Publications by authors named "Yiyi Li"

59 Publications

Olfaction-Related Gene Expression in the Antennae of Female Mosquitoes From Common Laboratory Strains.

Front Physiol 2021 23;12:668236. Epub 2021 Aug 23.

Department of Biology, New Mexico State University, Las Cruces, NM, United States.

Adult female mosquitoes rely on olfactory cues like carbon dioxide and other small molecules to find vertebrate hosts to acquire blood. The molecular physiology of the mosquito olfactory system is critical for their host preferences. Many laboratory strains of the yellow fever mosquito have been established since the late 19th century. These strains have been used for most molecular studies in this species. Some earlier comparative studies have identified significant physiological differences between different laboratory strains. In this study, we used a Y-tube olfactometer to determine the attraction of females of seven different strains of to a human host: UGAL, Rockefeller, Liverpool, Costa Rica, Puerto Rico, and two odorant receptor co-receptor (Orco) mutants Orco2 and Orco16. We performed RNA-seq using antennae of Rockefeller, Liverpool, Costa Rica, and Puerto Rico females. Our results showed that female from the Puerto Rico strain had significantly reduced attraction rates toward human hosts compared to all other strains. RNA-seq analyses of the antenna transcriptomes of Rockefeller, Liverpool, Costa Rica, and Puerto Rico strains revealed distinct differences in gene expression between the four strains, but conservation in gene expression patterns of known human-sensing genes. However, we identified several olfaction-related genes that significantly vary between strains, including receptors with significantly different expression in mosquitoes from the Puerto Rico strain and the other strains.
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http://dx.doi.org/10.3389/fphys.2021.668236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419471PMC
August 2021

The chicken pan-genome reveals gene content variation and a promoter region deletion in IGF2BP1 affecting body size.

Mol Biol Evol 2021 Jul 30. Epub 2021 Jul 30.

College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China.

Domestication and breeding have reshaped the genomic architecture of chicken, but the retention and loss of genomic elements during these evolutionary processes remain unclear. We present the first chicken pan-genome constructed using 664 individuals, which identified an additional ∼66.5 Mb sequences that are absent from the reference genome (GRCg6a). The constructed pan-genome encoded 20,491 predicated protein-coding genes, of which higher expression level are observed in conserved genes relative to dispensable genes. Presence/absence variation (PAV) analyses demonstrated that gene PAV in chicken was shaped by selection, genetic drift, and hybridization. PAV-based GWAS identified numerous candidate mutations related to growth, carcass composition, meat quality, or physiological traits. Among them, a deletion in the promoter region of IGF2BP1 affecting chicken body size is reported, which is supported by functional studies and extra samples. This is the first time to report the causal variant of chicken body size QTL located at chromosome 27 which was repeatedly reported. Therefore, the chicken pan-genome is a useful resource for biological discovery and breeding. It improves our understanding of chicken genome diversity and provides materials to unveil the evolution history of chicken domestication.
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http://dx.doi.org/10.1093/molbev/msab231DOI Listing
July 2021

Intercalated architecture of MAZ family layered van der Waals materials with emerging topological, magnetic and superconducting properties.

Nat Commun 2021 Apr 21;12(1):2361. Epub 2021 Apr 21.

Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, 110016, Shenyang, People's Republic of China.

The search for new two-dimensional monolayers with diverse electronic properties has attracted growing interest in recent years. Here, we present an approach to construct MAZ monolayers with a septuple-atomic-layer structure, that is, intercalating a MoS-type monolayer MZ into an InSe-type monolayer AZ. We illustrate this unique strategy by means of first-principles calculations, which not only reproduce the structures of MoSiN and MnBiTe that were already experimentally synthesized, but also predict 72 compounds that are thermodynamically and dynamically stable. Such an intercalated architecture significantly reconstructs the band structures of the constituents MZ and AZ, leading to diverse electronic properties for MAZ, which can be classified according to the total number of valence electrons. The systems with 32 and 34 valence electrons are mostly semiconductors. Whereas, those with 33 valence electrons can be nonmagnetic metals or ferromagnetic semiconductors. In particular, we find that, among the predicted compounds, (Ca,Sr)GaTe are topologically nontrivial by both the standard density functional theory and hybrid functional calculations. While VSiP is a ferromagnetic semiconductor and TaSiN is a type-I Ising superconductor. Moreover, WSiP is a direct gap semiconductor with peculiar spin-valley properties, which are robust against interlayer interactions. Our study thus provides an effective way of designing septuple-atomic-layer MAZ with unusual electronic properties to draw immediate experimental interest.
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http://dx.doi.org/10.1038/s41467-021-22324-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060390PMC
April 2021

Ceramides and sphingosine-1-phosphate mediate the distinct effects of M1/M2-macrophage infusion on liver recovery after hepatectomy.

Cell Death Dis 2021 03 26;12(4):324. Epub 2021 Mar 26.

Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Post-hepatectomy liver dysfunction is a life-threatening morbidity that lacks efficient therapy. Bioactive lipids involved in macrophage polarization crucially regulate tissue injury and regeneration. Herein, we investigate the key bioactive lipids that mediate the cytotherapeutic potential of polarized-macrophage for post-hepatectomy liver dysfunction. Untargeted lipidomics identified elevation of ceramide (CER) metabolites as signature lipid species relevant to M1/M2 polarization in mouse bone-marrow-derived-macrophages (BMDMs). M1 BMDMs expressed a CER-generation-metabolic pattern, leading to elevation of CER; M2 BMDMs expressed a CER-breakdown-metabolic pattern, resulting in upregulation of sphingosine-1-phosphate (S1P). After infusing M1- or M2-polarized BMDMs into the mouse liver after hepatectomy, we found that M1-BMDM infusion increased M1 polarization and CER accumulation, resulting in exaggeration of hepatocyte apoptosis and liver dysfunction. Conversely, M2-BMDM infusion enhanced M2 polarization and S1P generation, leading to alleviation of liver dysfunction with improved hepatocyte proliferation. Treatment of exogenous CER and S1P or inhibition CER and S1P synthesis by siRNA targeting relevant enzymes further revealed that CER induced apoptosis while S1P promoted proliferation in post-hepatectomy primary hepatocytes. In conclusion, CER and S1P are uncovered as critical lipid mediators for M1- and M2-polarized BMDMs to promote injury and regeneration in the liver after hepatectomy, respectively. Notably, the upregulation of hepatic S1P induced by M2-BMDM infusion may have therapeutic potential for post-hepatectomy liver dysfunction.
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http://dx.doi.org/10.1038/s41419-021-03616-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998020PMC
March 2021

[Aeromonas immobilized on chitosan for treating high-oil wastewater from kitchens].

Sheng Wu Gong Cheng Xue Bao 2021 Feb;37(2):615-624

School of Environmental and Resource, Zhejiang A&F University, Hangzhou 310000, Zhejiang, China.

To effectively solve the serious impact of high oil in the kitchen wastewater on the downstream treatment process, an excellent oil-degrading strain Aeromonas allosaccarophila CY-01 was immobilized to prepare Chitosan-Aeromonas pellets (CH-CY01) by using chitosan as a carrier. Oil degradation condition and efficiency of CH-CY01 pellets were assessed. The growth of immobilized CH-CY01 was almost unaffected, and the maximum degradation rate of soybean oil was 89.7%. Especially at 0.5% NaCl concentration, oil degradation efficiency of CH-CY01 was increased by 20% compared with free cells. In the presence of a surfactant (sodium dodecylbenzene sulfonate) at 1 mg/L, the degradation efficiency of oil by CH-CY01 was increased by 40%. Moreover, using the high-oil catering wastewater as the substrate, more than 80% of the solid oil was degraded with 1% (V/V) CH-CY01 pellets treatment for 7 days, significantly higher than that of free cells. In summary, immobilized CH-CY01 significantly improved the efficiency of oil degradation.
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http://dx.doi.org/10.13345/j.cjb.200315DOI Listing
February 2021

Environmental Response of 2D Thermal Cloak under Dynamic External Temperature Field.

Entropy (Basel) 2020 Apr 18;22(4). Epub 2020 Apr 18.

School of Energy Science and Engineering, Harbin Institute of Technology, Harbin 150001, China.

As a typical representative of transformation thermodynamics, which is the counterpart of transformation optics, the thermal cloak has been explored extensively while most current research focuses on the structural design instead of adaptability and practicability in a dynamic environment. The evaluation of energy processes involved in the thermal cloak under dynamic conditions are also lacking, which is essential to the engineering application of this functional structure. In this paper, based on the dynamic environment of a sinusoidal form with ambient amplitude, distribution density, phase, and temperature difference as variables, we evaluated the cloaking performance and environmental response of a 2D thermal cloak. Considering the heat dissipation and energy loss in the whole procedure, local entropy production rate and response entropy were introduced to analyze the different influences of each environmental parameter on the cloaking system. Moreover, we constructed a series of comprehensive schemes to obtain the fitting equation as well as an appropriate scope to apply the thermal cloak. The results are beneficial to the novel use of the concept of entropy and valuable for further improving the working efficiency and potential engineering applications of the thermal cloak.
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http://dx.doi.org/10.3390/e22040461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516946PMC
April 2020

Alterations of the Gut Microbiome Composition and Lipid Metabolic Profile in Radiation Enteritis.

Front Cell Infect Microbiol 2020 21;10:541178. Epub 2020 Oct 21.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Radiation enteritis (RE) is a common complication in cancer patients receiving radiotherapy. Although studies have shown the changes of this disease at clinical, pathological and other levels, the dynamic characteristics of local microbiome and metabolomics are hitherto unknown. We aimed to examine the multi-omics features of the gut microecosystem, determining the functional correlation between microbiome and lipid metabolites during RE activity. By delivering single high-dose irradiation, a RE mouse model was established. High-throughput 16S rDNA sequencing and global lipidomics analysis were performed to examine microbial and lipidomic profile changes in the gut microecosystem. Spearman correlation analysis was used to determine the functional correlation between bacteria and metabolites. Clinical samples were collected to validate the above observations. During RE activity, the intestinal inflammation of the mice was confirmed by typical signs, symptoms, imaging findings and pathological evidences. 16S datasets revealed that localized irradiation dramatically altered the gut microbial composition, resulting in a decrease ratio of to . Lipidomics analysis indicated the remarkable lipidomic profile changes in enteric epithelial barrier, determining that glycerophospholipids metabolism was correlated to RE progression with the highest relevance. Spearman correlation analysis identified that five bacteria-metabolite pairs showed the most significant functional correlation in RE, including -PC(36:0e), -DG(18:0/20:4), -PC(35:2), -PC(35:6), and -TG(18:2/18:2/20:4). These observations were partly confirmed in human specimens. Our study provided a comprehensive description of microbiota dysbiosis and lipid metabolic disorders in RE, suggesting strategies to change local microecosystem to relieve radiation injury and maintain homeostasis.
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http://dx.doi.org/10.3389/fcimb.2020.541178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609817PMC
June 2021

Identification of immune landscape signatures associated with clinical and prognostic features of hepatocellular carcinoma.

