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1.
Bioresour Technol ; 302: 122881, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32014732

RESUMO

In this study, a reliable approach using ammonia nitrogen was proposed to increase lactate production during semi-continuous food waste (FW) fermentation under mesophilic conditions. Both free ammonia nitrogen (FAN) and ammonium ion (NH4+-N) were present in mesophilic reactors, with a wide FAN/NH4+-N ratio variation due to the intermittent pH control. The investigation of responsible mechanisms revealed that the increased production yield of LA was associated with the acceleration of solubilization, hydrolysis, glycolysis and acidification. The presence of FAN and NH4+-N in proper concentrations increased lactate production by 2.4 folds and recovered lactate production to 24.5 g COD/L from low rate control reactor (9.6 g COD/L) under mesophilic conditions. Furthermore, the microorganisms responsible for LA accumulation (Bavariicoccus, Enterococcus, Bifidobacterium and Corynebacterium) were selectively enriched, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways associated with carbohydrate transport and LA production were enhanced in nitrogen fed reactors.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32002604

RESUMO

Establishment of the rhizobia-legume symbiosis is usually accompanied by hydrogen peroxide (H2O2) production by the legume host at the site of infection, a process detrimental to rhizobia. In Azorhizobium caulinodans ORS571, deletion of chp1, a gene encoding c-di-GMP phosphodiesterase, led to increased resistance against H2O2 and to elevated nodulation efficiency on its legume host Sesbania rostrata. Three domains were identified in the Chp1: a PAS domain, a degenerate GGDEF domain, and an EAL domain. An in vitro enzymatic activity assay showed that the degenerate GGDEF domain of Chp1 did not have diguanylate cyclase activity. The phosphodiesterase activity of Chp1 was attributed to its EAL domain which could hydrolyse c-di-GMP into pGpG. The PAS domain functioned as a regulatory domain by sensing oxygen. Deletion of Chp1 resulted in increased intracellular c-di-GMP level, decreased motility, increased aggregation, and increased EPS (extracellular polysaccharide) production. H2O2-sensitivity assay showed that increased EPS production could provide ORS571 with resistance against H2O2. Thus, the elevated nodulation efficiency of the ∆chp1 mutant could be correlated with a protective role of EPS in the nodulation process. These data suggest that c-di-GMP may modulate the A. caulinodans-S. rostrata nodulation process by regulating the production of EPS which could protect rhizobia against H2O2.

3.
Colloids Surf B Biointerfaces ; 189: 110820, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32045843

RESUMO

The photothermal/photodynamic synergistic therapy is a promising tumor treatment, but developing nanosystems that achieve synchronous photothermal/photodynamic functions is still quite challenging. Here, we use a simple method to synthesize molybdenum selenide nanoparticles (MoSe2 NPs) with a photothermal effect as a carrier, and load a photosensitizer ICG to form a nanosystem (MoSe2@ICG-PDA-HA)with dual photothermal/photodynamic functions under near-infrared irradiation. In addition, the surface modification of the nanosystem with acid-responsive release polydopamine (PDA) and tumor-targeted hyaluronic acid (HA) enhanced the stability of the photosensitizer ICG and the accumulation of ICG at tumor sites. The multicellular sphere assay simulated solid tumors and demonstrated that MoSe2@ICG-PDA-HA could significantly inhibit the 4T1 cell growth. The anti-tumor experiments in tumor-bearing mice showed that MoSe2@ICG-PDA-HA not only significantly inhibited the growth of 4T1 subcutaneous tumors, but also inhibited their metastasis. This study presented a nanosystem that could improve the photostability of optical materials and enhance the photothermal/photodynamic synergy effect, providing a new idea for finding a way to effectively treat breast cancer.

4.
Biomaterials ; 237: 119822, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-32035322

RESUMO

Alzheimer's disease (AD) seriously affects human health and life and lacks effective treatments. The lessons of many clinical trial failures suggest that targeting amyloid beta to treat AD is difficult, and finding new targets is an important direction for AD drug research. The neurofibrillary tangles formed by hyperphosphorylation of tau protein induce the production of cytotoxic reactive oxygen species (ROS) and cause neuronal apoptosis. Therefore, inhibition of hyperphosphorylation of tau protein and reduction of neuronal damage have become promising methods for the treatment of AD. We herein designed a novel nanocomposite with high stability and good biocompatibility by using flower-shaped hollow nano-ruthenium (Ru NPs) as a carrier, loading nerve growth factor (NGF) and sealing with phase change material (PCM). Due to its excellent photothermal effect, under the near-infrared (NIR) irradiation, the nanocomposite could effectively penetrate the blood-brain barrier (BBB) and respond to phase changes in the lesion area, releasing NGF, which inhibited tau hyperphosphorylation, reduced oxidative stress, and more importantly restored nerve damage and maintained neuronal morphology, thereby significantly improving learning and memory in AD mice. Thus, the experimental results indicate that multifunctional nanocomposites may be a promising drug in the treatment of AD.

