Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress.

Endonuclease G (ENDOG), a nuclear-encoded mitochondrial intermembrane space protein, is well known to be translocated into the nucleus during apoptosis. Recent studies have shown that ENDOG might enter the mitochondrial matrix to regulate mitochondrial genome cleavage and replication. However, little is known about the role of ENDOG in the cytosol. Our previous work showed that cytoplasmic ENDOG competitively binds with 14-3-3γ, which released TSC2 to repress mTORC1 signaling and induce autophagy. Here, we demonstrate that cytoplasmic ENDOG could also release Rictor from 14-3-3γ to activate the mTORC2-AKT-ACLY axis, resulting in acetyl-CoA production. Importantly, we observe that ENDOG could translocate to the ER, bind with Bip, and release IRE1a/PERK to activate the endoplasmic reticulum stress response, promoting lipid synthesis. Taken together, we demonstrate that loss of ENDOG suppresses acetyl-CoA production and lipid synthesis, along with reducing endoplasmic reticulum stress, which eventually alleviates high-fat diet-induced nonalcoholic fatty liver disease in female mice.

A recyclable polyester library from reversible alternating copolymerization of aldehyde and cyclic anhydride.

Our society is pursuing chemically recyclable polymers to accelerate the green revolution in plastics. Here, we develop a recyclable polyester library from the alternating copolymerization of aldehyde and cyclic anhydride. Although these two monomer sets have little or no thermodynamic driving force for homopolymerization, their copolymerization demonstrates the unexpected alternating characteristics. In addition to readily available monomers, the method is performed under mild conditions, uses common Lewis/Brønsted acids as catalysts, achieves the facile tuning of polyester structure using two distinct monomer sets, and yields 60 polyesters. Interestingly, the copolymerization exhibits the chemical reversibility attributed to its relatively low enthalpy, which makes the resulting polyesters perform closed-loop recycling to monomers at high temperatures. This study provides a modular, efficient, and facile synthesis of recyclable polyesters using sustainable monomers.

The Identification of a Yield-Related Gene Controlling Multiple Traits Using GWAS in Sorghum (Sorghum bicolor L.).

Sorghum bicolor (L.) is one of the oldest crops cultivated by human beings which has been used in food and wine making. To understand the genetic diversity of sorghum breeding resources and further guide molecular-marker-assisted breeding, six yield-related traits were analyzed for 214 sorghum germplasm from all over the world, and 2,811,016 single-nucleotide polymorphisms (SNPs) markers were produced by resequencing these germplasms. After controlling Q and K, QTLs were found to be related to the traits using three algorisms. Interestingly, an important QTL was found which may affect multiple traits in this study. It was the most likely candidate gene for the gene SORBI_3008G116500, which was a homolog of Arabidopsis thaliana gene-VIP5 found by analyzing the annotation of the gene in the LD block. The haplotype analysis showed that the SORBI_3008G116500hap3 was the elite haplotype, and it only existed in Chinese germplasms. The traits were proven to be more associated with the SNPs of the SORBI_3008G116500 promoter through gene association studies. Overall, the QTLs and the genes identified in this study would benefit molecular-assisted yield breeding in sorghum.

Impact of Resource on Green Growth and Threshold Effect of International Trade Levels: Evidence from China.

International trade levels can change the relationship between resource endowments and green economic growth. Therefore, this study tested the resource curse hypothesis from the perspective of green growth in China using provincial-level panel data for 2005-2017. Energy conservation and environmental improvement were considered under green growth to further analyze the regional mechanism of the resource curse. A panel threshold model was used to identify the impact of import and export threshold effects on the transformation of this mechanism. The resource curse hypothesis was found to be valid nationwide; it hindered green economic growth mainly by impeding energy conservation and curbing environmental improvement. In terms of regional differences in green growth, resource endowment had a positive impact on the eastern region, a negative impact on the central region, and no effect on the western region. When the levels of import and export trade exceeded the threshold values, the resource curse effect was enhanced by reducing energy conservation and weakened by promoting environmental improvement, respectively. Therefore, the Chinese government should establish a more reasonable import and export trade structure, promote changes to the energy structure and green technological innovation, and reduce the negative impact of resource endowment on green growth.

Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation.

Space microgravity condition has great physiological influence on astronauts' health. The interaction of endothelial cells, which control vascular permeability and immune responses, is sensitive to mechanical stress. However, whether microgravity has significant effects on the physiological function of the endothelium has not been investigated. In order to address such a question, a clinostat-based culture model with a HUVEC monolayer being inside the culture vessel under the simulated microgravity (SMG) was established. The transmittance of FITC-tagged dextran was used to estimate the change of integrity of the adherens junction of the HUVEC monolayer. Firstly, we found that the permeability of the HUVEC monolayer was largely increased after SMG treatment. To elucidate the mechanism of the increased permeability of the HUVEC monolayer under SMG, the levels of total expression and activated protein levels of Rap1 and Rap2 in HUVEC cells, which regulate the adherens junction of endothelial cells, were detected by WB and GST pull-down after SMG. As the activation of both Rap1 and Rap2 was significantly decreased under SMG, the expression of Rap1GEF1 (C3G) and Rap1GAP in HUVECs, which regulate the activation of them, was further determined. The results indicate that both C3G and Rap1GAP showed a time-dependent increase with the expression of Rap1GAP being dominant at 48 h after SMG. The down-regulation of the expression of junctional proteins, VE-cadherin and ß-catenin, in HUVEC cells was also confirmed by WB and immunofluorescence after SMG. To clarify whether up-regulation of Rap1GAP is necessary for the increased permeability of the HUVEC monolayer after SMG, the expression of Rap1GAP was knocked down by Rap1GAP-shRNA, and the change of permeability of the HUVEC monolayer was detected. The results indicate that knock-down of Rap1GAP reduced SMG-induced leaking of the HUVEC monolayer in a time-dependent manner. In total, our results indicate that the Rap1GAP-Rap signal axis was necessary for the increased permeability of the HUVEC monolayer along with the down-regulation of junctional molecules including VE-cadherin and ß-catenin.

Long Noncoding RNA LINC01518 Modulates Proliferation and Migration in TGF-ß1-Treated Human Tenon Capsule Fibroblast Cells Through the Regulation of hsa-miR-216b-5p.

In this study, we investigated the expression and functions of long noncoding RNAs (LncRNAs) of LINC01518 in an in vitro model of TGF-ß1-treated human Tenon capsule fibroblast (HTF) cells. qRT-PCR was used to examine LINC01518 expression in in situ human glaucoma tissues, and in vitro HTF cells treated with TGF-ß1. Lentivirus-mediated LINC01518 knockdown was performed in HTF cells to investigate its effect on TGF-ß1-induced cell proliferation, migration and autophagy signaling pathway. The potential ceRNA candidate of LINC01518, hsa-miR-216b-5p, was probed by dual-luciferase assay and qRT-PCR. Hsa-miR-216b-5p was also knocked down in LINC01518-downregulated HTF cells to investigate the function of this lncRNA-miRNA epigenetic axis in TGF-ß1-treated HTF cells. LINC01518 was upregulated in human glaucoma tissues and cultured HTF cells. LINC01518 downregulation significantly suppressed TGF-ß1-induced cell proliferation, migration and autophagy signaling pathway in HTF cells. Hsa-miR-216b-5p was confirmed to be a ceRNA target of LINC01518. Knocking down hsa-miR-216b-5p reversed the suppressing effects of LINC01518 downregulation in TGF-ß1-treated HTF cells. Our study demonstrated that LINC01518 is a functional factor in regulating proliferation and migration in TGF-ß1-treated HTF cells, and hsa-miR-216b -5p may also be involved. Targeting the epigenetic axis of LINC01518/hsa-miR-216b-5p may provide new insight into the pathological development of human glaucoma.

