cement (W/C) ratio is low, the S/C ratio has a significant effect on the strength, and the strength will increase with the increasing of the PCE dosage. When the W/C ratio is high, the strength of the mortar will be reduced once the PCE dosage exceeds the saturation value. In the case of different S/C ratios or different PCE dosages, the WFT can be used as a measure of mortar cohesiveness and flow spread.
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http://dx.doi.org/10.3390/ma14174850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432667PMC
August 2021

Cathepsin C inhibitors as anti-inflammatory drug discovery: Challenges and opportunities.

Eur J Med Chem 2021 Sep 3;225:113818. Epub 2021 Sep 3.

Engineering Research Center of Biomass Conversion and Pollution Prevention of Anhui Educational Institutions, Fuyang Normal University, Fuyang, 236037, PR China; School of Pharmacy, Anhui Medical University, Hefei, 230032, China. Electronic address:

Cathepsin C, an important lysosomal cysteine protease, mediates the maturation process of neutrophil serine proteases, and participates in the inflammation and immune regulation process associated with polymorphonuclear neutrophils. Therefore, cathepsin C is considered to be an attractive target for treating inflammatory diseases. With INS1007 (trade name: brensocatib) being granted a breakthrough drug designation by FDA for the treatment of Adult Non-cystic Fibrosis Bronchiectasis and Coronavirus Disease 2019, the development of cathepsin C inhibitor will attract attentions from medicinal chemists in the future soon. Here, we summarized the research results of cathepsin C as a therapeutic target, focusing on the development of cathepsin C inhibitor, and provided guidance and reference opinions for the upcoming development boom of cathepsin C inhibitor.
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http://dx.doi.org/10.1016/j.ejmech.2021.113818DOI Listing
September 2021

Six-month versus nine-month therapy for intestinal tuberculosis: a protocol for a randomized controlled study.

Ann Palliat Med 2021 Aug;10(8):9223-9228

Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: The optimal duration of treatment for intestinal tuberculosis (TB), which remains a common disease worldwide, has not yet been established. The proposed randomized controlled study will aim to compare the efficacy of short-term six-month with nine-month anti-TB therapy for treating intestinal TB.

Methods: This multicenter, open-label, double-blinded, randomized controlled trial conducted in the Affiliated Hangzhou Chest Hospital of Zhejiang University will include a total of 80 patients. Patients who meet the inclusion criteria will be randomly assigned to either the six-month (n=40) or nine-month (n=40) treatment group. The primary outcome will be complete response, which is defined as endoscopy displaying active lesion healing at the end of treatment. Participants will be scheduled for follow-up visits once a month in the first three months, then once every three months until the end of the treatment. The last follow-up will be one year after the treatment. Recurrence will be assessed one year after the end of treatment, which is defined as endoscopy displaying recurrent lesions after complete response.

Discussion: In addition to the reports of tuberculous lymphadenitis and spinal TB, there are few appropriate randomized trials for the treatment of extrapulmonary TB with appropriate clinical endpoints. We believe that the proposed randomized controlled trial will provide further data on the efficacy of short-term six-month anti-TB therapy in intestinal TB patients.

Trial Registration: This trial will be registered on ClinicalTrial.gov.
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http://dx.doi.org/10.21037/apm-21-1642DOI Listing
August 2021

Functional significance of gain-of-function H19 lncRNA in skeletal muscle differentiation and anti-obesity effects.

Genome Med 2021 Aug 28;13(1):137. Epub 2021 Aug 28.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Background: Exercise training is well established as the most effective way to enhance muscle performance and muscle building. The composition of skeletal muscle fiber type affects systemic energy expenditures, and perturbations in metabolic homeostasis contribute to the onset of obesity and other metabolic dysfunctions. Long noncoding RNAs (lncRNAs) have been demonstrated to play critical roles in diverse cellular processes and diseases, including human cancers; however, the functional importance of lncRNAs in muscle performance, energy balance, and obesity remains elusive. We previously reported that the lncRNA H19 regulates the poly-ubiquitination and protein stability of dystrophin (DMD) in muscular dystrophy.