5.
BMC Cancer ; 20(1): 106, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041568

RESUMO

OBJECTIVE: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer. METHOD: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18. RESULTS: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm. CONCLUSIONS: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.

6.
Braz J Microbiol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31933178

RESUMO

Antimicrobial peptides are considered to be one of the candidate antimicrobial agents for antibiotic-resistant bacterial infection in the future. The effects of antimicrobial peptide hBD3-CBD on Pseudomonas aeruginosa PA14 and PA14 ΔexsA were analyzed by the bactericidal effects, hemolysis assays, pyocyanin pigment productions, and virulence factor expressions (exoU, exoS, hcnA, and lasB). Pyocyanin production and virulence factor expressions are important features of the type III secretion system in Pseudomonas aeruginosa. HBD3-CBD killed PA14 and PA14 ΔexsA with similar efficiency; it lowered the hemolysis levels of PA14 and PA14 ΔexsA and reduced the pyocyanin production, biofilm formation, and exoU, exoS, and lasB expressions in PA14. Compared with PA14, PA14 ΔexsA showed a lower hemolysis effect, pyocyanin production, exoU, and lasB expressions. The effects of hBD3-CBD on the PA14 toxin secretion were similar to the changes in the type III secretion system mutant isolate PA14 ΔexsA. Our results demonstrated that the type III secretion system was involved in the biological functions on PA 14 from hBD3-CBD.

7.
Bioresour Technol ; 300: 122709, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901771

RESUMO

Bio-valorization of organic waste streams, such as food waste and waste activated sludge, to lactic acid (LA) has recently drawn much attention. It offers an opportunity for resource recovery, alleviates environmental issues and potentially turns a profit. In this study, both stable and high LA yield (0.72 ± 0.15 g/g total chemical oxygen demand) and productivity rate (0.53 g/L•h) were obtained through repeated batch fermentation. Moreover, stable solubilization and increase in the critical hydrolase activities were achieved. Depletions of ammonia and phosphorus were correlated with the LA production. The relative abundance of the key LA bacteria genera (i.e., Alkaliphilus, Dysgonomonas, Enterococcus and Bifidobacterium) stabilized in the repeated batch reactor at a higher level (44.5 ± 2.53%) in comparison with the batch reactor (26.2 ± 4.74%). This work show a practical way for the sustainable valorization of organic wastes to LA by applying the repeated batch mode during biological treatment.


Assuntos
Eliminação de Resíduos , Esgotos , Reatores Biológicos , Fermentação , Alimentos , Ácido Láctico
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 117992, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31935654

RESUMO

With the development of social society, sleep deprivation has become a serious and common issue. Previous studies documented that there is a correlation between sleep deprivation and oxidative stress. However, the information of sleep deprivation related ROS has rarely been obtained. Also, it has been demonstrated that sleep deprivation can induce endoplasmic reticulum (ER) stress. As such, for a better understanding of sleep deprivation as well as its related diseases, it is important to develop probes with ER-targeting ability for detecting ROS generated in this process. Herein, a novel two-photon fluorescent molecular probe, JX-1, was designed for sensing HClO in live cells and zebrafish. The investigation data showed that in addition to real-time response (about 150 s), the probe also exhibited high sensitivity and selectivity. Moreover, the probe JX-1 demonstrated two-photon fluorescence, low cytotoxicity and ER targeting ability. These prominent properties enabled the utilization of the probe for monitoring exogenous and endogenous HClO in both live cells and zebrafish. Using this useful tool, it was found that sleep deprivation can induce the generation of HClO in zebrafish.

