Publications by authors named "Yi Guan"

316 Publications

Clinical decision-making framework against over-testing based on modeling implicit evaluation criteria.

J Biomed Inform 2021 May 24;119:103823. Epub 2021 May 24.

Unisound AI Technology Co., Ltd, Beijing 100083, China.

Different statistical methods include various subjective criteria that can prevent over-testing. However, no unified framework that defines generalized objective criteria for various diseases is available to determine the appropriateness of diagnostic tests recommended by doctors. We present the clinical decision-making framework against over-testing based on modeling the implicit evaluation criteria (CDFO-MIEC). The CDFO-MIEC quantifies the subjective evaluation process using statistics-based methods to identify over-testing. Furthermore, it determines the test's appropriateness with extracted entities obtained via named entity recognition and entity alignment. More specifically, implicit evaluation criteria are defined-namely, the correlation among the diagnostic tests, symptoms, and diseases, confirmation function, and exclusion function. Additionally, four evaluation strategies are implemented by applying statistical methods, including the multi-label k-nearest neighbor and the conditional probability algorithms, to model the implicit evaluation criteria. Finally, they are combined into a classification and regression tree to make the final decision. The CDFO-MIEC also provides interpretability by decision conditions for supporting each clinical decision of over-testing. We tested the CDFO-MIEC on 2,860 clinical texts obtained from a single respiratory medicine department in China with the appropriate confirmation by physicians. The dataset was supplemented with random inappropriate tests. The proposed framework excelled against the best competing text classification methods with a Mean_F of 0.9167. This determined whether the appropriate and inappropriate tests were properly classified. The four evaluation strategies captured the features effectively, and they were imperative. Therefore, the proposed CDFO-MIEC is feasible because it exhibits high performance and can prevent over-testing.
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http://dx.doi.org/10.1016/j.jbi.2021.103823DOI Listing
May 2021

A SCID mouse-human lung xenograft model of SARS-CoV-2 infection.

Theranostics 2021 3;11(13):6607-6615. Epub 2021 May 3.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection . Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.
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http://dx.doi.org/10.7150/thno.58321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120224PMC
May 2021

Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma determine response to SLC7A11 inhibition.

Cancer Res 2021 May 12. Epub 2021 May 12.

Personalised Cancer Therapeutics, Cancer Division, The Kinghorn Cancer Centre, The Garvan Institute of Medical Research.

Cancer-Associated Fibroblasts (CAF) are major contributors to pancreatic ductal adenocarcinoma (PDAC) progression through pro-tumor signaling and the generation of fibrosis that creates a physical barrier to drugs. CAF inhibition is thus an ideal component of any therapeutic approach for PDAC. SLC7A11, a cystine transporter, has been identified as a potential therapeutic target in PDAC cells. However, the role of SLC7A11 in PDAC tumor stroma and its prognostic significance has not been evaluated. Here we show that high expression of SLC7A11 in human PDAC tumor stroma, but not tumor cells, is independently prognostic of poor overall survival. Orthogonal approaches showed that PDAC-derived CAFs were dependent on SLC7A11 for cystine uptake and glutathione synthesis. SLC7A11 inhibition significantly decreased CAF proliferation, reduced their resistance to oxidative stress, and inhibited their ability to remodel collagen and support PDAC cell growth. Specific ablation of SLC7A11 from the tumor compartment of transgenic mice did not affect PDAC growth, suggesting the stroma can substantially influence PDAC response to SLC7A11 inhibition. In an orthotopic PDAC mouse model utilizing human PDAC cells and CAFs, stable knockdown of SLC7A11 was required in both cell types to reduce tumor growth, metastatic spread, and intratumoral fibrosis, demonstrating the importance of targeting SLC7A11 in both compartments. Finally, treatment with a nanoparticle SLC7A11-silencing drug developed by our laboratory reduced PDAC tumor growth, metastasis, CAF activation, and fibrosis in orthotopic PDAC tumors. Overall, these findings identify an important role of SLC7A11 in PDAC-derived CAFs in supporting tumor growth.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2496DOI Listing
May 2021

Alignment free sequence comparison methods and reservoir host prediction.

Bioinformatics 2021 May 8. Epub 2021 May 8.

State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Rd., Pok Fu Lam, Hong Kong.

Motivation: The emergence and subsequent pandemic of the SARS-CoV-2 virus raised urgent questions about its origin and, particularly, its reservoir host. These types of questions are long-standing problems in the management of emerging infectious diseases and are linked to virus discovery programs and the prediction of viruses that are likely to become zoonotic. Conventional means to identify reservoir hosts have relied on surveillance, experimental studies and phylogenetics. More recently, machine learning approaches have been applied to generate tools to swiftly predict reservoir hosts from sequence data.

Results: Here, we extend a recent work that combined sequence alignment and a mixture of alignment-free approaches using a gradient boosting machines (GBMs) machine learning model, which integrates genomic traits (GT) and phylogenetic neighbourhood (PN) signatures to predict reservoir hosts. We add a more uniform approach by applying Machine Learning with Digital Signal Processing (MLDSP)-based structural patterns (M-SP). The extended model was applied to an existing virus/reservoir host dataset and to the SARS-CoV-2 and related viruses and generated an improvement in prediction accuracy.

Availability And Implementation: The source code used in this work is freely available at https://github.com/bill1167/hostgbms.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135978PMC
May 2021

First Report of Anthracnose of American Ginseng caused by in Northeast China.

Plant Dis 2021 May 4. Epub 2021 May 4.

Chinese Academy of Agricultural Sciences, 12661, Institute of Special Wild Economic Animal and Plant Science, Chinese Academy of Agricultural Sciences, Juye Street No. 4899, Changchun, Jilin, China, 130112.

