AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis.

Unrestrained chronic inflammation leads to the abnormal activity of NOX4 and the subsequent production of excessive hydrogen peroxide (H2O2). Excessive H2O2 signaling triggered by prolonged inflammation is thought to be one of the important reasons for the progression of some types of cancer including cervical cancer. Aquaporin 3 (AQP3) is a member of the water channel protein family, and it remains unknown whether AQP3 can regulate the transmembrane transport of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4)-derived H2O2 induced by the stimulation of inflammatory factors to facilitate the malignant progression in cervical cancer. In this study, cervical cancer HeLa cell line was respectively treated with diphenyleneiodonium (DPI), N-Acetylcysteine (NAC) or lentivirus-shRNA- AQP3. Plate cloning, cell migration or transwell invasion assays, etc. were performed to detect the invasive and migration ability of the cells. Western blot and CO-IP were used to analyze the mechanism of AQP3 regulating H2O2 conduction. Finally, in vivo assays were performed for validation in nude mice. AQP3 Knockdown, DPI or NAC treatments all reduced intracellular H2O2 influx, and the activation of Syk/PI3K/Akt signal axis was inhibited, the migration and invasive ability of the cells was attenuated. In vivo assays confirmed that the excessive H2O2 transport through AQP3 enhanced the infiltration and metastasis of cervical cancer. These results suggest that AQP3 activates H2O2/Syk/PI3K/Akt signaling axis through regulating NOX4-derived H2O2 transport to contribute to the progression of cervical cancer, and AQP3 may be a potential target for the clinical treatment of advanced cervical cancer.

Culturable and inhalable airborne bacteria in a semiunderground municipal wastewater treatment plant: Distribution, transmission, and health risk assessment.

Airborne pathogens constitute a growing threat to global public health. Wastewater treatment plants (WWTPs) are important sources of airborne bacteria, which pose great health risks to the employee and nearby residents. In this study, the distribution, transmission and health risk of the airborne culturable and inhalable bacteria carried by PM2.5 in a semiunderground WWTP were evaluated. The concentrations of culturable bacteria in the air were 21.2-1431.1 CFU/m3, with the main contributions of primary and biological treatments. The relative abundances of culturable and total inhalable bacterial taxa were positively correlated (p < 0.05). However, certain bacteria, including Bacillus, Acinetobacter and Enterococcus, exhibited high reproductive capacity despite their low concentration in the air, suggesting that they can survive and regrow in suitable environments. Transmission modeling revealed that the concentrations of airborne bacteria exponentially decreased with distance from 18.67 to 24.12 copies /m3 at the source to 0.06-0.14 copies /m3 at 1000 m downwind. The risks of 8-h exposure in this WWTP except the outlet exceeded the reference value recommended by WHO, which were primarily dependent on P. aeruginosa, Salmonella, and E. coli. Management practices should consider improved controls for bioaerosols in order to reduce the risk of disease transmission.

Quinoa husk peptides reduce melanin content via Akt signaling and apoptosis pathways.

To improve the treatment of pigmentation disorders, looking for natural and safe inhibitors of melanin synthesis has become an area of research interest. The quinoa husk peptides reportedly elicit various biological activities (e.g., anti-cancer, antioxidant, anti-hypertensive, and so forth), but its effects on melanin inhibition remain unknown. In the current study, we purified quinoa husk peptides with 30 and 80% ethanol using a macroporous adsorption resin (DA201-C). Component screening revealed that the 80%-ethanol fraction (i.e., QHP fraction) contained numerous short peptides (84.41%) and hydrophobic amino acids (45.60%), while eliciting a superior tyrosinase [TYR]-inhibition rate, 2,2-diphenyl-1-picryhydrazil-scavenging rate, reducing activity, and chelating capacity compared to the 30% fraction and was thus applied in subsequent analyses. Differentially expressed genes in the QHP fraction were primarily enriched in the Akt-signaling pathways based on transcriptomics. Thus, we assessed the expression of related proteins and genes in A375 cells and rat skin cells following treatment with QHP.

Combined treatment of marizomib and cisplatin modulates cervical cancer growth and invasion and enhances antitumor potential in vitro and in vivo.

