Publications by authors named "Lin Fu"

360 Publications

Prediction and analysis of novel key genes ITGAX, LAPTM5, SERPINE1 in clear cell renal cell carcinoma through bioinformatics analysis.

PeerJ 2021 20;9:e11272. Epub 2021 Apr 20.

Institute of Chronic Disease, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China.

Background: Clear Cell Renal Cell Carcinoma (CCRCC) is the most aggressive subtype of Renal Cell Carcinoma (RCC) with high metastasis and recurrence rates. This study aims to find new potential key genes of CCRCC.

Methods: Four gene expression profiles (GSE12606, GSE53000, GSE68417, and GSE66272) were downloaded from the Gene Expression Omnibus (GEO) database. The TCGA KIRC data was downloaded from The Cancer Genome Atlas (TCGA). Using GEO2R, the differentially expressed genes (DEG) in CCRCC tissues and normal samples were analyzed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in DAVID database. A protein-protein interaction (PPI) network was constructed and the hub gene was predicted by STRING and Cytoscape. GEPIA and Kaplan-Meier plotter databases were used for further screening of Key genes. Expression verification and survival analysis of key genes were performed using TCGA database, GEPIA database, and Kaplan-Meier plotter. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of key genes in CCRCC, which is plotted by R software based on TCGA database. UALCAN database was used to analyze the relationship between key genes and clinical pathology in CCRCC and the methylation level of the promoter of key genes in CCRCC.

Results: A total of 289 up-regulated and 449 down-regulated genes were identified based on GSE12606, GSE53000, GSE68417, and GSE66272 profiles in CCRCC. The upregulated DEGs were mainly enriched with protein binding and PI3K-Akt signaling pathway, whereas down-regulated genes were enriched with the integral component of the membrane and metabolic pathways. Next, the top 35 genes were screened out from the PPI network according to Degree, and three new key genes ITGAX, LAPTM5 and SERPINE1 were further screened out through survival and prognosis analysis. Further results showed that the ITGAX, LAPTM5, and SERPINE1 levels in CCRCC tumor tissues were significantly higher than those in normal tissues and were associated with poor prognosis. ROC curve shows that ITGAX, LAPTM5, and SERPINE1 have good diagnostic value with good specificity and sensitivity. The promoter methylation levels of ITGAX, LAPTM5 and SERPINE1 in CCRCC tumor tissues were significantly lower than those in normal tissues. We also found that key genes were associated with clinical pathology in CCRCC.

Conclusion: ITGAX, LAPTM5, and SERPINE1 were identified as novel key candidate genes that could be used as prognostic biomarkers and potential therapeutic targets for CCRCC.
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http://dx.doi.org/10.7717/peerj.11272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063882PMC
April 2021

X-shaped thiadiazole-containing double [7]heterohelicene with strong chiroptical response and π-stacked homochiral assembly.

Chem Commun (Camb) 2021 May 10. Epub 2021 May 10.

College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China.

An X-shaped double [7]heterohelicene 1 bearing four thiadiazole units is synthesized by regioselective cyclodehydrogenation. Enantiopure 1 exhibits excellent chiroptical properties with an impressive absorption dissymmetry factor of up to 0.027, as well as a compact π-stacked homochiral assembly which is unprecedented in the realm of double helicenes.
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http://dx.doi.org/10.1039/d1cc01631hDOI Listing
May 2021

Correlations among Pulmonary DJ-1, VDR and Nrf-2 in patients with Chronic Obstructive Pulmonary Disease: A Case-control Study.

Int J Med Sci 2021 22;18(11):2449-2456. Epub 2021 Apr 22.

Respiratory and critical care medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.

Parkinson protein 7 (PARK7)/DJ-1 (DJ-1) is a redox sensitive molecular and stabilizer of nuclear factor erythroid 2-related factor 2 (Nrf-2). Nrf-2 regulates the downstream antioxidant defense system and exerts a significant function in patients with chronic obstructive pulmonary disease (COPD). Vitamin D receptor (VDR) is the nuclear receptor that regulates the downstream target genes. This study aimed to analyze the associations among pulmonary function, DJ-1, VDR and Nrf-2 in COPD patients. Serum was collected from 180 COPD patients and control subjects. Thirty-five lung tissues were obtained. DJ-1 was measured using ELISA and western blotting. Nrf-2 and VDR were detected by immunohistochemistry. Serum and pulmonary DJ-1 levels were lower in COPD patients than those in control subjects. Pulmonary VDR-positive nuclei were reduced in COPD patients. Nrf-2-positive nuclei were reduced in lung tissues of COPD patients. On the contrary, Nrf-2-related downstream target proteins were elevated in COPD patients. Further correlation analysis indicated that forced expiratory volume in 1 second (FEV1) was positively associated with pulmonary DJ-1, VDR and Nrf-2 in patients with COPD. In addition, there were positive correlations among DJ-1, VDR and Nrf-2 in lung tissues of COPD patients. In conclusion, DJ-1, VDR and Nrf-2 were decreased in COPD patients compared with control subjects. The reduction of DJ-1 and VDR associating with Nrf-2 downregulation may be involved in the process of COPD.
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http://dx.doi.org/10.7150/ijms.58452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100631PMC
April 2021

Tauroursodeoxycholic acid alleviates pulmonary endoplasmic reticulum stress and epithelial-mesenchymal transition in bleomycin-induced lung fibrosis.

