Identification of TFRC as a biomarker for pulmonary arterial hypertension based on bioinformatics and experimental verification.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there is a paucity of studies that reflect the available biomarkers from separate gene expression profiles in PAH. METHODS: The GSE131793 and GSE113439 datasets were combined for subsequent analyses, and batch effects were removed. Bioinformatic analysis was then performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and a protein-protein interaction (PPI) network analysis were then used to further filter the hub genes. Functional enrichment analysis of the intersection genes was performed using Gene Ontology (GO), Disease Ontology (DO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA). The expression level and diagnostic value of hub gene expression in pulmonary arterial hypertension (PAH) patients were also analyzed in the validation datasets GSE53408 and GSE22356. In addition, target gene expression was validated in the lungs of a monocrotaline (MCT)-induced pulmonary hypertension (PH) rat model and in the serum of PAH patients. RESULTS: A total of 914 differentially expressed genes (DEGs) were identified, with 722 upregulated and 192 downregulated genes. The key module relevant to PAH was selected using WGCNA. By combining the DEGs and the key module of WGCNA, 807 genes were selected. Furthermore, protein-protein interaction (PPI) network analysis identified HSP90AA1, CD8A, HIF1A, CXCL8, EPRS1, POLR2B, TFRC, and PTGS2 as hub genes. The GSE53408 and GSE22356 datasets were used to evaluate the expression of TFRC, which also showed robust diagnostic value. According to GSEA enrichment analysis, PAH-relevant biological functions and pathways were enriched in patients with high TFRC levels. Furthermore, TFRC expression was found to be upregulated in the lung tissues of our experimental PH rat model compared to those of the controls, and the same conclusion was reached in the serum of the PAH patients. CONCLUSIONS: According to our bioinformatics analysis, the observed increase of TFRC in the lung tissue of human PAH patients, as indicated by transcriptomic data, is consistent with the alterations observed in PAH patients and rodent models. These data suggest that TFRC may serve as a potential biomarker for PAH.

Research on the Influence of the Material Removal Profile of a Spherical Polishing Tool on the Mid-Spatial Frequency Errors of Optical Surfaces.

Elastic spherical polishing tools effectively conform to the polishing surface and exhibit high efficiency in the removal of materials, so they are extensively used in the sub-aperture polishing stages of optical components. However, their processing is often accompanied by significant mid-spatial frequency (MSF) errors, which critically degrade the performance of optical systems. To suppress the MSF errors generated during polishing with spherical tools, this study investigates the influence factor of MSF errors during the polishing process through an analysis of the convolution effect in material removal. A material removal profile model is established, and a uniform removal simulation is conducted to assess the influence of different shape material removal profiles on MSF errors. Simulation and experimental results show that a Gaussian-like shape material removal profile is more effective in suppressing the MSF errors during polishing compared to the "W" and trapezoidal shape material removal profiles. In addition, based on the characteristics of the RMS decreasing in a serrated trend with the decrease in path spacing, a path spacing optimization method considering the polishing efficiency is proposed to improve the polishing efficiency while controlling the MSF errors, and the effectiveness of the path spacing optimization method is verified by comparing the MSF error at the maximum theoretical path spacing and the path spacing that is less than this. Finally, the path spacing optimization method is used to polish single-crystal silicon to further illustrate its practicality.

Trigonometric-spline dwell time scheduling and real-time interpolator under dynamic constraints for deterministic polishing.