American ginseng () is a medicinal plant that is commercially cultivated in China. Anthracnose is a devastating disease of American ginseng, with annual production losses exceeding 20%. In July 2019, anthracnose of American ginseng was observed on 3-year-old plants in Fusong County, Jilin Province, China, the most important region of American ginseng. Round or irregular-shaped, brown, sunken and necrotic lesions (5 to 11 mm in diameter), occasionally with a concentric ring or surrounded by brown halos, were detected on leaves (Fig. 1). Multiple lesions gradually coalesced, eventually causing yellowing and wilting. More than 36% of plants in a 30-ha field were infected. Symptomatic leaves (n=16) were collected and the diseased tissue was cut into small pieces, immersed in 1% NaOCl for 2 min, rinsed three times with sterile water, and placed on acidified potato dextrose agar (PDA) in Petri dishes. After incubation in darkness at 25°C for 4 days, 15 suspected single-spore isolates purified in water agar were obtained. The isolate XTJ2 was randomly selected for identification. On PDA, colonies were white to gray, occasionally mixed with gray-black strips, and the reverse was similar to the surface. Colonies on nutrient-poor agar (SNA) were flat, thin, floccose, with an entire margin, whitish to pale gray with the same colors on the reverse. The conidia were hyaline, smooth-walled, straight with a rounded base and apex, ranging from 11.1 to 21.2 × 4.0 to 5.5 μm (n=100), with length/width =3.5. Conidia were initially aseptate, but became septate with age. Setae were dark brown with a slightly acute tip, 2 to 3-septa, and 31.5 to 81.6 μm long. Appressoria were rarely observed, brown, smooth-walled, oval, bullet-shaped or irregular. Chlamydospores were not observed. The isolate was initially identified as sp. (Damm et al. 2019). Initial BLAST searches of XTJ2 sequences of the rDNA internal transcribed spacer region (GenBank accession no. MW048745), a partial glyceraldehyde-3-phosphate dehydrogenase (MW053381), chitin synthase 1 (MW053382), histone H3 (MW053383), actin (MW053384) and beta-tubulin (MW053385) in GenBank showed that the sequences were respectively 100% similar to Colletotrichum sojae sequences: NR_158358, MG600810, MG600860, MG600899, MG600954 and MG601016 (Carbone and Kohn 1999; Crous et al. 2004;Guerber et al. 2003). The identity of XTJ2 was confirmed by constructing a phylogenetic tree combining all loci, which grouped the isolate and the type strain of into one clade (Fig. 2). The sequences of all isolates were genetically identical to the XTJ2 sequences. For pathogenicity tests, 15 healthy 3-year-old plants grown in five pots were spray-inoculated with the XTJ2 conidial suspension (1×105 spores/mL), and the same number of plants were sprayed with water as the control. This experiment was repeated twice. Plants were kept in a greenhouse (28°C, natural light, and 85% relative humidity) under clear plastic bags. After 10 days, inoculated leaves exhibited symptoms that were similar to those observed in the field, whereas the controls were symptomless. The same fungus was recovered and sequenced, and its identity was confirmed by a phylogenetic analysis. This is the first report of causing anthracnose of American ginseng in China, being a potential threat to the production of this culture. More studies on the epidemiology of this disease are needed to improve disease management.
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http://dx.doi.org/10.1094/PDIS-11-20-2440-PDNDOI Listing
May 2021

RB/E2F1 as a master regulator of cancer cell metabolism in advanced disease.

Cancer Discov 2021 Apr 20. Epub 2021 Apr 20.

Depts of Cancer Biology, Urology, Medical Oncology, and Radiation Oncology, Sidney Kimmel Cancer Center at Jefferson Health

Loss of the retinoblastoma (RB) tumor suppressor protein is a critical step in reprogramming biological networks that drive cancer progression, although mechanistic insight has been largely limited to the impact of RB loss on cell cycle regulation. Here, isogenic modeling of RB loss identified disease stage-specific rewiring of E2F1 function, providing the first-in-field mapping of the E2F1 cistrome and transcriptome after RB loss across disease progression. Biochemical and functional assessment using both in vitro and in vivo models identified an unexpected, prominent role for E2F1 in regulation of redox metabolism after RB loss, driving an increase in the synthesis of the antioxidant, glutathione, specific to advanced disease. These E2F1-dependent events resulted in protection from reactive oxygen species (ROS) in response to therapeutic intervention. On balance, these findings reveal novel pathways through which RB loss promotes cancer progression and highlight potentially new nodes of intervention for treating RB-deficient cancers.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1114DOI Listing
April 2021

Dsk2 involves in conidiation, multi-stress tolerance and thermal adaptation in Beauveria bassiana.

Environ Microbiol Rep 2021 Jun 18;13(3):384-393. Epub 2021 Apr 18.

Key Laboratory for Humid Subtropical Eco-Geographical Processes of the Ministry of Education, School of Geographical Sciences, Fujian Normal University, Fuzhou, 350007, China.

Dsk2 is a nuclear-enriched ubiquitin-like polyubiquitin-binding protein that regulates protein degradation in yeast but has not been explored yet in filamentous fungi, such as Beauveria bassiana. Here, we report Beauveria bassiana Dsk2 located both in the nucleus and in cytoplasm of hyphal cells. Deletion of Dsk2 resulted in mild growth defect on scant media with various carbon/nitrogen sources and dramatic attenuation in conidiation capability at optimal condition. Compared to the wild-type, ΔDsk2 strains are much more sensitive to high osmotic and oxidative pressure during vegetative growth. Meanwhile, the mutant strains showed an increased chemical tolerance to Congo red and calcofluor white, two cell wall perturbing agents. The transcriptional changes of genes involved in central development, superoxide dismutase and chitin synthesis pathway indicate that Dsk2 acts as a multi-functional regulator in adapting to environmental changes. Importantly, Dsk2 negatively regulated the ability of thermal resistance in B. bassiana, which makes it a potential target gene for constructing engineering anti-thermal strains in the circumstance of global warming. Altogether, our finding highlights novel roles of Dsk2 involved in the asexual cycle, multi-stress tolerance and pest control potential of B. bassiana.
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http://dx.doi.org/10.1111/1758-2229.12946DOI Listing
June 2021

Kennedy F Shortridge PhD (April 6, 1941 to November 8, 2020): Obituary.