BMC Pulm Med 2021 May 5;21(1):149. Epub 2021 May 5.

Second Affiliated Hospital, Anhui Medical University, Hefei, 230032, China.

Background: Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis.

Methods: The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily.

Results: BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA.

Conclusions: These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.
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http://dx.doi.org/10.1186/s12890-021-01514-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097922PMC
May 2021

Changes in circumpapillary retinal vessel density after acute primary angle closure episode via OCT angiography.

Int Ophthalmol 2021 May 5. Epub 2021 May 5.

Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.

Purpose: To investigate the changes and evaluate the diagnosis value of circumpapillary vessel density (VD) in cases of acute primary angle closure (APAC).

Design: Case-control study.

Methods: APAC patients with a history of unilateral acute attack were enrolled. The eyes with acute episode constituted the case group while the contralateral eyes without attack consisted of the control group. Ophthalmic examinations including slit-lamp examination, best-corrected visual acuity, intraocular pressure and visual field were carried out. Retinal nerve fiber layer (RNFL), macular ganglion cell complex (GCC) were measured by spectral-domain optical coherence tomography, while VD was assessed by optical coherence tomography angiography.

Results: The whole en face image vessel density (wiVD), circumpapillary vessel density (cpVD) and inside disk VD for both all vessels and capillary were all significantly lower in the APAC eyes compared to the fellow eyes (P < 0.01 for all). In APAC eyes, the wiVD, inside disk VD and cpVD both for all vessels and capillary were all positively correlated with RNFL and GCC thicknesses but negatively correlated with the mean deviation (MD), pattern standard deviation (PSD) and the duration of acute attack (all P < 0.01). From the ROC curve, the cpVD wiVD, cpVD and wiVD all showed comparable diagnostic ability with RNFL, GCC and MD to differentiate eyes with APAC from the fellow eyes (all P > 0.05). The inside disk VD and VD demonstrated significant lower diagnostic ability than the cpVD wiVD, cpVD and wiVD (all P < 0.001).

Conclusions: In APAC eyes, circumpapillary VD decreased significantly compared with the fellow unaffected eyes. They were significantly correlated with thicknesses of RNFL and GCC, and visual field MD and PSD in the APAC eyes. The patients with longer duration of acute attack were more likely to have lower cpVD. For APAC, the diagnostic ability of wiVD and cpVD was similar with RNFL, GCC and MD and was higher than inside disk VD.
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http://dx.doi.org/10.1007/s10792-021-01793-2DOI Listing
May 2021

The Role of Cation Diffusion Facilitator CDF-1 in Lipid Metabolism in Caenorhabditis elegans.

G3 (Bethesda) 2021 Apr 19. Epub 2021 Apr 19.

Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China.

Zinc is one of the most important trace elements as it plays a vital role in many biological processes. As well, aberrant zinc metabolism has been implicated in lipid-related metabolic diseases. Previously, we showed that zinc antagonizes iron to regulate sterol regulatory element-binding proteins and the stearoyl-CoA desaturase (SREBP-SCD) pathway in lipid metabolism in the model organism Caenorhabditis elegans. In this study we present the identification of another cation diffusion facilitator, CDF-1, which regulates lipid metabolism along with SUR-7 in response to zinc. Inactivation of SBP-1, the only homolog of SREBPs, leads to an increased zinc level but decreased lipid accumulation. However, either the cdf-1(n2527) or sur-7(tm6523) mutation could successfully restore the altered fatty acid profile, fat content, and zinc level of the sbp-1(ep79) mutant. Furthermore, we found that CDF-1/SUR-7 may functionally bypass SBP-1 to directly affect the conversion activity of SCD in the biosynthesis of unsaturated fatty acids and lipid accumulation. Collectively, these results consistently support the link between zinc homeostasis and lipid metabolism via the SREBP-SCD axis by the cation diffusion facilitators CDF-1 and SUR-7.
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http://dx.doi.org/10.1093/g3journal/jkab120DOI Listing
April 2021

Serum 8-iso-PGF2α Predicts the Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Retrospective Cohort Study.

Front Med (Lausanne) 2021 29;8:633442. Epub 2021 Mar 29.

Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Many studies have identified the important role of 8-isoprostane (8-iso-PGF2α) in pulmonary diseases. However, the role of 8-iso-PGF2α in community-acquired pneumonia (CAP) remains unclear. Therefore, the main goal was to investigate the correlations of serum 8-iso-PGF2α with the severity and prognosis in CAP patients through a hospital-based retrospective cohort study. All 220 patients with CAP were enrolled. Demographic information and clinical data were collected. Levels of 8-iso-PGF2α and inflammatory cytokines were detected in serum using ELISA. The levels of 8-iso-PGF2α were gradually increased in parallel with the CAP severity scores. Univariate and multivariate logistic regression analyses revealed a positive association between serum 8-iso-PGF2α and the CAP severity scores. Additionally, serum 8-iso-PGF2α levels were positively correlated with circulating inflammatory cytokines (CRP and TNFα). Serum 8-iso-PGF2α levels were increased in the patients with a longer hospital stay than those with a shorter hospital stay. Additionally, 20 patients died after hospitalization. Dead patients presented a higher serum 8-iso-PGF2α than surviving patients. A subsequent survival analysis revealed that higher serum 8-iso-PGF2α levels positively correlated with the risk of death in patients with CAP. Serum 8-iso-PGF2α levels on admission are positively associated with the severity of CAP patients. Elevated serum 8-iso-PGF2α on admission prolongs hospital stay and increases the risk of death in patients with CAP, indicating that 8-iso-PGF2α may be involved in the progression of CAP and serve as an early serum prognostic biomarker for CAP.
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http://dx.doi.org/10.3389/fmed.2021.633442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044775PMC
March 2021