9.
Org Lett ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999127

RESUMO

A highly efficient Pd/Ca catalytic system for the directly dehydrative cross-coupling of allylic alcohols with terminal alkynes was developed. This calcium salt cocatalyst facilitates the oxidative addition of the palladium catalyst (1 mol %) to the C-OH bond. Then, the in situ-generated hydroxide ion deprotonates the terminal alkynes to promote the formation of the allylalkynylpalladium intermediate, liberating water as the only byproduct. This proposed mechanism is also supported by density functional theory calculations. An anticancer agent was prepared from inexpensive starting materials on a 10 g scale.

10.
ACS Appl Mater Interfaces ; 12(5): 6309-6318, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31934738

RESUMO

Damage to the responsive superwetting material by external stimuli during the responsive process has been a ticklish question in recent years. We overcome this barrier by imitating a peanut leaf and designing a humidity-responsive MIL-100 (Fe)/octadecylamine-coated stainless steel mesh (HR-MOS). Such a material shows superhydrophilicity when ambient humidity is higher than saturated humidity, while it shows superhydrophobicity and high adhesion to water when ambient humidity is lower than saturated humidity. The peanut leaf-like two-level nanostructure of MIL-100 (Fe) is speculated as the principal factor to bring about the binary synergy wettability of the material. Accordingly, the material can realize humidity-controlled separation of at least 12 types of emulsions along with satisfactory durability. The responsive condition of the material is mild and green, which does lower damage to the material and environment. This strategy is the first to realize humidity-responsive wettability transition and provides a novel approach for manually controlled environmental protection.

11.
Oncol Rep ; 43(2): 591-600, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894331

RESUMO

Mutation of the p53 tumor suppressor frequently occurs in lung cancer, and can be as high as 75­90% in small­cell lung cancer. Mutant p53 (mtp53) can inhibit the wild­type p53 protein, disrupting its tumor suppressor functions. In addition, mutant p53 often acquires the functions of an oncogene. Post­translational modification of the p53 protein is important for its transcriptional and tumor suppressive functions. We previously revealed that high levels of mutant p53 expression were associated with reduced expression of the deacetylation enzyme sirtuin 3 (SIRT3) in lung cancer tissues. Given this negative correlation between p53 and SIRT3 expression, and given that SIRT3 is a deacetylase, we speculated that SIRT3 participates in the post­translational modification of mutant p53, regulating its stability and function, thereby inhibiting the growth of lung cancer cells. Light microscopy, MTT and flow cytometric assays revealed that SIRT3 overexpression inhibited growth and promoted apoptosis in NCI­H446 human small cell lung cancer cells. SIRT3 overexpression also resulted in necroptosis, and this could be partially reversed following cell treatment with the necroptosis inhibitor necrostatin­1 (Nec­1), which could restore certain cells to survive. Western blotting assays revealed that SIRT3 overexpression resulted in the reduced expression and half­life of mutant p53, indicating that SIRT3 decreases mutant p53 stability. Proteasome inhibitor experiments revealed that the decrease in mutant p53 stability was a result of increased proteasomal degradation of the protein. Immunoprecipitation studies revealed that ubiquitination of mutant p53 was elevated in SIRT3­overexpressing cells, indicating that SIRT3 affected ubiquitination­mediated protein degradation. In the present study, it was therefore revealed that SIRT3 can inhibit the growth of human small­cell lung cancer cells by promoting apoptosis and necroptosis. It was also revealed that SIRT3 expression could regulate the stability of mutant p53 by controlling ubiquitination­mediated proteasomal degradation of the protein. SIRT3 expression may therefore play an important role in the growth of mutant p53­associated lung cancer.

