Publications by authors named "Wu Yang"

1,397 Publications

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Epidemiological Analysis of Rabies in Central China from 2013 to 2018.

Infect Drug Resist 2021 17;14:2753-2762. Epub 2021 Jul 17.

School of Health Sciences, Wuhan University, Wuhan, 430071, People's Republic of China.

Objective: The study aimed to timely grasp the epidemiologic status of rabies in Central China from 2013 to 2018 and provide scientific evidence for the implementation of follow-up prevention and control measures.

Methods: We initiated a retrospective observational and descriptive study of bite-related injuries data and rabies disease data in Hubei province from 2013 to 2018, managed by the Center for Disease Control and Prevention.

Results: A total of 2,028,691 individuals were exposed to bites from 2013 to 2018, of which 221 were diagnosed with rabies and deceased. Among those cases, the incubation periods of rabies varied from 3 days to 18,406 days, which has been shown to be statistically associated with where the infected person was exposed and whether the wound care has been conducted.

Conclusion: Epidemiological studies have shown that from 2013 to 2018, the current situation of rabies in Central China is still severe. The case fatality rate keeps virtually 100%. The rural population is still the most vulnerable group to rabies, characterized by a high exposure ratio and low treatment rate as well as poor vaccination compliance. Hoewever, larger populations are warranted to validate our findings.
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http://dx.doi.org/10.2147/IDR.S314881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297554PMC
July 2021

Glioblastoma Multiforme (GBM): An overview of current therapies and mechanisms of resistance.

Pharmacol Res 2021 Jul 21:105780. Epub 2021 Jul 21.

Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, 94305, USA; Department of Neuropathology, Institute of Pathology, Technical University of Munich, Munich, Bayern, 81675, Germany. Electronic address:

Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. Thus, durable GBM management will require the invention of innovative treatment strategies. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.
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http://dx.doi.org/10.1016/j.phrs.2021.105780DOI Listing
July 2021

Effect of SOCS3 on apoptosis of human trophoblasts via adjustment of the JAK2/STAT3 signaling pathway in preterm birth.

Transl Pediatr 2021 Jun;10(6):1637-1646

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: The expression of suppressor of cytokine signaling 3 (SOCS3) was induced by interleukin-6 (IL-6) in preterm placental tissues. However, its role in IL-6 induced apoptosis of trophoblast cells derived from preterm placental tissues remains to be elucidated.

Methods: Primary cytotrophoblasts from human preterm placental tissues were used to stably knock down and overexpress the level of SOCS3 by corresponding lentiviral vectors and the expression of SOCS3 was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. The effect of SOCS3 overexpression or knockdown on the proliferation and apoptosis of IL-6 treated human cytotrophoblasts were determined by Cell Counting Kit-8 (CCK8) assay and Annexin-V/Propidium Iodide (PI) double-staining assay, respectively. Based on it, we detected the proteins associated with the Janus Tyrosine Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway and apoptosis, such as JAK2, p-JAK2, STAT3, p-STAT3, B-cell lymphoma-2 (Bcl-2) and BCL2-associated X (Bax) by Western blot.

Results: IL-6-treatment resulted in significant apoptosis of human cytotrophoblasts. Overexpressing SOCS3 in the cytotrophoblasts reduced cell apoptosis, while the knockdown of SCOS3 had the opposite effects. Further analyses showed that SOCS3 overexpression inhibited JAK2 and STAT3 phosphorylation, which was induced by IL-6 stimulation.

Conclusions: SOCS3 plays a protective role in human preterm placental tissue-derived cytotrophoblasts from IL-6 induced apoptosis by feedback inhibition of JAK2/STAT3 signaling.
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http://dx.doi.org/10.21037/tp-21-39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261589PMC
June 2021

The Protective Effect of Liquiritin in Hypoxia/Reoxygenation-Induced Disruption on Blood Brain Barrier.

Front Pharmacol 2021 6;12:671783. Epub 2021 Jul 6.

Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Stroke is the second leading cause of death in human life health, but current treatment strategies are limited to thrombolytic therapy, and because of the tight time window, many contraindications, and only a very small number of people can benefit from it, new therapeutic strategies are needed to solve this problem. As a physical barrier between the central nervous system and blood, the blood-brain barrier (BBB) maintains the homeostasis of the central nervous system. Maintaining the integrity of the BBB may emerge as a new therapeutic strategy. Liquiritin (LQ) is a flavonoid isolated from the medicinal plant Fisch. ex DC. (Fabaceae), and this study aims to investigate the protective effects of LQ on brain microvascular endothelial cells (BMECs), to provide a new therapeutic strategy for stroke treatment, and also to provide research ideas for the development of traditional Chinese medicine (TCM). The protective effects of LQ on HBMECs under the treatment of hypoxia reoxygenation (H/R) were investigated from different aspects by establishing a model of H/R injury to mimic ischemia-reperfusion while administrating different concentrations of LQ, which includes: cell proliferation, migration, angiogenesis, mitochondrial membrane potential as well as apoptosis. Meanwhile, the mechanism of LQ to protect the integrity of BBB by antioxidation and inhibiting endoplasmic reticulum (ER) stress was also investigated. Finally, to search for possible targets of LQ, a proteomic analysis approach was employed. LQ can promote cell proliferation, migration as well as angiogenesis and reduce mitochondrial membrane potential damage and apoptosis. Meanwhile, LQ can also reduce the expression of related adhesion molecules, and decrease the production of reactive oxygen species. In terms of mechanism study, we demonstrated that LQ could activate Keap1/Nrf2 antioxidant pathway, inhibit ER stress, and maintain the integrity of BBB. Through differential protein analysis, 5 disease associated proteins were found. Studies have shown that LQ can promote cell proliferation, migration as well as angiogenesis, and reduce cell apoptosis, which may be related to its inhibition of oxidative and ER stress, and then maintain the integrity of BBB. Given that five differential proteins were found by protein analysis, future studies will revolve around the five differential proteins.
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http://dx.doi.org/10.3389/fphar.2021.671783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290897PMC
July 2021

Mechanistic understanding of interspecific interaction between a C4 grass and a C3 legume via arbuscular mycorrhizal fungi as influenced by soil phosphorus availability using a C and N dual-labelled organic patch.