The relative importance of environmental factors in predicting phytoplankton shifting and cyanobacteria abundance in regulated shallow lakes.

The phytoplankton community can be affected by multiple environmental factors such as climate, meteorology, hydrology, nutrients, and grazing. The complex interactive effects of these environmental factors as well as the resilience of phytoplankton communities further make the prediction of phytoplankton communities' dynamics challenging. In this study, we analyzed multiple environmental factors and their relative importance in predicting both phytoplankton shifting and cyanobacteria abundance in two regulated shallow lakes in central China. Our results indicated that the phytoplankton community in the study areas could be mainly classified into 1. Cryptophyta dominated group, 2. Biologically diverse group, and 3. Cyanobacteria dominated group. The Multinomial Logistic Regression model indicated the Cryptophyta dominated group was sensitive to temperature, while other groups were sensitive to both temperature and nutrients. The interactive effects of temperature and nutrients were synergistic in the cyanobacteria dominated group, while they were antagonistic or minor in other groups. The Negative Binomial Regression model suggested high total phosphorus and low total nitrogen but not temperature were responsible for high cyanobacteria abundance. The conditional plot indicated nutrients affected cyanobacteria abundance more significantly under low wind speeds and lake volume fluctuations, and cyanobacteria abundance in the cyanobacteria dominated group maintained high levels with increasing hydrological dynamics. Our results demonstrated that environmental factors played inconsistently significant roles in different phytoplankton groups, and reducing nutrients could decrease adverse effects of warming and water project constructions. Our models can also be applied to forecast phytoplankton shifting and cyanobacteria abundance in the management of regulated shallow lakes.

A high-quality genome of taro (Colocasia esculenta (L.) Schott), one of the world's oldest crops.

Taro (Colocasia esculenta (L.), Schott), from the Araceae family, is one of the oldest crops with important edible, medicinal, nutritional and economic value. Taro is a highly polymorphic species including diverse genotypes adapted to a broad range of environments, but the taro genome has rarely been investigated. Here, a high-quality chromosome-level genome of C. esculenta was assembled using data sequenced by Illumina, PacBio and Nanopore platforms. The assembled genome size was 2,405 Mb with a contig N50 of 400.0 kb and a scaffold N50 of 159.4 Mb. In total, 2,311 Mb (96.09%) of the contig sequences was anchored onto 14 chromosomes to form pseudomolecules, and 2,126 Mb (88.43%) was annotated as repetitive sequences. Of the 28,695 predicted protein-coding genes, 26,215 genes (91.4%) could be functionally annotated. On the basis of phylogenetic analysis using 769 genes, C. esculenta and Spirodela polyrhiza were placed on one branch of the tree that diverged approximately 73.23 million years ago. The synteny analyses showed that there have been two whole-genome duplication events in C. esculenta separated by a relatively short gap. According to comparative genome analysis, a larger number (1,189) of distinct gene families and long terminal repeats were enriched in C. esculenta. Our high-quality taro genome will provide valuable resources for further genetic, ecological and evolutionary analyses of taro or other species in the Araceae.

[Anti-scarring effect of rapamycin following filtering surgery in rabbit eyes].

OBJECTIVE: To study the effect of rapamycin on scar formation in rabbit eyes following filtering operation and explore the possible mechanism. METHODS: Ninety-six healthy adult rabbits were subjected to trabeculectomy of the left eye and subsequently randomly divided into 4 groups (n=24) for treatment with castor oil (control) or rapamycin (1%, 3%, or 5%) eye drops of the operated eyes 4 times a day. The morphology and function of the filtering blebs of the rabbits were compared at 7, 14, 21 and 28 days after the operation; at each of the time points, 6 rabbits from each group were euthanized for detection of expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in the tissues in the surgical area using immunohistochemistry. Cultured rabbit subconjunctival fibroblasts (RTFSs) were treated with different concentrations of rapamycin (0.06, 0.25, 1, and 4 mg/L) and the cell apoptosis was detected using flow cytometry. RESULTS: In the first, second and third weeks after the operation, the rate of functional follicle formation was significantly higher in the 3 rapamycin groups than in the control group (P < 0.05), and the number of α- SMA-positive fibroblasts decreased over time in the 3 rapamycin groups. In cultured RTFSs, treatment with rapamycin at different concentrations resulted in increased apoptosis of the cells, and rapamycin above 0.25 mg/L significantly increased the cell apoptosis in a dose-dependent manner. CONCLUSIONS: Rapamycin can inhibit hyperplasia of the filtering passage tissue, helps to preserve the functional filtering blebs and prolong their life span, and induces apoptosis of RTFS.