Methods: Here, we identified mouse/human H19-interacting proteins using mouse/human skeletal muscle tissues and liquid chromatography-mass spectrometry (LC-MS). Human induced pluripotent stem-derived skeletal muscle cells (iPSC-SkMC) from a healthy donor and Becker Muscular Dystrophy (BMD) patients were utilized to study DMD post-translational modifications and associated proteins. We identified a gain-of-function (GOF) mutant of H19 and characterized the effects on myoblast differentiation and fusion to myotubes using iPSCs. We then conjugated H19 RNA gain-of-function oligonucleotides (Rgof) with the skeletal muscle enrichment peptide agrin (referred to as AGR-H19-Rgof) and evaluated AGR-H19-Rgof's effects on skeletal muscle performance using wild-type (WT) C57BL/6 J mice and its anti-obesity effects using high-fat diet (HFD)- and leptin deficiency-induced obese mouse models.

Results: We demonstrated that both human and mouse H19 associated with DMD and that the H19 GOF exhibited enhanced interaction with DMD compared to WT H19. DMD was found to associate with serine/threonine-protein kinase MRCK alpha (MRCKα) and α-synuclein (SNCA) in iPSC-SkMC derived from BMD patients. Inhibition of MRCKα and SNCA-mediated phosphorylation of DMD antagonized the interaction between H19 and DMD. These signaling events led to improved skeletal muscle cell differentiation and myotube fusion. The administration of AGR-H19-Rgof improved the muscle mass, muscle performance, and base metabolic rate of WT mice. Furthermore, mice treated with AGR-H19-Rgof exhibited resistance to HFD- or leptin deficiency-induced obesity.

Conclusions: Our study suggested the functional importance of the H19 GOF mutant in enhancing muscle performance and anti-obesity effects.
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http://dx.doi.org/10.1186/s13073-021-00937-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403366PMC
August 2021

Double-Antibody Sandwich Immunoassay and Plasmonic Coupling Synergistically Improved Long-Range SPR Biosensor with Low Detection Limit.

Nanomaterials (Basel) 2021 Aug 22;11(8). Epub 2021 Aug 22.

School of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China.

A long-range surface plasmonic resonance (LR-SPR) biosensor modified with double-antibody sandwich immunoassay and plasmonic coupling is demonstrated for human-immunoglobulin G detection with a low limit of detection (LOD). The double-antibody sandwich immunoassay dramatically changes the average refractive index of the medium layer on the sensor surface. The near-field electron coupling between the localized surface plasmon and the long-range surface plasmon leads to a significant perturbation of the evanescent field. The large penetration depth and the long propagation distance of the long-range surface plasmonic waves facilitate the LR-SPR sensor in the detection of biological macromolecules. The unique light absorption characteristic of the nanocomposite material in the sensor provides the in situ self-compensation for the disturbance. Therefore, besides the inherent advantages of optical fiber sensors, the developed biosensor can realize the detection of biomolecules with high sensitivity, low LOD and high accuracy and reliability. Experimental results demonstrate that the LOD of the biosensor is as low as 0.11 μg/mL in the detection of the phosphate-buffered saline sample, and the spike-and-repetition rate is 105.56% in the detection of the real serum sample, which partly shows the practicability of the biosensor. This indicates that the LR-SPR biosensor provides better response compared with existing similar sensors and can be regarded as a valuable method for biochemical analysis and disease detection.
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http://dx.doi.org/10.3390/nano11082137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400597PMC
August 2021

Application of Artificial Intelligence in the MRI Classification Task of Human Brain Neurological and Psychiatric Diseases: A Scoping Review.

Diagnostics (Basel) 2021 Aug 3;11(8). Epub 2021 Aug 3.

715-3 Teaching Building No.5, Department of Biomedical Engineering, School of Life Sciences, Beijing Institute of Technology, 5 South Zhongguancun Road, Haidian District, Beijing 100081, China.

