Publications by authors named "Peng Cao"

494 Publications

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine.

Elife 2021 Apr 20;10. Epub 2021 Apr 20.

Department of Cell Biology, Wuhan University, Wuhan, China.

The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.
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http://dx.doi.org/10.7554/eLife.68128DOI Listing
April 2021

Comparative analysis of DNA extraction protocols for ancient soft tissue museum samples.

Zool Res 2021 May;42(3):280-286

Key Laboratory of Vertebrate Evolution and Human Origins, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China.

DNA studies of endangered or extinct species often rely on ancient or degraded remains. The majority of ancient DNA (aDNA) extraction protocols focus on skeletal elements, with skin and hair samples rarely explored. Similar to that found in bones and teeth, DNA extracted from historical or ancient skin and fur samples is also extremely fragmented with low endogenous content due to natural degradation processes. Thus, the development of effective DNA extraction methods is required for these materials. Here, we compared the performance of two DNA extraction protocols (commercial and custom laboratory aDNA methods) on hair and skin samples from decades-old museum specimens to Iron Age archaeological material. We found that apart from the impact sample-specific taphonomic and handling history has on the quantity and quality of DNA preservation, skin yielded more endogenous DNA than hair of the samples and protocols tested. While both methods recovered DNA from ancient soft tissue, the laboratory method performed better overall in terms of DNA yield and quality, which was primarily due to the poorer performance of the commercial binding buffer in recovering aDNA.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.377DOI Listing
May 2021

First Report of Leaf Spot Caused by Cladosporium tenuissimum on Panicle Hydrangea (Hydrangea paniculate) in China.

Plant Dis 2021 Apr 6. Epub 2021 Apr 6.

Northeast Agricultural University, 12430, School of Life Science, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, P.R. China, Harbin, China, 150030;

Panicle Hydrangea (Hydrangea paniculate) is an ornamental flowering plant native to China and Japan. In August 2019, leaf spot symptoms with about 30% disease incidence were observed on panicle hydrangea in two grower fields (about 0.1 ha in total) of Northeast Agriculture University, China (126.72°E, 45.74°N). Symptoms initially appeared on the lower and older leaves and showed small subcircular brown spots with dark-brown edges on both sides. As the disease progressed, the necrotic spots enlarged, became irregular, coalesced, and the infected leaf blighted in approximately 2 weeks. Panicle hydrangea leaf samples (n=15) from different plants that showed spot symptoms were collected and surface sterilized with 70% ethanol for 10 s, followed by 0.5% NaClO treatment for 4 min, and rinsed in sterile water 3 times. Thereafter, leaf samples were placed on potato dextrose agar (PDA) and incubated at 25°C for 7 days. Fifteen hyphal-tipped pure cultures were obtained. Colonies growing on PDA for 7 days were olive green to dark green, exhibited a velvet-like texture and sometimes were radially furrowed and wrinkled. Margins varied from white gray to dark green without prominent exudates. The back of the plate showed dark green to black. Conidiophores were up to 180 to 600 µm long, 2.8 to 4.5 µm wide (n=50), subcylindrical-filiform, straight, septate, and unbranched or rarely branched. Ramoconidia were 0 to 1 septate, cylindrical to clavate, smooth-walled, 8 to 22 μm long (n=50). Conidia were single-celled, lemon-shaped, smooth-walled and 2.0 to 5.0 µm (diameter) (n=50). To confirm the identity, three genomic DNA regions, internal transcribed spacer (ITS), partial translation elongation factor-1 alpha (EF), and actin (ACT) of the representative isolate BAI-1 were amplified with primer pairs ITS1/4, EF1-728F/986R, and ACT-512F/783R, respectively (Bensch et al. 2012; Jo et al. 2018). DNA sequences of the isolate from ITS, EF, and ACT showed 99.81% (514/515 bp), 99.10% (219/221 bp), and 99.54% (216/217 bp) nucleotide identity with those of C. tenuissimum CBS 125995, respectively (GenBank accession nos. HM148197, HM148442, and HM148687). The sequences of isolate BAI-1 were deposited in GenBank (accession nos. MW045455, MW052465, and MW052466). To fulfill Koch's postulates, five healthy 2-year-old panicle hydrangea plants grown in pots were surface sterilized with 70% ethanol, washed twice with sterile distilled water, and sprayed with a conidial suspension of strain BAI-1 (adjusted to 1×106 conidia/ml using a hemocytometer), maintained in a greenhouse at 25°C and 85% relative humidity. Five plants sprayed with sterilized water served as controls. The inoculated plants showed leaf spot symptoms that were similar to those previously observed in the fields after 7 days, whereas control leaves remained healthy. The fungus was reisolated from symptomatic leaves and its identity was confirmed by morphological and molecular method. These experiments were repeated twice. So far, C. tenuissimum was reported to cause leaf spot of alfalfa (Han et al. 2019) and castor (Liu et al. 2019). To our knowledge, this is the first report of leaf spot disease in panicle hydrangea caused by C. tenuissimum in China. Leaf spot has a negative effect on the aesthetic value of panicle hydrangea, and this report will assist with monitoring distribution of the disease as well as developing management recommendations.
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http://dx.doi.org/10.1094/PDIS-12-20-2640-PDNDOI Listing
April 2021

Genome-Wide Analysis of Tubulin Gene Family in Cassava and Expression of Family Member during Various Stress.

Plants (Basel) 2021 Mar 31;10(4). Epub 2021 Mar 31.

