Publications by authors named "Zhihao Wu"

179 Publications

A zebrafish screen reveals Renin-angiotensin system inhibitors as neuroprotective via mitochondrial restoration in dopamine neurons.

Elife 2021 09 22;10. Epub 2021 Sep 22.

Department of Bioengineering and Therapeutic Sciences and Programs in BiologicalSciences and Human Genetics, University of California, San Francisco, San Francisco, United States.

Parkinson's disease (PD) is a common neurodegenerative disorder without effective disease-modifying therapeutics. Here, we establish a chemogenetic dopamine (DA) neuron ablation model in larval zebrafish with mitochondrial dysfunction and robustness suitable for high-content screening. We use this system to conduct an in vivo DA neuron imaging-based chemical screen and identify the Renin-Angiotensin-Aldosterone System (RAAS) inhibitors as significantly neuroprotective. Knockdown of the angiotensin receptor 1 () in DA neurons reveals a cell-autonomous mechanism of neuroprotection. DA neuron-specific RNA-seq identifies mitochondrial pathway gene expression that is significantly restored by RAAS inhibitor treatment. The neuroprotective effect of RAAS inhibitors is further observed in a zebrafish Gaucher disease model and -deficient PD model. Finally, examination of clinical data reveals a significant effect of RAAS inhibitors in delaying PD progression. Our findings reveal the therapeutic potential and mechanisms of targeting the RAAS pathway for neuroprotection and demonstrate a salient approach that bridges basic science to translational medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.69795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457844PMC
September 2021

Example of removing printing ink from plastic surface using quaternary ammonium-modified waste cooking oil.

Environ Technol 2021 Oct 3:1-12. Epub 2021 Oct 3.

Department of Environmental Science and Engineering, Fujian Provincial Engineering Research Center of Rural Waste Recycling Technology, Fuzhou University, Minhou, People's Republic of China.

The printing ink on the plastic surface greatly reduces the quality of recycled plastic products. In this work, quaternary ammonium-modified waste cooking oil (WCOQE) was fabricated, using waste cooking oil, epichlorohydrin and trimethylamine aqueous solution as raw materials, by ring-opening esterification and quaternary amination reaction. The synthesis conditions of WCOQE were optimized, and the structure and properties of WCOQE were characterized by FTIR, zeta potential and H NMR. Furthermore, WCOQE had excellent emulsifying performance, low kraft point, low CMC value, good foaming and stability, which could effectively reduce the surface tension of water, showing application potential in the field of plastic deinking. Importantly, compared with the waste cooking oil without deinking effect, the WCOQE had an excellent deinking performance on the ink on plastic surface, and the deinking efficiency could be improved by increasing the concentration of deinking agent, the deinking temperature, and prolonging the pre-soaking and stirring time. The results of AFM, EDS, optical photos and Leica microscope showed that the roughness changed significantly, and the ink molecules were gradually peeling off. This work highlighted the excellent potential of quaternary ammonium-modified waste cooking oil for the removal of printing inks on the plastic surface.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09593330.2021.1983026DOI Listing
October 2021

Honey bee Apis mellifera larvae gut microbial and immune, detoxication responses towards flumethrin stress.

Environ Pollut 2021 Sep 4;290:118107. Epub 2021 Sep 4.

Honeybee Research Institute, Jiangxi Agricultural University, Nanchang, 330045, PR China; Jiangxi Province Key Laboratory of Honeybee Biology and Beekeeping, Nanchang, 330045, PR China. Electronic address:

Mites are considered the worst enemy of honey bees, resulting in economic losses in agricultural production. In apiculture, flumethrin is frequently used to control mites. It causes residues of flumethrin in colonies which may threaten honey bees, especially for larvae. Still, the impact of flumethrin-induced dysbiosis on honey bees larval health has not been fully elucidated, and any impact of microbiota for decomposing flumethrin in honey bees is also poorly understood. In this study, 2-day-old larvae were fed with different flumethrin-sucrose solutions (0, 0.5, 5, 50 mg/kg) and the dose increased daily (1.5, 2, 2.5 and 3 μL) until capped, thereafter the expression level of two immune genes (hymenoptaecin, defensin1) and two detoxication-related genes (GST, catalase) were measured. Meanwhile, the effect of flumethrin on honey bee larvae (Apis mellifera) gut microbes was also explored via 16S rRNA Illumina deep sequencing. We found that flumethrin at 5 mg/kg triggered the over expression of immune-related genes in larvae, while the larval detoxification-related genes were up-regulated when the concentrations reached 50 mg/kg. Moreover, the abundance and diversity of microbes in flumethrin-treated groups (over 0.5 mg/kg) were significantly lower than control group, but it increased with flumethrin concentrations among the flumethrin-treated groups. Our results revealed that microbes served as a barrier in the honey bee gut and were able to protect honey bee larvae to a certain extent, and reduce the stress of flumethrin on honey bee larvae. In addition, as the concentration of flumethrin increases, honey bee larvae activate their immune system then detoxification system to defend against the potential threat of flumethrin. This is the first report on the impact of flumethrin on gut microbiota in honey bees larvae. The findings revealed new fundamental insights regarding immune and detoxification of host-associated microbiota.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.118107DOI Listing
September 2021

Targeting Mitochondrial Oxidative Phosphorylation in Glioblastoma Therapy.

Neuromolecular Med 2021 Sep 6. Epub 2021 Sep 6.

Department of Neurosurgery, Dell Medical School, The University of Texas at Austin, Austin, TX, 78712, USA.