Plant J 2021 Jul 22. Epub 2021 Jul 22.

State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, Northwest A&F University, Yangling, 712100, PR China.

Arbuscular mycorrhizal fungi (AMF) can improve plant nutrient acquisition either by directly supplying nutrients to plants or by promoting soil organic matter mineralisation, thereby affecting interspecific plant relationships in natural communities. We examined the mechanism by which P addition affects interspecific interactions between a C4 grass (Bothriochloa ischaemum, a dominant species in natural grasslands) and C3 legume (Lespedeza davurica, a subordinate species in natural grasslands) via AMF for plant growth by continuous C and N labelling combined with soil enzyme analyses. The results of N labelling revealed that P addition differently affected shoot N uptake via AMF by B. ischaemum and L. davurica. Specifically, P addition significantly increased shoot N uptake via AMF by B. ischaemum, but significantly decreased that by L. davurica. Interspecific plant interactions via AMF significantly facilitated plant N uptake via AMF by B. ischaemum but significantly inhibited that by L. davurica under soil P-limited conditions, while the opposite effect was observed in case of excess P addition. This was consistent with the impact of interspecific plant interaction via AMF on arbuscular mycorrhizal (AM) benefit for plant growth. Our data indicated that the capability of plant N uptake via AMF is an important mechanism which influences interspecific relationships between C4 grasses and C3 legumes. Moreover, the effect of AMF on the activities of soil enzymes responsible for N and P mineralization substantially contributed to the consequence of interspecific plant interaction via AMF for plant growth.
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http://dx.doi.org/10.1111/tpj.15434DOI Listing
July 2021

Distribution patterns of microbial community and functional characteristics in full-scale wastewater treatment plants: Focusing on the influent types.

Chemosphere 2021 Oct 22;281:130899. Epub 2021 May 22.

Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes, Ministry of Education, Hohai University, Nanjing, 210098, China; College of Environment, Hohai University, Nanjing, 210098, China. Electronic address:

The impacts of the influent type in wastewater treatment plants (WWTPs) on the distribution patterns of the microbial community and functional characteristics were investigated. The obtained results indicated that the influent types exhibited evident influences on the microbial distribution patterns. The diversity and richness of functional microbes in HI-WWTP (with a ratio of >30% industrial wastewater in influents) were evidently decreased compared with those in HM- (with 70-90% municipal wastewater in influents) and M-WWTPs (with >90% municipal wastewater in influents). The core functional bacteria included denitrifiers, anaerobic fermentation bacteria (AFB), organic degrading bacteria (ODB), phosphorus accumulating organisms (PAO) and nitrite oxidizing bacteria (NOB), but they exhibited distinct abundances in WWTPs receiving different categories of wastewater. The denitrifiers in HI-WWTPs was 15.6-32.5% higher than that in other WWTPs, while PAOs had higher abundances in M - and HI-WWTPs (28.9% and 39.3%, respectively) compared with HM-WWTPs. Clear co-occurrence relationships were found among the main functional microbes with similar metabolic characteristics. Moreover, information on functional genes related to carbon, nitrogen and phosphorus metabolism, which is closely associated with pollutant removal efficiency, was obtained. M-WWTPs had higher abundances of genetic expressions for organic matters degradation (i.e. amino acid (10.42%) and carbohydrate (9.86%) metabolisms). Nar, Nir and Nor showed lowest abundances in HM-WWTPs, causing the low nitrogen removal (63.04-65.79%). However, influent type had little effect on genetic expression related with phosphorus removal. This work provided new insights into the interrelationship among bacterial co-occurrence, microbial activity and pollutant removal in WWTPs with different influent types.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130899DOI Listing
October 2021

Longitudinal neural connection detection using a ferritin-encoding adeno-associated virus vector and in vivo MRI method.

Hum Brain Mapp 2021 Jul 20. Epub 2021 Jul 20.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.

The investigation of neural circuits is important for interpreting both healthy brain function and psychiatric disorders. Currently, the architecture of neural circuits is always investigated with fluorescent protein encoding neurotropic virus and ex vivo fluorescent imaging technology. However, it is difficult to obtain a whole-brain neural circuit connection in living animals, due to the limited fluorescent imaging depth. Herein, the noninvasive, whole-brain imaging technique of MRI and the hypotoxicity virus vector AAV (adeno-associated virus) were combined to investigate the whole-brain neural circuits in vivo. AAV2-retro are an artificially-evolved virus vector that permits access to the terminal of neurons and retrograde transport to their cell bodies. By expressing the ferritin protein which could accumulate iron ions and influence the MRI contrast, the neurotropic virus can cause MRI signal changes in the infected regions. For mice injected with the ferritin-encoding virus vector (rAAV2-retro-CAG-Ferritin) in the caudate putamen (CPu), several regions showed significant changes in MRI contrasts, such as PFC (prefrontal cortex), HIP (hippocampus), Ins (insular cortex) and BLA (basolateral amygdala). The expression of ferritin in those regions was also verified with ex vivo fluorescence imaging. In addition, we demonstrated that changes in T2 relaxation time could be used to identify the spread area of the virus in the brain over time. Thus, the neural connections could be longitudinally detected with the in vivo MRI method. This novel technique could be utilized to observe the viral infection process and detect the neural circuits in a living animal.
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http://dx.doi.org/10.1002/hbm.25596DOI Listing
July 2021

Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway

J BUON 2021 May-Jun;26(3):1180

Department of General Surgery, Shenzhen University General Hospital, Shenzhen, Guangdong 518055, China

The Editors of JBUON issue an Expression of Concern to 'Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway', by Shijian Yi, Guowen Liu, Yang Wu, Qiankun Liang, Lanlan Li; JBUON 2020;25(1):389-394; PMID: 32277659. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.
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July 2021

Machine Learning for Predicting the 3-Year Risk of Incident Diabetes in Chinese Adults.