Reactive oxygen species-evoked endoplasmic reticulum stress mediates 1-nitropyrene-induced epithelial-mesenchymal transition and pulmonary fibrosis.

Environ Pollut 2021 Apr 13;283:117134. Epub 2021 Apr 13.

Department of Toxicology, Anhui Medical University, Hefei, 230032, China. Electronic address:

1-Nitropyrene (1-NP) is one component of atmospheric fine particles. Previous report revealed that acute 1-NP exposure induced respiratory inflammation. This study aimed to investigate whether chronic 1-NP exposure induces pulmonary fibrosis. Male C57BL6/J mice were intratracheally instilled to 1-NP (20 μg/mouse/week) for 6 weeks. Diffuse interstitial inflammation, a-smooth muscle actin (a-SMA)-positive cells, a marker of epithelial-mesenchymal transition (EMT), and an extensive collagen deposition, measured by Masson staining, were observed in 1-NP-exposed mouse lungs. Pulmonary function showed that lung dynamic compliance (Cydn-min) was reduced in 1-NP-exposed mice. Conversely, inspiratory resistance (Ri) and expiratory resistance (Re) were elevated in 1-NP-exposed mice. Mechanistically, cell migration and invasion were accelerated in 1-NP-exposed pulmonary epithelial cells. In addition, E-cadherin, an epithelial marker, was downregulated, and vimentin, a-SMA and N-cadherin, three mesenchymal markers, were upregulated in 1-NP-exposed pulmonary epithelial cells. Although TGF-β wasn't altered, phosphorylated Smad2/3 were enhanced in 1-NP-exposed pulmonary epithelial cells. Moreover, reactive oxygen species (ROS) were increased and endoplasmic reticulum (ER) stress was activated in 1-NP-exposed pulmonary epithelial cells. N-Acetylcysteine (NAC), an antioxidant, attenuated 1-NP-evoked excess ROS, ER stress and EMT in pulmonary epithelial cells. Similarly, pretreatment with NAC alleviated 1-NP-caused pulmonary EMT and lung fibrosis in mice. These results demonstrate that ROS-evoked ER stress contributes, at least partially, to 1-NP-induced EMT and pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.envpol.2021.117134DOI Listing
April 2021

Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns.

Exp Hematol Oncol 2021 Apr 9;10(1):27. Epub 2021 Apr 9.

Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.

Background: The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML).

Methods: We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients.

Results: FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 10/L vs. 24.2 × 10/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3AML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup.

Conclusions: Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.
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http://dx.doi.org/10.1186/s40164-021-00207-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033687PMC
April 2021

The associations of serum S100A9 with the severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study.

BMC Infect Dis 2021 Apr 7;21(1):327. Epub 2021 Apr 7.

Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Furong Road no 678, Hefei, 230601, China.

Background: Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study.

Methods: A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured.

Results: Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients.

Conclusion: Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.
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http://dx.doi.org/10.1186/s12879-021-06020-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028176PMC
April 2021

Brain transcriptomics of nonhuman primates: A review.

Neurosci Lett 2021 05 1;753:135872. Epub 2021 Apr 1.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing, 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, 100191, China. Electronic address:

The brain is one of the most important and intricate organs in our bodies. Interpreting brain function and illustrating the changes and molecular mechanisms during physiological or pathological processes are essential but sometimes difficult to achieve. In addition to histology, ethology and pharmacology, the development of transcriptomics alleviates this condition by enabling high-throughput observation of the brain at various levels of anatomical specificity. Moreover, because human brain samples are scarce, the brains of nonhuman primates are important alternative models. Here in this review, we summarize the applications of transcriptomics in nonhuman primate brain studies, including investigations of brain development, aging, toxic effects and diseases. Overall, as a powerful tool with developmental potential, transcriptomics has been widely utilized in neuroscience.
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http://dx.doi.org/10.1016/j.neulet.2021.135872DOI Listing
May 2021

High expression of CPNE5 and CPNE9 predicts positive prognosis in multiple myeloma.

Cancer Biomark 2021 Mar 26. Epub 2021 Mar 26.

Department of Hematology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.

Background: CPNEs are significant biomarkers which can affect the progression and prognosis of various tumor diseases. However, the prognosis role of CPNEs in multiple myeloma (MM) is still unclear.

Objectives: To investigate the prognosis role of CPNEs in MM.

Methods: Seven hundred and thirty-five samples from two independent data sets were involved to analyze the clinical and molecular characteristics, and prognosis role of the expression of CPNE1-9 in MM.