Department of Biosciences, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China.

Filamentous temperature-sensitive protein Z (Tubulin/FtsZ) family is a group of conserved GTP-binding (guanine nucleotide-binding) proteins, which are closely related to plant tissue development and organ formation as the major component of the cytoskeleton. According to the published genome sequence information of cassava (), 23 genes () were identified, which were divided into four main groups based on their type and phylogenetic characteristics. The same grouping generally has the same or similar motif composition and exon-intron structure. Collinear analysis showed that fragment repetition event is the main factor in amplification of cassava superfamily gene. The expression profiles of genes in various tissue were analyzed, and it was found that were mainly expressed in leaf, petiole, and stem, while was highly expressed in storage root. The qRT-PCR results of the gene under hormone and abiotic stresses showed that indole-3-acetic acid (IAA) and gibberellin A3 (GA3) stresses could significantly increase the expression of the gene, thereby revealing the potential role of in IAA and GA3 stress-induced responses.
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http://dx.doi.org/10.3390/plants10040668DOI Listing
March 2021

A New Perspective for Improving the Human Resource Development of Primary Medical and Health Care Institutions: A Structural Equation Model Study.

Int J Environ Res Public Health 2021 03 4;18(5). Epub 2021 Mar 4.

School of Public Health, Jilin University, Changchun 130000, China.

In some countries, including China, primary health care is rarely utilized because of medical personnel shortages at primary medical and health care institutions (PMHCIs). Several studies suggest that the most effective solution is to guide qualified doctors and medical graduates to work in PMHCIs, but the studies and measures have been formulated only from the perspective of the government and PMHCIs; few have considered the subjective willingness of medical personnel. Therefore, it is necessary to explore the measures to develop human resources of PMHCIs from the guiding object. This research was divided into two parts based on implicit theory and a lexical approach. The first part collected the factors affecting their choosing PMHCIs for employment, and the second part used exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and structural equation modeling (SEM) to explore the dimensions and paths of the influencing factors. At last, seven factors were obtained from the EFA, and the SEM hypothesis fit the data well. Internal Organization Development, Patient Factor, Remuneration and Development, and Family Support had a significantly positive effect on the Sense of Gain of medical personnel seeking employment at PMHCIs, whereas both Job Responsibilities and Condition of the City Where the PMHCI Is Located had no significant effect. In addition, the indirect effects of Internal Organization Development and Condition of the City Where the PMHCI Is Located on the Sense of Gain were significant. The Patient Factor, Family Support, and Remuneration and Development significantly mediated the relationship between the internal and external environment of the institution and the Sense of Gain, whereas the mediating effect of Job Responsibilities was not significant. The improvement of family support, remuneration and development, and patient factors increase the willingness of medical personnel to seek employment at PMHCIs. In addition, the internal and external environments of a PMHCI play a vital role in guiding medical personnel to PMHCIs for employment. This research provides theoretical support for improving the development of human resources, guiding medical personnel to work in PMHCIs, and promoting the use of primary care services.
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http://dx.doi.org/10.3390/ijerph18052560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967509PMC
March 2021

Ancient Xinjiang mitogenomes reveal intense admixture with high genetic diversity.

Sci Adv 2021 Mar 31;7(14). Epub 2021 Mar 31.

Key Laboratory of Vertebrate Evolution and Human Origins, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China.

Xinjiang is a key region in northwestern China, connecting East and West Eurasian populations and cultures for thousands of years. To understand the genetic history of Xinjiang, we sequenced 237 complete ancient human mitochondrial genomes from the Bronze Age through Historical Era (41 archaeological sites). Overall, the Bronze Age Xinjiang populations show high diversity and regional genetic affinities with Steppe and northeastern Asian populations along with a deep ancient Siberian connection for the Tarim Basin Xiaohe individuals. In the Iron Age, in general, Steppe-related and northeastern Asian admixture intensified, with North and East Xinjiang populations showing more affinity with northeastern Asians and South Xinjiang populations showing more affinity with Central Asians. The genetic structure observed in the Historical Era of Xinjiang is similar to that in the Iron Age, demonstrating genetic continuity since the Iron Age with some additional genetic admixture with populations surrounding the Xinjiang region.
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http://dx.doi.org/10.1126/sciadv.abd6690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011967PMC
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

Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states.

Nat Neurosci 2021 04 8;24(4):542-553. Epub 2021 Mar 8.

Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China.

In humans, tissue injury and depression can both cause pain hypersensitivity, but whether this involves distinct circuits remains unknown. Here, we identify two discrete glutamatergic neuronal circuits in male mice: a projection from the posterior thalamic nucleus (PO) to primary somatosensory cortex glutamatergic neurons (S1) mediates allodynia from tissue injury, whereas a pathway from the parafascicular thalamic nucleus (PF) to anterior cingulate cortex GABA-containing neurons to glutamatergic neurons (ACC) mediates allodynia associated with a depression-like state. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that PO and PF populations undergo different adaptations in the two conditions. Artificial manipulation of each circuit affects allodynia resulting from either tissue injury or depression-like states, but not both. Our study demonstrates that the distinct thalamocortical circuits PO→S1 and PF→ACC subserve allodynia associated with tissue injury and depression-like states, respectively, thus providing insights into the circuit basis of pathological pain resulting from different etiologies.
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http://dx.doi.org/10.1038/s41593-021-00811-xDOI Listing
April 2021

Antibiotics-induced intestinal dysbacteriosis caused behavioral alternations and neuronal activation in different brain regions in mice.