Front Public Health 2021 29;9:626331. Epub 2021 Jun 29.

Department of Endocrinology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

We aimed to establish and validate a risk assessment system that combines demographic and clinical variables to predict the 3-year risk of incident diabetes in Chinese adults. A 3-year cohort study was performed on 15,928 Chinese adults without diabetes at baseline. All participants were randomly divided into a training set ( = 7,940) and a validation set ( = 7,988). XGBoost method is an effective machine learning technique used to select the most important variables from candidate variables. And we further established a stepwise model based on the predictors chosen by the XGBoost model. The area under the receiver operating characteristic curve (AUC), decision curve and calibration analysis were used to assess discrimination, clinical use and calibration of the model, respectively. The external validation was performed on a cohort of 11,113 Japanese participants. In the training and validation sets, 148 and 145 incident diabetes cases occurred. XGBoost methods selected the 10 most important variables from 15 candidate variables. Fasting plasma glucose (FPG), body mass index (BMI) and age were the top 3 important variables. And we further established a stepwise model and a prediction nomogram. The AUCs of the stepwise model were 0.933 and 0.910 in the training and validation sets, respectively. The Hosmer-Lemeshow test showed a perfect fit between the predicted diabetes risk and the observed diabetes risk ( = 0.068 for the training set, = 0.165 for the validation set). Decision curve analysis presented the clinical use of the stepwise model and there was a wide range of alternative threshold probability spectrum. And there were almost no the interactions between these predictors (most -values for interaction >0.05). Furthermore, the AUC for the external validation set was 0.830, and the Hosmer-Lemeshow test for the external validation set showed no statistically significant difference between the predicted diabetes risk and observed diabetes risk ( = 0.824). We established and validated a risk assessment system for characterizing the 3-year risk of incident diabetes.
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http://dx.doi.org/10.3389/fpubh.2021.626331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275929PMC
June 2021

Metallic microswimmers driven up the wall by gravity.

Soft Matter 2021 Jul;17(27):6597-6602

Applied Mathematics Laboratory, Courant Institute, New York University, NY, NY 10012, USA and Department of Physics, New York University, NY, NY 10003, USA and NYU-ECNU Physics and Mathematics Research Institutes, New York University Shanghai, Shanghai 200062, China.

Experiments on autophoretic bimetallic nanorods propelling within a fuel of hydrogen peroxide show that tail-heavy swimmers preferentially orient upwards and ascend along inclined planes. We show that such gravitaxis is strongly facilitated by interactions with solid boundaries, allowing even ultraheavy microswimmers to climb nearly vertical surfaces. Theory and simulations show that the buoyancy or gravitational torque that tends to align the rods is reinforced by a fore-aft drag asymmetry induced by hydrodynamic interactions with the wall.
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http://dx.doi.org/10.1039/d1sm00554eDOI Listing
July 2021

Exosomal miR-100-5p inhibits osteogenesis of hBMSCs and angiogenesis of HUVECs by suppressing the BMPR2/Smad1/5/9 signalling pathway.

Stem Cell Res Ther 2021 Jul 13;12(1):390. Epub 2021 Jul 13.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a common, progressive, and refractory orthopaedic disease. Decreased osteogenesis and angiogenesis are considered the main factors in the pathogenesis of NONFH. We aimed to figure out whether exosomes and exosomal miRNA from necrotic bone tissues of patients with NONFH are involved in the pathogenesis of NONFH and reveal the underlying mechanisms.

Methods: RT-PCR and western blotting (WB) were used to detect the expression of osteogenic, adipogenic, and angiogenic markers. ALP staining and Alizarin Red S (ARS) staining were used to evaluate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to assess the adipocyte deposition. A tube formation assay was used to study angiogenesis of human umbilical vascular endothelial cells (HUVECs). H&E staining and immunohistochemistry (IHC) staining were used to detect the effect of the NONFH exosomes in vivo. MicroRNA sequencing was conducted to identify potential regulators in the NONFH exosomes. The target relationship between miR-100-5p and BMPR2 was predicted and confirmed by a dual luciferase reporter assay and WB.

Results: The NONFH exosomes reduced the osteogenic differentiation of hBMSCs and angiogenesis of HUVECs. In addition, the injection of the NONFH exosomes caused thinning and disruption of bone trabeculae in the femoral heads of rats. MiR-100-5p expression was upregulated in the NONFH exosomes and inhibited the osteogenesis of hBMSCs and angiogenesis of HUVECs by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway. Silencing miR-100-5p expression rescued the reduction in osteogenesis and angiogenesis caused by the NONFH exosomes by activating the BMPR2/SMAD1/5/9 signalling pathway.

Conclusion: The NONFH exosomal miR-100-5p can lead to NONFH-like damage by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway, which may be involved in the pathophysiological mechanisms of nontraumatic osteonecrosis of the femoral head (NONFH).
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http://dx.doi.org/10.1186/s13287-021-02438-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278698PMC
July 2021

Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein.

Mol Brain 2021 Jul 8;14(1):109. Epub 2021 Jul 8.

Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute (BCBDI), Translational Research Center for the Nervous System (TRCNS), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Rabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic neurons. Here, we reshuffled the oG sequence, a chimeric glycoprotein, with positive codon pair bias score (CPBS) based on bioinformatic analysis of mouse codon pair bias, generating ooG, a further optimized glycoprotein. Our experimental data reveal that the ooG has a higher expression level than the oG in vivo, which significantly increases the tracing efficiency by up to 12.6 and 62.1-fold compared to oG and B19G, respectively. The new tool can be used for labeling neural circuits Therefore, the approach reported here provides a convenient, efficient and universal strategy to improve protein expression for various application scenarios such as trans-synaptic tracing efficiency, cell engineering, and vaccine and oncolytic virus designs.
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http://dx.doi.org/10.1186/s13041-021-00821-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265122PMC
July 2021

Agro-morphological and metabolomics analysis of low nitrogen stress response in .

AoB Plants 2021 Aug 7;13(4):plab022. Epub 2021 May 7.

Key Laboratory of Genetics and Germplasm Innovation of Tropical Special Forest Trees and Ornamental Plants, Ministry of Education, College of Forestry, Hainan University, Haikou, Hainan 570228, China.

also known as carpet grass is a robust, stoloniferous grass that can grow in minimal fertilization and resists well to abiotic and biotic stresses including low nitrogen (LN) stress. This study aimed at characterizing the agro-morphological and metabolome responses to LN in carpet grass leaves. Under LN stress, carpet grass increased yellowness of leaves and root dry matter while reduced turf quality and shoot dry weight. The metabolome comparison between samples from optimum and LN conditions indicated 304 differentially accumulated metabolites (DAMs), which could be classified into 12 major and 31 subclasses. The results revealed that the leaf tissues accumulated more anthocyanins and other flavonoid metabolites under LN stress. Conversely, amino acids, nucleic acids and their derivatives were reduced in response to LN stress. The overall evaluation of individual metabolites and pathways, and previous studies on metabolomes indicated that carpet grass reduced its energy consumption in leaves and increased the level of organic acid metabolism and secondary metabolism in order to resist LN stress conditions.
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http://dx.doi.org/10.1093/aobpla/plab022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256886PMC
August 2021

Research on Diagnosis Prediction of Traditional Chinese Medicine Diseases Based on Improved Bayesian Combination Model.

Evid Based Complement Alternat Med 2021 10;2021:5513748. Epub 2021 Jun 10.

Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Traditional Chinese Medicine (TCM) clinical intelligent decision-making assistance has been a research hotspot in recent years. However, the recommendations of TCM disease diagnosis based on the current symptoms are difficult to achieve a good accuracy rate because of the ambiguity of the names of TCM diseases. The medical record data downloaded from ancient and modern medical records cloud platform developed by the Institute of Medical Information on TCM of the Chinese Academy of Chinese Medical Sciences (CACMC) and the practice guidelines data in the TCM clinical decision supporting system were utilized as the corpus. Based on the empirical analysis, a variety of improved Naïve Bayes algorithms are presented. The research findings show that the Naïve Bayes algorithm with main symptom weighted and equal probability has achieved better results, with an accuracy rate of 84.2%, which is 15.2% higher than the 69% of the classic Naïve Bayes algorithm (without prior probability). The performance of the Naïve Bayes classifier is greatly improved, and it has certain clinical practicability. The model is currently available at http://tcmcdsmvc.yiankb.com/.
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http://dx.doi.org/10.1155/2021/5513748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211513PMC
June 2021

Prospective randomised controlled trial of adults with perianal fistulising Crohn's disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol.

BMJ Open 2021 Jul 1;11(7):e043921. Epub 2021 Jul 1.

South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia

Introduction: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.

Methods And Analysis: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate.

Ethics And Dissemination: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia.

Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-043921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252869PMC
July 2021

A Study on Capacitive Micromachined Ultrasonic Transducer Periodic Sparse Array.

Micromachines (Basel) 2021 Jun 11;12(6). Epub 2021 Jun 11.

State Key Laboratory of Dynamic Testing Technology, North University of China, Taiyuan 030051, China.

Capacitive micromachined ultrasonic transducer (CMUT) is an ultrasonic transducer based on the microelectromechanical system (MEMS). CMUT elements are easily made into a high-density array, which will increase the hardware complexity. In order to reduce the number of active channels, this paper studies the grating lobes generated by CMUT periodic sparse array (PSA) pairs. Through the design of active element positions in the transmitting and receiving processes, the simulation results of effective aperture and beam patterns show that the common grating lobes (CGLs) generated by the transmit and receive array are eliminated. On the basis of point targets imaging, a CMUT linear array with 256 elements is used to carry out the PSA pairs experiment. Under the same sparse factor (SF), the optimal sparse array configuration can be selected to reduce the imaging artifacts. This conclusion is of great significance for the application of CMUT in three-dimensional ultrasound imaging.
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http://dx.doi.org/10.3390/mi12060684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230818PMC
June 2021

Dihydroartemisinin Inhibits mTORC1 Signaling by Activating the AMPK Pathway in Rhabdomyosarcoma Tumor Cells.

Cells 2021 Jun 1;10(6). Epub 2021 Jun 1.

Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.

Dihydroartemisinin (DHA), an anti-malarial drug, has been shown to possess potent anticancer activity, partly by inhibiting the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) signaling. However, how DHA inhibits mTORC1 is still unknown. Here, using rhabdomyosarcoma (RMS) as a model, we found that DHA reduced cell proliferation and viability in RMS cells, but not those in normal cells, which was associated with inhibition of mTORC1. Mechanistically, DHA did not bind to mTOR or FK506 binding protein 12 (FKBP12). In addition, DHA neither inhibited insulin-like growth factor-1 receptor (IGF-1R), phosphoinositide 3-kinase (PI3K), and extracellular signal-regulated kinase ½ , nor activated phosphatase and tensin homolog (PTEN) in the cells. Rather, DHA activated AMP-activated protein kinase (AMPK). Pharmacological inhibition of AMPK, ectopic expression dominant negative or kinase-dead AMPK, or knockdown of AMPKa attenuated the inhibitory effect of DHA on mTORC1 in the cells. Additionally, DHA was able to induce dissociation of regulatory-associated protein of (raptor) from mTOR and inhibit mTORC1 activity. Moreover, treatment with artesunate, a prodrug of DHA, dose-dependently inhibited tumor growth and concurrently activated AMPK and suppressed mTORC1 in RMS xenografts. The results indicated that DHA inhibits mTORC1 by activating AMPK in tumor cells. Our finding supports that DHA or artesunate has a great potential to be repositioned for treatment of RMS.
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http://dx.doi.org/10.3390/cells10061363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226784PMC
June 2021

Toxic effect of cooking oil fume (COF) on lungs: Evidence of endoplasmic reticulum stress in rat.