Results: MM patients with higher expressions of CPNE5 and CPNE9 had longer event-free survival (EFS) and overall survival (OS) compared with CPNE5low and CPNE9low expression groups (EFS: P= 0.0054, 0.0065; OS: P= 0.015, 0.016, respectively). Multivariate regression analysis showed that CPNE5 was an independent favorable predictor for EFS and OS (EFS: P= 0.005; OS: P= 0.006), and CPNE9 was an independent positive indicator for EFS (P= 0.002). Moreover, the survival probability and the cumulative event of EFS and OS in CPNE5highCPNE9high group were significantly longer than other groups.

Conclusions: High expressions of CPNE5 and CPNE9 might be used as positive indicators for MM, and their combination was a better predictor for the survival of MM patients.
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http://dx.doi.org/10.3233/CBM-203108DOI Listing
March 2021

Circulatory cadmium positively correlates with epithelial-mesenchymal transition in patients with chronic obstructive pulmonary disease.

Ecotoxicol Environ Saf 2021 Jun 20;215:112164. Epub 2021 Mar 20.

The Second Affiliated Hospital, Anhui Medical University, Hefei 230032, China. Electronic address:

Environmental cadmium (Cd) exposure can cause several pulmonary diseases. Epithelial-mesenchymal transition (EMT) involved in the process of chronic obstructive pulmonary disease (COPD). However, the association between environmental Cd exposure and EMT was unclear in COPD patients. This study aimed to analyze the associations among circulatory Cd, EMT and COPD based on case-control study. Four hundred COPD patients and 400 control subjects were recruited. Circulatory Cd was detected using atomic adsorption spectrometer. MicroRNA-30 (miR-30) was measured by RT-PCR and the markers of pulmonary EMT were evaluated through western blotting. Circulatory Cd concentration was increased and serum miR-30 was decreased in COPD patients. Circulatory Cd was inversely associated with pulmonary function in COPD patients. Moreover, serum miR-30 was gradually decreased in parallel with FEV1 in COPD patients. Meanwhile, there was a negative association between serum miR-30 and circulatory Cd in COPD patients. Further analysis found that E-cadherin, one of epithelial biomarkers, was reduced in lung tissues of COPD patients with higher circulatory Cd. On the contrary, pulmonary N-cadherin, Vimentin and α-SMA, three of mesenchymal biomarkers, were increased in COPD patients with higher circulatory Cd. In vitro experiments revealed that Cd exposure repressed miR-30 levels and promoted EMT in BEAS-2B cells. Our results provide evidence that miR-30 reduction contributing to pulmonary EMT may involve in the process of Cd-induced COPD.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112164DOI Listing
June 2021

Prognostic significance of family in multiple myeloma.

J Cancer 2021 30;12(7):1936-1944. Epub 2021 Jan 30.

Department of Hematology, The Second Affiliated Hospital, Guangzhou Medical University, 510260 Guangzhou, China.

Multiple myeloma (MM) is a hematologic tumor with monoclonal proliferation of malignant plasma cells in the bone marrow. Fascin (FSCN) is an actin-binding protein that plays a crucial role in cell migration and invasion, contributing to tumor metastasis. There are three members () in family However, the prognostic role of family in MM remains unclear. In this study, we used four independent Gene Expression Omnibus (GEO) datasets to explore the relationships between expression profiles and patient survival in MM. We found that was dramatically down-regulated in MM compared to normal donors ( < 0.001) and monoclonal gammopathy of undetermined significance (MGUS) ( = 0.032). Patients with high expression of and had significantly longer OS ( = 0.023 and 0.028, respectively). Univariate and multivariate analysis showed that ( = 0.003, 0.002) and ( = 0.018, 0.013) were independent favorable prognostic factors for OS in MM. Moreover, the combination of high expression of and could effectively predict both longer EFS ( = 0.046) and OS ( = 0.015). Our study suggested that and can be used as favorable biomarkers for predicting clinical outcomes in MM.
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http://dx.doi.org/10.7150/jca.53675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974516PMC
January 2021

Targeting chemokines for acute lymphoblastic leukemia therapy.

J Hematol Oncol 2021 Mar 20;14(1):48. Epub 2021 Mar 20.

Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the malignant clonal expansion of lymphoid hematopoietic precursors. It is regulated by various signaling molecules such as cytokines and adhesion molecules in its microenvironment. Chemokines are chemotactic cytokines that regulate migration, positioning and interactions of cells. Many chemokine axes such as CXCL12/CXCR4 and CCL25/CCR9 have been proved to play important roles in leukemia microenvironment and further affect ALL outcomes. In this review, we summarize the chemokines that are involved in ALL progression and elaborate on their roles and mechanisms in leukemia cell proliferation, infiltration, drug resistance and disease relapse. We also discuss the potential of targeting chemokine axes for ALL treatments, since many related inhibitors have shown promising efficacy in preclinical trials, and some of them have entered clinical trials.
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http://dx.doi.org/10.1186/s13045-021-01060-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981899PMC
March 2021

Manipulating Oxidation of Silicon with Fresh Surface Enabling Stable Battery Anode.