Proteasome inhibition is an attractive approach for anticancer therapy. Cisplatin (cis-diamminedichloroplatinum, CDDP) is widely used as a standard chemotherapy drug in the treatment of solid malignant tumors, such as cervical cancer, ovarian cancer, colorectal cancer, and lung cancer. However, the development of CDDP resistance largely limits its clinical application. Proteasome inhibitors may enhance traditional chemotherapy agent-induced cytotoxicity and apoptosis. Marizomib (NPI-0052, salinosporamide A, Mzb), a second-generation proteasome inhibitor, shows synergistic anticancer activity with some drugs. Currently, the effect of Mzb on cervical cancer cell proliferation remains unclear. In this study, we explored the role of Mzb in three cervical cancer cell lines, HeLa, CaSki, and C33A, representing major molecular subtypes of cervical cancer and xenografts. We found that Mzb alone showed noteworthy cytotoxic effects, and its combination with CDDP resulted in more obvious cytotoxicity and apoptosis in cervical cancer cell lines and xenografts. In order to investigate the mechanism of this effect, we probed whether Mzb alone or in combination with CDDP had a better antitumor response by enhancing CDDP-induced angiopoietin 1 (Ang-1) expression and inhibiting the expression of TEK receptor tyrosine kinase (Tie-2) in the Ang-1/Tie-2 pathway, FMS-like tyrosine kinase 3 ligand (Flt-3L) and stem cell factor (SCF) as identified by a cytokine antibody chip test. The results suggest that Mzb has better antitumor effects on cervical cancer cells and can sensitize cervical cancer cells to CDDP treatment both in vitro and in vivo. Accordingly, we conclude that the combination of CDDP with Mzb produces synergistic anticancer activity and that Mzb may be a potential effective drug in combination therapy for cervical cancer patients.

Relation classification via BERT with piecewise convolution and focal loss.

Recent relation extraction models' architecture are evolved from the shallow neural networks to natural language model, such as convolutional neural networks or recurrent neural networks to Bert. However, these methods did not consider the semantic information in the sequence or the distance dependence problem, the internal semantic information may contain the useful knowledge which can help relation classification. Focus on these problems, this paper proposed a BERT-based relation classification method. Compare with the existing Bert-based architecture, the proposed model can obtain the internal semantic information between entity pair and solve the distance semantic dependence better. The pre-trained BERT model after fine tuning is used in this paper to abstract the semantic representation of sequence, then adopt the piecewise convolution to obtain semantic information which influence the extraction results. Compare with the existing methods, the proposed method can achieve a better accuracy on relational extraction task because of the internal semantic information extracted in the sequence. While, the generalization ability is still a problem that cannot be ignored, and the numbers of the relationships are difference between different categories. In this paper, the focal loss function is adopted to solve this problem by assigning a heavy weight to less number or hard classify categories. Finally, comparing with the existing methods, the F1 metric of the proposed method can reach a superior result 89.95% on the SemEval-2010 Task 8 dataset.

Less polar ginsenosides have better protective effects on mice infected by Listeria monocytogenes.

Listeria monocytogenes widely exists in the natural environment and does great harm, which can cause worldwide public safety problem. Infection with L. monocytogenes can cause rapid death of Kupffer cell (KCs) in liver tissue and liver damage. American ginseng saponins is a natural compound in plants, which has great potential in inhibiting L. monocytogenes infection. Therefore, American ginseng stem-leaf saponins (AGS) and American ginseng heat-transformed saponins (HTS) were used as raw materials to study their bacteriostatic experiments in vivo and in vitro. In this experiment, female Kunming mice were randomly divided into five groups: control group, negative group, AGS group, HTS group (10 mg/kg/day in an equal volume via gastric administration) and penicillin group, each group containing six mice. Profiles AGS and HTS components were evaluated by high-performance liquid chromatography (HPLC) analysis. The bacteriostatic effect of AGS and HTS on L. monocytogenes was evaluated by inhibition zone test, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The bacteriostatic effect of AGS and HTS pretreatment on mice infected with L. monocytogenes were studies by animal experimental. The results showed that the content of polar saponins in AGS was 0.81 ± 0.003 mg/mg, less polar saponins was 0.08 ± 0.02 mg/mg, the content of polar saponins in HTS was 0.10 ± 0.01 mg/mg, less polar saponins was 0.76 ± 0.02 mg/mg. The in vitro bacteriostatic diameter of HTS (16.6 ± 0.8 mm) is large than that of AGS (10.2 ± 1.2 mm). AGS and HTS pretreatment could reduce the colony numbers in the livers of mice infected with Listeria monocytogenes. The levels of alanine aminotransferase (ALT), IL-1ß, IL-6, TNF-α and IFN-γ in the livers of mice in the pretreatment group were significantly lower than those in the negative group. There were obvious leukoplakia, calcification and other liver damage on the liver surface in the negative control group, and obvious inflammatory cell infiltration in HE sections. AGS and HTS pretreatment can reduce liver injury caused by L. monocytogenes and protect the liver. Compared with AGS, HTS has higher content of less polar saponins and better bacteriostatic effect in vitro. The count of bacterial in liver tissue of HTS group was significantly lower, the survival rate was significantly higher than that of AGS group. Less polar saponins had better bacteriostatic effect. Collectively, less polar saponins pretreatment has a protective effect on mice infected with L. monocytogenes, to which alleviated liver damage, improved anti-inflammatory ability and immunity of the body, protected liver may contribute.

In vivo acute toxicity and mutagenic analysis of crude saponins from Chenopodium quinoa Willd husks.