Ecotoxicol Environ Saf 2021 Sep 29;221:112463. Epub 2021 Jun 29.

School of Public Health, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Background: Cooking oil fumes (COF) is one of the primary sources of indoor air pollution in China, which is associated with respiratory diseases such as acute lung injury and lung cancer. However, evidence of COF toxic effect was few.

Objectives: The research was aimed to investigate the toxic effect and the underlying mechanisms induced by COF.

Methods: The female Wistar rats were randomly divided into several groups, including control group, COF exposure group and VE protection group, and instilled intratracheally with different COF suspensions (0.2, 2, 20 mg/kg) or saline once every 3 days for 30 days. After 24 h of final exposure, all rat were anesthetic euthanasia to draw materials. The alveolar lavage fluid (BALF) was for inflammatory cell count. The lung homogenate was to determine the biochemical indexes such as oxidative stress, apoptosis factors, carcinogenic toxicity and endoplasmic reticulum (ER) stress. The left lung was made for immunohistochemical and histopathological analysis.

Results: The results showed that the levels of oxidative stress (ROS), apoptosis factors (NF-κB), carcinogenic toxicity (P53 and 8-OhdG), ER stress (IRE-1α and Caspase-12) in 2 mg/kg and 20 mg/kg COF exposure groups were significantly increased compared with the saline groups. The above pathological changes were improved after vitamin E (VE) supplementation. In addition, the immunohistochemical and histopathological analysis found the same trend.

Conclusion: The COF had health risk of heredity and potential carcinogenicity. Besides, COFs can not only induce oxidative stress, but also induce ER stress in lung and airway epithelial cells of female rats through the unfolded protein reaction (UPR) pathway. It revealed that the oxidative stress and ER stress interacted in aggravating lung injury. VE could effectively alleviate the lung injury causing by COF exposure.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112463DOI Listing
September 2021

Long-term efficacy of GPi DBS for craniofacial dystonia: a retrospective report of 13 cases.

Neurosurg Rev 2021 Jun 29. Epub 2021 Jun 29.

Department of Neurosurgery, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, 610041, Sichuan Province, China.

This study evaluated the long-term efficacy of globus pallidus internus (GPi) deep brain stimulation (DBS) in the treatment of craniofacial dystonia (Meige syndrome) and investigated the correlation between the volume of tissue activated (VTA) in the GPi and each subregion and movement score improvement. We retrospectively analyzed the clinical data of 13 patients with drug-refractory Meige syndrome who were treated with GPi DBS. The pre- and postoperative Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores were compared. The relationships between the preoperative baseline variables and improvement in the BFMDRS-Movement (BFMDRS-M) score were analyzed. LEAD-DBS software was used for the three-dimensional reconstruction of the GPi and implanted electrodes. The correlations between the GPi-VTA and score improvement were analyzed. The average follow-up period was 36.6 ± 11.0 months (18-55 months). At 3 months after the stimulation and the final follow-up visit, the improvements in the BFMDRS-M score were 58.2 and 54.6%, and the improvements in the BFMDRS-Disability (BFMDRS-D) score were 53.6 and 51.7%, respectively. At the final follow-up visit, the improvements in the BFMDRS-M scores of the eye, mouth, and speech/swallowing were significant (P < 0.001). Age was an independent predictor of improvement in the BFMDRS-M score after DBS (P = 0.005). A decrease in the BFMDRS-M score was significantly positively correlated with the GPi-VTA (r = 0.757, P = 0.003). GPi DBS is an effective method for treating drug-refractory Meige syndrome. LEAD-DBS software can be used as an effective aid for visualization programming after DBS.
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http://dx.doi.org/10.1007/s10143-021-01584-4DOI Listing
June 2021

Genome-Wide Association Mapping and Gene Expression Analysis Reveal the Negative Role of OsMYB21 in Regulating Bacterial Blight Resistance in Rice.

Rice (N Y) 2021 Jun 29;14(1):58. Epub 2021 Jun 29.

Rice Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China.

Background: Bacterial blight (BB), caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating diseases in rice all over the world. Due to the diversity and rapid evolution of Xoo, identification and use of the non-race specific quantitative resistance QTLs has been considered the preferred strategy for effective control of this disease. Although numerous QTLs for BB resistance have been identified, they haven't been effectively used for improvement of BB resistance in rice due to their small effects and lack of knowledge on the function of genes underlying the QTLs.

Results: In the present study, a genome-wide association study of BB resistance was performed in a rice core collection from South China. A total of 17 QTLs were identified to be associated with BB resistance. Among them, 13 QTLs were newly identified in the present study and the other 4 QTLs were co-localized with the previously reported QTLs or Xa genes that confer qualitative resistance to Xoo strains. Particularly, the qBBR11-4 on chromosome 11 explained the largest phenotypic variation in this study and was co-localized with the previously identified QTLs for BB and bacterial leaf streak (BLS) resistance against diverse strains in three studies, suggesting its broad-spectrum resistance and potential value in rice breeding. Through combined analysis of differential expression and annotations of the predicted genes within qBBR11-4 between two sets of rice accessions selected based on haplotypes and disease phenotypes, we identified the transcription factor OsMYB21 as the candidate gene for qBBR11-4. The OsMYB21 overexpressing plants exhibited decreased resistance to bacterial blight, accompanied with down-regulation of several defense-related genes compared with the wild-type plants.