Influenza Other Respir Viruses 2021 May;15(3):323-325

School of Public Health, The University of Hong Kong, Hong Kong, China.

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http://dx.doi.org/10.1111/irv.12849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051729PMC
May 2021

Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster.

Signal Transduct Target Ther 2021 03 31;6(1):136. Epub 2021 Mar 31.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, P. R. China.

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness. To experimentally demonstrate the epidemiological results, we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2. Remarkably, high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss, weakness, piloerection, hunched back and abdominal respiration, as well as severe pneumonia, pulmonary edema, consolidation, and fibrosis. In contrast with the males, the female hamsters showed much lower shedding viral titers, moderate symptoms, and relatively mild lung pathogenesis. The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.
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http://dx.doi.org/10.1038/s41392-021-00552-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009924PMC
March 2021

Inhibition of guanosine monophosphate synthetase (GMPS) blocks glutamine metabolism and prostate cancer growth.

J Pathol 2021 Jun 21;254(2):135-146. Epub 2021 Apr 21.

Translational Cancer Metabolism Laboratory, School of Medical Sciences and Prince of Wales Clinical School, UNSW Sydney, Sydney, Australia.

Glutamine is a critical nutrient in cancer; however, its contribution to purine metabolism in prostate cancer has not previously been determined. Guanosine monophosphate synthetase (GMPS) acts in the de novo purine biosynthesis pathway, utilizing a glutamine amide to synthesize the guanine nucleotide. This study demonstrates that GMPS mRNA expression correlates with Gleason score in prostate cancer samples, while high GMPS expression was associated with decreased rates of overall and disease/progression-free survival. Pharmacological inhibition or knockdown of GMPS significantly decreased cell growth in both LNCaP and PC-3 prostate cancer cells. We utilized [ N-(amide)]glutamine and [U- C ]glutamine metabolomics to dissect the pathways involved and despite similar growth inhibition by GMPS knockdown, we show unique metabolic effects across each cell line. Using a PC-3 xenograft mouse model, tumor growth was also significantly decreased after GMPS knockdown, highlighting the importance of glutamine metabolism and providing support for GMPS as a therapeutic target in prostate cancer. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5665DOI Listing
June 2021

Early Changes in Serologic Markers in Workers Exposed to Indium Compounds.

Biomed Environ Sci 2021 Mar;34(3):222-226

School of Public Health, North China University of Science and Technology, Tangshan 063000, Hebei, China;Xinxiang Medical University, Xinxiang 453003, Henan, China.

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http://dx.doi.org/10.3967/bes2021.027DOI Listing
March 2021

Diabetes mellitus is a risk factor of acute kidney injury in liver transplantation patients.

Hepatobiliary Pancreat Dis Int 2021 Mar 9. Epub 2021 Mar 9.

Division of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address:

Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury (AKI). Liver transplantation (LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear.

Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate (eGFR), the model for end-stage liver disease (MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI.

Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients (35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of eGFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes.

Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of eGFR within the first year after surgery.
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http://dx.doi.org/10.1016/j.hbpd.2021.02.006DOI Listing
March 2021

Analyses of transcriptomics and metabolomics reveal pathway of vacuolar Sur7 contributed to biocontrol potential of entomopathogenic Beauveria bassiana.

J Invertebr Pathol 2021 May 6;181:107564. Epub 2021 Mar 6.

Fujian Key Laboratory of Marine Enzyme Engineering, College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350116, China.

Beauveria bassiana is a critical entomopathogenic fungus for pest biocontrol, whose efficiency depends on fungal development and stress resistance. Unlike its revealed location in plasma membrane patches in other organisms, B. bassiana Sur7 specifically localized in vacuoles. This vacuolar Sur7 was previously demonstrated to affect stress tolerance, hyphal development and virulence. There, however, remain more mechanistic details to be explored. In this study, transcriptomics and metabolomics were applied to investigate the mechanism of vacuolar Sur7. Analyses of transcriptomics and metabolomics displayed many differentially expressed genes and abundant metabolites in response to Sur7 loss, respectively. Together with genes associated with vacuolar biofunction (including transportation and hydrolysis), the altered metabolites contributed to cell wall construction and stress resistance. Particularly, an N-acetylglucosamine-associated Brg1/Nrg1 pathway was enriched and partially affected by Sur7. Absence of Sur7 changed the expression level of Brg1/Nrg1 pathway-related transcript factors, which interfered with downstream phenotype of sporulation. In addition, Sur7 was involved in the accumulation of sphingoid bases, which may affect sphingolipid-related signaling pathway. Although experimental evidence is further required, our studies provide a preliminary framework for future exploring the regulatory mechanism of Sur7, and give a new version of metabolic agency connecting Sur7 and downstream signaling pathway.
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http://dx.doi.org/10.1016/j.jip.2021.107564DOI Listing
May 2021

Ubr1-mediated ubiquitylation orchestrates asexual development, polar growth, and virulence-related cellular events in Beauveria bassiana.

Appl Microbiol Biotechnol 2021 Apr 8;105(7):2747-2758. Epub 2021 Mar 8.

Institute of Microbiology, College of Life Sciences, Zhejiang University, Zhejiang, 310058, Hangzhou, China.