Dwell time scheduling is a critical stage of deterministic polishing for ultra-precision fabrication of optics. Recently the dwell time algorithms for deterministic polishing have been widely studied. Nevertheless, there exist some shortcomings when those methods were applied in the industry, including low computational efficiency, large memory consumption, insufficiently-considered dynamic constraints, poor smoothness of the feedrate profile, and reliance on non-open CNC interpolator. To overcome those deficiencies, this work proposes a highly-efficient dwell time algorithm under the dynamic constraints of machine tools. The method calculates the initial dwell time density (DTD) sequence through non-blind deconvolution algorithm, and provides the feasible set of DTD profiles based on trigonometric-spline model. And the DTD repairing tactics are developed based on a self-adaptive offset algorithm under confined feedrate and acceleration. Finally, a C1-continuous DTD profile satisfying dynamic constraints is generated. A real-time interpolator based on trigonometric-spline DTD profile is developed. The simulation results show that the proposed method generates a C1-continuous feedrate profile rigidly respecting dynamic constraints, and preserves the ideal dwell time gradient distribution, achieving a more ideal residual error with high computational efficiency compared with the previous methods. The comparative experiments demonstrate that the proposed method performs better in suppressing the multi-frequency errors compared with the previous methods, and achieves high computational efficiency. The algorithm is applicable to highly-precise and highly-efficient fabrication of large-aperture optical components.

Preparation of hepatocellular carcinoma mRNA vaccines based on potential tumor targets and immunophenotypes.

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries. Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines. Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1, which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness. Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C. HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries.

[Pollution Characteristics of Organochlorine Pesticides in Water and Sediments of Huixian Karst Wetland in Guilin].

Karst wetland plays an important role in the ecological environment; however, due to the existence of karst pipeline, pollutants can threaten the underground environment through the highly developed karst pipeline. Therefore, understanding the pollution characteristics of the karst surface environment is the premise of pollution ecological risk assessment and prevention. In this study, 24 organochlorine pesticides (OCPs) were analyzed to study the concentration, composition, source, and risk of OCPs in water and surface sediments in the Huixian Wetland of Guilin. The results showed that:the concentration of OCPs in water ranged from 3.17 ng·L-1 to 92.50 ng·L-1, and the concentration of OCPs in sediment ranged from 1.16 ng·g-1 to 219.52 ng·g-1, showing the main pollution characteristics of HCHs and DDTs. The concentration of OCPs in water was higher in the wet season than that in the dry season. The concentration of OCPs in sediments was higher in the dry season than that in the wet season. The isomer ratios revealed that OCPs in the study area were mainly derived from long-term degradation residues, and some sites had new input of lindane. Based on Monte Carlo simulation, the human health risk assessment of the study area showed that the 95% quantile carcinogenic risk of OCPs in water was greater than 1×10-6, with potential but acceptable health risk. The non-carcinogenic risk was lower than 1, which indicated that the level of OCPs residues in the water in the study area was not enough to cause non-carcinogenic risk to the human body.

Effects of plant residues on C:N:P of soil, microbial biomass, and extracellular enzyme in an alpine mea-dow on the Qinghai-Tibetan Plateau, China.

Plant residues can affect C:N:P of soil, microbial biomass, and extracellular enzyme, but the effects are still unclear. We conducted a field experiment in an alpine meadow on the eastern part of the Qinghai-Tibetan Plateau to explore the effects of removing aboveground plant or roots and adding plant residues on the C:N:P of soil, microbial biomass, and extracellular enzyme. The results showed that removing aboveground plant biomass significantly decreased soil C:N (the change was -23.7%, the same below) and C:P (-14.7%), microbial biomass C:P and N:P, while significantly increased microbial biomass C:N, and enzyme C:N:P compared with meadow without human disturbance. Removing all plant biomass (aboveground and roots) significantly reduced soil C:N (-11.6%), C:P (-24.0%), N:P (-23.3%) and microbial biomass C:N in comparison to removing aboveground plant, while significantly improved microbial biomass N:P and enzyme N:P. Adding plant residues after removing aboveground plant significantly increased microbial biomass C:N and C:P, enzyme C:N compared with removing aboveground plant, while significantly decreased enzyme N:P. Compared with removing all the plant, adding plant residues after removing whole plant significantly reduced soil C:N (-16.4%), microbial biomass C:P, N:P and enzyme N:P, while significantly increased enzyme C:N. Our results suggest that removal of plants could have a strong effect on C:N:P of soil, microbial biomass, and extracellular enzyme, and C:N:P of microbial biomass and that extracellular enzyme woule be more sensitive to plant residues. Roots could play a key role in stabilizing C:N:P of soil, microbial biomass, and extracellular enzyme under plant residues addition. Adding plant residues could be a suitable solution for restoring alpine meadows under the circumstance of intact roots, which was conducive to soil C storage, but might not be suitable for alpine meadows with serious root damage, which would increase soil CO2 emission.