Nano Lett 2021 Apr 18;21(7):3127-3133. Epub 2021 Mar 18.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

Silicon (Si)-based material is a promising anode material for next-generation lithium-ion batteries (LIBs). Herein, we report the fabrication of a silicon oxide-carbon (SiO/C) nanocomposite through the reaction between silicon particles with fresh surface and HO in a mild hydrothermal condition, as well as conducting carbon coating synchronously. We found that controllable oxidation could be realized for Si particles to produce uniform SiO after the removal of the native passivation layer. The uniform oxidation and conductive coating offered the as-fabricated SiO/C composite good stability at both particle and electrode level over electrochemical cycling. The as-fabricated SiO/C composite delivered a high reversible capacity of 1133 mAh g at 0.5 A g with 89.1% capacity retention after 200 cycles. With 15 wt % SiO/C composite, graphite-SiO/C hybrid electrode displayed a high reversible specific capacity of 496 mAh g and stable electrochemical cycling with a capacity retention of 90.1% for 100 cycles.
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http://dx.doi.org/10.1021/acs.nanolett.1c00317DOI Listing
April 2021

Increased expression of IFI16 predicts adverse prognosis in multiple myeloma.

Pharmacogenomics J 2021 Mar 12. Epub 2021 Mar 12.

Department of Clinical Laboratory, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells and does not have sufficient prognostic indicators. Interferon gamma inducible protein 16 (IFI16) plays a crucial role in B-cell differentiation. Several studies have shown that IFI16 predicted prognosis in many cancers. However, the relationship between MM prognosis and IFI16 expression has not been studied. In our study, we analyzed the prognostic role of IFI16 expression and explored the possible mechanism in MM progression by using 4498 myeloma patients and 52 healthy donors from 13 independent gene expression omnibus (GEO) datasets. The IFI16 expression increased with myeloma progression, ISS stage, 1q21 amplification, and relapse (all P < 0.01). MM patients with higher IFI16 expression had shorter survival in six datasets (all P < 0.05). Furthermore, multivariate analysis indicated that enhanced IFI16 expression was an independent poor prognostic factor for EFS and OS (P = 0.007, 0.009, respectively). And PPI, GO, KEGG, and GSEA also confirmed that IFI16 promoted MM progression by participating in tumor-related pathways. In conclusion, our study confirmed that IFI16 was a poor prognostic biomarker in MM.
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http://dx.doi.org/10.1038/s41397-021-00230-yDOI Listing
March 2021

Identification of TRIM56 as a Potential Biomarker for Lung Adenocarcinoma.

Cancer Manag Res 2021 4;13:2201-2213. Epub 2021 Mar 4.

Institute of Chronic Disease, School of Basic Medicine, Qingdao University, Qingdao, Shandong, People's Republic of China.

Background: Lung adenocarcinoma (LUAD) is the primary subtype of human lung cancer. The effectiveness of treatment and long-term survival of patients with LUAD are current suboptimal. Tripartite motif containing 56 (TRIM56) is a member of the TRIM protein family that have functions predominantly in immunity and cancer.

Purpose: To investigate the expression of TRIM56 in LUAD, and explore the potential regulatory role of TRIM56 in the invasion and migration of LUAD cells.

Methods: The Gene Expression Omnibus datasets and The Cancer Genome Atlas-LUAD cohort were used to analyze the mRNA expression of TRIM56 in LUAD. The differential expression profiles of miRNAs associated with TRIM56 were obtained from The Cancer Genome Atlas-LUAD cohort. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to determine the principal functions of miRNAs and interacting proteins. Transwell and wound healing were used to detect the effect of overexpression of TRIM56 on the invasion and migration of LUAD cells.

Results: The expression of TRIM56 was decreased in LUAD and associated with poor prognosis. We determined the genome copy number, negatively correlated miRNA and potential transcription factors of TRIM56, and conducted enrichment analysis. Among them, hsa-mir-542 and hsa-mir-627 were the most likely to inhibit the expression of TRIM56. We also predicted the interacting proteins and potential ubiquitination substrate of TRIM56. Finally, we demonstrated that overexpression of TRIM56 inhibits the invasion and migration of LUAD cells.

Conclusion: This study is the first to analyze the expression of TRIM56 and its inhibitory effect on the invasion and migration of LUAD. This evidence provides a new direction for further study of the reasons for the low expression of TRIM56 in LUAD and its regulatory mechanism.
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http://dx.doi.org/10.2147/CMAR.S288111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940991PMC
March 2021

Addressing the Low Solubility of a Solid Electrolyte Interphase Stabilizer in an Electrolyte by Composite Battery Anode Design.