The E3 ubiquitin ligase Ubr1 is a core player in yeast ubiquitylation and protein quality control required for cellular events including proteasomal degradation and gene activity but has been rarely explored in filamentous fungi. We show here an essentiality of orthologous Ubr1-mediated ubiquitylation for the activation of central developmental pathway (CPD) and the CPD-controlled cellular events in Beauveria bassiana, a filamentous fungal insect pathogen that undergoes an asexual cycle in vitro or in vivo. As a result of ubr1 disruption, intracellular free ubiquitin accumulation increased by 1.4-fold, indicating an impaired ability for the disruptant to transfer ubiquitin to target proteins. Consequently, the disruptant was compromised in polar growth featured with curved or hook-like germ tubes and abnormally branched hyphae, leading to impeded propagation of aberrant hyphal bodies in infected insect hemocoel and attenuated virulence. In the mutant, sharply repressed expression of three CDP activator genes (brlA, abaA, and wetA) correlated well with severe defects in aerial conidiation and submerged blastospore (hyphal body) production in insect hemolymph or a mimicking medium. Moreover, the disruptant was sensitive to cell wall perturbation or lysing and showed increased catalase activity and resistance to hydrogen peroxide despite null response to high osmolarity or heat shock. Most of the examined genes involved in polar growth and cell wall integrity were down-regulated in the disruptant. These findings uncover that the Ubr1-mediated ubiquitylation orchestrates polar growth and the CDP-regulated asexual cycle in vitro and in vivo in B. bassiana. KEY POINTS: • Ubr1 is an E3 ubiquitin ligase essential for ubiquitylation in Beauveria bassiana. • Ubr1-mediated ubiquitylation is required for activation of central development pathway. • Ubr1 orchestrates polar growth and asexual cycle in vitro and in vivo.
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http://dx.doi.org/10.1007/s00253-021-11222-0DOI Listing
April 2021

The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis.

Sci Adv 2021 Feb 24;7(9). Epub 2021 Feb 24.

Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35249-7331, USA.

Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage carcinomas of various organs. Mass spectrometry analysis revealed that SIRT2 interacts with and deacetylates the structural maintenance of chromosomes protein 1 (SMC1A), which then promotes SMC1A phosphorylation to properly drive mitosis. We have further demonstrated that inhibition of SIRT2 activity or continuously increasing SMC1A-K579 acetylation causes abnormal chromosome segregation, which, in turn, induces mitotic catastrophe in cancer cells and enhances their vulnerability to chemotherapeutic agents. These findings suggest that regulation of the SIRT2-SMC1A axis through deacetylation-phosphorylation permits escape from mitotic catastrophe, thus allowing early precursor lesions to overcome oncogenic stress.
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http://dx.doi.org/10.1126/sciadv.abe5518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904255PMC
February 2021

Biomonitorization of concentrations of 28 elements in serum and urine among workers exposed to indium compounds.

PLoS One 2021 22;16(2):e0246943. Epub 2021 Feb 22.

School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China.

Many studies have documented the abnormal concentrations of metals/metalloids in serum or urine of occupational workers, but no works systematically analysed the concentrations of elements in serum or urine of indium-exposed workers. This study was aimed to assess 28 elements in serum and urine from 57 individuals with occupational exposure to indium and its compounds. Control subjects were 63 workers without metal exposure. We collected information on occupation and lifestyle habits by questionnaire. Biological samples were collected to quantify elements by inductive coupled plasma-mass spectrometer. Air in the breathing zones was drawn at flow rates of 1.5-3 L/min for a sampling period of 6 to 8 h, using a Model BFC-35 pump. The average ambient indium level was 0.078 mg/m3. Serum/urine Indium levels were significantly higher in indium-exposed workers than in controls (P < 0.01). Moreover, serum/urine indium concentrations in the group with 6-14 years and ≥15 years of employment were significantly higher than those with ≤5 employment years(P < 0.05). Ten of the other 27 elements/metals measured were higher in serum/urine in indium-exposed workers compared to the controls (aluminum, beryllium, cadmium, cesium, chromium, lithium, manganese, magnesium, molybdenum and vanadium). Zinc levels in serum/urine were significantly decreased in the indium-exposed workers. Additionally, other elements/metals were higher in one specimen (serum or urine) but lower in the other (Selenium was lower in serum but higher in urine in the indium-exposed workers compared with the controls; likewise Thallium and Rubidium were higher in serum but lower in urine). Linear regression analyses, revealed significant correlations between serum and urine for indium, aluminum, arsenic, barium, cadmium, cesium, cobalt, selenium, silver, and zinc (P < 0.05). These data suggest that occupational exposure to indium and its compounds may disturb the homeostasis of trace elements in systemic circulation, indium concentrations in serum or urine appear reflective of workers' exposure to ambient indium and their years of working, respectively. The serum/urine levels of essential metals are modified by exposure to indium in occupationally exposed workers. Further studies including larger sample size and more kinds of biological sample are needed to validate our findings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246943PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899351PMC
February 2021

ZIF-derived "senbei"-like CoS/CeO/Co heterostructural nitrogen-doped carbon nanosheets as bifunctional oxygen electrocatalysts for Zn-air batteries.

Nanoscale 2021 Feb;13(5):3227-3236

College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China.

The rational design and construction of the efficient and robust non-noble metal bifunctional oxygen electrocatalysts is of critical significance due to the attention given to reversible metal-air batteries. In this paper, we report novel two-dimensional "senbei"-like Co9S8/CeO2/Co-NC nitrogen-doped carbon nanosheets (Co9S8/CeO2/Co-NC) derived from a unique 2D Co/Ce bimetallic ZIF. The phase transition from 3D spherical Co-ZIF to 2D Co/Ce-ZIF was achieved through the introduction of Ce ions. Profiting from the successful construction of the unique Co9S8/CeO2 heterostructure and the synergetic effect of two components, the as-prepared Co9S8/CeO2/Co-NC exhibited excellent electro-performance in both the oxygen evolution reaction (Ej=10 = 1.60 V) and oxygen reduction reaction (E1/2 = 0.875 V). Furthermore, when used as a bifunctional air electrode for Zn-air batteries, Co9S8/CeO2/Co-NC reached a high peak power density of ≈164.24 mW cm-2 at a high current density of ≈351 mA cm-2 and displayed an outstanding cycling stability of more than 668 h at 5 mA cm-2. This research provides new guidelines for preparing hybrid materials from cobalt-based sulfide species and CeO2 for electrocatalysis and energy storage or other fields.
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http://dx.doi.org/10.1039/d0nr07892aDOI Listing
February 2021

Transcriptomic analysis of Sur7-mediated response of Beauveria bassiana to different nutritional conditions.

FEMS Microbiol Lett 2021 Feb;368(3)

Fujian Key Laboratory of Marine Enzyme Engineering, College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian, 350116, China.