Conclusion: The results suggest that OsMYB21 negatively regulates bacterial blight resistance in rice, and this gene can be a promising target in rice breeding by using the gene editing method. In addition, the potential candidate genes for the 13 novel QTLs for BB resistance were also analyzed in this study, providing a new source for cloning of genes associated with BB resistance and molecular breeding in rice.
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http://dx.doi.org/10.1186/s12284-021-00501-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241976PMC
June 2021

Relationship of Bone Status with Serum Uric Acid and Bilirubin in Men with Type 2 Diabetes: A Cross-Sectional Study.

Med Sci Monit 2021 Jun 18;27:e930410. Epub 2021 Jun 18.

Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China (mainland).

BACKGROUND Accumulating evidence has shown that serum uric acid and bilirubin are associated with some chronic diseases, owing to their antioxidant capacity, but the previous research produced discrepant results regarding the relation between uric acid, as well as bilirubin, and bone health. This study was designed to assess the relationship of serum uric acid and total bilirubin with bone mineral density and bone turnover markers in men with type 2 diabetes. MATERIAL AND METHODS In total, 631 male patients with type 2 diabetes were included. Data of patients' medical history, biochemical index, bone mineral density of the lumbar vertebra, femoral neck, and total hip, and bone turnover markers including osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), type I collagen carboxy-terminal peptide (CTX), and parathyroid hormone were collected and retrospectively analyzed. RESULTS Both serum uric acid and total bilirubin were positively related to bone mineral density of the lumbar vertebra (b=0.179, p.
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http://dx.doi.org/10.12659/MSM.930410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218604PMC
June 2021

Association between postpartum low-carbohydrate-diet scores and glucose levels in Chinese women.

Nutrition 2021 May 8;89:111305. Epub 2021 May 8.

Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Sun Yat-sen University, Guangzhou, China. Electronic address:

Objectives: Views on the relationship between a low-carbohydrate diet (LCD) and glucose levels are controversial, and no study, to our knowledge, has examined this association in postpartum women. We aimed to explore the association between postpartum LCD scores and glucose levels.

Methods: We included 500 postpartum women from a prospective cohort study in Guangzhou, China, during 2017 and 2018. Dietary information during the first month after delivery was assessed via a validated food frequency questionnaire. The overall, animal, and plant LCD scores were determined based on percentages of energy from carbohydrate, protein, and fat. Higher scores reflected higher intakes of fat and protein and lower intakes of carbohydrate. At 6 to 8 wk postpartum, women with previous gestational diabetes mellitus underwent oral glucose tolerance tests (n = 104), and the others had fasting plasma glucose (FPG) tests (n = 396). Multivariable linear, quantile, and logistic regressions were conducted.

Results: Of the 500 participants, 71 (14.20%) developed impaired fasting glucose. Animal LCD score was positively associated with FPG levels (β = 0.007, P = 0.017), but quantile regression showed that LCD scores were related to FPG only in women with lower FPG levels; they had no significant association in those with higher FPG levels. No significant interaction effect on FPG was found between LCD scores and history of gestational diabetes mellitus (P > 0.40). Furthermore, the relationships between the three LCD scores and risk of developing impaired fasting glucose were not statistically significant.

Conclusions: Animal LCD score during puerperium may be positively associated with FPG levels in the early postpartum period in Chinese women, but no interactions with history of gestational diabetes mellitus were observed. Stronger associations were observed in women with lower FPG levels.
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http://dx.doi.org/10.1016/j.nut.2021.111305DOI Listing
May 2021

The role of lncRNA Meg3 in the proliferation of all-trans retinoic acid-treated mouse embryonic palate mesenchymal cells involves the Smad pathway.

Reprod Toxicol 2021 Jun 21;104:1-7. Epub 2021 Jun 21.

Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China; School of Public Health, Zhengzhou University, Zhengzhou, Henan, China. Electronic address:

Mesenchymal cell proliferation is critical for the growth of the palate shelf. All-trans retinoic acid (atRA), as well as pathways associated with TGF-β/Smad signaling, play crucial roles in the proliferation of mouse embryonic palate mesenchymal (MEPM) cells. We have found that MEPM-cell proliferation was regulated by atRA and exogenous TGF-β3 could significantly antagonize the atRA-mediated suppression of MEPM cell proliferation, which is closely associated with the regulation of TGF-β/Smad signaling pathway. The long non-coding RNA (lncRNA) MEG3 has been reported to activate TGF-β/Smad signaling, thereby regulating cellular proliferation, differentiation, and related processes. Here, we found that Meg3 expression increased significantly in atRA-treated MEPM cells while TGF-β3 treatment markedly inhibited Meg3 expression and antagonized the effect of atRA on Meg3. Moreover, Smad2 was found to interact directly with Meg3, and atRA treatment significantly enriched Meg3 in Smad2-immunoprecipitated samples. After Meg3 deletion, the effects of atRA on the proliferation of MEPM cells and TGF-β3-dependent protein expression were lost. Hence, we speculate that Meg3 has a role in the RA-induced suppression of MEPM cell proliferation by targeting Smad2 and thereby mediating TGF-β/Smad signaling inhibition.
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http://dx.doi.org/10.1016/j.reprotox.2021.06.011DOI Listing
June 2021

TRAP1 Shows Clinical Significance in the Early Diagnosis of Small Cell Lung Cancer.

J Inflamm Res 2021 14;14:2507-2514. Epub 2021 Jun 14.

Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, Jiangxi, People's Republic of China.

Purpose: To explore the clinical significance of tumor necrosis factor receptor-associated protein (TRAP1), mitotic arrest deficient 2 (mad2) and anti-nuclear mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC).