ACS Appl Mater Interfaces 2021 Mar 11;13(11):13354-13361. Epub 2021 Mar 11.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

Metallic sodium (Na) has been regarded as one of the most attractive anodes for Na-based rechargeable batteries due to its high specific capacity, low working potential, and high natural abundance. However, several important issues hinder the practical application of the metallic Na anode, including its high reactivity with electrolytes, uncontrolled dendrite growth, and poor processability. Metal nitrates are common electrolyte additives used to stabilize the solid electrolyte interphase (SEI) on Na anodes, though they typically suffer from poor solubility in electrolyte solvents. To address these issues, a Na/NaNO composite foil electrode was fabricated through a mechanical kneading approach, which featured uniform embedment of NaNO in a metallic Na matrix. During the battery cycling, NaNO was reduced by metallic Na sustainably, which addressed the issue of low solubility of an SEI stabilizer. Due to the supplemental effect of NaNO, a stable SEI with NaNO and NaN species was produced, which allowed fast ion transport. As a result, stable electrochemical performance for 600 h was achieved for Na/NaNO||Na/NaNO symmetric cells at a current density of 0.5 mA cm and an areal capacity of 0.5 mAh cm. A Na/NaNO||NaV(PO)OF cell with active metallic Na of ∼5 mAh cm at the anode showed stable cycling for 180 cycles. In contrast, a Na||NaV(PO)OF cell only displayed less than 80 cycles under the same conditions. Moreover, the processability of the Na/NaNO composite foil was also significantly improved due to the introduction of NaNO, in contrast to the soft and sticky pure metallic Na. Mechanical kneading of soft alkali metals and their corresponding nitrates provides a new strategy for the utilization of anode stabilizers (besides direct addition into electrolytes) to improve their electrochemical performance.
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http://dx.doi.org/10.1021/acsami.1c01571DOI Listing
March 2021

Prognostic Value of MicroRNA-20b in Acute Myeloid Leukemia.

Front Oncol 2020 18;10:553344. Epub 2021 Feb 18.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Acute myeloid leukemia (AML) is a highly heterogeneous disease that requires fine-grained risk stratification for the best prognosis of patients. As a class of small non-coding RNAs with important biological functions, microRNAs play a crucial role in the pathogenesis of AML. To assess the prognostic impact of miR-20b on AML in the presence of other clinical and molecular factors, we screened 90 AML patients receiving chemotherapy only and 74 also undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. In the chemotherapy-only group, high miR-20b expression subgroup had shorter event-free survival (EFS) and overall survival (OS, both  < 0.001); whereas, there were no significant differences in EFS and OS between high and low expression subgroups in the allo-HSCT group. Then we divided all patients into high and low expression groups based on median miR-20b expression level. In the high expression group, patients treated with allo-HSCT had longer EFS and OS than those with chemotherapy alone (both < 0.01); however, there were no significant differences in EFS and OS between different treatment subgroups in the low expression group. Further analysis showed that miR-20b was negatively correlated with genes in "ribosome," "myeloid leukocyte mediated immunity," and "DNA replication" signaling pathways. , the gene with the strongest correlation with miR-20b, also had significant prognostic value in patients undergoing chemotherapy but not in the allo-HSCT group. In conclusion, our findings suggest that high miR-20b expression is a poor prognostic indicator for AML, but allo-HSCT may override its prognostic impact.
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http://dx.doi.org/10.3389/fonc.2020.553344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930740PMC
February 2021

Novel Core-Sheath Cu/CuO-ZnO-FeO Nanocomposites with High-Efficiency Chlorine-Resistant Bacteria Sterilization and Trichloroacetic Acid Degradation Performance.

ACS Appl Mater Interfaces 2021 Mar 26;13(9):10878-10890. Epub 2021 Feb 26.

College of Environmental Science and Engineering, School of Chemical Science and Engineering, State Key Laboratory of Pollution Control and Resource Reuse, Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University, Shanghai 200092, PR China.

In order to solve two issues of chlorine-resistant bacteria (CRB) and disinfection byproducts (DBPs) in tap water after the chlorine-containing treatment process, an innovative core-sheath nanostructured Cu/CuO-ZnO-FeO was designed and synthesized. The fabrication mechanism of the materials was then systematically analyzed to determine the component and valence state. The properties of CRB inactivation together with trichloroacetic acid (TCAA) photodegradation by Cu/CuO-ZnO-FeO were investigated in detail. It was found that Cu/CuO-ZnO-FeO displayed excellent antibacterial activity with a relatively low cytotoxicity concentration due to its synergism of nanowire structure, ion release, and reactive oxygen species generation. Furthermore, the Cu/CuO-ZnO-FeO nanocomposite also exhibited outstanding photocatalytic degradation activity on TCAA under simulated sunlight irradiation, which was verified to be dominated by the surface reaction through kinetic analysis. More interestingly, the cell growth rate of Cu/CuO-ZnO-FeO was determined to be 50% and 10% higher than those of Cu/CuO and Cu/CuO-ZnO after 10 h incubation, respectively, manifesting a weaker cytotoxicity. Therefore, the designed Cu/CuO-ZnO-FeO could be a promising agent for tap water treatment.
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http://dx.doi.org/10.1021/acsami.0c21336DOI Listing
March 2021

A Replacement Reaction Enabled Interdigitated Metal/Solid Electrolyte Architecture for Battery Cycling at 20 mA cm and 20 mAh cm.