As a multi-functional cellular organelle, mitochondrial metabolic reprogramming is well recognized as a hallmark of cancer. The center of mitochondrial metabolism is oxidative phosphorylation (OXPHOS), in which cells use enzymes to oxidize nutrients, thereby converting the chemical energy to the biological energy currency ATPs. OXPHOS also creates the mitochondrial membrane potential and serve as the driving force of other mitochondrial metabolic pathways and experiences significant reshape in the different stages of tumor progression. In this minireview, we reviewed the major mitochondrial pathways that are connected to OXPHOS and are affected in cancer cells. In addition, we summarized the function of novel bio-active molecules targeting mitochondrial metabolic processes such as OXPHOS, mitochondrial membrane potential and mitochondrial dynamics. These molecules exhibit intriguing preclinical and clinical results and have been proven to be promising antitumor candidates in recent studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12017-021-08678-8DOI Listing
September 2021

Hsa_circ_0040809 regulates colorectal cancer development by upregulating methyltransferase DNMT1 via targeting miR-515-5p.

J Gene Med 2021 Aug 26:e3388. Epub 2021 Aug 26.

Department of Pathology, First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China.

Background: Circular RNAs (circRNAs) are key regulators in the progression of various cancers. Abnormal DNA methylation patterns feature prominently in the regulation of the expression of tumor-related genes. This study is aimed at investigating the molecular mechanism of circ_0040809 affecting colorectal cancer (CRC) progression by regulating DNA methyltransferase 1 (DNMT1).

Methods: circ_0040809 was selected from the circRNA microarray datasets (GSE142837 and GSE138589). Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the expression of circ_0040809, miR-515-5p, and DNMT1 mRNA in paired cancerous and paracancerous tissues of 40 CRC patients, as well as in cell lines. Western blotting was conducted for detecting DNMT1 protein expression in CRC cells. Cell proliferation, migration, and apoptosis were assessed through CCK-8, Transwell, and flow cytometry assays. Bioinformatics and dual-luciferase gene assay were conducted to predict and verify, respectively, the targeted relationships between circ_0040809 and miR-515-5p, as well as between miR-515-5p and DNMT1 mRNA.

Results: In CRC tissues and cells, circ_0040809 and DNMT1 expression are markedly increased, whereas miR-515-5p expression is decreased. Also, high circ_0040809 expression is significantly linked to shorter overall survival. Cell function compensation experiments reveal that circ_0040809 silencing inhibits CRC cell proliferation and migration and promotes apoptosis, while circ_0040809 overexpression has the opposite effects. Mechanistically, circ_0040809 competitively binds to miR-515-5p to elevate DNMT1 expression. Rescue assay reveals that overexpressed miR-515-5p partly counteracts the tumor-facilitating impact of circ_0040809.

Conclusions: circ_0040809 facilitates CRC cell proliferation and migration, and inhibits apoptosis, through modulating miR-515-5p/DNMT1 axis. Our study implies that targeting circ_0040809 may be a therapy strategy for CRC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgm.3388DOI Listing
August 2021

Insight into degradation mechanism of PCBs from thermal desorption off-gas over iron-based catalysts.

Chemosphere 2021 Aug 19;286(Pt 3):131925. Epub 2021 Aug 19.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China. Electronic address:

Iron-based catalysts were developed to achieve the hydrodechlorination (HDC)/oxidation of polychlorinated biphenyls (PCBs) from thermal desorption off-gas, and FeO/γ-AlO showed higher dechlorination efficiency than FeO/γ-AlO. The optimal Fe loading resulted in 95.5% degradation efficiency and 76.9% toxicity reduction of gaseous PCBs, and the optimal FeO/γ-AlO exhibited excellent stability during a 60-h test. The gas chromatography-mass spectrometry analysis of intermediate products indicated the presence of two competitive degradation pathways, namely, hydrodechlorination and oxidation with FeO/γ-AlO as catalyst. During the first stage (reductive dechlorination), the reductive activity of iron-based catalysts was effectively enhanced in the presence of water, which was confirmed by density functional theory (DFT) calculations. The removal of chlorine atoms was found in the order of meta > para > ortho. During the second stage (oxidation), hydroxyl and superoxide anion radicals were found to attack PCBs on the surface of FeO/γ-AlO. This study provides an insight into the HDC and oxidation mechanism of gaseous PCBs over iron-based catalysts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.131925DOI Listing
August 2021

Editorial: Molecular Links Between Mitochondrial Damage and Parkinson's Disease and Related Disorders.

Front Cell Dev Biol 2021 6;9:734475. Epub 2021 Aug 6.

Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.734475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377497PMC
August 2021

Sexual dimorphism of DNA and histone methylation profiles in the gonads of the olive flounder Paralichthys olivaceus.

Fish Physiol Biochem 2021 Oct 15;47(5):1341-1352. Epub 2021 Jul 15.

Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, 266071, Qingdao, China.

DNA methylation and histone methylation are two types of the most important epigenetic modifications. However, research on their differential expression in gonads of male and female fish is limited. In this study, we examined the characteristics of DNA methylation and tri-methylation of lysine 4 of histone H3 (H3K4me3) modification profiles in the gonads of the wild-type and meio-gynogenetic olive flounders Paralichthys olivaceus. Enzyme-linked immunosorbent assay (ELISA) analysis revealed that the global DNA methylation level was higher in the testis than in the ovary. Real-time quantitative PCR (qPCR) results indicated that maintenance DNA methyltransferase gene dnmt1 and de novo DNA methyltransferase gene dnmt3a are highly expressed in the ovary, while DNA demethyltransferase genes tets are highly expressed in the testis. The inconsistency of DNA methylation and methyltransferase genes in the gonads might associate with the differential distribution in the testis. 5-mC mainly located in the spermatids of the testis was shown with immunohistochemistry (IHC). Furtherly, dnmt3a and tets are mainly located in spermatocytes and oocytes with in situ hybridization (ISH) analysis. As for H3K4me3, total level is higher in the ovary detected with western blot assay. IHC results showed that the signals of H3K4me3 in Sertoli cells of the testis were stronger than those in spermatocytes and spermatids. Methyltransferase gene kmt2b and demethylase genes kdm5a and kdm5c also exhibit much higher expression in the testis with qPCR, and ISH stronger signals of kmt2b and kdm5s were detected in spermatocytes. These results implied that DNA methylation and H3K4me3 are involved in the flounder sex differences and gametogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10695-021-00986-xDOI Listing
October 2021

Multi-particle interaction in AC electric field driven by dielectrophoresis force.

