Genetic alterations and allele frequency of BRAF V600E and TERT mutation in papillary thyroid carcinoma with intermediate-to-high recurrence risk: a retrospective study.

The predictive value of allele frequency (AF) of BRAF V600E and TERT mutations in papillary thyroid carcinoma (PTC) remains controversial. We aimed to investigate the AF of BRAF V600E and TERT mutations in intermediate-to-high risk PTC and their association between tumor invasiveness, prognosis, and other mutations. Probe hybridization capture and high-throughput sequencing were used to quantitatively test 40 gene loci in 94 intermediate-to-high recurrence risk PTC patients, combined with clinical characteristics and follow-up for retrospective analysis. BRAF V600E mutation AF was linked to a increased risk of thyroid capsule penetration, recurrence, and concurrent mutations. Concurrent mutations could lead to a worse prognosis and increased invasiveness. TERT promoter mutation frequently accompanied other mutations and resulted in a poorer prognosis. However, there was no clear association between the TERT mutation AF and tumor invasiveness or recurrence. The sensitivity and specificity of predicting recurrence in intermediate-to-high risk PTC with BRAF V600E mutation AF > 28.2% were 60 and 80%. Although genetic alterations in PTC can differ among different ethnicities, the AF of BRAF V600E and TERT mutations may be similar. The AF of BRAF V600E has the potential to be a novel indicator in predicting PTC invasiveness and prognosis.

Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation.

The environmental behavior of and risks associated with nanoplastics (NPs) have attracted considerable attention. However, compared to pristine NPs, environmental factors such as ultraviolet (UV) irradiation that lead to changes in the toxicity of NPs have rarely been studied. We evaluated the changes in morphology and physicochemical properties of polystyrene (PS) NPs before and after UV irradiation, and compared their hepatotoxicity in mice. The results showed that UV irradiation caused particle size reduction and increased the carbonyl index (CI) and negative charge on the particle surface. UV-aged PS NPs (aPS NPs) could induce the generation of hydroxyl radicals (·OH), but also further promoted the generation of ·OH in the Fenton reaction system. Hepatic pathological damage was more severe in mice exposed to aPS NPs, accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein, alanine aminotransferase and aspartate aminotransferase levels. In addition, exposure to PS NPs and aPS NPs, especially aPS NPs, triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver. Compared with PS NPs, exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways, especially glutathione metabolism. Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of ·OH, enhancing PS NPs-induced liver damage and metabolic disorders. This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

Short term exposure to polystyrene nanoplastics in mice evokes self-regulation of glycolipid metabolism.

With the detection of nano-plastics (NPs) in daily essentials and drinking water, the potential harm of NPs to human health has become the focus of global attention. Studies have shown that long term exposure to NPs can lead to disorders of glucose and lipid metabolism in organisms, while the effects of short term exposure are rarely reported. Moreover, environmental factors cause the aging of NPs, and it is unclear whether this has an effect on their toxicity. In this study, we use 100 nm polystyrene (PS) NPs and ultraviolet (UV) aging PS (aPS) NPs to gavage mice for 7 days at an exposure dose of 50 mg/kg/day. To evaluate the effects of exposure on mice hepatic glucose lipid metabolism, we performed blood biochemical, pathological and metabolomic analyses. The results showed that exposure to PS NPs and aPS NPs increased serum glucose, disrupted serum lipoprotein levels, and up-regulated the expression levels of phosphatidylinositol 3-kinase (PI3K)/ phosphoprotein kinase B (p-AKT)/Glucose transporter 4 (GLUT4) proteins in the glucose metabolism pathway. The expression levels of key proteins sterol regulatory element binding protein-1 (SREBP-1)/peroxisome proliferator-activated receptor-γ (PPARγ)/adipose triglyceride lipase (ATGL) in the lipid metabolism signaling pathway were significantly increased. These findings suggest that short term exposure to PS NPs and aPS NPs induces glycolipid metabolism disturbance in mice, which may subsequently awaken the mice to self-regulate the serum levels of various lipoproteins and the expression of related key proteins. Compared with PS NPs, the aPS NPs interfered more strongly with glucose metabolism, and the corresponding self-regulation in mice was also more obvious. These findings not only provide a basis for environmental factors to increase the health risk of NPs but also provided a reference for the selection of test substances for further studies on the toxicity of NPs.

A 16S rDNA sequencing-based analysis of airway microecology in patients with an acute exacerbation of chronic obstructive pulmonary disease: A cross-sectional study in Inner Mongolia, China.