J Am Chem Soc 2021 Mar 17;143(8):3143-3152. Epub 2021 Feb 17.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

Metal anodes represent as a prime choice for the coming generation rechargeable batteries with high energy density. However, daunting challenges including electrode volume variation and inevitable side reactions preclude them from becoming a viable technology. Here, a facile replacement reaction was employed to fabricate a three-dimensional (3D) interdigitated metal/solid electrolyte composite electrode, which not only provides a stable host structure for buffering the volume change within the composite but also prevents side reactions by avoiding the direct contact between active metal and liquid electrolyte. As a proof-of-concept demonstration, a 3D interdigitated zinc (Zn) metal/solid electrolyte architecture was fabricated via a galvanic replacement reaction between Zn metal foil and indium (In) chloride solution followed by electrochemical activation, featuring the interdigitation between metallic Zn and amorphous indium hydroxide sulfate (IHS) with high Zn conductivity (56.9 ± 1.8 mS cm), large Zn transference number (0.55), and high electronic resistivity [(2.08 ± 0.01) × 10 Ω cm]. The as-designed Zn/IHS electrode sustained stable electrochemical Zn plating/stripping over 700 cycles with a record-low overpotential of 8 mV at 1 mA cm and 0.5 mAh cm. More impressively, it displayed cycle-stable performance with low overpotential of 10 mV under ultrahigh current density and areal capacity (20 mA cm, 20 mAh cm), which outperformed all the reported Zn metal electrodes in mild aqueous electrolyte. The fabrication of interdigitated metal/solid electrolyte was generalized to other metal pairs, including Zn/Sn and Zn/Co, which provide inspiration for next-generation Zn metal batteries with high energy density and reversibility.
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http://dx.doi.org/10.1021/jacs.0c11753DOI Listing
March 2021

Extraction, purification, bioactivity and pharmacological effects of capsaicin: a review.

Crit Rev Food Sci Nutr 2021 Feb 16:1-29. Epub 2021 Feb 16.

College of Food Science & Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruit and Vegetable Processing, Ministry of Agricultural and Rural Affairs, China Agricultural University, Beijing, China.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a well-known vanilloid, which is the main spicy component in chili peppers, showing several biological activities and the potential applications range from food flavorings to therapeutics. Traditional extraction of capsaicin by organic solvents was time-consuming, some new methods such as aqueous two-phase method and ionic liquid extraction method have been developed. During past few decades, an ample variety of biological effects of capsaicin have been evaluated. Capsaicin can be used in biofilms and antifouling coatings due to its antimicrobial activity, allowing it has a promising application in food packaging, food preservation, marine environment and dental therapy. Capsaicin also play a crucial role in metabolic disorders, including weight loss, pressure lowing and insulin reduction effects. In addition, capsaicin was identified effective on preventing human cancers, such as lung cancer, stomach cancer, colon cancer and breast cancer by inducing apoptosis and inhibiting cell proliferation of tumor cells. Previous research also suggest the positive effects of capsaicin on pain relief and cognitive impairment. Capsaicin, the agonist of transient receptor potential vanilloid type 1 (TRPV1), could selectively activate TRPV1, inducing Ca influx and related signaling pathways. Recently, gut microbiota was also involved in some diseases therapeutics, but its influence on the effects of capsaicin still need to be deeply studied. In this review, different extraction and purification methods of capsaicin, its biological activities and pharmacological effects were systematically summarized, as well as the possible mechanisms were also deeply discussed. This article will give an updated and better understanding of capsaicin-related biological effects and provide theoretical basis for its further research and applications in human health and manufacture development.
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http://dx.doi.org/10.1080/10408398.2021.1884840DOI Listing
February 2021

Renal dysfunction and prognosis of COVID-19 patients: a hospital-based retrospective cohort study.

BMC Infect Dis 2021 Feb 8;21(1):158. Epub 2021 Feb 8.

Second Affiliated Hospital, Anhui Medical University, Furong Road no 678, Hefei, 230601, Anhui Province, China.

Introduction: Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure.

Materials And Methods: All 154 patients with COVID-19 were recruited from the Second People's Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study.

Results: There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge.

Conclusion: Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.
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http://dx.doi.org/10.1186/s12879-021-05861-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868870PMC
February 2021

Supplementation with high-dose cholecalciferol throughout pregnancy induces fetal growth restriction through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition.

J Nutr Biochem 2021 05 3;91:108601. Epub 2021 Feb 3.

Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China. Electronic address:

Vitamin D deficiency has been associated with adverse pregnant outcomes. Several studies investigated the effects of maternal vitamin D3 supplementation on fetal development with inconsistent results. The aim of this study was to investigate the effects of maternal supplementation with different doses of vitamin D3 on fetal development. Pregnant mice were administered with different doses of cholecalciferol (0, 2,000, 10,000, 40,000 IU/kg/day) by gavage throughout pregnancy. Fetal weight and crown-rump length were measured. Placental proliferation and mesenchymal characteristics were detected. HTR-8/SVneo cells were incubated in the absence or presence of calcitriol (500 nmol/L) to evaluate the effects of active vitamin D3 on migration and invasion of human trophoblast cells. Although a low dose of cholecalciferol was safe, fetal weight and crown-rump length were decreased in dams treated with high-dose cholecalciferol throughout pregnancy. Placental weight and labyrinth thickness were reduced in mice administered with high-dose cholecalciferol. An obvious calcification was observed in placentae of mice administered with high-dose cholecalciferol. Ki67-positive cells, a marker of placental proliferation, were reduced in mice administered with high-dose cholecalciferol. N-cadherin and vimentin, two mesenchymal markers, were decreased in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. MMP-2 and MMP-9, two matrix metalloproteinases, were downregulated in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. In addition, trophoblast migration and invasion were suppressed by calcitriol. Supplementation with high-dose cholecalciferol induces fetal growth restriction partially through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition.
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http://dx.doi.org/10.1016/j.jnutbio.2021.108601DOI Listing
May 2021

Supratentorial ependymoma with YAP1:FAM118B fusion: A case report.