Evolution law of comet-shaped defects in magnetorheological finishing.

Ultraprecision optical systems such as high-energy laser systems have very strict requirements for surface defects of optical components. Comet-shaped defects are common in magnetorheological finishing, which is one of the main ultraprecision manufacturing technologies. Computational fluid dynamics is used to simulate the pressure and velocity of the magnetorheological fluid in pits during magnetorheological finishing for the first time, to the best of our knowledge. The simulation model analyzes the distribution of velocity and pressure in the process of the formation of comet-shaped defects. After the simulation, magnetorheological polishing experiments were carried out on the fused quartz silica glass. The polishing experiments use the rotation speed and immersion depth of the polishing wheel to verify the velocity and pressure distribution in the simulation experiment. The polishing experiment results are consistent with the simulation results, which show that the high polishing speed will increase the depth of the defect, and the uneven velocity and pressure distribution at the pits make the pits evolve into comet-shaped defects. We explain the cause of comet-shaped defects from the perspective of material removal and provide an optimization method of process parameters for high-efficiency removal of comet-shaped defects.

[WANG Ju-yi's meridian diagnosis method combined with Bobath rehabilitation training for post-stroke shoulder-hand syndrome typeâ ].

OBJECTIVE: To compare the clinical efficacy differences between WANG Ju-yi 's meridian diagnosis method combined with Bobath rehabilitation training and Bobath rehabilitation training alone for post-stroke shoulder-hand syndrome (SHS) typeⅠ. METHODS: A total of 106 patients with post-stroke SHS typeⅠwere randomly divided into an observation group (53 cases, 2 cases dropped off ) and a control group (53 cases, 3 cases dropped off ). The patients in the both groups were treated with medications for basic diseases and conventional acupuncture at Waiguan (TE 5), Shousanli (LI 10) and Jianyu (LI 15) on the affected side. In addition, the patients in the control group were treated with Bobath rehabilitation training, 20 minutes each time; on the basis of the control group, the patients in the observation group were treated with WANG Ju-yi's meridian diagnosis method to adjust the abnormal parts in meridians of the hand taiyin and hand yangming on the affected side, 20 minutes each time. Both groups were treated once a day, 5 times a week for 8 weeks. The scores of visual analogue scale (VAS), upper-limb Fugl-Meyer assessment (FMA) and Barthel index (BI) were recorded before and after treatment as well as 6 weeks after treatment (follow-up), and the clinical efficacy of the two groups was evaluated after treatment. RESULTS: Compared before treatment, the VAS scores were reduced and the scores of upper-limb FMA and BI were increased in the two groups after treatment and in the follow-up (P<0.05). The VAS score in the observation group was lower than that in the control group (P<0.05), and the scores of upper-limb FMA and BI in the observation group were higher than those of the control group (P<0.05). The total effective rate in the observation group was 82.4% (42/51), which was higher than 62.0% (31/50) in the control group (P<0.05). CONCLUSION: WANG Ju-yi 's meridian diagnosis method combined with Bobath rehabilitation training could effectively treat post-stroke SHS typeⅠ, reduce pain symptoms and improve joint motor dysfunction, and improve the quality of life. Its curative effect is better than Bobath rehabilitation training alone.

[Soil denitrifying enzyme activity and its influencing factors in a bamboo forest riparian zone in the upper reaches of the Taihu Lake Basin, China]. / å¤ªæ¹–æµåŸŸä¸Šæ¸¸ç«¹æž—æ²³å²¸å¸¦åœŸå£¤åç¡åŒ–é ¶æ´»æ€§åŠå ¶å½±å“å› ç´ .