Mol Brain 2021 03 6;14(1):49. Epub 2021 Mar 6.

Institute of Medical Research, Northwestern Polytechnical University, Xi`an, Shaanxi, 710072, P. R. China.

Antibiotics affect gut microbial composition, leading to Gut-Brain-Axis imbalance and neurobehavioral changes. However, the intestinal dysbacteriosis associated behavior changes are not consistently reported. It is not clear whether these changes are transient or permanent. The neuroprotective effect of probiotics against intestinal dysbacteriosis induced alternations needs to be determined either. In the present study, oral antibiotic mixture including Ampicillin, Streptomycin, and Clindamycin was utilized to induce intestinal dysbacteriosis in mice. Antibiotics application triggered mechanical allodynia in von frey test and spontaneous pain in open field test. It also resulted in increased anxiety and depressive-like behaviors and damaged spatial memory performance. After application of probiotics, the mechanical allodynia and spontaneous pain were alleviated significantly. The anxiety behaviors, depressive-like behaviors and recognitive performance were ameliorative as well. By using Fos protein as a marker, it is found that the sensory, emotion and memory related brain regions were activated in mice with intestinal dysbacteriosis. Our study is not only helpful for enriching our basic knowledge for understanding the changed pain responses and related brain disorders in antibiotics-induced dysbacteriosis mice, but also beneficial for providing a more comprehensive mechanistic explanation for the regulation of antibiotics and probiotics on gut microbiota and relevant alternations in animal neurological behaviors.
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http://dx.doi.org/10.1186/s13041-021-00759-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937204PMC
March 2021

Total Health Expenditure and Its Driving Factors in China: A Gray Theory Analysis.

Healthcare (Basel) 2021 Feb 14;9(2). Epub 2021 Feb 14.

School of Public Health, Jilin University, Changchun 130000, Jilin Province, China.

The continuous growth in total health expenditure (THE) has become a social issue of common concern in most countries. In China, the total health expenditure (THE) is maintaining a rapid growth trend that is higher than that of the economy, which has become increasingly obvious in the 21st century and has brought a heavy burden to the government and residents. To analyze the main driving factors of THE in China in the 21st century and establish a predictive model, gray system theory was employed to explore the correlation degree between THE and nine hot topics in the areas of the economy, population, health service utilization, and policy using national data from 2000 to 2018. Additionally, a New Structure of the Multivariate Gray Prediction Model of THE was established and compared with the traditional grey model and widely used BP neural network to evaluate the prediction effectiveness of the model. We concluded that the Chinese government and society have played a crucial role in reducing residents' medical burden. Besides this, the improved economy and aging population have increased the demand for health services, leading to the continual increase in THE. Lastly, the improved NSGM(1,N) model achieved good prediction accuracy and has unique advantages in simulating and predicting THE, which can provide a basis for policy formulation.
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http://dx.doi.org/10.3390/healthcare9020207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918561PMC
February 2021

Can Be Used as a Biomarker for Diagnosis of Renal Cell Carcinoma and Prediction of Patient Survival.

Front Genet 2021 15;12:599952. Epub 2021 Feb 15.

Department of Urology, Affiliated Beijing Chaoyang Hospital of Capital Medical University, Beijing, China.

The incidences of renal cell carcinoma (RCC) increase in number each year and account for about 2-3% of all malignant tumors. Many patients have metastasis by the time of diagnosis, and their prognosis is poor. Therefore, it is essential that new diagnostic and prognostic markers for kidney cancer are identified. In this study, we assessed the potential of as a diagnostic and prognostic marker for RCC. We analyzed the TCGA and UALCAN databases and found to be highly expressed in ccRCC. In addition, high levels positively correlated with lymphatic metastasis, tumor stage, and histopathological grade. Kaplan-Meier curve analysis showed that expression was related to the prognosis of patients, and high expression indicated a worse overall survival ( = 5.1E-0.7). Receiver operating characteristic curve analysis showed that a combination of expression and histopathological grade improved predictive accuracy (AUC = 0.697; 95%CI: 0.628-0.765, < 0.001). Finally, the relative levels of in ACHN and Caki-1 cells were higher than that of HK-2 cells by western blotting analysis and RT-PCR. Functional tests showed that knocking down expression inhibited migration and invasion . Therefore, is a potential biomarker for the diagnosis and prognosis of RCC patients.
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http://dx.doi.org/10.3389/fgene.2021.599952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917296PMC
February 2021

IL-6R blockade by chikusetsusaponin IVa butyl ester inhibits Th17 cell differentiation and ameliorates collagen-induced arthritis.

Cell Mol Immunol 2021 Feb 26. Epub 2021 Feb 26.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

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http://dx.doi.org/10.1038/s41423-021-00651-6DOI Listing
February 2021

sp. nov., an actinobacterium isolated from sandy soil in Sanya.

Int J Syst Evol Microbiol 2019 Jun 22;71(3). Epub 2021 Feb 22.

Key Laboratory of Agricultural Microbiology of Heilongjiang Province, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, PR China.