Aging (Albany NY) 2020 Oct 13;12(19):19641-19659. Epub 2020 Oct 13.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

While cancer immunotherapy has been remarkably successful in some malignancies, some cancers derive limited benefit from current immunotherapies. Here, we combined immune landscape signatures with hepatocellular carcinoma clinical and prognostic features to classify them into distinct subtypes. The immunogenomic profiles, stromal cell features and immune cell composition of the subtypes were then systematically analyzed. Two independent prognostic indexes were established based on 6 immune-related genes and 17 differentially expressed genes associated with stromal cell content. These indexes were significantly correlated with tumor mutation burden, deficient DNA mismatch repair and microsatellite instability. In addition, tumor-infiltrating lymphocytes, including activated NK cells, resting memory CD4 T-cells, eosinophils, and activated mast cells were significantly correlated with hepatocellular carcinoma survival. In conclusion, we have comprehensively described the immune landscape signatures and identified prognostic immune-associated biomarkers of hepatocellular carcinoma. Our findings highlight potential novel avenues for improving responses to immunotherapy.
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http://dx.doi.org/10.18632/aging.103977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732284PMC
October 2020

Genome-wide association study reveals the genetic determinism of growth traits in a Gushi-Anka F chicken population.

Heredity (Edinb) 2021 Feb 28;126(2):293-307. Epub 2020 Sep 28.

College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, China.

Chicken growth traits are economically important, but the relevant genetic mechanisms have not yet been elucidated. Herein, we performed a genome-wide association study to identify the variants associated with growth traits. In total, 860 chickens from a Gushi-Anka F resource population were phenotyped for 68 growth and carcass traits, and 768 samples were genotyped based on the genotyping-by-sequencing (GBS) method. Finally, 734 chickens and 321,314 SNPs remained after quality control and removal of the sex chromosomes, and these data were used to carry out a GWAS analysis. A total of 470 significant single-nucleotide polymorphisms (SNPs) for 43 of the 68 traits were detected and mapped on chromosomes (Chr) 1-6, -9, -10, -16, -18, -23, and -27. Of these, the significant SNPs in Chr1, -4, and -27 were found to be associated with more than 10 traits. Multiple traits shared significant SNPs, indicating that the same mutation in the region might have a large effect on multiple growth or carcass traits. Haplotype analysis revealed that SNPs within the candidate region of Chr1 presented a mosaic pattern. The significant SNPs and pathway enrichment analysis revealed that the MLNR, MED4, CAB39L, LDB2, and IGF2BP1 genes could be putative candidate genes for growth and carcass traits. The findings of this study improve our understanding of the genetic mechanisms regulating chicken growth and carcass traits and provide a theoretical basis for chicken breeding programs.
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http://dx.doi.org/10.1038/s41437-020-00365-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026619PMC
February 2021

Bullet signature measurement with chromatic confocal sensor.

Appl Opt 2020 Aug;59(22):6594-6599

A new, non-contact, three-dimensional (3D) bullet signature measuring system based on a chromatic confocal sensor is developed. The system is composed of a precision rotary table and a chromatic confocal sensor. The measurement uncertainty of the system is less than 1 µm. When measuring the surface topography of the object, the sensor acquires wavelength information reflected from the object instead of intensity information. This advantage is very suitable to bullet signature measurements. The chromatic confocal sensor works in the point measuring mode and can acquire data continuously with high speed. One round section measurement on the bullet body takes less than 1 minute.
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http://dx.doi.org/10.1364/AO.396273DOI Listing
August 2020

Generation of sphingosine-1-phosphate by sphingosine kinase 1 protects nonalcoholic fatty liver from ischemia/reperfusion injury through alleviating reactive oxygen species production in hepatocytes.

Free Radic Biol Med 2020 11 30;159:136-149. Epub 2020 Jul 30.

Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Background: Nonalcoholic fatty liver (NAFL) is emerging as a leading risk factor of hepatic ischemia/reperfusion (I/R) injury lacking of effective therapy. Lipid dyshomeostasis has been implicated in the hepatopathy of NAFL. Herein, we investigate the bioactive lipids that critically regulate I/R injury in NAFL.

Methods: Lipidomics were performed to identify dysregulated lipids in mouse and human NAFL with I/R injury. The alteration of corresponding lipid-metabolizing genes was examined. The effects of the dysregulated lipid metabolism on I/R injury in NAFL were evaluated in mice and primary hepatocytes.

Results: Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) were uncovered to be substantially activated by I/R in mouse NAFL. Sphingosine kinase 1 (Sphk1) was found to be essential for hepatic S1P generation in response to I/R in hepatocytes of NAFL mice. Sphk1 knockdown inhibited the hepatic S1P rise while accumulating ceramides in hepatocytes of NAFL mice, leading to aggressive hepatic I/R injury with upregulation of oxidative stress and increase of reactive oxygen species (ROS). In contrast, administration of exogenous S1P protected hepatocytes of NAFL mice from hepatic I/R injury. Clinical study revealed a significant activation of S1P generation by I/R in liver specimens of NAFL patients. In vitro studies on the L02 human hepatocytes consolidated that inhibiting the generation of S1P by knocking down SPHK1 exaggerated I/R-induced damage and oxidative stress in human hepatocytes of NAFL.

Conclusions: Generation of S1P by SPHK1 is important for protecting NAFL from I/R injury, which may serve as therapeutic targets for hepatic I/R injury in NAFL.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.07.004DOI Listing
November 2020

MLH1 Deficiency Induces Cetuximab Resistance in Colon Cancer via Her-2/PI3K/AKT Signaling.

Adv Sci (Weinh) 2020 Jul 26;7(13):2000112. Epub 2020 May 26.