12.
Ying Yong Sheng Tai Xue Bao ; 31(1): 113-121, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957387

RESUMO

Rainfall is limited and unevenly distributed across different seasons in the sub-humid but drought-prone area on Loess Plateau, China. Understanding the effects of water supply on the growth of forage crops is of great significance for guiding forage cultivation. Pot experiment was carried out in a shelter in this study. There were five cropping patterns, including monoculture of common vetch, oat and maize, oat/common vetch intercropping, and oat/maize intercropping. There were three water supply levels, including high (low limit of 70% field capacity), medium (low limit of 55% of field capacity) and low (low limit of 40% of field capacity) water. The results showed that land equivalent ratio in the oat/common vetch intercropping group were 1.20, 1.21 and 1.19 at the high, medium and low water supply levels, respectively, and those in the oat/maize intercropping were 1.17, 1.11 and 1.03. Such results indicate that all of the intercropping systems had yield advantages compared with all monoculture. Among the five planting patterns under the same water supply level, the total dry matter yield of maize monoculture was the highest, and that of common vetch monoculture was the lowest. Yields of dry matter and crude protein of oat increased with the decreases of water supply, while common vetch and corn monoculture showed opposite trends. On per plant basis, intercropping increased dry matter yield and crude protein yield of oat, while decreased the yield of common vetch and maize, oat showed an intercropping advantage. Compared with the high water treatment, dry matter yield of the oat/common vetch intercropping increased insignificantly by 4.1% and 4.8% respectively compared with that in the treatments of medium water and low water, whereas dry matter yield of the oat/maize intercropping was significantly reduced by 8.0% and 13.0% respectively. Compared with high water treatment, root/shoot ratio of the oat/common vetch intercropping was significantly increased by 33.4% and 58.4% under the treatments of medium and low water respectively. However, medium and low water supply significantly reduced root/shoot ratio in the oat/maize intercropping. Compared with high water treatment, water use efficiency of the oat/common vetch intercropping significantly increased by 11.7% and 12.9% under the treatments of medium and low water respectively, while water use efficiency of oat/maize intercropping was not affected by water application. In summary, yield of forage maize monoculture and oat/forage maize intercropping were higher, but they were sensitive to water shortage and had low yield stability. Under insufficient water conditions, yield stability, crude protein production and water use efficiency in oat/common vetch intercropping system were greater. Consequently, we suggest this system should be used in the study area.


Assuntos
Agricultura , Água , Biomassa , China , Abastecimento de Água , Zea mays
13.
Artigo em Inglês | MEDLINE | ID: mdl-31907645

RESUMO

PURPOSE: This is the first study to compare the pharmacokinetics of QL1101, a proposed bevacizumab biosimilar, with Avastin® sourced from Roche Diagnostics GmbH. METHODS: In this double-blind, single-dose, parallel-group study, healthy male subjects were randomized 1:1 to receive QL1101 or Avastin® 3 mg/kg intravenously. Pharmacokinetic assessments were conducted for 85 days, with additional safety and immunogenicity assessments until day 90. Primary study endpoints were area under the concentration-time curve (AUC) from time zero to infinity (AUC0-∞), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of the C0-max, AUC0-last, and AUC0-∞ were within the predefined bioequivalence margin of 80-125.00%. RESULTS: A total of 82 subjects were randomized to the following groups: 42 to QL1101 and 40 to Avastin®. The 90% CIs of the GMRs of AUC0-∞, AUC0-last, and Cmax of QL1101 and Avastin® were (97.8%, 107.0%), (94.5%, 106.9%), and (94.1%, 107.3%), respectively, which were all within the bioequivalence margin. The incidence of adverse events was 90.5% and 95.0% in the QL1101 and Avastin® groups, respectively. Mean serum concentration-time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across the two treatment groups. CONCLUSIONS: The study demonstrated the pharmacokinetic equivalence of QL1101 to Avastin®. QL1101 (3 mg/kg, iv) is safe and tolerable in healthy Chinese subjects. These data support the further clinical evaluation of QL1101 as a bevacizumab biosimilar.

14.
J Bone Miner Metab ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974677

RESUMO

INTRODUCTION: Arterial calcification is a major factor for cardiovascular events and is characterized by vascular smooth muscle cells (VSMCs) transformed into osteoblast-like cells. Long non-coding RNAs (lncRNA) were recognized as important regulators of diverse biological processes. Previous studies have demonstrated that lncRNAs could regulate the proliferation and apoptosis of VSMCs. LncRNA-ANCR (Anti-differentiation ncRNA) is an essential mediator governing the differentiation of human osteoblast. However, it is unclear whether ANCR could regulate the osteoblastic differentiation of VSMCs. In this study, we determined the effect of ANCR on VSMCs differentiation and arterial calcification. MATERIALS AND METHODS: Both cellular and mouse model of arterial calcification were, respectively, established to investigate the role of ANCR in the mechanism of arterial calcification. ANCR overexpressing lentivirus were used to investigate the effects of ANCR on the expression of bone proteins and autophagy-related molecules. RESULTS: ANCR could inhibit ß-glycerophosphate (ß-GP)-induced VSMCs osteoblastic differentiation and mineralization due to decreased expressions of Runt-related transcription factor 2, bone morphogenetic protein-2, and formation of mineralized nodule, and attenuate high calcitriol-induced mice model of arterial calcification. Furthermore, ANCR could significantly increase LC3 and autophagy protein 5 expression in ß-GP-stimulated VSMCs, and the effect could be inhibited by 3-methyladenine, a pharmacological inhibitor of autophagy. CONCLUSION: ANCR may inhibit the osteoblastic differentiation of VSMCs and attenuate mice arterial calcification through activating autophagy.