Soil denitrifying enzyme activity (DEA) was measured by acetylene inhibition technique, along with exploration of factors influencing DEA in a bamboo forest riparian zone in the upper reaches of the Taihu Lake Basin during summer. Our aim was to provide important insights into the assessment of ecological functions of bamboo forest riparian zone on reducing nitrogen pollution in rivers. The results showed that the riparian soil DEA ranged from 6.32 to 23.22 µg N·kg-1·h-1, with a mean value of 14.65 µg N·kg-1·h-1. The vertical distribution (0-40 cm soil profile) of DEA was affected by several factors, such as soil organic carbon (SOC), total nitrogen (TN), nitrate nitrogen (NO3--N), soil water content, and activity of carbon and nitrogen hydrolase, which resulted in decreased DEA with increasing soil depth. The horizontal changes in DEA (at the same soil depth but at different distances from river) was mainly governed by the variation in SOC concentration. In this area, the concentration of soil dissolved organic carbon was relatively low, which might inhibit the soil DEA during summer.

Transparent qubit manipulations with spin-orbit coupled two-electron nanowire quantum dot.

We report on the first set of exact orthonormalized states to an ac driven one-dimensional (1D) two-electron nanowire quantum dot with the Rashba-Dresselhaus coexisted spin-orbit coupling (SOC) and the controlled magnetic field orientation and trapping frequency. In the ground state case, it is shown that the spatiotemporal evolutions of probability densities occupying internal spin states and the transfer rates between different spin states can be adjusted by the ac electric field and the intensities of SOC and magnetic field. Effects of the system parameters and initial-state-dependent constants on the mean entanglement are revealed, where the approximately maximal entanglement associated with the stronger SOC and its insensitivity to the initial and parametric perturbations are demonstrated numerically. A novel resonance transition mechanism is found, in which the ladder-like time-evolution process of expected energy and the transition time between two arbitrary exact states are controlled by the ac field strength. Using such maximally entangled exact states to encode qubits can render the qubit control more transparent and robust. The results could be extended to 2D case and to an array of two-electron quantum dots with weak neighboring coupling for quantum information processing.

[Characteristics and Drivers of Dissolved Carbon Dioxide and Methane Concentrations in the Nantiaoxi River System in the Upper Reaches of the Taihu Lake Basin During Summer-Autumn].

Inland waters are vital sinks for active carbon (C) and potential sources of greenhouse gas emissions. In this study, the characteristics of dissolved carbon dioxide (CO2) and methane (CH4) concentrations in the Nantiaoxi River system in the upper reaches of the Taihu Lake basin were observed between Jul. 2019 and Nov. 2019 (summer and autumn) using headspace equilibration-gas chromatography. Simultaneously, physical and chemical parameters were also determined to understand the factors influencing dissolved CO2 and CH4 concentrations. The results showed that the mean dissolved CO2 concentrations and saturation levels in water were (505.47±16.99) µg·L-1 and (256.31±8.32)%, respectively, and the corresponding values for CH4 were (1.88±0.09) µg·L-1 and (5218.74±264.30)%, respectively. The saturation levels of dissolved CO2 and CH4 at all observation points were greater than 100%, indicating that the Nantiaoxi River system is a potential source of CO2 and CH4. The highest mean dissolved CO2 concentrations in water were found in agricultural areas followed by residential and forest areas, and there were significant differences among the three land-use types. The mean dissolved CH4 concentrations in the water in residential areas were significantly higher than those in agricultural area forest areas. The dissolved CO2 concentrations, saturation levels of CO2, dissolved CH4 concentrations, and saturation levels of CH4 in water were all negatively correlated with oxidation reduction potential (ORP) (P<0.01) and positively correlated with electrical conductivity (EC) (P<0.01). The discrepancies in chlorophyll (Chl-a), nitrate (NO3--N), total nitrogen (TN), and EC were the main reasons for differences in dissolved CO2 concentrations among the different land use types. Phytoplankton growth could be promoted by the higher input of nitrogen pollutants into rivers in agricultural and residential areas, and respiration could be also enhanced, resulting in higher dissolved CO2 concentrations. The higher concentrations of dissolved organic carbon (DOC) and ammonium nitrogen (NH4+-N) in the water, and the water temperature in residential areas, were probably the main causes of the higher dissolved CH4 concentrations. Rainfall also had some influence on dissolved CO2 and CH4 concentrations in the water associated with the different land use types. Specifically, higher concentrations of nitrogen pollutants and the enhancement of DOC were the main drivers of high dissolved CO2 concentrations in agricultural areas as well as the higher dissolved CH4 concentrations in residential areas following rainfall events.