Integrity of the cell wall is requisite for fungal growth and function. Sur7 governs cell wall composition, and affects conidial sporulation and germination in Beauveria bassiana, a filamentous entomopathogenic fungus. The role of Sur7 in fungal growth on various nutrients remains unclear. We have previously reported that Sur7 deletion results in the attenuation of B. bassiana growth on supplemented Sabouraud dextrose agar (SDAY) and minimal Czapek-Dox agar (CDA) compared to wild type (WT). Here, we used transcriptomic analysis to compare WT and Sur7 mutant (ΔSur7) responses to CDA and SDAY. Growth on CDA, compared with that on SDAY, affected the expression of more genes in the WT than in the mutant. Differentially expressed genes were enriched for transportation process terms in the ΔSur7 mutant and metabolic process terms in the WT. Different processes were repressed in the ΔSur7 (metabolic process) and WT (ribosome synthesis) cells. Despite the shared enrichment of nitrogen metabolism genes, differentially expressed genes were enriched in distinct saccharide-energy metabolism terms in each strain. We conclude that Sur7 ensures the growth of B. bassiana in a minimal medium by influencing the expression of genes involved in the consumption of sucrose via specific energy metabolism pathways.
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http://dx.doi.org/10.1093/femsle/fnab003DOI Listing
February 2021

GDF15 promotes glioma stem cell-like phenotype via regulation of ERK1/2-c-Fos-LIF signaling.

Cell Death Discov 2021 Jan 11;7(1). Epub 2021 Jan 11.

Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β family, is associated with tumor progression, metastasis, and cell apoptosis. However, controversy persists regarding the role of GDF15 in different tumor types, and its function in glioma stem cells (GSCs) remains unknown. Here, we report that GDF15 promotes the GSC-like phenotype in GSC-like cells (GSCLCs) through the activation of leukemia inhibitor factor (LIF)-STAT3 signaling. Mechanistically, GDF15 was found to upregulate expression of the transcription factor c-Fos, which binds to the LIF promoter, leading to enhanced transcription of LIF in GSCLCs. Furthermore, GDF15 may activate the ERK1/2 signaling pathway in GSCLCs, and the upregulation of LIF expression and the GSC-like phenotype was dependent on ERK1/2 signaling. In addition, the small immunomodulator imiquimod induced GDF15 expression, which in turn activated the LIF-STAT3 pathway and subsequently promoted the GSC-like phenotype in GSCLCs. Thus, our results demonstrate that GDF15 can act as a proliferative and pro-stemness factor for GSCs, and therefore, it may represent a potential therapeutic target in glioma treatment.
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http://dx.doi.org/10.1038/s41420-020-00395-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801449PMC
January 2021

Multi-Locus Phylogeny and Taxonomy of the Fungal Complex Associated With Rusty Root Rot of in China.

Front Microbiol 2020 16;11:618942. Epub 2020 Dec 16.

Engineering Research Center, Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China.

Panax rusty root rot caused by the species complex is a devastating disease, and it is one of the main factors contributing to the difficulty in continual cropping. Rusty root rot occurs in all ginseng fields, but little is known about the taxonomy of the fungal pathogen complex, especially and -like species. Rusty root rot samples were collected from commercial ginseng cultivation areas of China, and the pathogens were isolated and purified as single spores. Based on the combination analysis of multiple loci (rDNA-ITS, , , , , LSU, , , and SSU) and morphological characteristics, the pathogens causing ginseng rusty root rot were determined. Fungal isolates were obtained from infected roots in 56 locations within main cultivation areas in China. A total of 766 strains were identified as , -like and species, including (55.0%), (21.7%), (10.9%), (2.0%), (1.3%), (1.3%), (2.0%), (0.5%), sp. (0.5%), and (1.5%), and four novel species, (1.0%), (1.0%), (0.8%) and (0.5%), with a total of 14 species. As the pathogen present in the highest proportion, was the most prevalent and damaging species, unlike the pathogens reported previously. All of the examined strains were proven to cause ginseng rusty root rot. Our results indicate that the taxonomy of the fungal complex associated with ginseng rusty root rot includes , -like genera (, , and ) and .
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http://dx.doi.org/10.3389/fmicb.2020.618942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772391PMC
December 2020

Leaf Spot Caused by on Siberian ginseng in China.

Plant Dis 2020 Dec 29. Epub 2020 Dec 29.

Chinese Acadamy of Agricultural Science, Institute of Special Wild Economic Animal and Plant Science, 4899, Juye, Changchun, Jilin, China, 130112;