Electrophoresis 2021 Jun 12. Epub 2021 Jun 12.

State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou, 570228, China.

When the dielectrophoresis technology is used to manipulate micron-sized particles, the interaction between particles should not be ignored because of the particle-particle interaction. Especially, when multiple particles (number of particles is above 2) are simultaneously manipulated, the interaction between neighboring particles will affect the results of the manipulation. This research investigates the interaction of particles caused dielectrophoresis effect by the Arbitrary Lagrangian-Eulerian (ALE) method based on the hypothesis of the thin layer of the electric double layer at the microscale. The mathematics model can be solved simultaneously by the finite element method for the AC electric field, the flow field around the suspended particles and the particle mechanics at the micrometer scale. In this study, the particle conductivity and the direction of the electric field are investigated, we find that particle conductivity and electric field direction pose an impact on particle movement, and the research reveal the law of microparticle dielectrophoresis movement, which could offer theoretical and technology support to profoundly understand the precise manipulation of particles in microfluidic chips by the dielectrophoresis effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/elps.202100094DOI Listing
June 2021

Evaluation of Mitochondrial Function and Morphology in Drosophila.

Methods Mol Biol 2021 ;2322:195-206

Department of Biological Sciences, Dedman College of Humanities and Sciences, Southern Methodist University, Dallas, TX, USA.

Drosophila melanogaster (Drosophila, fruit fly, or fly) is an important model organism in the studies of molecular genetic analysis and mechanism of Parkinson's disease (PD), benefiting from its powerful genetic tools and massive available genetic mutants. People have generated different fly models to mimic the inherited PDs and most of them have obvious mitochondrial abnormalities. Here, we describe some common approaches to analyze mitochondrial functions and morphological changes in Drosophila PD models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-1495-2_19DOI Listing
August 2021

Urolithin A Inhibits Epithelial-Mesenchymal Transition in Lung Cancer Cells via P53-Mdm2-Snail Pathway.

Onco Targets Ther 2021 17;14:3199-3208. Epub 2021 May 17.

Research Laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu, 241001, People's Republic of China.

Purpose: The epithelial-to-mesenchymal transition (EMT) is a fundamental process in tumor progression that endows cancer cells with migratory and invasive potential. Snail, a zinc finger transcriptional repressor, plays an important role in the induction of EMT by directly repressing the key epithelial marker E-cadherin. Here, we assessed the effect of urolithin A, a major metabolite from pomegranate ellagitannins, on Snail expression and EMT process.

Methods: The role of Snail in urolithin A-induced EMT inhibition in lung cancer cells was explored by wound healing assay and cell invasion assay. The qRT-PCR and CHX assay were performed to investigate how urolithin A regulates Snail expression. Immunoprecipitation assays were established to determine the effects of urolithin A in mdm2-Snail interaction. In addition, the expression of p53 was manipulated to explore its effect on the expression of mdm2 and Snail.

Results: The urolithin A dose-dependently upregulated epithelial marker and decreased mesenchymal markers in lung cancer cells. In addition, exposure to urolithin A decreased cell migratory and invasive capacity. We have further demonstrated that urolithin A inhibits lung cancer cell EMT by decreasing Snail protein expression and activity. Mechanistically, urolithin A disrupts the interaction of p53 and mdm2 which leads Snail ubiquitination and degradation.

Conclusion: We conclude that urolithin A could inhibit EMT process by controlling mainly Snail expression. These results highlighted the role of pomegranate in regulation of EMT program in lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S305595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139733PMC
May 2021

Prevalence and impact of fibrinolytic dysregulation in patients with acute coronary syndromes.

Thromb J 2021 May 22;19(1):33. Epub 2021 May 22.

Department of Cardiology, Dongguan People's Hospital, Southern Medical University, Dongguan, 523059, Guangdong, China.

Objective: Dual antiplatelet therapy can reduce coronary thrombosis and improve the prognosis in patients with acute coronary syndrome (ACS). However, there was limited prognostic information about fibrinolytic dysregulation in patients with ACS. This study is aimed to evaluated the prevalence and impact of fibrinolytic dysregulation in patients with acute coronary syndrome (ACS).

Methods: We retrospectively analyzed coagulation and fibrinolysis related indexes of ACS in hospitalized adults with rapid thrombelastography between May 2016 and December 2018. All of the follow-up visits were ended by December 2019. The primary outcome was the occurrence of major adverse cardiovascular events (MACEs), which included unstable angina pectoris, non-fatal myocardial infarction, non-fatal cerebral infarction, heart failure and all-cause death.

Results: Three hundred thirty-eight patients were finally included with an average age of 62.5 ± 12.8 years old, 273 (80.5%) were males, 137(40.5%) patients were with ST-elevation myocardial infraction. Fibrinolysis shutdown (LY30<0.8%) and hyperfibrinolysis (LY30 >3.0%) were observed among 163 (48.2%) and 76(22.5%) patients, respectively. During a total of 603.2 person·years of follow-up period, 77 MACEs occurred (22.8%). Multivariate Cox regression analysis indicated that LY30 [HR: 1.101, 95% CI: 1.010-1.200, P = 0.028] was independently correlated with the occurrence of MACEs. The hazard ratios pertaining to MACEs in patients with fibrinolysis shutdown and hyperfibrinolysis compared with those in the physiologic range (LY30: 0.8-3.0%) were 1.196 [HR: 1.196, 95% CI: 0.679-2.109,P = 0.535] and 2.275 [HR: 2.275, 95% CI: 1.241-4.172, P = 0.003], respectively.

Conclusions: Fibrinolytic dysregulation is very common in selected patients with ACS, and hyperfibrinolysis (LY30 > 3%) is associated with poor outcomes in patients with ACS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12959-021-00288-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141118PMC
May 2021

Mobilization and geochemistry of nutrients in sediment evaluated by diffusive gradients in thin films: Significance for lake management.