Patients And Methods: Serum concentrations of TRAP1 and MSA were determined by enzyme-linked immunosorbent assay (ELISA), including SCLC group (Num.=86), non-small cell lung cancer (NSCLC) group (Num.=105), pulmonary nodules (PN) group (Num.=94), and 60 healthy subjects as control group (Num.=60). Whereas fluorescence quantitative PCR (qt-PCR) method was used to detect the expression of mad2.

Results: The expression of TRAP1 was low in SCLC and NSCLC compared with the other two groups, and was the lowest in SCLC, which was negatively correlated with the occurrence of the disease (P<0.05); the sensitivity and specificity of TRAP1 for SCLC were 75.29%, 93.33%, and the area under SCLC curve was 0.903; compared with the other three groups, the level of MSA was the highest in the SCLC, and the results were significantly different (P<0.05), while the area under the SCLC curve was 0.856, and the sensitivity and specificity were 62.78% and 95.24%, respectively. Mad2 is overexpressed in SCLC, but not in PN. The area under the SCLC curve is 0.835, and the sensitivity and specificity are 56.98% and 92.38%; TRAP1 levels are negatively correlated with SCLC tumor stage, the level of TRAP1 was significantly lower in stage III-IV than in stage I-II (P<0.05); combined analysis of TRAP1 and MAD2 and MSA showed that the sensitivity and specificity for SCLS were 95.35% and 99.05%, respectively.

Conclusion: TRAP1 is of great value in the early diagnosis of SCLC as well as differential diagnosis with NSCLC. TRAP1 combined with MAD2 and MSA improved the sensitivity and specificity and provided a new idea for the clinical diagnosis of SCLC.
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http://dx.doi.org/10.2147/JIR.S313440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214028PMC
June 2021

Preclinical metabolism and disposition of an orally bioavailable macrocyclic FXIa inhibitor.

Xenobiotica 2021 Aug 5;51(8):933-948. Epub 2021 Jul 5.

Department of Nonclinical Research and Development, Bristol Myers Squibb Pharmaceutical Research and Development, Princeton, NJ, USA.

FXIa-6f is a high affinity, orally bioavailable macrocyclic FXIa inhibitor with antithrombotic activity in preclinical species.The objectives of this study were to characterize the in vitro metabolism, determine circulating metabolites in pre-clinical species, and examine the disposition of the compound in a bile duct-cannulated rat study (BDC) study to inform clinical development of the compound and the medicinal chemistry approach to identify molecules with improved properties.Across species, metabolic pathways included several oxidative metabolites, including hydroxylated metabolites on the macrocycle or P1 region, descarbamoylation of the methyl carbamate side chain, and a glutathione conjugate on the 2,6-difluoro-3-chlorophenyl ring.In BDC rat, the absorbed dose of [H]FXIa-6f was cleared mainly by metabolism, with excretion of drug-related material in the bile, mostly as metabolites.In all preclinical species, the parent drug was the primary drug-related component in circulation, but the species differences in the metabolic pathways observed in vitro were reflected in the plasma, where M6, a descarbamoylated metabolite, was more prominent in rat plasma, and M9, a hydroxylated metabolite, was more prominent in monkey plasma. Based on the available data, the human metabolism appears to be most similar to monkey.
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http://dx.doi.org/10.1080/00498254.2021.1943565DOI Listing
August 2021

Knocking down LINC01116 can inhibit the regulation of TGF-β through miR-774-5p axis and inhibit the occurrence and development of glioma.

Am J Transl Res 2021 15;13(5):5702-5719. Epub 2021 May 15.

Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University Zhengzhou 450014, Henan Province, China.

Background: Many studies have shown that non-coding RNAs (ncRNAs), including long non-coding RNA (LncRNA) and micro RNA (miRNA), play a crucial regulatory role in glioma. LINC01116 is a newly discovered LncRNA, and the relationship between LncRNA and glioma is still under exploration.

Method: LncRNAs with potential differences were screened through GEO database, and the expressions of LINC01116 and miR-744-5p/TGF-β1 in glioma tissues were tested using qRT-PCR. Changes in proliferation and migration/invasion of glioma were tested using CCK-8 and transwell assay. The expression changes of TGF-β1 were tested using qRT-PCR and Western blot. Targeted binding among LINC01116, miR-744-5p and TGF-β1 was verified using double luciferase reporter, RNA Immunoprecipitation (PIR) and RNA pull-down experiments. The effect of LINC01116 on tumor growth was determined by tumor allografting test.

Results: GEO database and clinical research revealed that the expression level of LINC01116 in glioma increased, and the elevation of LINC01116 was closely related to the adverse prognosis of clinical patients. Functional experiments showed that the inhibition of LINC01116 could up-regulate miR-744-5p-mediated proliferation and metastasis of glioma cells. Western blot analysis and qRT-PCR analysis showed that LINC01116 regulated TGF-β1 by mediating miR-744-5p. Further cell behavior experiments showed that LINC01116 acted as miR-744-5p sponge to inhibit proliferation and metastasis caused by TGF-β1. Finally, the analysis of animal models in vivo showed that LINC01116 could regulate the tumor growth of glioma.

Conclusion: LncRNA LINC01116 acts as an oncogene and promotes TGF-β1 mediated proliferation and metastasis by acting as competitive endogenous RNA (ceRNA) in glioma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205728PMC
May 2021

Towards High-Energy and Anti-Self-Discharge Zn-Ion Hybrid Supercapacitors with New Understanding of the Electrochemistry.

Nanomicro Lett 2021 Mar 18;13(1):95. Epub 2021 Mar 18.

College of Chemistry and Materials Science, Jinan University, Guangzhou, 511443, People's Republic of China.