Department of Oncology Xiangya Hospital Central South University Changsha Hunan 410008 China.

The rapid onset of resistance to cetuximab (CTX) limits its clinical utility in colorectal cancer (CRC) patients. This study aims to understand a potential role of mismatch repair gene mutL homolog 1 (MLH1) in CTX response. Functional analysis of MLH1 in Her-2/phosphoinositide 3-kinases (PI3K)/PKB protein kinase (AKT)-regulated CTX sensitivity is performed using human CRC specimens, CRC cell lines with different MLH1 expression levels, and a subcutaneous xenograft model. Overexpression, knockdown, small interfering RNA, and inhibitors are used to examine the role of MLH1 and HER-2 downstream signaling and apoptotic targets in CTX sensitivity. Reduced MLH1 expression is correlated with unfavorable prognosis in cetuximab-treated patients. loss decreases CTX sensitivity through Her-2/PI3K/AKT signaling and apoptosis resistance in culture and in xenografts, while overexpression increases CTX sensitivity. Blocking Her-2 signaling increases CTX sensitivity of microsatellite instability CRC in vitro and in vivo. MLH1 loss induces activation of Her-2/PI3K/AKT signaling and leads to cetuximab resistance in colon cancer.
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http://dx.doi.org/10.1002/advs.202000112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341094PMC
July 2020

BMP4 promotes the metastasis of gastric cancer by inducing epithelial-mesenchymal transition via ID1.

J Cell Sci 2020 06 11;133(11). Epub 2020 Jun 11.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China

Epithelial-mesenchymal transition (EMT) is a crucial process for cancer cells to acquire metastatic potential, which primarily causes death in gastric cancer (GC) patients. Bone morphogenetic protein 4 (BMP4) is a member of the TGF-β family that plays an indispensable role in human cancers. However, little is known about its roles in GC metastasis. In this study, BMP4 was found to be frequently overexpressed in GC tissues and was correlated with poor patient's prognosis. BMP4 was upregulated in GC cell lines and promoted EMT and metastasis of GC cells both and , whereas knockdown of BMP4 significantly inhibited EMT and metastasis of GC cells. Furthermore, the inhibitor of DNA binding 1 (also known as DNA-binding protein inhibitor ID1) was identified as a downstream target of BMP4 using PCR arrays and was upregulated via SMAD1/5/8 phosphorylation. ID1 knockdown attenuated BMP4-induced EMT and invasion in GC cells. Moreover, ID1 overexpression in BMP4 knockdown cells restored the promotion of EMT and cell invasion. In summary, BMP4 induced EMT and promoted GC metastasis by upregulating ID1 expression. Antagonizing BMP4 could be a potential therapeutic strategy for GC metastasis.
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http://dx.doi.org/10.1242/jcs.237222DOI Listing
June 2020

Crystal structure of (,)-2-hy-droxy-4-(methyl-sulfan-yl)butanoic acid.

Acta Crystallogr E Crystallogr Commun 2020 Apr 17;76(Pt 4):562-566. Epub 2020 Mar 17.

Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.

The title compound, a major animal feed supplement, abbreviated as HMTBA and alternatively called dl-me-thio-nine hy-droxy analogue, CHOS, (), was isolated in pure anhydrous monomeric form. The melting point is 302.5 K and the compound crystallizes in the monoclinic space group 2/, with two conformationally non-equivalent mol-ecules [( ) and ( )] in the asymmetric unit. The crystal structure is formed by alternating polar and non-polar layers running along the plane and features an extensive hydrogen-bonding network within the polar layers. The Hirshfeld surface analysis revealed a significant contribution of non-polar H⋯H and H⋯S inter-actions to the packing forces for both mol-ecules.
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http://dx.doi.org/10.1107/S2056989020003138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133032PMC
April 2020

Correction: Targeting alkaline ceramidase 3 alleviates the severity of nonalcoholic steatohepatitis by reducing oxidative stress.

Cell Death Dis 2020 Mar 17;11(3):191. Epub 2020 Mar 17.

Department of Medicine and Cancer Center, the State University of New York at Stony Brook, Stony Brook, New York, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41419-020-2396-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078179PMC
March 2020

Local Concentration Effect-Derived Heterogeneous LiS/LiS Deposition on Dual-Phase MWCNT/Cellulose Nanofiber/NiCoS Self-Standing Paper for High Performance of Lithium Polysulfide Batteries.

ACS Appl Mater Interfaces 2020 Apr 20;12(13):15228-15238. Epub 2020 Mar 20.

School of Materials Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, P. R. China.

Lithium-sulfur (Li-S) batteries are highly attractive for their theoretical energy density and natural abundance, but the drawbacks of low sulfur utilization and rapid capacity fade in high-sulfur-loading cathodes still retard their practical use. To enhance kinetics in high-sulfur-loading Li-S cells, it is important to first understand and control the deposition of LiS/LiS from highly soluble lithium polysulfide (LiPS) during discharge processes. Here, we presented a series of multiphase-derived self-standing papers with diverse electronic conductivity and LiPS affinity for highly concentrated LiPS discharge processes and explained the LiS/LiS deposition behavior in detail. We demonstrated that high rate capacity and long cycle life of as-assembled paper-LiPS cathodes can be greatly depended on their phase material with high conductivity and LiPS affinity. A high-performance self-standing LiPS host-multiwalled carbon nanotube (MWCNT)/cellulose nanofiber (CNF)/NiCoS (3.5 mg cm) can catalyze 2.85 mg cm (based on sulfur) loaded LiPS to deliver a high specific capacity of 1154 mAh g at 0.1C and a high rate performance of 963 mAh g at 1C. We suggest that the insulating phase defect of nano-CNF and both highly electronic conductive (above 50 S cm) and LiPS adsorptive NiCoS can promote the local concentration effect of LiPS, thus contributing to fast and stable heterogeneous particle-shaped deposition of LiS/LiS and leading to high kinetics of the LiPS cathode.
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http://dx.doi.org/10.1021/acsami.0c00618DOI Listing
April 2020

Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway.