15.
J Hazard Mater ; 387: 121688, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31776082

RESUMO

Perfluorooctanoic acid (PFOA) from contaminated soil accumulates in higher organisms, and causes health risks to humans. In this research, 71 % of the PFOA was degraded, of which 51 % was decomposed into short chain by-products, 19 % mineralized, and 1 % volatilized with 30 kV of voltage, 50 Hz of discharge frequency, 1 % of soil moisture, 300 ppm of PFOA concentration and 6.3 of soil pH using pulsed positive discharge plasma. From a series of experiments, electrons were identified as the dominant active means of PFOA degradation. The decomposition by-products were analyzed by LC-MS. The results indicated that PFOA was decomposed into small by-products including perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluoropentanoic acid (PFPeA), perfluorobutyric acid (PFBA), pentafluoropropionic acid (PFPrA) and trifluoroacetic acid (TFA). Moreover, in plasma treated soil, the concentration of ammonia nitrogen increased from less than 10 ppm-462 ppm, and the average dry weight of lettuce was 1.6 mg higher than that in natural soil. Additionally, Planctomycetes and Nitrospirae increased after treatment, indicating that plasma technology promotes the process of nitrogen cycle. Thus, PFOA polluted soil could be remediated using this pulse corona plasma technology, and simultaneously improve the fertility of soil without chemical injections.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117681, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31685425

RESUMO

The azido asymmetric stretching motion is widely used for the elucidation of the intrinsic conformational preference and folding mechanism of protein since it has strong vibrational absorbance in the spectral transparent windows. However, the possible secondary structural disturbance induced by the insertion of azido group in the side chain of polypeptides should be carefully evaluated. Here, DFT calculation and enhanced sampling method were employed for model dipeptides with or without azido substitution, and the outcome results show that the lower potential energy basins of isolated model dipeptides are consistent with the preferred structural distributions of model dipeptides in aqueous solution. The azido asymmetric stretching frequency shows its sensitivity to the backbone configurations just like amide-I vibration does, and the azido vibration exhibits great potential as a structural reporter in the transparent window. For the evaluation of the application of azido group in biologically related system, the structural dynamics of Aß37-42 and N3-Aß37-42 fragments and the self-assemble process of their protofiliments in aqueous solution were demonstrated. The outcome results show that the structural fluctuations of Aß37-42 and its protofilament in aqueous solution are quite similar with or without azido substitution, and the dewetting transitions of Aß37-42 and N3-Aß37-42 ß-sheet layers are both complete within 30 ns and assemble into stable protofilaments. Therefore, the azido asymmetric vibrational motion is a minimally invasive structural probe and would not introduce much disturbance to the structural dynamics of polypeptides.

17.
Org Lett ; 22(1): 31-35, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31841010

RESUMO

An alkaline-earth metal catalytic system for environmentally benign allylic alkylation was developed. Allylic alcohols can be utilized directly at room temperature in this transition-metal-free process, producing water as the only byproduct. A variety of allylic compounds, including the ones containing all-carbonyl quaternary centers, can be obtained with high yields.