J Environ Manage 2021 Aug 18;292:112770. Epub 2021 May 18.

State Environmental Protection Key Laboratory for Lake Pollution Control, Institute of Lake Environment, Chinese Research Academy of Environmental Sciences (CRAES), Beijing, 100012, China; College of Water Science, Beijing Normal University, Beijing, 100875, China.

Investigation of in-situ mobilization of both nitrogen (N) and phosphate (PO) in sediment is important for lake management strategy. In this paper, diffusion gradients in thin films (DGT) and DGT induced flux in sediments (DIFS) model are newly designed for in-situ measurement of iron (Fe), PO, nitrate (NO-N) and ammonium (NH-N), and nutrients' mobility in sediment in Lake Nanhu (China). According to DGT profiles together with physicochemical properties in sediment, (I) PO is released from (i) Fe-bound P plus loosely sorbed P in anoxic sediment and (ii) the loosely sorbed P in oxic sediment; (II) anoxic sediment inhibits nitrification and NO-N release, but it favors denitrification and dissimilatory nitrate reduction to ammonium (DNRA), leading to NH-N release; (III) Eh and organic matter are two key influence factors on mobility of PO, NO-N and NH-N. According to DIFS calculation, the dynamics of desorption and diffusion at two sites belong to (i) slow rate of resupply and (ii) fast resupply cases, respectively. Internal loadings are estimated to be 92.74 (PO), 268.1 (NH-N) and -2466 kg a (NO-N), which reflects sediment mainly acts as a source for PO and NH-N, and a sink for NO-N in water. Based on sediment P release risk index (SPRRI), P release risks in lake sediments are estimated, ranging from light to relative high level. DGT and SPRRI aid choice of restoration methods for sediment, including sediment dredging, phytoremediation and in-situ inactivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvman.2021.112770DOI Listing
August 2021

Sexually dimorphic expression and regulatory sequence of dnali1 in the olive flounder Paralichthys olivaceus.

Mol Biol Rep 2021 Apr 20;48(4):3529-3540. Epub 2021 Apr 20.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao, 266071, P.R. China.

Dynein axonemal light intermediate chain 1 (dnali1) is an important part of axonemal dyneins and plays an important role in the growth and development of animals. However, there is little information about dnali1 in fish. Herein, we cloned dnali1 gene from the genome of olive flounder (Paralichthys olivaceus), a commercially important maricultured fish in China, Japan, and Korea, and analyzed its expression patterns in different gender fish. The flounder dnali1 DNA sequence contained a 771 bp open reading frame (ORF), two different sizes of 5' untranslated region (5'UTR), and a 1499 bp 3' untranslated region (3'UTR). Two duplicated 922 nt fragments were found in dnali1 mRNA. The first fragment contained the downstream coding region and the front portion of 3'UTR, and the second fragment was entirely located in 3'UTR. Multiple alignments indicated that the flounder Dnali1 protein contained the putative conserved coiled-coil domain. Its expression showed sexually dimorphic with predominant expression in the flounder testis, and lower expression in other tissues. The gene with the longer 5'UTR was specifically expressed in the testis. The highest expression level in the testis was detected at stages IV and V. Transient expression analysis showed that the 922 bp repeated sequence 3'UTR of dnali1 down-regulated the expression of GFP at the early stage in zebrafish. The flounder dnali1 might play an important role in the testis, especially in the period of spermatogenesis, and the 5'UTR and the repetitive sequences in 3'UTR might contain some regulatory elements for the cilia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-021-06342-9DOI Listing
April 2021

Resveratrol induces PD-L1 expression through snail-driven activation of Wnt pathway in lung cancer cells.

J Cancer Res Clin Oncol 2021 Apr 20;147(4):1101-1113. Epub 2021 Jan 20.

Research Laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu, 241001, China.

Purpose: Recent clinical trials with agents targeting immune checkpoint pathway have emerged as an important therapeutic approach for a broad range of cancer types. Resveratrol has been shown to possess cancer preventive and therapeutic effects and has potential to be chemotherapeutic agent/adjuvant. Here, we assessed the effect of resveratrol on immune checkpoint pathways.

Methods: The expression patterns of Wnt components and PD-L1 were examined by Western blot, Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction, the promoter activity was determined by luciferase reporter assay, apoptosis was analyzed by flow cytometry and the ability of the resveratrol to modulate T cell function was assessed in a co-culture system.

Results: Although the dose-, and cell-type dependent effects of resveratrol on PD-L1 expression have been reported, we show here that resveratrol dose-dependently upregulates PD-L1 expression at the range of pharmacologic-achievable concentrations in lung cancer cells and that is essential for suppression of T-cell-mediated immune response. We also found that Wnt pathway is critical for mediating resveratrol-induced PD-L1 upregulation. Mechanistically, resveratrol activates SirT1 deacetylase to deacetylate and stabilize transcriptional factor Snail. Snail in turn inhibits transcription of Axin2, which leads in disassembly of destruction complex and enhanced binding of β-catenin/TCF to PD-L1 promoter.

Conclusion: We conclude that resveratrol is capable to suppress anti-tumor immunity by controlling mainly PD-L1 expression. This finding will extend the understanding of resveratrol in regulation of tumor immunity and is relevant to the debate on resveratrol supplements for lung cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-021-03510-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954741PMC
April 2021

Corrigendum to "A lactate-induced Snail/STAT3 pathway drives GPR81 expression in lung cancer cells" [Biochim. Biophys. Acta (BBA) - Mol. Basis Dis. 1866 (2020) Article 165576].

Biochim Biophys Acta Mol Basis Dis 2021 Mar 6;1867(3):166030. Epub 2020 Dec 6.

Research laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu 241001, China; School of Preclinical Medicine, Wannan Medical College, Wuhu 241001, China; Anhui Province Key Laboratory of Active Biological Macro-molecules Research, Wannan Medical College, Wuhu 241001, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbadis.2020.166030DOI Listing
March 2021

Artificial intelligence method for predicting the maximum stress of an off-center casing under non-uniform ground stress with support vector machine.