Aim: To study the microecological characteristics of the airway and similarities and differences between healthy people and patients with the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Inner Mongolia, and analyze the correlation between the characteristics of the airway microecological structure and clinical indicators of AECOPD patients. Methods: Sputum samples from 36 healthy volunteers and 34 patients with AECOPD were detected by 16S rDNA high-throughput sequencing, and the airway microecological characteristics of healthy people and AECOPD patients were revealed by an alpha diversity analysis, beta diversity analysis, and LefSe difference analysis. Results: There were differences in the airway microecological structure between healthy people and AECOPD patients in Inner Mongolia. The airway microbiota composition of AECOPD patients showed an increase in the abundance of common pathogens and a decrease in the abundance of commensal bacteria, and the airway microbial diversity in AECOPD patients was lower than that in healthy people. Long-term use of inhaled glucocorticoid + long-acting ß2 agonist mixture (ICS + LABA), procalcitonin (PCT), blood monocyte count (MONO), hemoglobin (HGB), D-dimer (D-D), and body temperature were negatively correlated with the alpha diversity of the airway micro-ecosystem. Conclusion: The airway microecological composition of the AECOPD population in Inner Mongolia was different from that of the healthy population, and the airway microecological diversity was lower than that of the healthy population. The long-term use of ICS + LABA preparation by patients with AECOPD leads to lower alpha diversity. Alpha diversity was negatively correlated with inflammatory markers (PCT, MONO, D-dimer, body temperature) and HGB in AECOPD patients.

Plant UVRAG interacts with ATG14 to regulate autophagosome maturation and geminivirus infection.

Autophagy is an essential degradation pathway that assists eukaryote survival under multiple stress conditions. Autophagosomes engulfing cargoes accomplish degradation only when they have matured through fusing with lysosomes or vacuoles. However, the molecular machinery mediating autophagosome maturation in plants remains unknown. Using the combined approaches of mass spectrometry, biochemistry, reverse genetics and microscopy, we uncover that UVRAG, a subunit of the class III phosphatidylinositol 3-kinase complexes in Nicotiana benthamiana, plays an essential role in autophagsome maturation via ATG14-assisted recruitment to autophagosomes and by facilitating RAB7 activation. An interaction between N. benthamiana UVRAG and ATG14 was observed in vitro and in vivo, which strikingly differed from their mutually exclusive appearance in different PI3KC3 complexes in yeast and mammals. This interaction increased the localisation of UVRAG on autophagosomes and enabled the convergence of autophagic and late endosomal structures, where they contributed to fusions between these two types of organelles by recruiting the essential membrane fusion factors RAB7 GTPase and the homotypic fusion and protein sorting (HOPS) complex. In addition, we uncovered a joint contribution of ATG14 and UVRAG to geminiviral infection, beyond autophagy. Our study provides insights into the mechanisms of autophagosome maturation in plants and expands the understanding of organisations and roles of the PI3KC3 complexes.

Linking Autophagy to Potential Agronomic Trait Improvement in Crops.

Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, by which the superfluous or damaged cytoplasmic components can be delivered into vacuoles or lysosomes for degradation and recycling. Two decades of autophagy research in plants uncovers the important roles of autophagy during diverse biological processes, including development, metabolism, and various stress responses. Additionally, molecular machineries contributing to plant autophagy onset and regulation have also gradually come into people's sights. With the advancement of our knowledge of autophagy from model plants, autophagy research has expanded to include crops in recent years, for a better understanding of autophagy engagement in crop biology and its potentials in improving agricultural performance. In this review, we summarize the current research progress of autophagy in crops and discuss the autophagy-related approaches for potential agronomic trait improvement in crop plants.

Source analysis of heavy metal pollution in agricultural soil irrigated with sewage in Wuqing, Tianjin.

In this study, the contents of heavy metals and Cd and Pb isotope ratios of agricultural soil and potential source samples collected from farmland receiving sewage irrigation in Wuqing District, Tianjin, China were determined. Multiple methods were used for source analysis, including positive matrix factorization (PMF), correlation analysis, principal component analysis (PCA), and the Cd and Pb isotope ratio method. The results showed that agricultural soil was slightly contaminated by heavy metals in the research area, with relatively higher Cd and Pb accumulation levels compared to those of other heavy metals. Four types of pollution sources, including the soil parent material sources, industrial emission sources, agricultural practice sources, and mixed sources of sewage irrigation and transportation were apportioned and quantified by PMF, combined with the results of PCA and correlation analysis. The contribution rates quantified by the Cd and Pb isotope ratio method were similar, suggesting that no single source dominates Pb and Cd pollution. The contribution rates of Pb analyzed by the isotope ratio method were almost identical to those of the PMF model, indicating the rationality of the PMF result. Our results suggested that correlation analysis and PCA should be utilized to provide information for obtaining reasonable results and defining source categories for PMF, whereas the isotope ratio method should be applied to verify the accuracy of source contributions analyzed by PMF.