Distribution model of the surface roughness in magnetorheological jet polishing.

Magnetorheological jet polishing (MJP) plays an important role in polishing complex cavities and special optical elements with high precision. However, the roughness distribution function that describes the variation with polishing time of the roughness value of every area in the polishing area has not been studied deeply. In this paper, the influence of the roughness distribution on the removal function of MJP in optics (with a roughness of less than 10 nm) and its evolution model in the spatial and time domains are studied. With the increase of polishing time, the surface roughness of the central area linearly increases, forming surface defects, such as pits. The roughness of the polishing area exhibits a limited growth trend. Verification experiments are carried out on BK7 glass. The results of the roughness distribution on the removal function prove the correctness of the model. The model laid a foundation; therefore, it has important guidance and reference value for the application to the whole aperture polishing.

Comprehensive study of the rapid stressed mirror polishing method for off-axis aspheric SiC thin-plate mirrors.

In this study, the stressed mirror polishing technique is used to perform off-axis aspheric silicon carbide (SiC) mirror full-aperture polishing for the first time. Mechanical and optical parameter analysis methods have been proposed. A medium-diameter off-axis aspheric SiC thin-plate mirror is used as a scaling model for an optical system mirror. A full diameter polishing simulation was completed, and a conceptual design for stress loading equipment is presented. An initial aspheric surface method for stressed mirror polishing of an off-axis aspheric SiC thin-plate mirror, providing a reference for rapid stress mirror polishing of SiC mirrors, is also proposed.

MicroRNA-34c suppresses proliferation of vascular smooth muscle cell via modulating high mobility group box protein 1.

BACKGROUND: Atherosclerosis is the most frequent pathological process that causes cardiovascular diseases. OBJECTIVE: The present study aimed to confirm miRNAs associated with atherosclerosis and explore the molecular mechanism of miR-34c and its target high mobility group box protein 1 (HMGB1) in the control of growth of smooth muscle cells in the development of atherosclerosis. METHODS: Real-time PCR was firstly performed to confirm miRNA correlation with atherosclerosis, and computational analysis and luciferase assay were performed to explore the target of miR-34c, Western blot, and real-time PCR were also utilized to reveal the effect of whether high glucose (HG) and miR-34c affect miR-34c, HMGB1 levels, NF-κB p65 and TNF-α levels, and the role of miR-34c on vascular smooth muscle cells (VSMCs) viability induced by HG. Students' unpaired t test was performed to compare data between two groups. RESULTS: MiR-34c level was associated with atherosclerosis with different expression between VSMCs treated with high glucose or normal VSMCs. Then, HMGB1 is a virtual target of miR-34c with predicted binding site resided in HMGB1 3'UTR and further verified by that miR-34c remarkably reduced luciferase activity of wild HMGB1 3'UTR under a concentration-dependent fashion, and miR-34c cannot influence luciferase activity of mutant HMGB1 3'UTR. CONCLUSIONS: The results suggested miR-34c might be a novel therapeutic strategy in the management of atherosclerosis by suppressing the expression of HGMB1 and its downstream effectors.

Dysregulation of the Urothelial Cancer Associated 1 Long Noncoding RNA Promotes Proliferation of Vascular Smooth Muscle Cells by Modulating Expression of P27KIP1/CDK2.