Artificial intelligence (AI) for medical imaging is a technology with great potential. An in-depth understanding of the principles and applications of magnetic resonance imaging (MRI), machine learning (ML), and deep learning (DL) is fundamental for developing AI-based algorithms that can meet the requirements of clinical diagnosis and have excellent quality and efficiency. Moreover, a more comprehensive understanding of applications and opportunities would help to implement AI-based methods in an ethical and sustainable manner. This review first summarizes recent research advances in ML and DL techniques for classifying human brain magnetic resonance images. Then, the application of ML and DL methods to six typical neurological and psychiatric diseases is summarized, including Alzheimer's disease (AD), Parkinson's disease (PD), major depressive disorder (MDD), schizophrenia (SCZ), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). Finally, the limitations of the existing research are discussed, and possible future research directions are proposed.
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http://dx.doi.org/10.3390/diagnostics11081402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392727PMC
August 2021

βKlotho Inhibits Cell Proliferation by Downregulating ELK4 and Predicts Favorable Prognosis in Prostate Cancer.

Cancer Manag Res 2021 12;13:6377-6387. Epub 2021 Aug 12.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China.

Objective: Prostate cancer (PCa) ranks as the second common malignancy in males worldwide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on βKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa.

Methods: Western blotting was used to determine the expression of βKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of βKlotho and ELK4 in the proliferation of PCa cells. The expression of βKlotho and ELK4 in PCa tissue samples was determined by immunochemistry. Pearson's χ2 test and Fisher's exact test were performed to investigate the associations among βKlotho, ELK4 and various clinical factors. Kaplan-Meier curves and Cox regression model were established to reveal the correlation among βKlotho, ELK4 expression and the prognosis of patients.

Results: βKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. βKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher βKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, βKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa.

Conclusion: βKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both βKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.
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http://dx.doi.org/10.2147/CMAR.S320490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366951PMC
August 2021

Lactobacillus paracasei R3 protects against dextran sulfate sodium (DSS)-induced colitis in mice via regulating Th17/Treg cell balance.

J Transl Med 2021 08 18;19(1):356. Epub 2021 Aug 18.

Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, 523808, China.

Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis (UC) and Crohn's Disease, are most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. Strategies that target the microbiota have emerged as potential therapies and, of these, probiotics have gained the greatest attention. Herein, we isolated a strain of Lactobacillus paracasei R3 (L.p R3) with strong biofilm formation ability from infant feces. Interestingly, we also found L.p R3 strain can ameliorate the general symptoms of murine colitis, alleviate inflammatory cell infiltration and inhibit Th17 while promote Treg function in murine dextran sulfate sodium (DSS)-induced colitis. Overall, this study suggested that L.p R3 strain significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.
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http://dx.doi.org/10.1186/s12967-021-02943-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371868PMC
August 2021

Neuronal chemokine-like-factor 1 (CKLF1) up-regulation promotes M1 polarization of microglia in rat brain after stroke.

Acta Pharmacol Sin 2021 Aug 12. Epub 2021 Aug 12.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

The phenotypic transformation of microglia in the ischemic penumbra determines the outcomes of ischemic stroke. Our previous study has shown that chemokine-like-factor 1 (CKLF1) promotes M1-type polarization of microglia. In this study, we investigated the cellular source and transcriptional regulation of CKLF1, as well as the biological function of CKLF1 in ischemic penumbra of rat brain. We showed that CKLF1 was significantly up-regulated in cultured rat cortical neurons subjected to oxygen-glucose deprivation/reoxygenation (ODG/R) injury, but not in cultured rat microglia, astrocytes and oligodendrocytes. In a rat model of middle cerebral artery occlusion, we found that CKLF1 was up-regulated and co-localized with neurons in ischemic penumbra. Furthermore, the up-regulated CKLF1 was accompanied by the enhanced nuclear accumulation of NF-κB. The transcriptional activity of CKLF1 was improved by overexpression of NF-κB in HEK293T cells, whereas application of NF-κB inhibitor Bay 11-7082 (1 μM) abolished it, caused by OGD/R. By using chromatin-immunoprecipitation (ChIP) assay we demonstrated that NF-κB directly bound to the promoter of CKLF1 (at a binding site located at -249 bp to -239 bp of CKLF1 promoter region), and regulated the transcription of human CKLF1. Moreover, neuronal conditional medium collected after OGD/R injury or CKLF1-C27 (a peptide obtained from secreted CKLF1) induced the M1-type polarization of microglia, whereas the CKLF1-neutralizing antibody (αCKLF1) or NF-κB inhibitor Bay 11-7082 abolished the M1-type polarization of microglia. Specific knockout of neuronal CKLF1 in ischemic penumbra attenuated neuronal impairments and M1-type polarization of microglia caused by ischemic/reperfusion injury, evidenced by inhibited levels of M1 marker CD16/32 and increased expression of M2 marker CD206. Application of CKLF1-C27 (200 nM) promoted the phosphorylation of p38 and JNK in microglia, whereas specific depletion of neuronal CKLF1 in ischemic penumbra abolished ischemic/reperfusion-induced p38 and JNK phosphorylation. In summary, CKLF1 up-regulation in neurons regulated by NF-κB is one of the crucial mechanisms to promote M1-type polarization of microglia in ischemic penumbra.
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http://dx.doi.org/10.1038/s41401-021-00746-wDOI Listing
August 2021