Parametric analysis of the output performance of a valveless piezoelectric pump with a bullhorn-shaped structure.

In response to the serious problem of backflow in valveless piezoelectric pumps, this paper proposes a valveless piezoelectric pump with a bullhorn-shaped structure. In this paper, we analyze the flow guide by using the "tail flow space pressure comparison method" and "fluid unit dynamic analysis method," revealing the working principle of the flow guide in the valveless piezoelectric pump. The effects of the height, sharp angle, and filter angle of the bullhorn-shaped structure on the output flow were investigated separately by the experiment. The experimental results show that the output flow rate is best when the height of the bullhorn structure is 2 mm, the choke of the bullhorn-shaped structure is 2, and the sharp angle and fillet angle are 180°. The output flow rate of this valveless piezoelectric pump can reach 170.6 ml/min at a drive voltage of 210 V and a drive frequency of 45 Hz, indicating that the valveless piezoelectric pump has good pumping capability and can effectively alleviate the backflow phenomenon. This study offers some valuable insights into improving its performance and practical application.

Effects of astaxanthin on plasma membrane function and fertility of boar sperm during cryopreservation.

Mammalian sperm is highly susceptible to reactive oxygen species (ROS) during the cryopreservation process. Astaxanthin (AST), a red pigment of the carotenoid family, is recognized as having a variety of beneficial biological activities and effects, including antioxidant, anticancer, anti-diabetic, and anti-inflammatory. The present study aimed to investigate whether the presence of AST protected boar sperm from ROS stress during cryopreservation. Boar sperm was diluted with a freezing medium supplemented with different concentrations of AST (0, 0.5, 1, 2, or 5 µM). The addition of AST, especially at a concentration of 2 µM, exerted positive effects on post-thaw sperm motility parameters. Meanwhile, sperm plasma membrane integrity and acrosome integrity of post-thaw sperm were significantly increased, while lipid peroxidation was inhibited in response to 2 µM AST treatment. Interestingly, compared to the control, supplementation with 2 µM AST increased unsaturated fatty acids (UFAs) levels and decreased saturated fatty acids (SFAs) content in post-thaw sperm, leading to a decreased ratio of SFAs/UFAs in the AST group. In conclusion, the addition of AST to freezing extenders inhibited lipid peroxidation and regulated fatty acid composition of the sperm membrane, improved post-thaw sperm quality, and had no adverse effect on boar sperm in vitro fertilization (IVF) capacity and potential for embryonic development. Our data provide a novel insight into understanding the mechanisms of AST concerning protecting boar sperm quality against ROS damage during cryopreservation.

Effect of L-carnitine on sperm quality during liquid storage of boar semen.

OBJECTIVE: This study was conducted to investigate the effect of L-carnitine on the pig semen characteristics during storage. METHODS: Spermatozoa samples were examined for spermatozoa quality and then randomly divided into 5 groups: 0 (control), 12.5, 25, 50, and 100 mM L-carnitine. Sperm motility, plasma membrane integrity and antioxidant parameters (total reactive oxygen species, total antioxidant capacity, and malondialdehyde) were evaluated after 0, 3, 5, and 10 day cooledstorage at 17°C. Moreover, ATP content, mitochondria activity as well as sperm-binding and in vitro fertilizing ability of preserved boar sperm were also investigated. RESULTS: Supplementation with 50 mM L-carnitine could effectively maintain boar sperm quality parameters such as sperm motility and membrane integrity. Besides, we found that L-carnitine had positive effects on boar sperm quality mainly through improving antioxidant capacities and enhancing ATP content and mitochondria activity. Interestingly, by assessing the effect of L-carnitine on sperm fertility and developmental potential, we discovered that the extender containing L-carnitine could improve sperm quality and increase the number of sperms bounding to zona pellucida, without improving in vitro fertility and development potential. CONCLUSION: These findings suggested that the proper addition of L-carnitine to the semen extender improved boar sperm quality during liquid storage at 17°C.

Protective influence of rosiglitazone against time-dependent deterioration of boar spermatozoa preserved at 17°C.