Background: Atherosclerosis is one of the leading causes of morbidity and mortality worldwide. A variety of long noncoding RNAs (lncRNAs) have been reported to be significantly involved in vascular smooth muscle cell (VSMC) proliferation, which is an essential process for atherosclerotic plaque formation. The aim of this study was to investigate the mechanism of lncRNA urothelial cancer associated 1 (UCA1) involvement in atherosclerosis. Method: The effects of oxidized low-density lipoprotein (oxLDL) and UCA1 on VSMC proliferation and colony-forming ability was measured by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, real-time polymerase chain reaction (PCR), and western blots, as well as to determine the effect that oxLDL has on UCA1 expression, and the effect of oxLDL and UCA1 on the expression of cyclin-dependent kinase 2 (CDK2). Results: oxLDL treatment increased the proliferation rate of VSMCs in a concentration-dependent manner. Importantly, UCA1 apparently increased the viability of VSMCs as the VSMCs exhibited a significantly reduced growth rate when UCA1 expression was knocked down by specific small interfering RNAs (siRNAs). In conjunction with increasing cell viability, oxLDL also enhanced the colony-forming ability of VSMCs while UCA1 siRNA decreased the colony-forming ability of VSMCs. Furthermore, UCA1 significantly decreased the percentage of VSMCs in G1 phase, while increasing their percentage in S phase. In contract siRNA knockdown of UCA1 caused an increased percentage of cell in G1 phase, and a reduction in the percentage of cells in S phase. Using real-time PCR and western blot assays, we showed that oxLDL significantly increased the expression levels of UCA1 and CDK2. Furthermore, UCA1 siRNA and CDK2 siRNA almost abolished the positive effect of oxLDL on CDK2 expression. Finally, overexpression of UCA1 induced an increase in CDK2 levels, and knockdown of UCA1 caused inhibition of CDK2 expression. Conclusion: Upregulation of UCA1 enhances abnormal proliferation of VSMC by promoting G1/S transition through modulating the expression of CDK2.

Prevalence of allergen sensitization among 1,091 patients with urticaria.

The etiology of urticaria is heterogeneous and allergic responses may be involved in it. The aim of the present study was to investigate the prevalence and distribution of sensitivity to inhaled and food allergens among patients with urticaria in Henan province (China). The levels of specific immunoglobulin E (sIgE) were detected using the AllergyScreen test and a total of 524/1,091 cases (48.0%) tested positive for sIgE to at least one of the 19 allergens. The most common inhaled allergens the urticaria patients were sensitive to were D. pteronyssinus (34.5%), cockroach (12.5%) and tree pollen mix (11.1%), while the food allergens with the highest rate of allergic reactions were cashew nut (8.1%), shrimp (6.8%) and crab (6.4%). The positive rates for D. pteronyssinus, dog hair, cockroach, mold mix, tree pollen mix and shrimp in the chronic urticaria group were higher than those in the acute urticaria group (P<0.05). Furthermore, positive rates for the majority of allergens were higher in males than in females and were significantly different between age groups (P<0.05). The results of the present study provided information on the characteristics of allergen sensitization of patients with urticaria and may facilitate the prevention, diagnosis and management of urticaria in Henan province.

[Accumulation Characteristics and Release Regularity of Nutrients in Sediments of a Surface-flow Constructed Wetland After Long-term Operation].

Sediments serve as an important carrier during the migration and transformation of pollutants in surface-flow constructed wetlands. Exploring the accumulation characteristics and release patterns of nutrients is of great significance for assessing the purification functions of constructed wetlands after long-term operation. The contents of total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP) in sediments at various locations of the 5-year-old Yanlong Lake surface-flow constructed wetland were analyzed and static release experiments with cylindrical core samples were carried out. The results showed that after five years, sediments at this site have become moderately polluted and the nutrient accumulation level is mainly being affected by the influent flow, water depth, and plant effects. Additionally, ① nutrients in sediments were found to increase along the flow direction; ② they also increase as the depth of overlying water increases and are relatively affected by the carbon; ③ healthier growth of the wetland plants could lead to more nutrients being accumulated in sediments. The release trend of nutrients fell after a rise and basically reached equilibrium after 20 days, and the release rate was mainly affected by the accumulation level of nutrients, which is similar to the trend in light nutrient containing reservoirs. Plant residues contained in the sediments were associated with the stronger release of nutrients. These results can provide a scientific basis for solutions aimed at maintaining the purification capacity of long-running surface-flow constructed wetlands.