Front Mol Neurosci 2020 6;13:16. Epub 2020 Feb 6.

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.

Lysophosphatidic acid is a small extracellular signaling molecule, which is elevated in pathological conditions such as ischemic stroke and traumatic brain injury (TBI). LPA regulates the survival of neurons in various diseases. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Here we report that LPA activates LPA1 and LPA2 receptors, and the downstream MAPK pathway to induce the apoptosis of PC12 cells through mitochondrial dysfunction. LPA elicits the activation of ERK1/2, p38, and JNK pathways, decreases the expression of Bcl2, promotes the translocation of Bax, and enhances the activation of caspase-3, resulting in mitochondrial dysfunction and cell apoptosis. This process can be blocked by LPA1 receptor antagonist and LPA2 receptor antagonist and MAPK pathway inhibitors. Our results indicate that LPA1 receptor, LPA2 receptor and MAPK pathway play a critical role in LPA-induced neuronal injury. LPA receptors and MAPK pathways may be novel therapeutic targets for ischemic stroke and TBI, where excessive LPA signaling exist.
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http://dx.doi.org/10.3389/fnmol.2020.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016214PMC
February 2020

VX-765 attenuates atherosclerosis in ApoE deficient mice by modulating VSMCs pyroptosis.

Exp Cell Res 2020 04 20;389(1):111847. Epub 2020 Jan 20.

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address:

Background And Aims: Recent clinical evidences show that patients with atherosclerotic cardiovascular disease can benefit from a targeting IL-1β treatment. Caspase-1 is an important factor for pyroptosis and is responsible for mature and release of interleukin (IL)-1β. Here we investigated the effect of caspase-1 inhibitor VX-765 on atherosclerosis and vascular smooth muscle cells (VSMCs) pyroptosis.

Methods: Human carotid artery plaques and aortas from ApoE-/- mice which were gavaged with VX-765 or vehicle while fed with western diet were examined for plaque burden using Oil Red O staining and Immunohistochemistry staining. Dedifferentiated primary cultured mice VSMCs treated with oxidized low-density lipoprotein (OxLDL) were applied to examine cell pyroptosis.

Results: The distribution of a-SMA and active pyroptotic indicators had a lot of overlaps near the necrotic core, at the lesion surface and in the intra-plaque hemorrhage area in human or mice plaque. In vitro studies further demonstrated that OxLDL induced VSMCs pyroptosis through activating NLRP3 inflammasome. What's more, VX-765 significantly inhibited the progression of established atheroma and the development of atherosclerosis, without substantially influence lipoprotein level in plasma. VX-765 also significantly reduced VSMCs pyroptosis and IL-1β processing induced by OxLDL.

Conclusions: VX-765 inhibits VSMCs pyroptosis during atherogenesis and targeting caspase-1 activity may be a potential treatment strategy for atherosclerotic diseases.
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http://dx.doi.org/10.1016/j.yexcr.2020.111847DOI Listing
April 2020

Targeting alkaline ceramidase 3 alleviates the severity of nonalcoholic steatohepatitis by reducing oxidative stress.

Cell Death Dis 2020 01 16;11(1):28. Epub 2020 Jan 16.

Department of Medicine and Cancer Center, the State University of New York at Stony Brook, Stony Brook, New York, USA.

Overload of palmitic acids is linked to the dysregulation of ceramide metabolism in nonalcoholic steatohepatitis (NASH), and ceramides are important bioactive lipids mediating the lipotoxicity of palmitic acid in NASH. However, much remains unclear about the role of ceramidases that catalyze the hydrolysis of ceramides in NASH. By analyzing the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, we found that alkaline ceramidase 3 (ACER3) is upregulated in livers of patients with NASH. Consistently, we found that Acer3 mRNA levels and its enzymatic activity were also upregulated in mouse livers with NASH induced by a palmitate-enriched Western diet (PEWD). Moreover, we demonstrated that palmitate treatment also elevated Acer3 mRNA levels and its enzymatic activity in mouse primary hepatocytes. In order to investigate the function of Acer3 in NASH, Acer3 null mice and their wild-type littermates were fed a PEWD to induce NASH. Knocking out Acer3 was found to augment PEWD-induced elevation of C-ceramide and alleviate early inflammation and fibrosis but not steatosis in mouse livers with NASH. In addition, Acer3 deficiency attenuated hepatocyte apoptosis in livers with NASH. These protective effects of Acer3 deficiency were found to be associated with suppression of hepatocellular oxidative stress in NASH liver. In vitro studies further revealed that loss of ACER3/Acer3 increased C-ceramide and inhibited apoptosis and oxidative stress in mouse primary hepatocytes and immortalized human hepatocytes induced by palmitic-acid treatment. These results suggest that ACER3 plays an important pathological role in NASH by mediating palmitic-acid-induced oxidative stress.
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http://dx.doi.org/10.1038/s41419-019-2214-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965144PMC
January 2020

Underlying Topological Dirac Nodal Line Mechanism of the Anomalously Large Electron-Phonon Coupling Strength on a Be (0001) Surface.

Phys Rev Lett 2019 Sep;123(13):136802

Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Science, 110016 Shenyang, Liaoning, People's Republic of China.