A novel actinobacterium, designated strain NEAU-AAG5, was isolated from sandy soil collected from Niuwang island in Sanya, Hainan Province, PR China. The taxonomic position of the strain was investigated using a polyphasic approach. On the basis of 16S rRNA gene sequence analysis, strain NEAU-AAG5 belongs to the genus and shared highest sequence similarity with NBRC 14102 (98.8 %). Strain NEAU-AAG5 grows at 20-40 °C (optimum, 28 °C), pH 6-10 (optimum, pH 7) and has NaCl tolerance of 0-3 %. The menaquinones were identified as MK-9(H) (4.2 %), MK-9(H) (49.2 %) and MK-9(H) (46.5 %). The major fatty acids were C (31.4 %), 10-methyl C (21.3 %) and C9 (15.7 %). The polar lipids were diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositolmannoside, phosphatidylglycerol and phosphoglycolipid. The genomic DNA G+C content of strain NEAU-AAG5 based on whole genome sequences was 72.8 mol%. Digital DNA-DNA hybridization between strain NEAU-AAG5 and its closest phylogenetic neighbour, NBRC 14102, resulted in similarity value of 28.0 % (<70 %). Additionally, the average nucleotide identity was 84.2 % for NBRC 14102. On the basis of phenotypic, genotypic and phylogenetic data, strain NEAU-AAG5 can be characterized to represent a novel species of the genus , for which the name sp. nov. is proposed. The type strain is NEAU-AAG5 (=JCM 33456=CCTCC AA 2019043).
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http://dx.doi.org/10.1099/ijsem.0.004708DOI Listing
June 2019

First Report of Leaf Blight Caused by Limonomyces roseipellis on Maize (Zea mays L) in China.

Plant Dis 2021 Feb 9. Epub 2021 Feb 9.

Northeast Agricultural University, 12430, Key Laboratory of Agricultural Microbiology of Heilongjiang Province, Harbin, China;

Maize (Zea mays L.) is one of the major crops in China. In July 2020, leaf blight was observed on approximately 18% of maize plants at the 852 Farm, Heilongjiang province. Symptoms appeared as yellow necrotic lesions on leaf tips and margins, which later expanded to the entire. The disease was first observed on the lower leaves of the plants and then progressed up the plant. Thirty symptomatic leaves were collected in 2020, and tissue samples between healthy and necrotic area (4 × 2 mm) were surface disinfected with 1% NaOCl for 3 min, 70% ethanol for 10 s, and washed three times with sterile water. Disinfected tissues were placed on potato dextrose agar (PDA) amended with streptomycin sulfate (50 mg/liter) and incubated at 25°C for 1 week. Cultures were purified using the hyphal-tip technique for morphological and molecular analyses. Morphological characteristics were observed on 1-week-old PDA cultures grown at 25°C. Mycelium changed from cream colored to pale pink or reddish, and the back of plate turned pink with time. Hyphae were hyaline, 2 to 7 μm wide, with clamps at primary septa. Hyaline basidiospores were sphere to ellipsoid, and ranged from 8 to 10 × 6 to 9 μm. Based on the presence of clamp connections and morphological features, the fungus was preliminarily identified as Limonomyces roseipellis (Stalpers et al. 1982). To confirm the identity of L. roseipellis, primers ITS1/ITS4 (White et al. 1990), MS1/MS2 (White et al. 1990), and LR0R/LR5 (Vilgalys and Hester 1990) were used to amplify the internal transcribed spacer (ITS) region, the partial mitochondrial small subunit rDNA (mtSSU) and nuclear large subunit rDNA (nuLSU), respectively. These sequences were deposited in GenBank (GenBank accession no.s MW067756, MW322806 and MW386178). The ITS sequence had 99.55% nucleotide identity (660 bp/668 bp) with L. roseipellis isolate EF82 (GenBank accession no. MK918632). The mtSSU sequence was 99.69% identical (634 bp/636 bp) to that of L. roseipellis strain SY-LQG101 (Genbank accession no. KF824718). The nuLSU sequence was 99.14% identical (924 bp/932 bp) to that of L. roseipellis (GenBank accession no. EU622844). A single basidiospore was isolated and cultured on PDA for pathogenicity testing. To fulfill Koch's postulates, ten healthy, surface-disinfected maize plants grown in pots (four to five leaves stage) were sprayed with basidiospore suspension (1×106 spores/ml); another ten healthy surface-disinfected maize plants sprayed with distilled water to serve as controls. Plants were sealed in plastic bags immediately after inoculation and maintained at 90% relative humidity in a mist chamber for 24 h at 25°C with a 12-h light cycle (Nicoli et al. 2016). Plants were moved and maintained in the greenhouse and observed for disease development. The experiment was conducted twice. Leaf blight symptoms appeared on all inoculated plants 3 to 5 days postinoculation and were consistent with symptoms observed in the field. No disease symptoms were observed on control plants. The pathogen was reisolated from diseased plants, and species identification was confirmed by the morphological and molecular method described. L. roseipellis has been reported to infect Cynodon dactylon, Lolium perenne and Festuca arundinacea, respectively. To our knowledge, this is the first report of the identification of L. roseipellis as a pathogen of maize in China, and this report will assist with monitoring distribution of the disease to assist with developing management recommendations.
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http://dx.doi.org/10.1094/PDIS-10-20-2299-PDNDOI Listing
February 2021

Autophagy-induced p62 accumulation is required for curcumol to regulate KLF5-mediated angiogenesis in liver sinusoidal endothelial cells.