Neuropathology 2021 Apr 22;41(2):133-138. Epub 2021 Jan 22.

Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.

We report a case of a 26-year-old Chinese man who had experienced three grand mal seizures in the past two months. Magnetic resonance imaging revealed a relatively well-circumscribed lesion in the left frontal lobe. A craniotomy with total excision of the tumor was performed. Histopathological investigations confirmed a grade 2 ependymoma according to the World Health Organization classification. Genetic analysis revealed a tumor harboring FAM118B fusion to YAP1, and no other genetic alterations or methylation of the O -methylguanine-DNA methyltransferase gene promoter were detected. This is the second case report of ependymoma with YAP1:FAM118B fusion.
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http://dx.doi.org/10.1111/neup.12712DOI Listing
April 2021

Design of Variable Spray System for Plant Protection UAV Based on CFD Simulation and Regression Analysis.

Sensors (Basel) 2021 Jan 18;21(2). Epub 2021 Jan 18.

College of Information Engineering, Sichuan Agricultural University, Ya'an 625000, China.

Multi-rotor unmanned aerial vehicles (UAVs) for plant protection are widely used in China's agricultural production. However, spray droplets often drift and distribute nonuniformly, thereby harming its utilization and the environment. A variable spray system is designed, discussed, and verified to solve this problem. The distribution characteristics of droplet deposition under different spray states (flight state, environment state, nozzle state) are obtained through computational fluid dynamics simulation. In the verification experiment, the wind velocity error of most sample points is less than 1 m/s, and the deposition ratio error is less than 10%, indicating that the simulation is reliable. A simulation data set is used to train support vector regression and back propagation neural network with multiple parameters. An optimal regression model with the root mean square error of 6.5% is selected. The UAV offset and nozzle flow of the variable spray system can be obtained in accordance with the current spray state by multi-sensor fusion and the predicted deposition distribution characteristics. The farmland experiment shows that the deposition volume error between the prediction and experiment is within 30%, thereby proving the effectiveness of the system. This article provides a reference for the improvement of UAV intelligent spray system.
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http://dx.doi.org/10.3390/s21020638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831310PMC
January 2021

Prognostic value of family expression in acute myeloid leukemia.

Future Oncol 2021 Feb 20;17(5):541-548. Epub 2021 Jan 20.

Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China.

The objective of this work was to investigate the prognostic role of the family in acute myeloid leukemia (AML). A total of 155 AML patients with expression data from the Cancer Genome Atlas database were enrolled in this study. In the chemotherapy-only group, patients with high expression had significantly longer event-free survival (EFS) and overall survival (OS) than those with low expression (all p < 0.05), whereas high expressers had shorter EFS and OS than the low expressers (all p < 0.05). Multivariate analysis identified that high expression was an independent favorable prognostic factor for patients who only received chemotherapy (all p < 0.05).  family expression had no impact on EFS and OS in AML patients receiving allogeneic hematopoietic stem cell transplantation. High expression is a potential prognostic indicator for AML.
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http://dx.doi.org/10.2217/fon-2020-0555DOI Listing
February 2021

iRoot SP Promotes Osteo/Odontogenesis of Bone Marrow Mesenchymal Stem Cells via Activation of NF-B and MAPK Signaling Pathways.

Stem Cells Int 2020 24;2020:6673467. Epub 2020 Dec 24.

Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing 210029, China.

The regeneration of bone and tooth tissues, and related cellular therapies, has attracted widespread attention. Bone marrow mesenchymal stem cells (BMSCs) are potential candidates for such regeneration. iRoot SP is a premixed bioceramic root canal sealer widely used in clinical settings. However, the effect of iRoot SP on the biological features of BMSCs has not been elucidated. In the present study, we found that 0.2 mg/ml iRoot SP conditioned medium promoted osteo/odontogenic differentiation and enhanced mineralization of BMSCs without affecting the proliferative ability. Mechanistically, the NF-B and MAPK signaling pathways were activated in SP-treated BMSCs, and differentiation was inhibited when cultured with the specific inhibitor. Taken together, these findings demonstrate that iRoot SP promotes osteo/odontogenic differentiation of BMSCs via the NF-B and MAPK signaling pathways, which could provide a new theoretical basis for clinical applications of iRoot SP and a new therapeutic target for the regeneration of bone and tooth tissue in the future.
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http://dx.doi.org/10.1155/2020/6673467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775135PMC
December 2020

Prognostic role of Wnt and Fzd gene families in acute myeloid leukaemia.

J Cell Mol Med 2021 Feb 8;25(3):1456-1467. Epub 2021 Jan 8.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event-free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P < .05), whereas, in the allo-HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in 'cell morphogenesis involved in differentiation', 'haematopoietic cell lineage', 'platelet activation, signalling and aggregation' and 'mitochondrial RNA metabolic process' signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo-HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML.
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http://dx.doi.org/10.1111/jcmm.16233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875934PMC
February 2021