Spermatozoa are highly specialized cells, and energy metabolism plays an important role in modulating sperm viability and function. Rosiglitazone is an antidiabetic drug in the thiazolidinedione class that regulates metabolic flexibility and glucose uptake in various cell types, but its effects on boar sperm metabolism are unknown. In this study, we investigated the potential effect of rosiglitazone against time-dependent deterioration of boar spermatozoa during liquid preservation at 17°C. Freshly ejaculated semen was diluted with Beltsville Thawing Solution (BTS) containing different concentrations of rosiglitazone, and the motility, membrane and acrosome integrity of sperm were detected. Besides, we measured glucose uptake capacity, l-lactate production level, mitochondrial membrane potential, adenosine triphosphate (ATP) content and mitochondrial reactive oxygen species (mROS) production of sperm after boar semen had been incubated with or without rosiglitazone, iodoacetate (glycolysis inhibitor) and rotenone (electron transport chain inhibitor) for 5 days. The addition of rosiglitazone significantly enhanced sperm quality and had a strong protective effect on the sperm membrane and acrosome integrity during storage. BTS containing 50 µM rosiglitazone maintained the total motility of liquid-preserved sperm above 60% for 7 days. Rosiglitazone improved sperm quality by regulating energy metabolism manner of preserved sperm, protected the sperm mitochondrial membrane potential, enhanced sperm ATP production and in the meanwhile reduced mROS through enhancing glycolysis but not oxidative phosphorylation. The data suggested the practical feasibility of using rosiglitazone for improving boar spermatozoa quality during semen preservation.

Effects of L-glutamine on boar sperm quality during liquid storage at 17°C.

The quality of boar spermatozoa is affected by oxidative stress during preservation in vitro. It has been demonstrated that L-Glutamine (Gln) can effectively protect cells from oxidative stress-induced injury. There are, however, no reports to date evaluating the effects of Gln on boar semen liquid preservation at 17 °C. The aims of the present study were to elucidate whether the addition of Gln to the extender BTS could improve the quality of boar spermatozoa when stored at 17 °C and to determine the mechanism underlying Gln protection of spermatozoa against preservation-induced damage. Boar semen samples were collected and diluted with Beltsville Thawing Solution (BTS) containing different concentrations (0, 10, 20, 40 or 80 mM) of Gln. The results indicated the addition of 20 mM Gln to the BTS improved (P < 0.05) the motility, acrosome integrity and membrane integrity of boar sperm during liquid preservation. Interestingly, treatment of spermatozoa with Gln addition to the extender resulted in ROS quenching, while enhancing γ-glutamyl cysteine synthetase (γ-GCS) activity, and glutathione (GSH) content of spermatozoa. These results suggest that BTS supplemented with Gln can provide greater protective capacity to boar sperm against oxidative stress by enhancing GSH synthesis during liquid preservation.

Exploration of miR-1202 and miR-196a in human endometrial cancer based on high throughout gene screening analysis.

Altered microRNA (miRNA) expression has been reported to participate in the pathogenesis of several human diseases, and particularly cancer. The present study examined the involvement of various miRNAs in the pathophysiology of endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). We performed a high-throughput analysis of the miRNAs (miRNA microarray) found in samples of endometrial tissue obtained from 45 patients; among whom, 15 patients were diagnosed with EC, 15 patients were diagnosed with AEH, and the remainder were healthy donors. Next, we selected several miRNAs which exhibited at least a 2-fold difference in expression with a P<0.05 to validate these changes in 3 independent in vitro experiments that used real-time PCR analysis. Finally, miR-1202 and miR-196a were selected as target molecules whose effects on cell apoptosis, cell cycle changes, cell migratory and invasive abilities were investigated using flow cytometric and Transwell assays, respectively, after pre-treatment in vitro. After analyzing 125 miRNAs in a microarray assay, 6 miRNAs (3-high and 3-low expression) were further evaluated via paired comparison in all 3 groups. The validation test revealed a positive correlation between the microarray results and a high level of miR-1202 and a low level of miR-196a in the EC group, when compared with the AEH group. All of the data were normalized with data obtained from normal control donors. We found that either miR-1202 silencing or miR-196a overexpression affected AN3CA and HEC-1-A cells by increasing their apoptosis level and inducing G1 phase arrest while decreasing their migratory and invasive abilities. Inhibitors of miR-1202 and mimics of miR­196a may exert a protective effect, suggesting that miR-1202 and miR­196a may serve as biomarkers for evaluating the effectiveness of EC treatment.

Assessing Cardiovascular Health Using Life's Simple 7 in a Chinese Population Undergoing Stroke Prevention.