Siberian ginseng ( (Rupr. & Maxim.) S. Y. Hu, Araliaceae), is a perennial medicinal plant that is widely cultivated in China. Leaf spot was observed in 2- and 3-year-old Siberian ginseng in Zuojia County (126°05'23.2″E, 44°03'09.5″N), northeast China, in August 2019. Polygonal or irregular black spots ranging from 2 to 9 mm in diameter were found on infected leaves, and each leaf had dozens of spots. The green color around the lesions gradually faded. As the disease progressed, the spots withered and multiple lesions merged into large disease spots, causing leaf wilting (Fig. 1). More than 38% of plants in one 25-ha field were infected in 2019. Fifteen diseased leaves were collected from those plants and cut into 5-mm pieces. The pieces were surface-disinfected by immersion in 1% NaOCl for 2 min and then rinsing twice with sterile distilled water. The leaf pieces were placed on acidified potato dextrose agar (PDA, pH 4.7) in Petri plates, and incubated in the dark at 25°C. Nineteen isolates were obtained and all were purified from a single spore in water agar. Isolate CWJ7 was randomly selected for identification and pathogenicity testing. The colonies on PDA were olivaceous gray to olivaceous black, velvet, with dense hyphae and a scalloped or irregular margin. The reverse side was gray-black and surrounded by tawny halos. The conidia were aseptate and variable in shape and dimension: piriform, columnar, drop-shaped, dumbbell-shaped or oval, measuring 4.90 (7.03) 9.50 × 2.10 (2.78) 3.40 µm (n=100), and chlamydospores were absent. Black pycnidia (132.2-241.5 µm in diameter) appeared after 7 days. The pathogen was initially identified as or -like (Boerema et al. 2004). Further confirmation was also determined by sequencing the nuclear ribosomal internal transcribed spacer region (GenBank accession no. MT912950), 28S ribosomal RNA gene (MT912968), and genes encoding β-tubulin (MT920618), the second largest subunit of RNA polymerase II (MT920619) and translation elongation factor (MT946526) (de Hoog and Gerrits van den Ende 1998; Rehner & Samuels 1994; Liu et al. 1999; Vilgalys & Hester 1990), and Blast searches showed 90%-100% homology with GU237754, GU237938, KT389780, KT389575, and KY484705, respectively. In a phylogenetic analysis combining all loci, CWJ7 and the type strains of clustered in one group (Fig. 2). Based on its morphological characteristics and phylogenetic analysis, isolate CWJ7 was identified as as revised in 2019 (Jayawardena et al. 2019). Healthy 2-year-old plants were used for pathogenicity testing. The leaves of nine potted plants (one plant per pot, three plants per replicate) were spray-inoculated with a suspension of conidia (1×10 spores/ml) from colonies on PDA for 7 days and cultured for 48 h under continuous black light. Nine plants were sprayed with sterile water as the control. This experiment was repeated twice. All plants were cultured in a greenhouse (25°C, 12-h photoperiod, 78% relative humidity). Clear plastic bags were used to maintain high humidity. After 7 days, the inoculated plants showed lesions on the leaves, similar to those observed in the field. The control plants remained symptomless. The pathogen was reisolated and identified by sequencing. This is the first report of causing Siberian ginseng leaf spot, and a new record of this species in China. This disease poses a threat to production and management strategies should be developed.
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http://dx.doi.org/10.1094/PDIS-09-20-2076-PDNDOI Listing
December 2020

Occurrence of Causing Root Rot on in northeastern China.

Plant Dis 2020 Dec 1. Epub 2020 Dec 1.

Chinese Academy of Agricultural Sciences, 12661, Institute of Special Wild Economic Animal and Plant Science, Chinese Academy of Agricultural Sciences, Changchun, Jilin, China;

Bunge (Fabaceae) is a perennial medicinal herb widely cultivated in China. In June 2018, root rot was observed on two-year-old plants in Chaoyangshan town (northeastern China). In a 40-ha field, over 40% of the plants exhibited root rot and the infected area ranged from 10 to 70% of the roots. The roots first exhibited circular or irregular brown, sunken and necrotic lesions, and finally multiple lesions coalesced. The infected root surface was destroyed, showing rusty and dry rot (Fig. 1). Symptoms were concentrated in the main roots (Carlucci et al. 2017). The aboveground parts of infected plants did not initially show symptoms but gradually wilted; 7.6% of the plants died when root decay became severe. Infected roots were not used for processing and were not marketable. Ten infected roots were collected from May to October 2018 from the above location. The diseased root tissue was cut into 25 mm3 pieces, immersed in 1% NaOCl for 2 minutes, rinsed three times with sterile water and placed on water agar in Petri plates. After 15 days of incubation at 20°C, 11 single-spore isolates were obtained. Isolates HQ1 and HQ2 were randomly selected for morphological and molecular identification. Colonies grown for 10 days produced yellow, cottony to felty aerial mycelium on potato dextrose agar. Conidiophores originating laterally or terminally from the mycelium were solitary to loosely aggregated and unbranched or sparsely branched. Macroconidia predominated and were cylindrical, with a tendency to gradually widen towards the tip; 1- to 3-septate; and 20.2 to 31.0 × 3.0 to 6.7 µm (n=100). Microconidia had mostly 0¬- to 1-septate and 8.6 to 16.7 × 1.9 to 5.1 µm (n=100) (Fig. 1). Chlamydospores were rare, but occasional chlamydospore chains were observed. The isolates were tentatively identified as (Cabral et al. 2012a). Further confirmation of the two isolates was conducted by DNA sequencing of the internal transcribed spacer (ITS, GenBank accession no. MN558983 and MN558984), β-tubulin (, MN561692 and MN561693), histone 3 (, MN561694 and MN561695), and translation elongation factor (, MN561696 and MN561697) genes (Cabral et al. 2012b). These sequences had 99 to 100% match with D. torresensis (JF735362 for ITS, JF735492 for , JF735681 for and JF735870 for TEF). Phylogenetic trees based on analyses of a concatenated alignment of all loci grouped these isolates into the clade (Fig. 2). The same two isolates were tested for pathogenicity. Healthy two-year-old plants were taken from the field, and their roots were disinfected with 75% alcohol for 3 minutes, rinsed with sterile water three times, immersed in a 1×10/ml spore suspension or sterile water (control) for 10 minutes, transferred to a tray filled with sterile sand and placed in a greenhouse (12 h photoperiod, 25°C). Twelve plants grown in three pots were used for each isolate, and the same number of plants were inoculated as a control. This experiment was repeated three times. After one month, inoculated plant roots showed the same symptoms as those observed in the field, while the controls remained symptomless and no pathogen was recovered. The same fungus was reisolated from all the infected plants and confirmed by sequencing all of the above genes. This is the first report of causing root rot in in China. The occurrence of this disease poses a threat, and management strategies need to be developed.
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http://dx.doi.org/10.1094/PDIS-02-20-0278-PDNDOI Listing
December 2020

Neuroimaging Markers for Studying Gulf-War Illness: Single-Subject Level Analytical Method Based on Machine Learning.

Brain Sci 2020 Nov 20;10(11). Epub 2020 Nov 20.

School of Medicine, Boston University, Boston, MA 02118, USA.