Impact of Laryngocarcinoma at Different Sites in 16,255 Individuals.

Ear Nose Throat J 2021 Aug 11:1455613211036771. Epub 2021 Aug 11.

Department of Otolaryngology, Hubei NO.3 People's Hospital of Jianghan University, Wuhan 430033, Hubei, China.

Background: Laryngocarcinoma (LC) is a common malignant tumor of the head and neck, accounting for 1% to 5% of human tumors. The primary objective of the present study was to evaluate the survival time of patients with LC at different sites.

Methods: Information concerning patients with LC was extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2016.

Results: In total, 16 255 patients with LC were selected from the SEER database. Among all patients, 80.2% were male; males also predominated in each tumor site subgroup. Most of the patients were aged between 60 and 69 years, had white ethnicity, were single, and had American Joint Committee on Cancer (AJCC) stage I cancer with T1, N0, and M0. The present study investigated the role of interventions in all LCs at different AJCC stages. Across the whole population, regardless of the intervention used, survival increased in patients at any cancer site.

Conclusions: The study found that male sex, age ≥80 years, black ethnicity, single status, T4, N4, M1, and AJCC stage IV were associated with higher mortality rates at all sites of LC. Aggressive interventions, especially surgery and radiotherapy, may improve survival in patients with LC at different sites and with different AJCC stages.
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http://dx.doi.org/10.1177/01455613211036771DOI Listing
August 2021

Preparation and characterization of soybean insoluble dietary fiber and its prebiotic effect on dyslipidemia and hepatic steatosis in high fat-fed C57BL/6J mice.

Food Funct 2021 Sep 20;12(18):8760-8773. Epub 2021 Sep 20.

College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin, 130118, China.

The potential benefits of insoluble dietary fiber (IDF) in the regulation of lipid metabolism have been reported in large prospective cohort studies although the molecular regulatory mechanism is still unclear. Okara is a by-product obtained during soybean processing for soy milk and soybean curd (tofu), which is rarely utilized and can be a cheap potential dietary fiber (DF) resource. In this study, the structure and physicochemical properties of insoluble dietary fiber (SIDF) extracted from okara were characterized, and the prebiotic effects on fat metabolism were investigated . The results showed that the main monosaccharides of SIDF (90.50%) identified were galactose, arabinose, xylose, rhamnose and glucose. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) analyses suggested that SIDF had a loose and porous structure, polysaccharide functional groups, and a typical crystalline cellulose I structure. In addition, SIDF had ideal oil-adsorption capacity (OAC; 7.95 g g) and significantly improved cholesterol adsorption (11.14 mg g) at pH 7.0. , IDF supplementation reduced the serum lipid levels and inhibited hepatic fat accumulation. Additionally, SIDF administration improved hepatic steatosis by stimulating lipolysis upregulation of PPARα, CYP4a10 and CPT1a. This is the first systematic study on the composition, structure, physicochemical properties, adsorption function and biological effects of SIDF. The above results show that SIDF could be used as an ideal functional ingredient in food processing as well as play a positive role in improving the added value of okara and promoting its comprehensive utilization.
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http://dx.doi.org/10.1039/d1fo01050fDOI Listing
September 2021

Spill-over effect of Wuhan travel ban on population flow in the outbreak stage of COVID-19 in China.