Beryllium has recently been discovered to harbor a Dirac nodal line (DNL) in its bulk phase and the DNL-induced nontrivial surface states (DNSSs) on its (0001) surface, rationalizing several already-existing historic puzzles [Phys. Rev. Lett. 117, 096401 (2016)PRLTAO0031-900710.1103/PhysRevLett.117.096401]. However, to date the underlying mechanism as to why its (0001) surface exhibits an anomalously large electron-phonon coupling effect (λ_{e-ph}^{s}≈1.0) remains unresolved. Here, by means of first-principles calculations, we show that the coupling of the DNSSs with the phononic states mainly contributes to its novel surface e-ph enhancement. Besides the fact that the experimentally observed λ_{e-ph}^{s} and the main Eliashberg coupling function (ECF) peaks are reproduced well in our current calculations, we decompose the ECF α^{2}F(k,q;v) and the e-ph coupling strength λ(k,q;v) as a function of each electron momentum (k), each phonon momentum (q), and each phonon mode (v), evidencing the robust connection between the DNSSs and both α^{2}F(k,q;v) and λ(k,q;v). The results reveal the strong e-ph coupling between the DNSSs and the phonon modes, which contributes over 80% of the λ_{e-ph}^{s} coefficient on the Be (0001) surface. It highlights that the anomalously large e-ph coefficient on the Be (0001) surface can be attributed to the presence of its DNL-induced DNSSs, clarifying the long-debated mechanism.
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http://dx.doi.org/10.1103/PhysRevLett.123.136802DOI Listing
September 2019

Increased long noncoding RNA LASP1-AS is critical for hepatocellular carcinoma tumorigenesis via upregulating LASP1.

J Cell Physiol 2019 08 24;234(8):13493-13509. Epub 2019 Jan 24.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Aberrant long noncoding RNAs (lncRNA) have been proved to be associated with the many types of malignant tumors (including hepatocellular carcinoma [HCC]). In this study, a lncRNAs and mRNAs microarray analysis was performed in three pairs of HCC patitents' tumor. We found lncRNA LIM and SH3 protein 1 antisense (LASP1-AS) and its sense-cognate gene LIM and SH3 protein 1 (LASP1) were upregulated in HCC and both are correlated with poorer prognosis and lower survival of HCC patients. Meanwhile, the expression of LASP1-AS correlated positively with LASP1 expression in HCC tissues. LASP1-AS promoted the proliferation, migration, and invasion abilities of HCC in vitro and vivo by enhancing LASP1 expression. Our study explored lncRNA LASP1-AS as an oncogene in HCC and promoted proliferation and metastasis capabilities of HCC via increasing the expression of its sense-cognate gene LASP1. LncRNA LASP1-AS might be a potential valuable prognostic biomarker and potential therapeutic target of HCC.
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http://dx.doi.org/10.1002/jcp.28028DOI Listing
August 2019

Synthesis of urchin-like CoO spheres for application in oxygen evolution reaction.

Nanotechnology 2018 Nov 12;29(48):485403. Epub 2018 Sep 12.

College of Materials Science and Engineering, Hunan University, Changsha, 410082, People's Republic of China.

For oxygen evolution electrocatalysis of water splitting, unique urchin-shaped CoO spheres were successfully grown on nickel foam by hydrothermal synthesis of Co(OH)F precursor and subsequent annealing method. The formation process was investigated by the evolution of phase structure and morphology with hydrothermal reaction time. And it can be explained by a 'disks-flowers-urchins' mechanism. Moreover, the CoO urchins/NF exhibits considerable catalytic properties. It shows a low overpotential of 308 mV at a current density of 20 mA cm in alkaline solution. In the meantime, such material has a small Tafel slope of 82.1 mV dec, large electrochemical active surface area and good long-term stability. The obvious promotion of oxygen evolution reaction performance can be attributed to the special morphology and the direct attachment to the substrate, which improve the exposed active sites, lower the internal resistance and accelerate the charge transport. Thus, the CoO urchins/NF not only has a great potential promising behavior, but also provides the basis for subsequent performance improvement.
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http://dx.doi.org/10.1088/1361-6528/aae0ddDOI Listing
November 2018

The Effect of SkitoSnack, an Artificial Blood Meal Replacement, on Aedes aegypti Life History Traits and Gut Microbiota.

Sci Rep 2018 07 23;8(1):11023. Epub 2018 Jul 23.

Department of Biology, New Mexico State University, Las Cruces, NM, 88003, USA.

Public health research and vector control frequently require the rearing of large numbers of vector mosquitoes. All target vector mosquito species are anautogenous, meaning that females require vertebrate blood for egg production. Vertebrate blood, however, is costly, with a short shelf life. To overcome these constraints, we have developed SkitoSnack, an artificial blood meal replacement for the mosquito Aedes aegypti, the vector of dengue, Zika and chikungunya virus. SkitoSnack contains bovine serum albumin and hemoglobin as protein source as well as egg yolk and a bicarbonate buffer. SkitoSnack-raised females had comparable life history traits as blood-raised females. Mosquitoes reared from SkitoSnack-fed females had similar levels of infection and dissemination when orally challenged with dengue virus type 2 (DENV-2) and significantly lower infection with DENV-4. When SkitoSnack was used as a vehicle for DENV-2 delivery, blood-raised and SkitoSnack-raised females were equally susceptible. The midgut microbiota differed significantly between mosquitoes fed on SkitoSnack and mosquitoes fed on blood. By rearing 20 generations of Aedes exclusively on SkitoSnack, we have proven that this artificial diet can replace blood in mosquito mass rearing.
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http://dx.doi.org/10.1038/s41598-018-29415-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056539PMC
July 2018

BMP4 promotes hepatocellular carcinoma proliferation by autophagy activation through JNK1-mediated Bcl-2 phosphorylation.