Toxicology 2021 Mar 4;452:152707. Epub 2021 Feb 4.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address:

Liver pathological angiogenesis is considered to be one of the key events in the development of liver fibrosis. Autophagy is a defense and stress regulation mechanism. However, whether autophagy regulates pathological angiogenesis in liver fibrosis is still questionable. Here, we aimed to study how curcumol regulated liver sinusoidal endothelial cells (LSECs) angiogenesis through autophagy. We found that curcumol (10, 20 and 40 μM) could inhibit the expression of angiogenesis markers in the LSECs. Importantly, we showed that curcumol might influence LSEC pathological angiogenesis by regulating autophagy level. Furthermore, we indicated that the transcription factor Krüppel-like factor 5 (KLF5) was considered as a key target for curcumol to regulate LSEC angiogenesis. Interestingly, we also suggested that autophagy was as a potential mechanism for curcumol to restrain KLF5 expression. Increased autophagy level could impair the suppression effect of curcumol on KLF5. Fascinatingly, our results indicated that curcumol inhibited autophagy and led to p62 accumulation, which might be a regulation mechanism of KLF5 degradation. Finally, in mice liver fibrosis model, we unanimously showed that curcumol (30 mg/kg) inhibited pathological angiogenesis by reducing LSEC autophagy level and suppressing KLF5 expression. Collectively, these results provided a deeper insight into the molecular mechanism of curcumol to inhibit LSEC pathological angiogenesis during liver fibrosis.
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http://dx.doi.org/10.1016/j.tox.2021.152707DOI Listing
March 2021

The safety and efficacy of doxazosin in medical expulsion therapy for distal ureteric calculi: A meta-analysis.

PLoS One 2021 25;16(1):e0245741. Epub 2021 Jan 25.

Affiliated Beijing Chaoyang Hospital of Capital Medical University, Beijing, China.

Purpose: Alpha-adrenergic receptor blockers can be effectively used in the context of medical expulsion therapy (MET) to treat ureteric stones. This study was designed to evaluate the safety and efficacy of doxazosin in MET relative to placebo or tamsulosin.

Methods: We systematically searched the PubMed, the Cochrane Library, EMBASE, Chinese Academic Database, and Web of Science databases to select randomized controlled trials (RCT) that compared the use of doxazosin with placebo or tamsulosin to treat ureteric stones. All patients we included were limited to those diagnosed with visible stones in the distal ureter. The diameter of ureteric stones does not exceed 10 mm.

Results: Eight trials comparing doxazosin with placebo or tamsulosin containing 667 patients were assessed in the final analysis. The meta-analysis showed that doxazosin effectively treated ureteric stones and was better than placebo in terms of efficacy. Relative to the placebo group, the expulsion rate of stones from the distal ureter (OR = 3.00, 95% CI [2.15, 4.19], I2 = 0%, P < 0.00001) was significantly increased, and the expulsion time (days) was shortened (mean difference) (MD) = -4.03, 95% CI [-4.53, -3.53], P < 0.00001). The doxazosin group experienced fewer pain episodes (MD = -0.78, CI = [-0.94, -0.23], I2 = 0%, P < 0.00001) than the placebo group. A subgroup analysis showed that the doxazosin group had a higher expulsion rate (of 5-10 mm stones) compared with the placebo group. Although doxazosin resulted in significantly more adverse effects compared with the placebo, the patient's symptoms were mild and no further medical interventions were required. Moreover, the expulsion time (days) was shorter for patients receiving doxazosin (MD = -0.61, 95% CI [-0.97, -0.24], I2 = 39%, P = 0.001) than those receiving tamsulosin.

Conclusion: Compared with the placebo group, patients receiving doxazosin had a greater expulsion rate, a reduced expulsion time, and fewer pain episodes. The expulsion time of doxazosin was shorter than that of tamsulosin.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245741PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833139PMC
January 2021

Genome-wide signatures of mammalian skin covering evolution.

Sci China Life Sci 2021 Jan 19. Epub 2021 Jan 19.

College of Life Sciences, Nanjing Normal University, Nanjing, 210046, China.

Animal body coverings provide protection and allow for adaptation to environmental pressures such as heat, ultraviolet radiation, water loss, and mechanical forces. Here, using a comparative genomics analysis of 39 mammal species spanning three skin covering types (hairless, scaly and spiny), we found some genes (e.g., UVRAG, POLH, and XPC) involved in skin inflammation, skin innate immunity, and ultraviolet radiation damage repair were under selection in hairless ocean mammals (e.g., whales and manatees). These signatures might be associated with a high risk of skin diseases from pathogens and ultraviolet radiation. Moreover, the genomes from three spiny mammal species shared convergent genomic regions (EPHB2, EPHA4, and NIN) and unique positively selected genes (FZD6, INVS, and CDC42) involved in skin cell polarity, which might be related to the development of spines. In scaly mammals, the shared convergent genomic regions (e.g., FREM2) were associated with the integrity of the skin epithelium and epidermal adhesion. This study identifies potential convergent genomic features among distantly related mammals with the same skin covering type.
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http://dx.doi.org/10.1007/s11427-020-1841-5DOI Listing
January 2021

Interferon-inducible protein 16 may be a biomarker and prognostic factor in renal cell carcinoma by bioinformatics analysis.

Medicine (Baltimore) 2021 Jan;100(1):e24257

Department of Urology, Affiliated Beijing Chaoyang Hospital of Capital Medical University.

Background: Renal cell carcinoma (RCC) accounts for 2% to 3% of all human malignancies and is the 9th most common malignancy in Western countries. Due to the development of surgical procedures and the use of novel drugs, survival has been significantly prolonged. However, current challenges include how to diagnose RCC earlier and how to overcome drug resistance. Methods: We explored the relationship between the transcription level of IFI16 and clinical data in RCC through various online databases, including ONCOMINE, GEPIA, HPA, Timer and COEXPEDIA.