Cities 2021 Aug 2:103404. Epub 2021 Aug 2.

School of Transportation Science and Engineering, Beihang University, Beijing 100191, China.

This paper investigates the impact of COVID-19 travel restrictions on population flow in the People's Republic of China. We discover an "unreasonable" surge in population flow after the Wuhan travel ban. We further find out that such a sure of population flow is attributed to the "spill-over" effect of the Wuhan travel ban. We utilize a logistic regression model to quantify that the spill-over effect linearly decays with the travel distance to the Pandemic center city. Because of the "spill-over" effect of the travel ban policy, government authorities should design redundancy polity to simultaneously implement a travel ban for the pandemic center city and its neighboring cities to restrain human movement and pandemic transmission.
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http://dx.doi.org/10.1016/j.cities.2021.103404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326014PMC
August 2021

The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy.

Pathogens 2021 Jul 12;10(7). Epub 2021 Jul 12.

Department of Digestive Disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global concern. Immunoglobin A (IgA) contributes to virus neutralization at the early stage of infection. Longitudinal studies are needed to assess whether SARS-CoV-2-specific IgA production persists for a longer time in patients recovered from severe COVID-19 and its lasting symptoms that can have disabling consequences should also be alerted to susceptible hosts. Here, we tracked the anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the patients produced more anti-SARS-CoV-2 RBD IgA than IgG or IgM, and the levels of IgA remained stable during 4-41 days of infection. One of these IgA-dominant COVID-19 patients, concurrently with IgA nephropathy (IgAN), presented with elevated serum creatinine and worse proteinuria during the infection, which continued until seven months post-infection. The serum levels of anti-SARS-CoV-2 RBD and total IgA were higher in this patient than in healthy controls. Changes in the composition of the intestinal microbiota, increased IgA highly coated bacteria, and elevated concentration of the proinflammatory cytokine IL-18 were indicative of potential involvement of intestinal dysbiosis and inflammation to the systemic IgA level and, consequently, the disease progression. Collectively, our work highlighted the potential adverse effect of the mucosal immune response to SARS-CoV-2 infection, and that additional care should be taken with COVID-19 patients presenting with chronic diseases such as IgAN.
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http://dx.doi.org/10.3390/pathogens10070881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308514PMC
July 2021

A noncoding RNA modulator potentiates phenylalanine metabolism in mice.

Science 2021 08;373(6555):662-673

Division of Metabolism, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland.

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. Here, we demonstrate that the mouse lncRNA and human associate with phenylalanine hydroxylase (PAH). -knockout mice exhibited excessive blood phenylalanine (Phe), musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell-differentiated hepatocytes. Mechanistically, modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that exhibit liver enrichment. Treatment with GalNAc- mimics reduced excessive Phe in and mice and improved the Phe tolerance of these mice.
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http://dx.doi.org/10.1126/science.aba4991DOI Listing
August 2021

Regulation of telomere homeostasis and genomic stability in cancer by -adenosine methylation (mA).

Sci Adv 2021 Jul 28;7(31). Epub 2021 Jul 28.

Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

The role of RNA methylation on -adenosine (mA) in cancer has been acknowledged, but the underlying mechanisms remain obscure. Here, we identified homeobox containing 1 () as an authentic target mRNA of mA machinery, which is highly methylated in malignant cells compared to the normal counterparts and subject to expedited degradation upon the modification. mA-mediated down-regulation of causes telomere dysfunction and inactivation of p53 signaling, which leads to chromosome abnormalities and aggressive phenotypes. CRISPR-based, mA-editing tools further prove that the methyl groups on per se contribute to the generation of altered cancer genome. In multiple types of human cancers, expression of the RNA methyltransferase is negatively correlated with the telomere length but favorably with fractions of altered cancer genome, whereas mRNA levels show the opposite patterns. Our work suggests that the cancer-driving genomic alterations may potentially be fixed by rectifying particular epitranscriptomic program.
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http://dx.doi.org/10.1126/sciadv.abg7073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318370PMC
July 2021

Recycling of photovoltaic silicon waste for high-performance porous silicon/silver/carbon/graphite anode.