J Exp Clin Cancer Res 2018 Jul 16;37(1):156. Epub 2018 Jul 16.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Background: Autophagy is a conserved catabolic process with complicated roles in tumor development. Bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF-β) family of regulatory proteins, plays a crucial role in human malignancies. However, whether BMP4 contributes to the regulation of autophagy in hepatocellular carcinoma (HCC) progression remains elusive.

Methods: Functional analysis of BMP4 on HCC proliferation and autophagy was performed both in vitro and in vivo in HepG2 and HCCLM3 cells. Autophagic activity was estimated by Western blot for autophagic marker proteins and by transmission electron microscopy (TEM). Transfection of mRFP-GFP-LC3 adenovirus was applied to observe autophagic flux and high content screening was used for quantification. The signaling pathway of BMP4-regulated HCC proliferation and autophagy was investigated by Western blot.

Results: BMP4 treatment promoted HCC cells proliferation and induced autophagy. The in vivo xenograft model supported that BMP4 overexpression promoted the growth of HCC cells and autophagy induction while BMP4 knockdown exerted the opposite effect. 3-MA pre-treatment or knockdown of Beclin-1 (BECN1) blocked HCC autophagy by decreasing the expression of LC3-II and subsequently attenuated BMP4-induced autophagy and cells proliferation enhanced by BMP4 in vitro and in vivo. Mechanistic study revealed that the induction of autophagy by BMP4 was mediated through activating the JNK1/Bcl2 pathway. Furthermore, the JNK1 inhibitor and knockdown of JNK1 could attenuate autophagy induced by BMP4 and eliminated BMP4-promoted HCC cells growth.

Conclusions: BMP4 promoted HCC proliferation by autophagy activation through JNK1/Bcl-2 signaling.
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http://dx.doi.org/10.1186/s13046-018-0828-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048721PMC
July 2018

Knockdown of Beclin-1 impairs epithelial-mesenchymal transition of colon cancer cells.

J Cell Biochem 2018 08 8;119(8):7022-7031. Epub 2018 May 8.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Activation of autophagy significantly affects cancer cell behaviors, such as proliferation, differentiation, and invasiveness. Epithelial-to-mesenchymal transition (EMT) as an initial step of malignant transformation of cancer cells was linked to the activation of autophagy, but the detailed molecular mechanisms are still unknown. The present study investigates the effects of Beclin-1, a key molecule involved in activation of autophagy, on EMT of colon cancer cells. The normal colon epithelia cell line of CCD-18Co and six colon cancer cell lines with different expression levels of Beclin-1 were used in this study. The activation of autophagy and EMT markers of cancer cells were monitored by Western blotting and quantitative real-time PCR assay in the presence or absence of rapamycin (autophagy activator) and 3-MA (autophagy inhibitor). The expression of Beclin-1 in selected cell lines was modulated using small interfering RNA, and consequentially EMT markers, and cancer cell behaviors including migration and invasion, were also explored. Activation or inhibition of autophagy in colon cancer cells had positive or negative impacts on the expression of EMT markers and malignant behaviors such as cell migration and invasion. Knockdown of beclin-1 by siRNA apparently inhibited the activation of autophagy induced by rapamycin, consequentially resulted in suppression of EMT and attenuation of invasiveness of colon cancer cells. The results in this study demonstrated an association between activation of autophagy and EMT in colon cancer cells. The results showed suppression of Beclin-1 expression significantly reduced EMT and invasive behaviors in colon cancer cells.
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http://dx.doi.org/10.1002/jcb.26912DOI Listing
August 2018

Effect of postoperative radiotherapy on outcome in resectable stage IIIA-N2 non-small-cell lung cancer: an updated meta-analysis.

Nucl Med Commun 2018 Jan;39(1):51-59

Department of Cardiothoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Background: In a previous meta-analysis-based modeling study, it was hypothesized that modern postoperative radiotherapy (PORT) may improve both local recurrence and overall survival (OS) in stage IIIA-N2 non-small-cell lung cancer (NSCLC). There were only four single-arm trials with a total of 357 patients. As other trials have provided new and controversial data, we performed this updated meta-analysis to test the hypothesis.

Patients And Methods: Systematic reviews in Medline, Cochrane, and Science Direct up to December 2015 identified publications exploring the efficacy of PORT in resectable stage IIIA-N2 NSCLC.

Results: Overall, 16 trials comprising 3278 patients were included. There was a significant benefit in favor of PORT regarding OS [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.58-0.92, P=0.008; absolute benefit at 5 years=8%], disease-free survival (HR: 0.70, 95% CI: 0.60-0.83, P<0.0001), and locoregional recurrence-free survival (HR: 0.37, 95% CI: 0.24-0.58, P<0.0001). Restriction of the analysis to trials with induction and/or adjuvant chemotherapy led to similar results. PORT significantly decreased the risk of local recurrence (risk ratio: 0.64, 95% CI: 0.50-0.82, P=0.0006) and DM (risk ratio: 0.74, 95% CI: 0.62-0.88, P=0.0005), and the absolute risk differences were 13 and 14%, respectively.

Conclusion: The addition of PORT, with or without chemotherapy, significantly improves local control and survival in patients with resectable stage IIIA-N2 NSCLC.
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http://dx.doi.org/10.1097/MNM.0000000000000764DOI Listing
January 2018

ZEB1 Promotes Oxaliplatin Resistance through the Induction of Epithelial - Mesenchymal Transition in Colon Cancer Cells.

J Cancer 2017 30;8(17):3555-3566. Epub 2017 Sep 30.

Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China 410008.