High Intake of Energy and Fat in Southwest Chinese Women with PCOS: A Population-Based Case-Control Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrinological disease with heterogeneous phenotype. Obesity contributes to the increased prevalence and severity of PCOS. Whether the intakes of major nutrients are higher in Chinese PCOS patients is still unknown. OBJECTIVES: To study the intakes of total energy, protein, fat and carbohydrate in Southwest Chinese PCOS patients. METHODS: 1854 women were included in the cross-sectional study. A population-based case-control study was conducted. The dietary habits and nutrients intake status of 169 PCOS patients and 338 age-matched controls were investigated by the method of semi-quantitative food frequency questionnaire. RESULTS: The actual intake of total energy (P = 0.01) and fat (P = 0.01) were higher, but carbohydrate was lower (P = 0.01) in PCOS patients as compared with the controls. The energy percentage supplied by protein (12.33% ± 2.27% vs. 19.26% ± 5.91%, P<0.001) and carbohydrate (48.72% ± 6.41% vs. 68.31% ± 8.37%, P<0.001) were lower in Southwest Chinese PCOS patients than those of control, however, the energy percentage supplied by fat was higher (38.95% ± 5.71% vs. 12.42% ± 5.13%, P<0.001) in PCOS. CONCLUSIONS: Limit the intake of total energy and fat shall be recommended to the Southwest Chinese PCOS patients. Women with PCOS in Southwest China shall consult with the nutritionist for improving the dietary structure.

Covalent functionalization of gold nanoparticles as electronic bridges and signal amplifiers towards an electrochemical immunosensor for botulinum neurotoxin type A.

This work introduced an efficient approach for modification of AuNPs with multicomponents by diazonium salt couplings. The multifunctionalized AuNPs with protruding functional groups that allow simple bioconjugation to large amounts of biomolecules have been successfully used as electronic bridges and signal amplifiers for an electrochemical immunosensor towards the detection of BoNT/A. The one-step anchoring AuNPs strategy has greatly increased the efficiency for attachment of biomolecules and subsequently increased the sensitivity. Sensitivity was further amplified by preparation of bioconjugates particles containing horseradish peroxidase (HRP) labels along with detection antibodies (AbL) attached to AuNPs. The immunosensor can be used for the detection of BoNT/A over the range of 4-35 pg mL(-1) with the lowest detection limit of 1 pg mL(-1) and assay time of 10 min. The herein sensing strategy is rapid, robust, selective, sensitive, and is promising for future fabrication of point-of-care devices.

Prevalence of the polycystic ovary syndrome in female residents of Chengdu, China.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. The data on this syndrome in a Chinese community are limited. METHODS: A community-based cross-sectional survey was undertaken. Cluster-randomized sampling was used. Female residents of Chengdu aged between 12 and 44 were included according to the constituent ratio of the female population of Sichuan province. We used three diagnostic criteria to determine the prevalence: the National Institutes of Health diagnostic criteria of PCOS (NIH-1990), the revised Rotterdam diagnostic criteria of PCOS (Rott-2003), and the recommended diagnostic criteria of PCOS by the Androgen Excess Society (AES-2006). RESULTS: 1,645 participants were included. The prevalence of PCOS in women aged between 12 and 44 was 7.1, 11.2 and 7.4%, respectively, according to the three different criteria. After the onset of puberty, the prevalence of PCOS increased rapidly from 12 to 14 years of age, peaked between 15 and 24 and decreased gradually thereafter and reached its lowest point before menopause. CONCLUSIONS: The prevalence of PCOS in this study was in the PCOS prevalence range from existing studies. According to the trend of prevalence, PCOS might be a temporary condition.