Aqueous Zn-ion hybrid supercapacitors (ZHSs) are increasingly being studied as a novel electrochemical energy storage system with prominent electrochemical performance, high safety and low cost. Herein, high-energy and anti-self-discharge ZHSs are realized based on the fibrous carbon cathodes with hierarchically porous surface and O/N heteroatom functional groups. Hierarchically porous surface of the fabricated free-standing fibrous carbon cathodes not only provides abundant active sites for divalent ion storage, but also optimizes ion transport kinetics. Consequently, the cathodes show a high gravimetric capacity of 156 mAh g, superior rate capability (79 mAh g with a very short charge/discharge time of 14 s) and exceptional cycling stability. Meanwhile, hierarchical pore structure and suitable surface functional groups of the cathodes endow ZHSs with a high energy density of 127 Wh kg, a high power density of 15.3 kW kg and good anti-self-discharge performance. Mechanism investigation reveals that ZHS electrochemistry involves cation adsorption/desorption and ZnSO(OH)·5HO formation/dissolution at low voltage and anion adsorption/desorption at high voltage on carbon cathodes. The roles of these reactions in energy storage of ZHSs are elucidated. This work not only paves a way for high-performance cathode materials of ZHSs, but also provides a deeper understanding of ZHS electrochemistry.
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http://dx.doi.org/10.1007/s40820-021-00625-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006207PMC
March 2021

Lewis acid-assisted Ir(iii) reductive elimination enables construction of seven-membered-ring sulfoxides.

Chem Sci 2020 Sep 3;11(37):10149-10158. Epub 2020 Sep 3.

Shenzhen Grubbs Institute, Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology Shenzhen 518055 Guangdong China http://faculty.sustech.edu.cn/hec/en/.

Iridium has played an important role in the evolution of C-H activation chemistry over the last half century owing to its high reactivity towards stoichiometric C-H bond cleavage; however, the use of Ir(iii) complexes in catalytic C-H functionalization/C-C bond formation appears to have fallen off significantly. The main problem lies in the reductive elimination step, as iridium has a tendency to form stable and catalytically inactive Ir(iii) species. Herein, with a rationally designed Lewis acid assisted oxidatively induced strategy, the sluggish Ir(iii) reductive elimination is successfully facilitated, enabling the facile C-C bond formation. The X-ray crystal structure of a silver salt adduct of iridacycle and DFT calculations demonstrate that the sulfoxide group acts as a key bridge connecting the Ir(iii) metal centre with the silver Lewis acid, which facilitates the reductive elimination of the Ir(iii) metallacycle. Further identification of oxidants was carried out by performing stoichiometric reactions, which enables the development of catalytic construction of various highly functionalized seven-membered-ring sulfoxides, that are of great interest in medicinal chemistry and materials science.
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http://dx.doi.org/10.1039/d0sc04180gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162422PMC
September 2020

DeepOmix: A scalable and interpretable multi-omics deep learning framework and application in cancer survival analysis.

Comput Struct Biotechnol J 2021 1;19:2719-2725. Epub 2021 May 1.

Key Laboratory of Intelligent Information Processing, Advanced Computer Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China.

Integrative analysis of multi-omics data can elucidate valuable insights into complex molecular mechanisms for various diseases. However, due to their different modalities and high dimension, utilizing and integrating different types of omics data suffers from great challenges. There is an urgent need to develop a powerful method to improve survival prediction and detect functional gene modules from multi-omics data. To deal with these problems, we present DeepOmix (a scalable and interpretable multi-Omics Deep learning framework and application in cancer survival analysis), a flexible, scalable, and interpretable method for extracting relationships between the clinical survival time and multi-omics data based on a deep learning framework. DeepOmix enables the non-linear combination of variables from different omics datasets and incorporates prior biological information defined by users (such as signaling pathways and tissue networks). Benchmark experiments demonstrate that DeepOmix outperforms the other five cutting-edge prediction methods. Besides, Lower Grade Glioma (LGG) is taken as the case study to perform the prognosis prediction and illustrate the functional module nodes which are associated with the prognostic result in the prediction model.
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http://dx.doi.org/10.1016/j.csbj.2021.04.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131983PMC
May 2021

The OsOXO2, OsOXO3 and OsOXO4 Positively Regulate Panicle Blast Resistance in Rice.

Rice (N Y) 2021 Jun 5;14(1):51. Epub 2021 Jun 5.

Rice Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China.

Background: Although panicle blast is more destructive to yield loss than leaf blast in rice, the cloned genes that function in panicle blast resistance are still very limited and the molecular mechanisms underlying panicle blast resistance remain largely unknown.

Results: In the present study, we have confirmed that the three Oxalate oxidase (OXO) genes, OsOXO2, OsOXO3 and OsOXO4 from a blast-resistant cultivar BC10 function in panicle blast resistance in rice. The expression of OsOXO2, OsOXO3 and OsOXO4 were induced by panicle blast inoculation. Subcellular localization analysis revealed that the three OXO proteins are all localized in the nucleus and cytoplasm. Simultaneous silencing of OsOXO2, OsOXO3 and OsOXO4 decreased rice resistance to panicle blast, whereas the OsOXO2, OsOXO3 and OsOXO4 overexpression rice plants individually showed enhanced panicle blast resistance. More HO and higher expression levels of PR genes were observed in the overexpressing plants than in the control plants, while the silencing plants exhibited less HO and lower expression levels of PR genes compared to the control plants. Moreover, phytohormone treatment and the phytohormone signaling related gene expression analysis showed that panicle blast resistance mediated by the three OXO genes was associated with the activation of JA and ABA signaling pathways but suppression of SA signaling pathway.

Conclusion: OsOXO2, OsOXO3 and OsOXO4 positively regulate panicle blast resistance in rice. The OXO genes could modulate the accumulation of HO and expression levels of PR gene in plants. Moreover, the OXO genes mediated panicle blast resistance could be regulated by ABA, SA and JA, and may be associated with the activation of JA and ABA signaling pathways but suppression of the SA signaling pathway.
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http://dx.doi.org/10.1186/s12284-021-00494-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179873PMC
June 2021
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