Sci China Technol Sci 2020 Nov 16:1-9. Epub 2020 Nov 16.

Shanghai Institute of Applied Mathematics and Mechanics, School of Mechanics and Engineering Science, Shanghai University, Shanghai, 200444 China.

The situation of an off-center casing under non-uniform ground stress can occur in the process of drilling a salt-gypsum formation, and the related casing stress calculation has not yet been solved analytically. In addition, the experimental equipment in many cases cannot meet the actual conditions and the experimental cost is very high. These comprehensive factors cause the existing casing design to not meet the actual conditions and cause casing deformation, affecting the drilling operation in Tarim oil field. The finite element method is the only effective method to solve this problem at present, but the re-modelling process is time-consuming because of the changes in the parameters, such as the cement properties, casing centrality, and the casing size. In this article, an artificial intelligence method based on support vector machine (SVM) to predict the maximum stress of an off-center casing under non-uniform ground stress has been proposed. After a program based on a radial basis function (RBF)-support vector regression (SVR) (-SVR) model was established and validated, we constructed a data sample with a capacity of 120 by using the finite element method, which could meet the demand of the nine-factor -SVR model to predict the maximum stress of the casing. The results showed that the artificial intelligence prediction method proposed in this manuscript had satisfactory prediction accuracy and could be effectively used to predict the maximum stress of an off-center casing under complex downhole conditions.

Electronic Supplementary Material: Supplementary material is available for this article at 10.1007/s11431-019-1694-4 and is accessible for authorized users.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11431-019-1694-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678604PMC
November 2020

Study on antimony mobility in a contaminated shallow lake sediment using the diffusive gradients in thin films technique.

Chemosphere 2021 Mar 19;267:128913. Epub 2020 Nov 19.

National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environmental Protection Key Laboratory for Lake Pollution Control, Chinese Research Academy of Environmental Sciences, Anwai, Beiyuan, Beijing, 100012, China.

Antimony is a priority environmental contaminant. Increasing attention is being paid to the behaviors and mobilities of the various Sb species in the environment. Sb speciation in the environment and the mobilities of Sb species at mining sites have been studied well, but Sb speciation and mobility in shallow lakes requires further study. Here, we studied Sb behavior in sediment of a shallow lake in the plain rivers network in Taihu Basin that suffers continual Sb inputs from textile plants. The diffusive gradients in thin films techniques (DGT) made of zirconium oxide based binding resin gel (ZrO-Chelex), agarose diffusive gel and polyvinylidene fluoride filter were deployed in water and sediment to obtain a high-resolution record in situ. The results indicated that (1) pollutants released by textile plants caused relatively high Sb(Ⅲ), Sb(Ⅴ) and organoantimony concentrations in the eutrophic shallow lake, (2) Sb was seldomly mobile in the oxic layer where Sb(Ⅲ) was sorbed on Fe(Ⅲ) oxides and gradually formed Fe-Sb complexes in the sediment, but in the anoxic environment (oxidation-reduction potential: 366 - -344 mv) Sb(V), Fe(Ⅱ) and P (V) were simultaneously released to resupply the porewater, (3) the release of Sb from solid phase is decided by the redox condition, and the rate of release is dependent on the labile Sb content of the sediment. The mobility of Sb should be given sufficient attention when the potential ecological risk of metal(loid)s in shallow lakes and wetlands sediment are evaluated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.128913DOI Listing
March 2021

Lactate-induced MRP1 expression contributes to metabolism-based etoposide resistance in non-small cell lung cancer cells.

Cell Commun Signal 2020 10 23;18(1):167. Epub 2020 Oct 23.

Research laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu, 241001, China.

Background: Metabolic reprogramming contributes significantly to tumor development and is tightly linked to drug resistance. The chemotherapeutic agent etoposide (VP-16) has been used clinically in the treatment of lung cancer but possess different sensitivity and efficacy towards SCLC and NSCLC. Here, we assessed the impact of etoposide on glycolytic metabolism in SCLC and NSCLC cell lines and investigated the role of metabolic rewiring in mediating etoposide resistance.

Methods: glycolytic differences of drug-treated cancer cells were determined by extracellular acidification rate (ECAR), glucose consumption, lactate production and western blot. DNA damage was evaluated by the comet assay and western blot. Chemoresistant cancer cells were analyzed by viability, apoptosis and western blot. Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction.

Results: Here we showed that exposure to chemotherapeutic drug etoposide induces an exacerbation of ROS production which activates HIF-1α-mediated the metabolic reprogramming toward increased glycolysis and lactate production in non-small cell lung cancer (NSCLC). We identified lactic acidosis as the key that confers multidrug resistance through upregulation of multidrug resistance-associated protein 1 (MRP1, encoded by ABCC1), a member of ATP-binding cassette (ABC) transporter family. Mechanistically, lactic acid coordinates TGF-β1/Snail and TAZ/AP-1 pathway to induce formation of Snail/TAZ/AP-1 complex at the MRP1/ABCC1 promoter. Induction of MRP1 expression inhibits genotoxic and apoptotic effects of chemotherapeutic drugs by increasing drug efflux. Furthermore, titration of lactic acid with NaHCO was sufficient to overcome resistance.

Conclusions: The chemotherapeutic drug etoposide induces the shift toward aerobic glycolysis in the NSCLC rather than SCLC cell lines. The increased lactic acid in extracellular environment plays important role in etoposide resistance through upregulation of MRP expression. These data provide first evidence for the increased lactate production, upon drug treatment, contributes to adaptive resistance in NSCLC and reveal potential vulnerabilities of lactate metabolism and/or pathway suitable for therapeutic targeting. Video Abstract The chemotherapeutic drug etoposide induces metabolic reprogramming towards glycolysis in the NSCLC cells. The secreted lactic acid coordinates TGF-β1/Snail and TAZ/AP-1 pathway to activate the expression of MRP1/ABCC1 protein, thus contributing to chemoresistance in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12964-020-00653-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583203PMC
October 2020

Quality-control mechanisms targeting translationally stalled and C-terminally extended poly(GR) associated with ALS/FTD.