Waste Manag 2021 Aug 24;132:56-63. Epub 2021 Jul 24.

School of Photovoltaic and Renewable Energy Engineering (SPREE), University of New South Wales, Sydney 2052, Australia.

The rapid development photovoltaic industry has generated a huge amount of waste ultra-fine silicon cutting powder. The management and value-added recovery of silicon cutting waste is highly important for both environmental remediation and economic efficiency. In this work, silicon waste was used as a cost-effective raw material for the preparation of silicon/graphite anode for lithium-ion batteries. First, porous Si embedded with Ag particles (pSi/Ag) was produced by silver-assisted chemical etching (Ag-ACE). Then, pSi/Ag was loaded on a micron-sized graphite matrix (pSi/Ag/G), and organic carbon (C) produced by the pyrolysis of polyvinylpyrrolidone (PVP) acted as a link to closely connect pSi/Ag and graphite to form the pSi/Ag/C/G composite. The incorporated Ag particles and the porous structure improve electron transfer and mitigate the volume expansion effect of silicon. The novel design and structure of the anode can maintain the integrity of the electrode during cycling, and thus strongly improve cycling stability. The prepared pSi/Ag/C/G composite exhibited a large initial discharge capacity of 2353 mAh/g at 0.5 A/g and good initial coulombic efficiency of 83%, delivering a high capacity of 972 mAh/g at 1 A/g after 200 cycles. This work confirmed the possibility of the preparation of lithium battery silicon-carbon anode from silicon waste and provides a promising new avenue for value-added utilization of silicon cutting waste materials.
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http://dx.doi.org/10.1016/j.wasman.2021.07.014DOI Listing
August 2021

Mapping groundwater-dependent ecosystems in arid Central Asia: Implications for controlling regional land degradation.

Sci Total Environ 2021 Nov 14;797:149027. Epub 2021 Jul 14.

Eurasia Institute of Earth Sciences, Istanbul Technical University, Maslak, Istanbul 34469, Turkey.

Groundwater-dependent ecosystems (GDEs) exist all over the world, especially in water-limited regions. To achieve better water management, it is necessary to map and identify GDEs. Central Asia (CA) is one of the most arid regions in the mid-latitudes and one of the major regions with shallow groundwater tables. However, the role of groundwater in the impacts of climate change and regional anthropogenic activities on environmental risks, especially regional desertification, is inadequately understood due to the limited available research on GDEs. In the present study, a remote sensing-based method was used for mapping GDEs in regional CA, and three means-overlay analysis, correlation analysis, and the water balance method-were adopted to validate the accuracy of the mapping outcomes. Our results indicated that: 1) GDEs were concentrated around large lakes and in central Kazakhstan (between 46°N and 50°N latitudes), and areas "Very Likely" and "Likely" to be GDEs accounted for 36.89%, and 28.85% of the total natural vegetation areas, respectively; 2) at the watershed scale, the Sarysu Basin had the largest proportion (94.02% of the area) of potential GDEs while the Ysyk-Kol Basin had the lowest proportion (17.84%); 3) all the three validation methods indicated a good performance for our GDE mapping results. We concluded that the remote sensing-based GDE identification method can be considered a potential approach for mapping GDEs regionally. Better recognition of relationships among groundwater availability, ecosystem health and groundwater management policies should be developed by conducting further studies, to protect GDEs and to prevent regional land degradation.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149027DOI Listing
November 2021

Structure-Based Discovery of Novel Nonpeptide Inhibitors Targeting SARS-CoV-2 M.

J Chem Inf Model 2021 08 19;61(8):3917-3926. Epub 2021 Jul 19.

School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China.