Toxoplasma gondii ROP17 inhibits the innate immune response of HEK293T cells to promote its survival.

Toxoplasma gondii secretes a group of rhoptry-secreted kinases (ROPs), which play significant roles in promoting intracellular infection. T. gondii rhoptry organelle protein 17 (ROP17) is one of these important effector proteins. However, its role in modulating host cell response during infection remains poorly understood. Here, we reveal that ROP17 (genotype I) induces significant changes in the expression genes and transcription factors of host cells. HEK293T cells were transfected with PCMV-N-HA-ROP17 plasmid or empty control PCMV-N-HA plasmid. Transcriptomic analysis revealed 3138 differentially expressed genes (DEGs) in PCMV-N-HA-ROP17-transfected HEK293T cells, including 1456 upregulated, 1682 downregulated DEGs. Also, 715 of the DEGs were transcription factors (TFs), including 423 downregulated TFs and 292 upregulated TFs. Most differentially expressed TFs, whether belong to signal transduction, cancer-related pathways or immune-related pathways, were downregulated in ROP17-expressing cells. ROP17 also decreased alternative splicing events in host cells, presumably via alteration of the expression of genes involved in the alternative splicing pathway. Taken together, our findings suggest a novel strategy whereby T. gondii ROP17 manipulates various cellular processes, including immune response through reprogramming host gene expression to promote its own colonization and survival in the infected host cells.

Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. METHOD: A single subcutaneous injection of monocrotaline (MCT) (60 mg kg- 1) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. RESULTS: Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. CONCLUSION: The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile.

A single nucleotide polymorphism located in microRNA-499a causes loss of function resulting in increased expression of osbpl1a and reduced serum HDL level.

Atherosclerosis is the main pathological process that induces CVD (cardiovascular diseases), and the objective of our study was explore whether miR­499a rs3746444 polymorphism was associated with the HDL level, one of the risk factors of atherosclerosis. Online public miRNA database was utilized to predict the miR­499a target, and luciferase assay was conducted to confirm that miR­499a targeted osbpl1a, then western blot analysis and real-time PCR were performed to verify miRNA-mRNA regulatory relationship between miR­499a and osbpl1a. Based on results of bioinformatics algorithms, osbpl1a was predicted as a candidate target gene of miR­499a, luciferase reporter was generated, and it was found that the luciferase activity of cells was substantial downregulated following co-transfection with wild osbpl1a 3'UTR and miR­499a compared to that in scramble control, while the inhibitory effect of miR­499a was abolished after transfection of mutant osbpl1a 3'UTR. Then, miRNA-mRNA regulatory relationship between miR­499a and osbpl1a was detected, a concentration-dependent effect of miR­499a on the miR­499a expression was observed, and both osbpl1a mRNA and protein levels of cells transfected with miR­449a (30 and 60 nM) or osbpl1a siRNA were markedly reduced, while notably improved subsequent to transfect with anti­miR­449a (30 and 60 nM) in comparison with NC groups, moreover, the inhibitory effect among 30 or 60 nM miR­499a, osbpl1a siRNA was similar, the improved effect of 30 or 60 nM anti­miR­499a showed no significant change. The influence of rs3746444 A allele on expression level of miR­499a represented a recessive pattern in high-grade group with a higher level of miR­499a in AA group, and HDL level in AA group was significantly reduced related to those in AG and GG groups. This study validated that rs3746444 polymorphism influenced the expression of miR­499a, its target gene, osbpl1a, and thereby associated with the HDL level, which makes it a potential factor involved in the mechanism of atherosclerosis.