Gulf War illness (GWI) refers to the multitude of chronic health symptoms, spanning from fatigue, musculoskeletal pain, and neurological complaints to respiratory, gastrointestinal, and dermatologic symptoms experienced by about 250,000 GW veterans who served in the 1991 Gulf War (GW). Longitudinal studies showed that the severity of these symptoms often remain unchanged even years after the GW, and these veterans with GWI continue to have poorer general health and increased chronic medical conditions than their non-deployed counterparts. For better management and treatment of this condition, there is an urgent need for developing objective biomarkers that can help with simple and accurate diagnosis of GWI. In this study, we applied multiple neuroimaging techniques, including T1-weighted magnetic resonance imaging (T1W-MRI), diffusion tensor imaging (DTI), and novel neurite density imaging (NDI) to perform both a group-level statistical comparison and a single-subject level machine learning (ML) analysis to identify diagnostic imaging features of GWI. Our results supported NDI as the most sensitive in defining GWI characteristics. In particular, our classifier trained with white matter NDI features achieved an accuracy of 90% and F-score of 0.941 for classifying GWI cases from controls after the cross-validation. These results are consistent with our previous study which suggests that NDI measures are sensitive to the microstructural and macrostructural changes in the brain of veterans with GWI, which can be valuable for designing better diagnosis method and treatment efficacy studies.
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http://dx.doi.org/10.3390/brainsci10110884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699718PMC
November 2020

Diabetes is a risk factor for high-dose methotrexate-associated AKI in lymphoma patients.

Ren Fail 2020 Nov;42(1):1111-1117

Division of Nephrology, Huashan Hospital, and Nephrology Research Institute, Fudan University, Shanghai, China.

Purpose: The aim of the study was to investigate the incidence of acute kidney injury (AKI) occurring after high-dose methotrexate (HDMTX) administration and the role of type 2 diabetes (T2D) playing in the occurrence of AKI.

Methods: We assessed associations between T2D along with other confounding factors mainly including baseline estimated glomerular filtration rate (eGFR), methotrexate (MTX) elimination and urine pH, and AKI occurrence. Patients who were diagnosed as primary central nervous system lymphoma with treatment of HDMTX and with eGFR ≥60 mL/min/1.73 m were enrolled in this study.

Results: Of the 507 courses enrolled in this study, 132 courses have T2D. Lower baseline eGFR, delayed MTX elimination, lower urine pH, and higher incidence of AKI were observed in T2D group. Using univariate logistic regression, several confounding factors including baseline eGFR, hypertension, MTX elimination, and urine alkalinization statistically and clinically important were screened out. After adjusting for these factors, T2D remained an independent association with AKI occurrence. AKI outcome had no significant relationship with severe hematological toxicity or hepatotoxicity. AKI was associated with faster eGFR decline after a series of HDMTX treatment courses.

Conclusions: Patients with T2D have a higher sensitivity to AKI when administrated with HDMTX. This conclusion addresses safety concerns for making chemotherapy regimen for this population.
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http://dx.doi.org/10.1080/0886022X.2020.1838926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655081PMC
November 2020

Using serological measures to estimate influenza incidence in the presence of secular trends in exposure and immuno-modulation of antibody response.

Influenza Other Respir Viruses 2021 Mar 27;15(2):235-244. Epub 2020 Oct 27.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Background: Influenza infection is often measured by a fourfold antibody titer increase over an influenza season (ie seroconversion). However, this approach may fail when influenza seasons are less distinct as it does not account for transient effects from recent infections. Here, we present a method to determine seroconversion for non-paired sera, adjusting for changes in individuals' antibody titers to influenza due to the transient impact of recent exposures, varied sampling times, and laboratory processes.

Methods: We applied our method using data for five H3N2 strains collected from 942 individuals, aged 2-90 years, during the first two study visits of the Fluscape cohort study (2009-2012) in Guangzhou, China.

Results: After adjustment, apparent seroconversion rates for non-circulating strains decreased while we observed a 20% increase in seroconversion rates to recently circulating strains. When examining seroconversion to the most recently circulating strain (A/Brisbane/20/2007) in our study, participants aged under 18, and over 64 had the highest seroconversion rates compared to other age groups.

Conclusions: Our results highlight the need for improved methods when using antibody titers as an endpoint in settings where there is no clear influenza "off" season. Methods, like those presented here, that use titers from circulating and non-circulating strains may be key.
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http://dx.doi.org/10.1111/irv.12807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902255PMC
March 2021

Cerebral pleomorphic xanthoastrocytoma mimicking inflammatory granuloma: Two case reports.

Medicine (Baltimore) 2020 Oct;99(41):e22478

Department of Oncological neurosurgery, First Hospital of Jilin University.

Rationale: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial neoplasm of the central nervous system, which is difficult to distinguish from other neoplastic and non-neoplastic entities. Herein, we report 2 cases of PXA that had been misdiagnosed as an inflammatory granuloma.

Patient Concerns: The first case was a 22-year-old man who originally presented with a generalized seizure 7 years previously. Magnetic resonance imaging (MRI) revealed a lesion in the right parietal lobe, leading to a diagnosis of inflammatory granuloma. The second case was a 43-year-old man who presented with repeated generalized seizures. MRI revealed a nodular lesion in the left temporal lobe. The magnetic resonance spectrum showed elevated Cho and NAA peaks and a decreased Cr peak. An inflammatory granuloma was suspected.

Diagnosis: After surgical treatment, histopathological examination revealed PXA.

Interventions: In the first case, after 10 months of anti-inflammatory treatment, the lesion was significantly reduced in size. During the following 7 years, the patient experienced generalized seizures 3 to 4 times annually. To control intractable epilepsy, the lesion was resected. In the second case, conservative treatment provided no benefit, and then the lesion was resected.

Outcomes: In the first case, during a follow-up period of 14 months, the patient was seizure-free with no tumor recurrence. In the second case, after a 6 months of follow-up, the patient remained seizure-free with no tumor recurrence.

Lessons: The preoperative differential diagnosis of PXA is challenging due to the nonspecific symptoms and imaging manifestations. Considering the potential risk of malignant transformation of PXA, early surgery should be highlighted, and gross total resection is associated with a favorable prognosis.
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http://dx.doi.org/10.1097/MD.0000000000022478DOI Listing
October 2020

Bioinformatic analysis reveals hub genes and pathways that promote melanoma metastasis.