[Compensation effect of cotton growth and development after soil salt content reduction at bud stage].

To elucidate the dynamic characteristics of cotton growth and development after soil salt content reduction (SD) at bud stage and its effect on yield formation, a pot experiment was conducted in which soil salt content was declined from 5 per thousand level to 2 per thousand level at cotton bud stage. The results showed that the plant height, biomass, total fruit branch and fruit node number, boll number, boll mass of cotton plants increased after soil salt content reduction at bud stage. The distribution proportions of biomass in root and boll decreased after soil salt content reduction, however, the distribution proportions of biomass in leaf, main stem and fruit branch were on the rise. The growth rate of cotton plant increased after soil salt content reduction. Plant dry matter accumulation rate of SD cotton exceeded CK cotton at 22 days after soil salt content reduction. The response of different organs of cotton plant were different to soil salt content reduction, the plant height was the earliest, followed by the fruit branch and fruit node formation, and the bud and boll were the latest, which indicated that the compensation effect of cotton growth and development after soil salt content reduction at bud stage firstly appeared on the formation and growth of new leaf, fruit branch and fruit node, and on this basis, gradually brought out yield compensation.

[GM6001 suppresses scar formation after glaucoma filtration surgery in rabbits].

OBJECTIVE: To study the effect of matrix metalloproteinases inhibitor GM6001 in suppressing scar tissue formation in the filtering passage after glaucoma filtration surgery. METHODS: Twenty-four pigmented rabbits (48 eyes) underwent trabeculectomy followed by subconjunctival injection of GM6001 in the right eye (treated eyes) and injection of PBS in the left eye (control) once a day. The intraocular pressure was monitored postoperatively and proliferating cell nuclear antigen (PCNA)- and α-smooth muscle actin (α-SMA)-positive cells in the filtering pathway were detected using immunohistochemistry. RESULTS: On postoperative days 7, 14, 21, and 28, the intraocular pressure was significantly lower in the treated eyes (GM6001) than in the control eyes (P<0.01). The counts of PCNA- and α-SMA-positive cells were also significantly lowered in the treated than in the control eyes (P<0.01). CONCLUSION: GM6001 can inhibit excessive proliferation of the fibroblasts in the filtering pathway to suppress scar tissue formation and prolong the existence of the functional filtration bleb in rabbits.

Covalent fabrication of methyl parathion hydrolase on gold nanoparticles modified carbon substrates for designing a methyl parathion biosensor.

A biosensor based on AuNP modified GC electrodes has been developed for direct detection of methyl parathion. AuNP can be introduced to mixed monolayers of aryldiazonium salt modified GC electrodes by Au-C bonding through aryldiazonium salt chemistry, which provides a stable interface showing efficient electron transfer between biomolecules and electrodes. PEG molecules were introduced to the interface to resist non-specific protein adsorption. AuNP surfaces were further modified with 4-carboxyphenyl followed by covalent immobilization of methyl parathion hydrolase (MPH), a specific biocatalytic enzyme to methyl parathion. Exposure of this interface to methyl parathion resulted in a change in amperometric signal due to the MPH catalytic hydrolysis of methyl parathion producing electroactive compound 4-nitrophenol. This biosensor shows high selectivity, specificity, reproducibility and stability, and is functional for the detection of methyl parathion in real samples. The linear range for detection of methyl parathion is 0.2-100 ppb with a detection limit of 0.07 ppb in 0.1M phosphate buffer at pH 7.0.

A multianalyte electrochemical immunosensor based on patterned carbon nanotubes modified substrates for detection of pesticides.