Results: In comparison with corresponding normal tissues, IFI16 mRNA expression levels were higher in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) tissues. In KIRC, the higher expression of IFI16 was associated with lower overall survival (P = .037). In KIRP, the higher expression IFI16 was associated with lower disease-free survival and overall survival (P = .037 and P = .011). In contrast, the IFI16 expression was negatively correlated with tumor purity in kidney chromophobe, KIRC and KIRP (all P < .05). In KIRC and KIRP, the expression of IFI16 was positively correlated with tumor-infiltrating immune cells (TIICs) (all P < .05), except macrophages in KIRP. In KIRC, the main TIICs were B cells, CD4+T cells, neutrophils, and dendritic cells, while the main TIICs in the high amplification state were macrophage (all P < .0001). Functional enrichment analysis by gene ontology and Kyoto Encyclopedia of Genes and Genomes highlighted enrichment of neutrophil degranulation, phagocytosis and vesicle-mediated transport regulation, and pathways including tuberculosis, toxoplasmosis, phagosome, leishmaniasis, and Fc gamma R-mediated.

Conclusions: IFI16 is overexpressed in RCC and may be an important oncogene in the progression of kidney. In addition, IFI16 may a marker for RCC diagnosis and prognosis, which may be related to immune infiltration.
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http://dx.doi.org/10.1097/MD.0000000000024257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793379PMC
January 2021

The characteristics of regulatory macrophages and their roles in transplantation.

Int Immunopharmacol 2021 Feb 5;91:107322. Epub 2021 Jan 5.

Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. Electronic address:

Regulatory macrophages (Mregs) are a subtype of macrophages that are involved in regulating immune responses and inhibiting activated T lymphocyte proliferation. With advances in our basic understanding of Mregs and the revelation of their biological characteristics, Mregs have become a focus of research. In addition to promoting malignant tumor progression, Mregs also play an immunosuppressive role in inflammatory diseases and transplantation. Recent studies have shown that Mregs are closely associated with the induction of transplantation immune tolerance. Immune regulatory cell treatment as an adjunct immunosuppressive therapy offers new insights into the mechanism by which transplantation immune tolerance is established. The application of Mreg-based cellular immunotherapy has shown promise in clinical solid organ transplantation. Here, we provide a comprehensive overview of Mreg morphology, phenotype, induction and negative immunoregulatory function and discuss the role of Mregs in different transplantation models as well as their potential application value in clinical organ transplantation.
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http://dx.doi.org/10.1016/j.intimp.2020.107322DOI Listing
February 2021

CT texture analysis in histological classification of epithelial ovarian carcinoma.

Eur Radiol 2021 Jan 6. Epub 2021 Jan 6.

Department of Diagnostic Radiology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR.

Objectives: The study aimed to compare the ability of morphological and texture features derived from contrast-enhanced CT in histological subtyping of epithelial ovarian carcinoma (EOC).

Methods: Consecutive 205 patients with newly diagnosed EOC who underwent contrast-enhanced CT were included and dichotomised into high-grade serous carcinoma (HGSC) and non-HGSC. Clinical information including age and cancer antigen 125 (CA-125) was documented. The pre-treatment images were analysed using commercial software, TexRAD, by two independent radiologists. Eight qualitative CT morphological features were evaluated, and 36 CT texture features at 6 spatial scale factors (SSFs) were extracted per patient. Features' reduction was based on kappa score, intra-class correlation coefficient (ICC), univariate ROC analysis and Pearson's correlation test. Texture features with ICC ≥ 0.8 were compared by histological subtypes. Patients were randomly divided into training and testing sets by 8:2. Two random forest classifiers were determined and compared: model 1 incorporating selected morphological and clinical features and model 2 incorporating selected texture and clinical features.

Results: HGSC showed specifically higher texture features than non-HGSC (p < 0.05). Both models performed highly in predicting histological subtypes of EOC (model 1: AUC 0.891 and model 2: AUC 0.937), and no statistical significance was found between the two models (p = 0.464).

Conclusion: CT texture analysis provides objective and quantitative metrics on tumour characteristics with HGSC demonstrating specifically high texture features. The model incorporating texture analysis could classify histology subtypes of EOC with high accuracy and performed as well as morphological features.

Key Points: • A number of CT morphological and texture features showed good inter- and intra-observer agreements. • High-grade serous ovarian carcinoma showed specifically higher CT texture features than non-high-grade serous ovarian carcinoma. • CT texture analysis could differentiate histological subtypes of epithelial ovarian carcinoma with high accuracy.
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http://dx.doi.org/10.1007/s00330-020-07565-3DOI Listing
January 2021

Nickel-Catalyzed Carboalkenylation of 1,3-Dienes with Aldehydes and Alkenylzirconium Reagents: Access to Skipped Dienes.

Org Lett 2021 Jan 5;23(2):535-541. Epub 2021 Jan 5.

College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610066, China.

A regio- and stereoselective nickel-catalyzed three-component coupling reaction of aldehydes, 1,3-dienes, and alkenylzirconium reagents was realized. The ligand- and additive-free protocol afforded a convenient approach to the synthesis of skipped diene compounds bearing various functionals (e.g., hydroxyl, carbonyl, halide) and heterocyclic groups. The products were readily transformed into structurally diverse polyenes. The utility of this reaction was also demonstrated by the one-pot operation and scale-up preparation.
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http://dx.doi.org/10.1021/acs.orglett.0c04059DOI Listing
January 2021

Thermomechanical Processing of a Near-α Ti Matrix Composite Reinforced by TiB.