BMC Cancer 2020 Sep 7;20(1):863. Epub 2020 Sep 7.

Department of Pathology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Street, Suzhou, 215000, Jiangsu, People's Republic of China.

Background: Melanoma has the highest mortality rate of all skin tumors, and metastases are the major cause of death from it. The molecular mechanism leading to melanoma metastasis is currently unclear.

Methods: With the goal of revealing the underlying mechanism, three data sets with accession numbers GSE8401, GSE46517 and GSE7956 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed gene (DEG) of primary melanoma and metastatic melanoma, three kinds of analyses were performed, namely functional annotation, protein-protein interaction (PPI) network and module construction, and co-expression and drug-gene interaction prediction analysis.

Results: A total of 41 up-regulated genes and 79 down-regulated genes was selected for subsequent analyses. Results of pathway enrichment analysis showed that extracellular matrix organization and proteoglycans in cancer are closely related to melanoma metastasis. In addition, seven pivotal genes were identified from PPI network, including CXCL8, THBS1, COL3A1, TIMP3, KIT, DCN, and IGFBP5, which have all been verified in the TCGA database and clinical specimens, but only CXCL8, THBS1 and KIT had significant differences in expression.

Conclusions: To conclude, CXCL8, THBS1 and KIT may be the hub genes in the metastasis of melanoma and thus may be regarded as therapeutic targets in the future.
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http://dx.doi.org/10.1186/s12885-020-07372-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487637PMC
September 2020

Learning an expandable EMR-based medical knowledge network to enhance clinical diagnosis.

Artif Intell Med 2020 07 3;107:101927. Epub 2020 Jul 3.

School of Management, Harbin Institute of Technology, Harbin 150001, China.

Electronic medical records (EMRs) contain a wealth of knowledge that can be used to assist doctors in making clinical decisions like disease diagnosis. Constructing a medical knowledge network (MKN) to link medical concepts in EMRs is an effective way to manage this knowledge. The quality of the diagnostic result made by MKN-based clinical decision support system depends on the accuracy of medical knowledge and the completeness of the network. However, collecting knowledge is a long-lasting and cumulative process, which means it's hard to construct a complete MKN with limited data. This study was conducted with the objective of developing an expandable EMR-based MKN to enhance capabilities in making an initial clinical diagnosis. A network of symptom-indicate-disease knowledge in 992 Chinese EMRs (CEMRs) was manually constructed as Original-MKN, and an incremental expansion framework was applied to it to obtain an expandable MKN based on new CEMRs. The framework was composed by: (1) integrating external knowledge extracted from the medical information websites and (2) mining potential knowledge with new EMRs. The framework also adopts a diagnosis-driven learning method to estimate the effectiveness of each knowledge in clinical practice. Experimental results indicate that our expanded MKN achieves a precision of 0.837 for a recall of 0.719 in clinical diagnosis, which outperforms Original-MKN and four classical machine learning methods. Furthermore, both external medical knowledge and potential medical knowledge benefit MKN expansion and disease diagnosis. The proposed incremental expansion framework sustains the MKN learning new knowledge.
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http://dx.doi.org/10.1016/j.artmed.2020.101927DOI Listing
July 2020

Associations between polymorphisms in gene and the risk of osteoporosis: a meta-analysis.

Arch Physiol Biochem 2020 Aug 6:1-8. Epub 2020 Aug 6.

Department of Diabetes, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China.

The authors conducted this meta-analysis to robustly estimate relationships between polymorphisms in gene and the risk of osteoporosis by integrating the results of previous works. Medline, Embase, Wanfang, VIP and CNKI were searched thoroughly for eligible studies, and 73 genetic association studies were finally included in this meta-analysis. We noticed that ApaI rs7975232, BsmI rs1544410 and TaqI rs731236 polymorphisms were significantly associated with the risk of osteoporosis in Caucasians. Moreover, BsmI rs1544410 and FokI rs10735810 polymorphisms were significantly associated with the risk of osteoporosis in Asians. In conclusion, this meta-analysis demonstrates that ApaI rs7975232, BsmI rs1544410 and TaqI rs731236 polymorphisms may influence the risk of osteoporosis in Caucasians, while BsmI rs1544410 and TaqI rs731236 polymorphisms may influence the risk of osteoporosis in Asians.
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http://dx.doi.org/10.1080/13813455.2020.1787457DOI Listing
August 2020

Vulnerability of global coral reef habitat suitability to ocean warming, acidification and eutrophication.

Glob Chang Biol 2020 Oct 9;26(10):5646-5660. Epub 2020 Aug 9.

Systems Ecology Group, Leibniz Centre for Tropical Marine Research, Bremen, Germany.

Coral reefs are threatened by global and local stressors. Yet, reefs appear to respond differently to different environmental stressors. Using a global dataset of coral reef occurrence as a proxy for the long-term adaptation of corals to environmental conditions in combination with global environmental data, we show here how global (warming: sea surface temperature; acidification: aragonite saturation state, Ω ) and local (eutrophication: nitrate concentration, and phosphate concentration) stressors influence coral reef habitat suitability. We analyse the relative distance of coral communities to their regional environmental optima. In addition, we calculate the expected change of coral reef habitat suitability across the tropics in relation to an increase of 0.1°C in temperature, an increase of 0.02 μmol/L in nitrate, an increase of 0.01 μmol/L in phosphate and a decrease of 0.04 in Ω . Our findings reveal that only 6% of the reefs worldwide will be unaffected by local and global stressors and can thus act as temporary refugia. Local stressors, driven by nutrient increase, will affect 22% of the reefs worldwide, whereas global stressors will affect 11% of these reefs. The remaining 61% of the reefs will be simultaneously affected by local and global stressors. Appropriate wastewater treatments can mitigate local eutrophication and could increase areas of temporary refugia to 28%, allowing us to 'buy time', while international agreements are found to abate global stressors.
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http://dx.doi.org/10.1111/gcb.15293DOI Listing
October 2020