18.
PLoS Pathog ; 15(12): e1008110, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31790500

RESUMO

Viroids are small, non-protein-coding RNAs which can induce disease symptoms in a variety of plant species. Potato (Solanum tuberosum L.) is the natural host of Potato spindle tuber viroid (PSTVd) where infection results in stunting, distortion of leaves and tubers and yield loss. Replication of PSTVd is accompanied by the accumulation of viroid-derived small RNAs (sRNAs) proposed to play a central role in disease symptom development. Here we report that PSTVd sRNAs direct RNA silencing in potato against StTCP23, a member of the TCP (teosinte branched1/Cycloidea/Proliferating cell factor) transcription factor family genes that play an important role in plant growth and development as well as hormonal regulation, especially in responses to gibberellic acid (GA). The StTCP23 transcript has 21-nucleotide sequence complementarity in its 3' untranslated region with the virulence-modulating region (VMR) of PSTVd strain RG1, and was downregulated in PSTVd-infected potato plants. Analysis using 3' RNA ligase-mediated rapid amplification of cDNA ends (3' RLM RACE) confirmed cleavage of StTCP23 transcript at the expected sites within the complementarity with VMR-derived sRNAs. Expression of these VMR sRNA sequences as artificial miRNAs (amiRNAs) in transgenic potato plants resulted in phenotypes reminiscent of PSTVd-RG1-infected plants. Furthermore, the severity of the phenotypes displayed was correlated with the level of amiRNA accumulation and the degree of amiRNA-directed down-regulation of StTCP23. In addition, virus-induced gene silencing (VIGS) of StTCP23 in potato also resulted in PSTVd-like phenotypes. Consistent with the function of TCP family genes, amiRNA lines in which StTCP23 expression was silenced showed a decrease in GA levels as well as alterations to the expression of GA biosynthesis and signaling genes previously implicated in tuber development. Application of GA to the amiRNA plants minimized the PSTVd-like phenotypes. Taken together, our results indicate that sRNAs derived from the VMR of PSTVd-RG1 direct silencing of StTCP23 expression, thereby disrupting the signaling pathways regulating GA metabolism and leading to plant stunting and formation of small and spindle-shaped tubers.

19.
Dis Markers ; 2019: 1569049, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772683

RESUMO

Background and Objective: Liver cancer is a common malignant tumor with few poor diagnostic and prognostic markers, which greatly shortens the potential life span of patients. The RNA-binding protein la ribonucleoprotein 4B (LARP4B) has a la motif (lam) that is important in the process of cancer. We aimed to explore the role of LARP4B in the diagnosis and prognosis of liver cancer. Methods: The Cancer Genome Atlas (TCGA) database was searched to detect LARP4B gene expression in liver cancer. The clinical relevance and diagnostic ability of LARP4B were evaluated by a chi-squared test and a receiver operating characteristic (ROC) curve, respectively. Survival and risk factors of patients with liver cancer were assessed by survival analysis and univariate/multivariate Cox regression model. Additionally, we carried out gene set enrichment analysis (GSEA) to identify LARP4B-related signaling pathways in liver cancer. Results: LARP4B mRNA was highly expressed in liver cancer tissues and was correlated with survival status. The chi-squared test showed that LARP4B had clinical relevance, while ROC curves showed that LARP4B had good diagnostic ability. Survival analysis showed that liver cancer patients with high LARP4B expression had shorter overall/relapse-free survival. The univariate/multivariate Cox regression model indicated that high LARP4B expression may be an independent risk factor for the prognosis of liver cancer patients. Finally, we found that genes involved in the G2M checkpoint, E2F targets, and mitotic spindle were differentially enriched in the high LARP4B-expression phenotype. Conclusions: LARP4B is a potential independent biomarker for diagnosis and prognosis in liver cancer patients.

20.
PLoS Negl Trop Dis ; 13(11): e0007829, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31765414

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus is an emerging infectious disease that was first identified in the rural areas of China in 2011. Severe cases often result in death due to multiple organ failure. To date, there are still numerous problems remain unresolved in SFTS, including unclear pathogenesis, lack of specific treatment, and no effective vaccines available. AIM: To analyze the clinical information of patients with early-stage SFTS and to establish a nomogram for the mortality risk. METHODS: Between April 2011 and December 2018, data on consecutive patients who were diagnosed with SFTS were prospectively collected from five medical centers distributed in central and northeastern China. Multivariable Cox analyses were used to identify the factors independently associated with mortality. A nomogram for mortality was established using those factors. RESULTS: During the study period, 429 consecutive patients were diagnosed with SFTS at the early stage of the disease (within 7 days of fever), among whom 69 (16.1%) died within 28 days. The multivariable Cox proportional hazard regression analysis showed that low lymphocyte percentage, early-stage encephalopathy, and elevated concentration of serum LDH and BUN were independent risk factors for fatal outcomes. Received-operating characteristic curves for 7-, 14-, and 28-days survival had AUCs of 0.944 (95% CI: 0.920-0.968), 0.924 (95% CI: 0.896-0.953), and 0.924 (95% CI: 0.895-0.952), respectively. Among low-risk patients, 6 patients died (2.2%). Among moderate-risk patients, 25 patients died (24.0%, hazard ratio (HR) = 11.957). Among high-risk patients, the mortality rate was 69.1% (HR = 57.768). CONCLUSION: We established a simple and practical clinical scoring system, through which we can identify critically ill patients and provide intensive medical intervention for patients as soon as possible to reduce mortality.

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