The continual spread of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posing a severe threat to the health worldwide. The main protease (M, alias 3CL) of SARS-CoV-2 is a crucial enzyme for the maturation of viral particles and is a very attractive target for designing drugs to treat COVID-19. Here, we propose a multiple conformation-based virtual screening strategy to discover inhibitors that can target SARS-CoV-2 M. Based on this strategy, nine M structures and a protein mimetics library with 8960 commercially available compounds were prepared to carry out ensemble docking for the first time. Five of the nine structures are apo forms presented in different conformations, whereas the other four structures are holo forms complexed with different ligands. The surface plasmon resonance assay revealed that 6 out of 49 compounds had the ability to bind to SARS-CoV-2 M. The fluorescence resonance energy transfer experiment showed that the biochemical half-maximal inhibitory concentration (IC) values of the six compounds could hamper M activities ranged from 0.69 ± 0.05 to 2.05 ± 0.92 μM. Evaluation of antiviral activity using the cell-based assay indicated that two compounds (Z1244904919 and Z1759961356) could strongly inhibit the cytopathic effect and reduce replication of the living virus in Vero E6 cells with the half-maximal effective concentrations (EC) of 4.98 ± 1.83 and 8.52 ± 0.92 μM, respectively. The mechanism of the action for the two inhibitors were further elucidated at the molecular level by molecular dynamics simulation and subsequent binding free energy analysis. As a result, the discovered noncovalent reversible inhibitors with novel scaffolds are promising antiviral drug candidates, which may be used to develop the treatment of COVID-19.
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http://dx.doi.org/10.1021/acs.jcim.1c00355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315252PMC
August 2021

A Novel Biological Activity of the STAT3 Inhibitor Stattic in Inhibiting Glutathione Reductase and Suppressing the Tumorigenicity of Human Cervical Cancer Cells via a ROS-Dependent Pathway.

Onco Targets Ther 2021 5;14:4047-4060. Epub 2021 Jul 5.

Medical Research Center, Changsha Central Hospital, University of South China, Changsha, Hunan, People's Republic of China.

Introduction: Glutathione reductase (GSR) provides reduced glutathione (GSH) to maintain redox homeostasis. Inhibition of GSR disrupts this balance, resulting in cell damage, which benefits cancer therapy. However, the effect of GSR inhibition on the tumorigenicity of human cervical cancer is not fully understood.

Materials And Methods: Tissue microarray analysis was employed to determine GSR expression in cervical cancer tissues by immunohistochemical staining. Cell death was measured with PI/FITC-annexin V staining. mRNA levels were measured via quantitative RT-PCR. Protein expression was measured by Western blotting and flow cytometry. deletion was performed with CRISPR/Cas9 technology. GSR knockdown was achieved by RNA interference. Reactive oxygen species (ROS) levels were measured by DCF staining. GSR enzymatic activity was measured with a GSR assay kit. The effect of GSR inhibition on the growth of tumors formed by cervical cancer cells was investigated using a xenograft model.

Results: The expression of GSR was increased in human cervical cancer tissues, as shown by immunohistochemical staining. GSR knockdown by RNA interference in human cervical cancer cell lines resulted in cell death, suggesting the ability of GSR to maintain cancer cell survival. The STAT3 inhibitor 6-nitrobenzo[b]thiophene 1,1-dioxide (Stattic) also inhibited the enzymatic activity of GSR and induced the death of cervical cancer cells. More importantly, Stattic decreased the growth of xenograft tumors formed by cervical cancer cells in nude mice. Mechanistically, tumor cell death induced by Stattic-mediated GSR inhibition was ROS-dependent, since the ROS scavengers GSH and N-acetyl cysteine (NAC) reversed the effect of Stattic. In contrast, pharmacological and molecular inhibition of did not induce the death of cervical cancer cells, suggesting a STAT3-independent activity of Stattic.

Conclusion: Stattic inhibits the enzymatic activity of GSR and induces STAT3-independent but ROS-dependent death of cervical cancer cells, suggesting its potential application as a therapeutic agent for human cervical cancers.
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http://dx.doi.org/10.2147/OTT.S313507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275107PMC
July 2021

Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning.

Proc Natl Acad Sci U S A 2021 Jul;118(28)

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390.

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation-phenotype association. At this time, CE has evaluated putative mutation-phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.
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http://dx.doi.org/10.1073/pnas.2106786118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285956PMC
July 2021
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