Materials (Basel) 2020 Dec 16;13(24). Epub 2020 Dec 16.

Department of Chemical and Materials Engineering, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.

To further improve the mechanical properties of the as-cast 7.5 vol.% TiB/Ti-6Al-2.5Sn-4Zr-0.7Mo-0.3Si composite, multi-directional forging (MDF) and subsequent heat treatments were carried out to adjust TiB whiskers (TiB) and matrix characteristics. The effect of various microstructures on the tensile properties and fracture toughness of the composites was analyzed in this paper. After MDF, the TiB are broken into short rods with a low aspect ratio and display a random distribution. Moreover, distinct microstructures were obtained after thermomechanical processing and different heat treatments. Both room-temperature and high-temperature tensile strength and ductility are improved after thermomechanical processing. By increasing the solution-treatment temperature, the microstructures transform from equiaxed to fully lamellar. A simultaneous improvement of the room-temperature and high-temperature properties is associated with the microstructural changes. In addition, the fracture toughness exhibits an increasing trend as the volume fraction of equiaxial α phases decreases. The lamellar microstructure demonstrates excellent fracture toughness due to deflection of the crack propagation path.
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http://dx.doi.org/10.3390/ma13245751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766251PMC
December 2020

Elevated serum ferritin level effectively discriminates severity illness and liver injury of coronavirus disease 2019 pneumonia.

Biomarkers 2021 May 10;26(3):207-212. Epub 2021 Feb 10.

Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aim: Ferritin is a hepatic protein that plays vital roles in diagnosing and predicting diseases, but its potential in coronavirus disease 2019 (COVID-19) remains unknown.

Method: We collected clinical records from 79 COVID-19 patients at Wuhan Union hospital (China). Spearman's correlation analysis, receiver operating characteristic (ROC) curve and Kaplan-Meier survival curves were employed.

Results: Patients with elevated ferritin levels had a higher incidence of severity illness (50.0 vs 2.9%) and liver injury (52.3 vs 20.0%) when compared with patients with normal ferritin levels ( < 0.05). Ferritin could effectively identify the severity of illness (ROC area 0.873) and liver injury (ROC area 0.752). The elevated ferritin group showed longer viral clearance time (median 16 vs 6 days,  < 0.001) and in-hospital length (median 18 vs 10 days,  < 0.001).

Conclusions: It suggests that ferritin could act as an easy-to-use tool to identify liver injury and severity illness and predict the prognosis of COVID-19 patients. Intensive surveillance is necessary for patients with abnormal ferritin levels.
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http://dx.doi.org/10.1080/1354750X.2020.1861098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885718PMC
May 2021

Deep learning-based thigh muscle segmentation for reproducible fat fraction quantification using fat-water decomposition MRI.

Insights Imaging 2020 Nov 30;11(1):128. Epub 2020 Nov 30.

Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.

Background: Time-efficient and accurate whole volume thigh muscle segmentation is a major challenge in moving from qualitative assessment of thigh muscle MRI to more quantitative methods. This study developed an automated whole thigh muscle segmentation method using deep learning for reproducible fat fraction quantification on fat-water decomposition MRI.

Results: This study was performed using a public reference database (Dataset 1, 25 scans) and a local clinical dataset (Dataset 2, 21 scans). A U-net was trained using 23 scans (16 from Dataset 1, seven from Dataset 2) to automatically segment four functional muscle groups: quadriceps femoris, sartorius, gracilis and hamstring. The segmentation accuracy was evaluated on an independent testing set (3 × 3 repeated scans in Dataset 1 and four scans in Dataset 2). The average Dice coefficients between manual and automated segmentation were > 0.85. The average percent difference (absolute) in volume was 7.57%, and the average difference (absolute) in mean fat fraction (meanFF) was 0.17%. The reproducibility in meanFF was calculated using intraclass correlation coefficients (ICCs) for the repeated scans, and automated segmentation produced overall higher ICCs than manual segmentation (0.921 vs. 0.902). A preliminary quantitative analysis was performed using two-sample t test to detect possible differences in meanFF between 14 normal and 14 abnormal (with fat infiltration) thighs in Dataset 2 using automated segmentation, and significantly higher meanFF was detected in abnormal thighs.

Conclusions: This automated thigh muscle segmentation exhibits excellent accuracy and higher reproducibility in fat fraction estimation compared to manual segmentation, which can be further used for quantifying fat infiltration in thigh muscles.
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http://dx.doi.org/10.1186/s13244-020-00946-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704819PMC
November 2020

M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2.

Mol Ther 2021 03 20;29(3):1226-1238. Epub 2020 Nov 20.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive tumors all over the world, has a generally poor prognosis, and its progression is positively correlated with the density of blood vessels. Recently, tumor-associated macrophages (TAMs) were proven to be beneficial for angiogenesis, but their mechanism of action remains unclear. Our study indicated that M2 macrophages were positively correlated with the microvessel density (MVD) of PDAC tissues, and M2 macrophage-derived exosomes (MDEs) could promote the angiogenesis of mouse aortic endothelial cells (MAECs) in vitro. At the same time, the M2 MDEs could also promote the growth of subcutaneous tumors and increase the vascular density of mice. Moreover, we also found that miR-155-5p and miR-221-5p levels in the M2 MDEs were higher than those in M0 MDEs, and they could be transferred into MAECs, as demonstrated by RNA sequencing (RNA-seq) and qPCR analysis. Our data confirmed the interaction between TAMs and the angiogenesis of PDAC by exosomes. Additionally, targeting the exosomal miRNAs derived from TAMs might provide diagnostic and therapeutic strategies for PDAC.
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http://dx.doi.org/10.1016/j.ymthe.2020.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934635PMC
March 2021

Hi-GCN: A hierarchical graph convolution network for graph embedding learning of brain network and brain disorders prediction.