BACKGROUND: The American Heart Association/American Stroke Association proposed a metric called Life's Simple 7 (LS7) to define cardiovascular health (CVH). The presence of a large number of ideal components of CVH is associated with lower cardiovascular disease and all-cause mortality. We aimed to assess CVH using LS7 in a Chinese population undergoing primary and secondary stroke prevention. METHODS: Patients with either ischemic stroke or cardiovascular risk factors were enrolled in the study from October 2010 to July 2013. LS7 components were scored as poor (0 points), intermediate (1 point), or ideal (2 points). The overall LS7 score was categorized as inadequate (0-4), average (5-9), or optimal (10-14) CVH. The Chi-square test, Mann-Whitney U-test, and Kruskal-Wallis test were used. RESULTS: In total, 706 patients were enrolled. (1) The distribution of the overall LS7 score (n = 255) indicated that 9.4%, 82.4%, and 8.2% of the patients had inadequate, average, and optimal CVH, respectively. The proportion of patients with optimal CVH undergoing secondary stroke prevention was lower than that for patients undergoing primary stroke prevention (3.8% vs. 12.8%, P = 0.005). The vast majority of participants (76.1%) presented with ≤2 ideal health components. (2) The proportions of patients with poor, intermediate, and ideal status, respectively, for the following LS7 components were assessed : t0 otal cholesterol (n = 275; 5.1%, 73.8%, and 21.1%), blood pressure (n = 351; 32.5%, 59.0%, and 8.5%), blood glucose (n = 280; 9.3%, 39.6%, and 51.1%), physical activity (n = 540; 90.7%, 8.7%, and 0.6%), diet (n = 524; 0.2%, 92.4%, and 7.4%), smoking (n = 619; 20.7%, 2.9%, and 76.4%), and body mass index (n = 259; 6.6%, 35.5%, and 57.9%). CONCLUSIONS: Few Chinese patients undergoing stroke prevention had optimal CVH (determined using LS7). Additionally, fewer patients undergoing secondary prevention had optimal CVH than those undergoing primary prevention. In particular, physical activity and diet status in this population require improvement.

Sandmeier model based topographic correction to lunar spectral profiler (SP) data from KAGUYA satellite.

The Moon may be considered as the frontier base for the deep space exploration. The spectral analysis is one of the key techniques to determine the lunar surface rock and mineral compositions. But the lunar topographic relief is more remarkable than that of the Earth. It is necessary to conduct the topographic correction for lunar spectral data before they are used to retrieve the compositions. In the present paper, a lunar Sandmeier model was proposed by considering the radiance effect from the macro and ambient topographic relief. And the reflectance correction model was also reduced based on the Sandmeier model. The Spectral Profile (SP) data from KAGUYA satellite in the Sinus Iridum quadrangle was taken as an example. And the digital elevation data from Lunar Orbiter Laser Altimeter are used to calculate the slope, aspect, incidence and emergence angles, and terrain-viewing factor for the topographic correction Thus, the lunar surface reflectance from the SP data was corrected by the proposed model after the direct component of irradiance on a horizontal surface was derived. As a result, the high spectral reflectance facing the sun is decreased and low spectral reflectance back to the sun is compensated. The statistical histogram of reflectance-corrected pixel numbers presents Gaussian distribution Therefore, the model is robust to correct lunar topographic effect and estimate lunar surface reflectance.

ARHGEF28 gene exon 6/intron 6 junction mutations in Chinese amyotrophic lateral sclerosis cohort.

It was reported that the intron 6, + 1 del G (GT>TT) mutation of the ARHGEF28 gene generates a shortened protein that might be related to amyotrophic lateral sclerosis (ALS). We sequenced this mutation in 25 familial ALS (FALS), 357 sporadic ALS (SALS) patients, and 442 healthy control subjects. We found just two SALS patients exhibited the mutation so that the incidence of this mutation was 0.52% (2/382) of all the ALS patients. The clinical features of the mutation-positive patients were quite different from the case reported in a previous study. These characteristics differed in terms of gender, site of onset, cognitive function, and family history.

Direct C-H arylation of thiophenes at low catalyst loading of a phosphine-free bis(alkoxo)palladium complex.

An efficient phosphine-free direct C-H arylation of thiophenes at the α-position has been developed at low catalyst loading of bis(alkoxo)palladium complex (Cat.I, 0.1-0.2 mol %). The developed synthetic method can be applied to the synthesis of α-aryl/heteroaryl thiophenes from aryl or heteroaryl bromides in good to excellent yields and is compatible with the substrates bearing electron-donating or electron-withdrawing groups. The reactivities of the 2- and 5-positions of thiophenes are equivalent and not dependent on steric hindrance under optimal conditions. This condition can also be applied to other heterocyclic moieties such as benzothiophene, benzofuran, and pyrrole with high conversion yields.