Proc Natl Acad Sci U S A 2020 10 21;117(40):25104-25115. Epub 2020 Sep 21.

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305;

Maintaining the fidelity of nascent peptide chain (NP) synthesis is essential for proteome integrity and cellular health. Ribosome-associated quality control (RQC) serves to resolve stalled translation, during which untemplated Ala/Thr residues are added C terminally to stalled peptide, as shown during C-terminal Ala and Thr addition (CAT-tailing) in yeast. The mechanism and biological effects of CAT-tailing-like activity in metazoans remain unclear. Here we show that CAT-tailing-like modification of poly(GR), a dipeptide repeat derived from amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD)-associated (G4C2) repeat expansion in , contributes to disease. We find that poly(GR) can act as a mitochondria-targeting signal, causing some poly(GR) to be cotranslationally imported into mitochondria. However, poly(GR) translation on mitochondrial surface is frequently stalled, triggering RQC and CAT-tailing-like C-terminal extension (CTE). CTE promotes poly(GR) stabilization, aggregation, and toxicity. Our genetic studies in uncovered an important role of the mitochondrial protease YME1L in clearing poly(GR), revealing mitochondria as major sites of poly(GR) metabolism. Moreover, the mitochondria-associated noncanonical Notch signaling pathway impinges on the RQC machinery to restrain poly(GR) accumulation, at least in part through the AKT/VCP axis. The conserved actions of YME1L and noncanonical Notch signaling in animal models and patient cells support their fundamental involvement in ALS/FTD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2005506117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547246PMC
October 2020

Hacking single-photon avalanche detectors in quantum key distribution via pulse illumination.

Opt Express 2020 Aug;28(17):25574-25590

Quantum key distribution (QKD) has been proved to be information-theoretically secure in theory. Unfortunately, the imperfect devices in practice compromise its security. Thus, to improve the security property of practical QKD systems, a commonly used method is to patch the loopholes in the existing QKD systems. However, in this work, we show an adversary's capability of exploiting the imperfection of the patch itself to bypass the patch. Specifically, we experimentally demonstrate that, in the detector under test, the patch of photocurrent monitor against the detector blinding attack can be defeated by the pulse illumination attack proposed in this paper. We also analyze the secret key rate under the pulse illumination attack, which theoretically confirmed that Eve can conduct the attack to learn the secret key. This work indicates the importance of inspecting the security loopholes in a detection unit to further understand their impacts on a QKD system. The method of pulse illumination attack can be a general testing item in the security evaluation standard of QKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.397962DOI Listing
August 2020

Whole blood dynamic platelet aggregation counting and 1-year clinical outcomes in patients with coronary heart diseases treated with clopidogrel.

Platelets 2021 Oct 6;32(7):968-974. Epub 2020 Sep 6.

Department of Cardiology, Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, China.

In the setting of coronary heart diseases (CHDs) on treatment with clopidogrel, ADP-induced platelet aggregation has been demonstrated with ischemic events. However, there were very limited data for predicting ischemic events by platelet function test via dynamic platelet aggregation counting (DPAC). The present study aimed to evaluate the relationship between adenosine diphosphate (ADP)-induced whole blood platelet aggregation rates (PARs) and clinical outcomes in patients with CHDs on treatment with clopidogrel. We have retrospectively analyzed the clinical data of consecutive patients with CHDs based on the electronic medical records between May 2016 and December 2018. The primary endpoint was a composite endpoint events (CEEs) of ischemic cardiovascular events (including acute coronary syndrome, heart failure, transient ischemic attack, and cerebral infarction) and all-cause death. A total of 490 patients (mean age 66.6 years, 71% man) were received ADP-induced PARs via DPAC. On follow-up (mean 374 days), 107 subjects (21.8%) developed CEEs. Cox regression analysis indicated that the risk of CEEs was independently associated with ADP-induced whole blood PARs [HR: 1.023, 95% CI: 1.005-1.041, = .011]. The distribution of CYP2C19 loss of function gene was higher in patients with on-treatment platelet hyperresponsiveness (10/12 vs 38/75, = .042). In conclusion, ADP-induced whole blood PARs via DPAC is feasible, which can predict the incidence of 1-year CEEs in patients with CHDs on treatment with clopidogrel. CYP2C19 gene polymorphism was associated with clopidogrel on-treatment platelet hyperresponsiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09537104.2020.1817886DOI Listing
October 2021

Sex-Dependent RNA Editing and -adenosine RNA Methylation Profiling in the Gonads of a Fish, the Olive Flounder ().

Front Cell Dev Biol 2020 5;8:751. Epub 2020 Aug 5.

Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

Adenosine-to-inosine (A-to-I) editing and -methyladenosine (m6A) are two of the most abundant RNA modifications. Here, we examined the characteristics of the RNA editing and transcriptome-wide m6A modification profile in the gonads of the olive flounder, , an important maricultured fish in Asia. The gonadal differentiation and development of the flounder are controlled by genetic as well as environmental factors, and the epigenetic mechanism may play an important role. In total, 742 RNA editing events were identified, 459 of which caused A to I conversion. Most A-to-I sites were located in 3'UTRs, while 61 were detected in coding regions (CDs). The number of editing sites in the testis was higher than that in the ovary. Transcriptome-wide analyses showed that more than one-half of the transcribed genes presented an m6A modification in the flounder gonads, and approximately 60% of the differentially expressed genes (DEGs) between the testis and ovary appeared to be negatively correlated with m6A methylation enrichment. Further analyses revealed that the mRNA expression of some sex-related genes (e.g., and ) in the gonads may be regulated by changes in mRNA m6A enrichment. Functional enrichment analysis indicated that the RNA editing and m6A modifications were enriched in several canonical pathways (e.g., Wnt and MAPK signaling pathways) in fish gonads and in some pathways whose roles have not been investigated in relation to fish sex differentiation and gonadal development (e.g., PPAR and RNA degradation pathways). There were 125 genes that were modified by both A-to-I editing and m6A, but the two types of modifications mostly occurred at different sites. Our results suggested that the presence of sex-specific RNA modifications may be involved in the regulation of gonadal development and gametogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.00751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419692PMC
August 2020

Altered MICOS Morphology and Mitochondrial Ion Homeostasis Contribute to Poly(GR) Toxicity Associated with C9-ALS/FTD.