A novel multianalyte electrochemical immunosensor based on the assembly of patterned SWNTs on glassy carbon (GC) substrates was developed for simultaneous detection of endosulfan and paraoxon. Based on aryldiazonium salt chemistry, forest of SWNTs can be patterned on GC substrates by C3C bonding using micro contact printing (MCP), which provides an interface showing efficient electron transfer between biomolecules and electrodes. Then redox molecules FDMA and PQQ can be attached to the SWNTs, respectively followed by the attachment of specific epitopes and antibodies. The modified sensing surfaces were characterized by XPS, SEM, AFM and electrochemistry. Based on the current change of specific redox probes, the fabricated immunosensor array can be used for simultaneous detection of endosulfan and paraoxon by a displacement assay. In phosphate buffer solution (50mM, pH 7.0), there is a linear relationship between electrochemical signal of FDMA and the concentration of endosulfan over the range of 0.05-100 ppb with a detection limit of 0.05ppb; the linear range between electrochemical signal of PQQ and the concentration of paraoxon is 2-2500 ppb with a detection limit of 2 ppb. The immunosensor array demonstrates high repeatability, reproducibility, stability and selectivity for the detection of endosulfan and paraoxon.

[Effects of nitrogen application rate on cotton leaf antioxidant enzyme activities and endogenous hormone contents under short-term waterlogging at flowering and boll-forming stage].

A pot experiment was conducted to study the effects of applying 0, 240, and 480 kg N x hm(-2) on the cotton leaf antioxidant enzyme activities and endogenous hormone contents under eight days waterlogging at flowering and boll-forming stage. Under this short-term waterlogging, the leaf soluble protein content and SOD and CAT activities decreased while the MDA content and POD activity increased, and in the meantime, the leaf ABA content increased while the ZR, GA, and IAA contents as well as the ZR/ABA, IAA/ABA, and GA/ABA ratios decreased, compared with those under normal watering. Treatment 240 kg N x hm(-2) had the lowest contents of leaf MDA and ABA, but the highest contents of leaf ZR, GA, and IAA, highest ratios of ZR/ABA, GA/ABA, and IAA/ABA, and highest net photosynthetic rate. At the 15th day after terminating waterlogging, no significant differences in the leaf antioxidant enzyme activities, MDA content, and endogenous hormone contents were observed between the short-term waterlogged and well-watered cotton. N application promoted the cotton leaf antioxidant enzyme activities, decreased the MDA and ABA contents, and increased the ZR, GA, and IAA contents as well as the ZR/ABA, IAA/ABA, and GA/ ABA ratios, with the highest cotton biomass and yield in treatment 240 kg N x hm(-2).

[Physiological responses of cotton plant to fertlizer nitrogen at flowering and boll-forming stages under soil drought].

With pot culture, the physiological responses of cotton plant to fertilizer nitrogen at flowering and boll-forming stages were studied under soil drought and after re-watering. The results showed that under soil drought, the net photosynthetic rate (Pn) and transpiration rate (Tr) declined rapidly with decreasing soil relative water content (SRWC). At the early stage of soil drought, owing to the declining degree of Tr was greater than that of Pn, the WUE had an increasing trend; but after then, the WUE decreased with declining SRWC and Pn. Soil drought altered the diurnal patters of Pn and Tr, i.e., decreased continuously from 8:00 to 16:00, while in CK, their peak values appeared at 10:00-11:00 and 12:00, respectively. The diurnal patterns of WUE in drought treatment and CK were the same, i.e., decreased first and increased then, with the bottom appeared at 12:00. Under soil drought, the Pn and Tr decreased with increasing fertilizer nitrogen level, while WUE was in adverse. After re-watering, the diurnal patterns of Pn, Tr and WUE were similar to CK, but their values were smaller than CK, especially under nitrogen application. It was suggested that under soil drought, nitrogen fertilization could be helpful to the increase of water use efficiency, but decreased the photosynthesis of cotton plant at its flowering and boll-forming stages.