Comput Biol Med 2020 Dec 3;127:104096. Epub 2020 Nov 3.

Amii, University of Alberta, Edmonton, Alberta, Canada.

Purpose: Recently, brain connectivity networks have been used for the classification of neurological disorder, such as Autism Spectrum Disorders (ASD) or Alzheimer's disease (AD). Network analysis provides a new way for exploring the association between brain functional deficits and the underlying structural disruption related to brain disorders. Network embedding learning that aims to automatically learn low-dimensional representations for brain networks has drawn increasing attention in recent years.

Method: In this work we build upon graph neural network in order to learn useful representations for graph classification in an end-to-end fashion. Specifically, we propose a hierarchical GCN framework (called hi-GCN) to learn the graph feature embedding while considering the network topology information and subject's association at the same time.

Results: To demonstrate the effectiveness of our approach, we evaluate the performance of the proposed method on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and Autism Brain Imaging Data Exchange (ABIDE) dataset. Extensive experiments on ABIDE and ADNI datasets have demonstrated competitive performance of the hi-GCN model. Specifically, we obtain an average accuracy of 73.1%/78.5% as well as AUC of 82.3%/86.5% on ABIDE/ADNI. The comprehensive experiments demonstrate that our hi-GCN is effective for graph classification with brain disorders diagnosis.

Conclusion: The proposed hi-GCN method performs the graph embedding learning from a hierarchical perspective while considering the structure in individual brain network and the subject's correlation in the global population network, which can capture the most essential embedding features to improve the classification performance of disease diagnosis. Moreover, the proposed jointly optimizing strategy also achieves faster training and easier convergence than both the hi-GCN with pre-training and two-step supervision.
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http://dx.doi.org/10.1016/j.compbiomed.2020.104096DOI Listing
December 2020

Curcumol inhibits KLF5-dependent angiogenesis by blocking the ROS/ERK signaling in liver sinusoidal endothelial cells.

Life Sci 2021 Jan 4;264:118696. Epub 2020 Nov 4.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address:

Aims: Liver fibrosis is a difficult problem in the medical field. We previously reported that curcumol, a bioactive substance, may inhibit the pathological angiogenesis of liver sinusoidal endothelial cells (LSECs) and play a good anti-hepatic fibrosis effect. However, the mechanism of curcumol inhibiting angiogenesis in LSEC needs to be further clarified. Here, we focus on how curcumol inhibits LSEC angiogenesis in liver fibrosis.

Materials And Methods: Primary rat LSECs were cultured in vitro, and various molecular experiments including real-time PCR, western blot, immunofluorescence, tube formation assay and transwell migration assay were used to clarify the potential mechanism of curcumol. Carbon tetrachloride (CCl) was applied to create a mouse liver fibrosis model. Blood and livers were taken to elucidate the efficacy of curcumol in vivo.

Key Findings: We found that curcumol could effectively inhibit LSEC angiogenesis in vitro. Interestingly, this process may depend on curcumol's inhibition of the expression of transcription factor KLF5. Mice experiment also showed that curcumol could alleviate chronic liver injury by reducing KLF5 expression. In addition, we suggested that curcumol could reduce the production of mitochondrial ROS and improve mitochondrial morphology in LSEC. More importantly, we proved that curcumol could suppress KLF5-mediated LSEC angiogenesis by inhibiting ROS/ERK signaling.

Significance: We suggested that transcription factor KLF5 could be considered as a new target molecule of curcumol in improving liver fibrosis, and pointed out that curcumol targeted ROS/ERK-mediated KLF5 expression could inhibit LSEC angiogenesis. This provided a new theoretical basis for curcumol to ameliorate liver fibrosis.
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http://dx.doi.org/10.1016/j.lfs.2020.118696DOI Listing
January 2021

Deep-Learning-Based Segmentation and Localization of White Matter Hyperintensities on Magnetic Resonance Images.

Interdiscip Sci 2020 Dec 2;12(4):438-446. Epub 2020 Nov 2.

YIWEI Medical Technology Co., Ltd, Room 1001, MAI KE LONG Building, Nanshan, ShenZhen, 518000, China.

White matter magnetic resonance hyperintensities of presumed vascular origin, which could be widely observed in elderly people, and has significant importance in multiple neurological studies. Quantitative measurement usually relies heavily on manual or semi-automatic delineation and intuitive localization, which is time-consuming and observer-dependent. Current automatic quantification methods focus mainly on the segmentation, but the spatial distribution of lesions plays a vital role in clinical diagnosis. In this study, we implemented four segmentation algorithms and compared the performances quantitatively and qualitatively on two open-access datasets. The location-specific analysis was conducted sequentially on 213 clinical patients with cerebral ischemia and lacune. The experimental results suggest that our deep-learning-based model has the potential to be integrated into the clinical workflow.
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http://dx.doi.org/10.1007/s12539-020-00398-0DOI Listing
December 2020