Cell Rep 2020 08;32(5):107989

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

Amyotrophic lateral sclerosis (ALS) manifests pathological changes in motor neurons and various other cell types. Compared to motor neurons, the contribution of the other cell types to the ALS phenotypes is understudied. G4C2 repeat expansion in C9ORF72 is the most common genetic cause of ALS along with frontotemporal dementia (C9-ALS/FTD), with increasing evidence supporting repeat-encoded poly(GR) in disease pathogenesis. Here, we show in Drosophila muscle that poly(GR) enters mitochondria and interacts with components of the Mitochondrial Contact Site and Cristae Organizing System (MICOS), altering MICOS dynamics and intra-subunit interactions. This impairs mitochondrial inner membrane structure, ion homeostasis, mitochondrial metabolism, and muscle integrity. Similar mitochondrial defects are observed in patient fibroblasts. Genetic manipulation of MICOS components or pharmacological restoration of ion homeostasis with nigericin effectively rescue the mitochondrial pathology and disease phenotypes in both systems. These results implicate MICOS-regulated ion homeostasis in C9-ALS pathogenesis and suggest potential new therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.107989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433775PMC
August 2020

Transcription profiles and fatty acid composition of the artificial induced triploid alevin in Atlantic salmon Salmo salar.

Theriogenology 2020 Oct 13;155:49-59. Epub 2020 Jun 13.

Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, PR China. Electronic address:

Triploid Atlantic salmon Salmo salar is commercially available and ideal means of achieving sterility in fish. The expression patterns of triploid parr and smolt were described before. However, little is known about the gene expression and fatty acid composition of triploid alevins at endogenous nutritional stage, which is an important period for their survival and development. In this study, the development of the diploid and triploid Atlantic salmon embryos and hatched alevins before feeding was compared, and the results showed that there was no obvious morphological difference between them. And then, the transcription profiles of the triploid and diploid alevins on 3, 23 and 33 days post hatching (dph) were investigated by using RNA-seq after the yolk sacs were removed. There were more differentially expressed genes (DEGs) on 3 dph (2925) than those on 23 (589) and 33 dph (606). Compared with the diploid groups, the up-regulated genes in the triploid groups at the three sampling times were 1189, 339 and 340, respectively, while 1736, 250 and 266 genes were down-regulated. There were 2088 and 5215 DEGs on 23 and 33 dph compared with on 3 dph in the diploid groups, while 6533 and 9340 DEGS on 23 and 33 dph compared with 3 dph in the triploid groups. The functional enrichment analysis showed that the DEGs were mainly enriched to digestion and metabolism function, especially on 33 dph when the larvae were about to feeding. Meanwhile, 15 out of 22 kinds of fatty acids of alevins on 33 dph showed significant differences (P < 0.05), in which all the fatty acids contents in the triploid were lower. The results indicated the specific nutritional requirement in the triploid was represented as early as yolk sac stage. The present study gave an important vision in triploid Atlantic salmon breeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.theriogenology.2020.06.007DOI Listing
October 2020

Fluorescence-Scattering Dual-Signal Response of Carbon [email protected] for Phosphate Ratiometric Detection.

ACS Sens 2020 07 13;5(7):2211-2220. Epub 2020 Jul 13.

College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.

Ratiometric fluorescence has drawn extensive attention owing to its self-calibration property. However, it is difficult to obtain appropriate fluorescent materials that can be excited under one excitation and possess well-resolved signals simultaneously. In this work, with the optical properties of the fluorescence of carbon dots (CDs) and the second-order scattering (SOS) of ZIF-90 (zeolitic imidazole frameworks-90) nanoparticles, the synthesized [email protected] can be applied to phosphate (PO) ratiometric detection. The fluorescence of CDs is greatly suppressed through encapsulating CDs into ZIF-90. Nevertheless, the SOS is quite obvious due to the high scattering intensity of large size ZIF-90. The competitive coordination between PO and the metal node of ZIF-90 decomposes [email protected], leading to the restoration of fluorescence and the diminution of SOS. On the basis of the PO-induced ZIF-90 decomposition and CD release, a novel method for PO ratiometric detection is developed through the dual-signal response of the fluorescence scattering. Under the optimal condition, the method shows a linear range from 1.0 to 50.0 μmol L with a detection limit of 0.23 μmol L. Furthermore, the probes are employed to assess PO in practical aqueous samples successfully. Compared with the traditional approach, which only records fluorescence signals, the method reported here provides a new strategy to design ratiometric sensors by fluorescence and scattering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssensors.0c00853DOI Listing
July 2020

Amh dominant expression in Sertoli cells during the testicular differentiation and development stages in the olive flounder Paralichthys olivaceus.

Gene 2020 Sep 15;755:144906. Epub 2020 Jun 15.

Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China. Electronic address:

The olive flounder Paralichthys olivaceus, an important marine fish, shows gender differences in growth. The mechanism on its gonadal differentiation direction affected with exogenous factors still needs to be clarified. The anti-Müllerian hormone (amh) gene is involved in fish testicular differentiation and maintenance. The aim of this study was to investigate the expression of the flounder amh in tissues and the gonads. The quantitative expression analysis results showed that it was highly expressed in the testis, especially in the testis at stages I - IV (P < 0.05). Also, amh was detected in Sertoli cells surrounding spermatogonia and peripheral seminiferous lobule of the testis with in situ hybridization (ISH) and immunohistochemistry (IHC). During the differentiation period, the amh expression in the testis of the tamoxifen treatment group (100 ppm) was higher than that in the ovary of the 17β-estradiol (E2, 5 ppm) group, and the expression levels of amh during process of the male differentiation in the tamoxifen group were higher than those in the 17ɑ-methyltestosterone (MT, 5 ppm) group (P < 0.05). ISH results also exhibited that amh was expressed in the somatic cells that surrounded the germ cells of juvenile flounder similar to adult ones. Furthermore, the flounder gonads in the tamoxifen group maintained more germ cells and somatic cells than those in the MT group from 20 to 80 mm total length (TL). Especially, at 60 and 80 mm TL, the numbers of germ and somatic cells in the tamoxifen group were significantly higher than those in the MT group (P < 0.05). In summary, amh might initiate the process of testicular differentiation, and is involved in the early development and maintenance of testis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2020.144906DOI Listing
September 2020

Knockdown of Dinoflagellate Condensin Subunit Leads to S-Phase Impediment and Decompaction of Liquid Crystalline Chromosomes.

Microorganisms 2020 Apr 14;8(4). Epub 2020 Apr 14.

Division of Life Science, Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong Special Administrative Region, China.

Dinoflagellates have some of the largest genomes, and their liquid-crystalline chromosomes (LCCs) have high degrees of non-nucleosomal superhelicity with cation-mediated DNA condensation. It is currently unknown if condensins, pentameric protein complexes containing structural maintenance of chromosomes 2/4, commonly involved in eukaryotic chromosomes condensation in preparation for M phase, may be involved in the LCC structure. We find that CcSMC4p (dinoflagellate SMC4 homolog) level peaked at S/G2 phase, even though LCCs do not undergo global-decondensation for replication. Despite the differences in the chromosomal packaging system, heterologous CcSMC4p expression suppressed conditional lethality of the corresponding fission yeast mutant, suggesting conservation of some canonical condensin functions. CcSMC4p-knockdown led to sustained expression of the S-phase marker PCNAp, S-phase impediment, and distorted nuclei in the early stage of CcSMC4p depletion. Prolonged CcSMC4p-knockdown resulted in aneuploidal cells and nuclear swelling with increasing LCC decompaction-decondensation. Cumulatively, our data suggested CcSMC4p function was required for dinoflagellate S-phase progression, and we propose that condensin-mediated higher-order compaction provisioning is involved in the provision of local rigidity for the replisome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms8040565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232253PMC
April 2020

Embracing imperfect datasets: A review of deep learning solutions for medical image segmentation.

Med Image Anal 2020 07 3;63:101693. Epub 2020 Apr 3.

VoxelCloud, Inc., United States.

The medical imaging literature has witnessed remarkable progress in high-performing segmentation models based on convolutional neural networks. Despite the new performance highs, the recent advanced segmentation models still require large, representative, and high quality annotated datasets. However, rarely do we have a perfect training dataset, particularly in the field of medical imaging, where data and annotations are both expensive to acquire. Recently, a large body of research has studied the problem of medical image segmentation with imperfect datasets, tackling two major dataset limitations: scarce annotations where only limited annotated data is available for training, and weak annotations where the training data has only sparse annotations, noisy annotations, or image-level annotations. In this article, we provide a detailed review of the solutions above, summarizing both the technical novelties and empirical results. We further compare the benefits and requirements of the surveyed methodologies and provide our recommended solutions. We hope this survey article increases the community awareness of the techniques that are available to handle imperfect medical image segmentation datasets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.media.2020.101693DOI Listing
July 2020

Characteristics and sex dimorphism of 17β-hydroxysteroid dehydrogenase family genes in the olive flounder Paralichthys olivaceus.

J Steroid Biochem Mol Biol 2020 05 17;199:105597. Epub 2020 Jan 17.

Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, PR China. Electronic address:

Sex steroid hormones play important roles in fish sex differentiation, gonadal development and secondary sexual characteristics. Olive flounder Paralichthys olivaceus is a valuable commercial marine fish species and has marked sexual dimorphism. However, the mechanisms of action of sex hormones in flounder sex are still unclear. In this study, a total of ten Hsd17b family genes, including Hsd17b3, -4, -7, -8, -9, -10, -12a, -12b, -14 and -15, were identified in the flounder, which encoded critical enzymes acting on sex steroid synthesis and metabolism. Hsd17b genes were distributed on eight chromosomes. Hsd17b12a and -12b were located on chromosomes 19 and 7, respectively. It was speculated that these two genes were just highly similar rather than different transcripts derived from the same gene. According to the results of domain and motif analyses, they all belonged to the SDR superfamily and contained conserved Hsd17b motifs TGxxxGxG, PGxxxT, NNAG and YxxxK. Analysis of amino acid sequences predicted that Hsd17b1, -4, -7, -12a and -14 were hydrophilic proteins. The stability of Hsd17b1, -3 and -12b proteins was predicted to be low. The various Hsd17b family genes differed in tissue expression pattern, and Hsd17b10, -12a and -12b were highly expressed in the flounder ovary. Moreover, throughout gonadal development, Hsd17b3 was highly expressed in the testis, and Hsd17b1, -12a and -12b were highly expressed in the ovary, suggesting that they might play an important role in testosterone synthesis in the testis or estrogen synthesis in the ovary. Activities of Hsd17b3 at stages I-V were all significantly higher in the testis than in the ovary (P < 0.05, P < 0.01). Transfection analysis in HEK293T cells showed that Hsd17b1 and -3 were located in both the cytoplasm and nucleus. Additionally, after challenging fish with tamoxifen, Hsd17b3 expression level in the testis decreased significantly (P < 0.01), and in the ovary no significant change was observed. Moreover, the expression of Hsd17b1 in the ovary was significantly upregulated after injection with flutamide (P < 0.05). These findings introduce the characteristics of the flounder Hsd17b in subfamily, which contribute to our understanding of the regulation of sex steroid hormone synthesis in fish gonadal development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsbmb.2020.105597DOI Listing
May 2020
-->