Oxaliplatin (OXA) chemotherapy is widely used in the clinical treatment of colon cancer. However, chemo-resistance is still a barrier to effective chemotherapy in cases of colon cancer. Accumulated evidence suggests that the epithelial mesenchymal transition (EMT) may be a critical factor in chemo-sensitivity. The present study investigated the effects of Zinc finger E-box binding homeobox 1 (ZEB1) on OXA-sensitivity in colon cancer cells. ZEB1expression and its correlation with clinicopathological characteristics were analyzed using tumor tissue from an independent cohort consisting of 118 colon cancer (CC) patients who receiving OXA-based chemotherapy. ZEB1 modulation of OXA-sensitivity in colon cancer cells was investigated in a OXA-resistant subline of HCT116/OXA cells and the parental colon cancer cell line: HCT116. A CCK8 assay was carried out to determine OXA-sensitivity. qRT-PCR, Western blot, Scratch wound healing and transwell assays were used to determine EMT phenotype of colon cells. ZEB1 knockdown using small interfering RNA (siRNA) was used to determine the ZEB1 contribution to OXA-sensitivity and (in a nude mice xenograft model). ZEB1 expression was significantly increased in colon tumor tissue, and was correlated with lymph node metastasis and the depth of invasion. Compared with the parental colon cancer cells (HCT116), HCT116/OXA cells exhibited an EMT phenotype characterized by up-regulated expression of ZEB1, Vimentin, MMP2 and MMP9, but down-regulated expression of E-cadherin. Transfection of Si-ZEB1 into HCT116/OXA cells significantly reversed the EMT phenotype and enhanced OXA-sensitivity and . HCT116/OXA cells acquired an EMT phenotype. ZEB1 knockdown effectively restored OXA-sensitivity by reversing EMT. ZEB1 is a potential therapeutic target for the prevention of OXA-resistance in colon cancer.
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http://dx.doi.org/10.7150/jca.20952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687171PMC
September 2017

Corrigendum: RNA-Seq Comparison of Larval and Adult Malpighian Tubules of the Yellow Fever Mosquito Reveals Life Stage-Specific Changes in Renal Function.

Front Physiol 2017 7;8:843. Epub 2017 Nov 7.

Department of Biology, New Mexico State University, Las Cruces, NM, United States.

[This corrects the article on p. 283 in vol. 8, PMID: 28536536.].
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http://dx.doi.org/10.3389/fphys.2017.00843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681913PMC
November 2017

BMP4 promotes oxaliplatin resistance by an induction of epithelial-mesenchymal transition via MEK1/ERK/ELK1 signaling in hepatocellular carcinoma.

Cancer Lett 2017 12 4;411:117-129. Epub 2017 Oct 4.

Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. Electronic address:

Background: Bone morphogenetic protein-4 (BMP4) is a key regulator of epithelial-mesenchymal transition (EMT), which is crucial for cancer cells to acquire chemoresistance. The effects of BMP4 on OXA sensitivity in HCC need to be elucidated.

Methods: Functional analysis of BMP4 on EMT-regulated OXA sensitivity was performed in human HCC specimens, in the HCC cell lines HepG2 and HCCLM3, and in a subcutaneous tumor model receiving OXA treatment. The downstream signaling targets of BMP4 in HCC were profiled and confirmed.

Results: BMP4 expression was significantly increased in HCC tissue, and was correlated with tumor de-differentiation and unfavorable prognosis. BMP4 promoted HCC EMT and was correlated with OXA resistance. Blocking of BMP4 reversed EMT and increased OXA chemosensitivity in vitro and in vivo. ELK1, a transcription factor involved in EMT, was an important mediator of BMP4-induced OXA resistance in HCC. Blocking of MEK/ERK/ELK1 attenuated BMP4-induced EMT and enhanced OXA sensitivity.

Conclusions: BMP4 induces EMT and OXA chemoresistance via MEK/ERK/ELK1 signaling pathway in HCC. BMP4 may be a valuable therapeutic target for HCC patients receiving OXA-based chemotherapy.
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http://dx.doi.org/10.1016/j.canlet.2017.09.041DOI Listing
December 2017

Fat Body Organ Culture System in Aedes Aegypti, a Vector of Zika Virus.

J Vis Exp 2017 08 19(126). Epub 2017 Aug 19.

Department of Biology, New Mexico State University; Institute of Applied Biosciences, New Mexico State University;

The insect fat body plays a central role in insect metabolism and nutrient storage, mirroring functions of the liver and fat tissue in vertebrates. Insect fat body tissue is usually distributed throughout the insect body. However, it is often concentrated in the abdomen and attached to the abdominal body wall. The mosquito fat body is the sole source of yolk proteins, which are critical for egg production. Therefore, the in vitro culture of mosquito fat body tissues represents an important system for the study of mosquito physiology, metabolism, and, ultimately, egg production. The fat body culture process begins with the preparation of solutions and reagents, including amino acid stock solutions, Aedes physiological saline salt stock solution (APS), calcium stock solution, and fat body culture medium. The process continues with fat body dissection, followed by an experimental treatment. After treatment, a variety of different analyses can be performed, including RNA sequencing (RNA-Seq), qPCR, Western blots, proteomics, and metabolomics. In our example experiment, we demonstrate the protocol through the excision and culture of fat bodies from the yellow fever mosquito, Aedes aegypti, a principal vector of arboviruses including dengue, chikungunya, and Zika. RNA from fat bodies cultured under a physiological condition known to upregulate yolk proteins versus the control were subject to RNA-Seq analysis to demonstrate the potential utility of this procedure for investigations of gene expression.
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http://dx.doi.org/10.3791/55508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614350PMC
August 2017
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