Background: As a functional food factor, quinoa saponins are valuable as additives and in medical care, pharmaceutical development, cosmetics and other fields. However, few studies have investigated the toxicity of saponins. The main purpose of this study was to evaluate the toxicity of crude saponins extracted from quinoa husks. Thus, acute toxicity and excretion experiments were carried out in rats. The Ames test, micronucleus test and mouse sperm aberration test were carried out in mice. Results: In the acute toxicity study, the obtained LD50 was more than 10 g per kg per bw for both sexes, the food intake of all rats decreased over a period of time, and some rats developed diarrhea. In the case of large-dose gavage, the saponin excretion time in rats was approximately four days. When the dosage was 10 mg kg-1, quinoa saponins were hydrolyzed into aglycone within 24 hours and excreted out of the body. The results of the mutagenicity experiment showed that saponins had no mutagenicity in mice. Conclusion: This work has demonstrated that quinoa saponins have limited acute toxicity effects, which provides a theoretical basis for their rational utilization.

Synthesis, characteristics and medical applications of plant nanomaterials.

MAIN CONCLUSION: The recent preparations of metal nanoparticles using plant extracts as reducing agents are summarized here. The synthesis and characterization of plant-metal nanomaterials and the progress in antibacterial and anti-inflammatory medical applications are detailed, providing a new vision for plant-based medical applications. The medical application of plant-metal nanoparticles is becoming a research hotspot. Compared with traditional preparation methods, the synthesis of plant-metal nanoparticles is less toxic and more eco-friendly, increasing application potential. Highly efficient plant-metal nanoparticles are usually smaller than 100 nm. This review describes the synthesis, characterization and bioactivities of gold- and silver-plant nanoparticles as examples and clearly explained their antibacterial and anticancer mechanisms. An analysis of actual cases shows that the synthetic method and type of plant extract affect the activities of the products.

A meta-analysis of renal outcomes in living kidney donors.

Given the increased burden of end-stage renal disease (ESRD), renal outcomes of kidney donation by living donors are of particular interest. PubMed, ProQuest, MEDLINE, EMBASE, Chinese national knowledge infrastructure, and Wanfang databases were searched for clinical outcomes of living kidney donors (LKDs) including renal death, ESRD, proteinuria/albuminuria, and renal function after donation. We included 62 studies from 19 countries involving 114,783 kidney donors and nondonors to evaluate the renal consequences less than 6 months, 6 months to 5 years, 5 to 10 years, and 10 years onward after donation. The pooled data showed that uninephrectomy significantly decreased glomerular filtration rate and creatinine clearance rate in parallel with increased serum creatinine concentration (all P < 0.05). The drastic changes in renal function occurred within 6 months rather than 5 to 10 years after donation. Ten years and onward, rate of proteinuria/albuminuria increased gradually: microalbuminuria from 5.3% to 20.9%, proteinuria from 4.7% to 18.9%, and overt proteinuria from 2.4% to 5.7% (all P < 0.05). Prevalence of ESRD was 1.1%. All-cause mortality was 3.8% and all the renal deaths on average occurred 10 years postnephrectomy. LKDs might have aggravated glomerular filtration and creatinine clearance within 6 months after donation. Five years and onward, albuminuria, proteinuria, ESRD, and death might be the major concerns of LKDs. Long-term studies may clarify the survival time after donation.

Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes.

BACKGROUND: Diabetic nephropathy (DN) is a multifactorial and polygenic disease with nodular glomerulosclerosis (NGS) pathognomonic for diabetes and hypertension. Patients with type 2 diabetes and hypertension have characteristic renin-angiotensin system (RAS) gene polymorphisms. METHODS AND RESULTS: In this retrospective cohort study, we correlated the presence of NGS with renal function, angiotensin-converting enzyme (ACE) genotypes (DD, DI, and II), angiotensinogen (AGT) genotypes (MM, MT, and TT) and immunohistochemical staining characteristics of RAS components in 847 patients and 172 consecutive autopsy cases with type 2 diabetes. T allele of AGT was associated with macroalbuminuria (P = 0.040). Multitude regression analysis revealed ACE insertion (I)/deletion (D) polymorphism as an independent determinant for estimated glomerular filtration rate (eGFR) less than 60 mL min(-1)·1.73 m(-2) (DD carriers: odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.08-11.07; DI carriers: OR = 3.51, 95% CI = 1.63-7.56). A significant association between NGS and eGFR less than 60 mL min(-1)·1.73 m(-2) also persisted after adjusting for nonlinear relationship (P < 0.001). In NGS patients, immunoreactivity of angiotensin I converting enzyme 2 (ACE2) significantly decreased in glomeruli with mesangial nodules compared with glomeruli without the mesangial nodules. CONCLUSIONS: These data suggest associations of ACE D allele with glomerular filtration impairment, and NGS with glomerular ACE2 down-regulation and reduced glomerular filtration in Chinese patients with type 2 diabetes.

The complete mitochondrial genome of the Hynobius maoershanensis (Caudata: hynobiidae).

The Hynobius maoershanensis is a member of hynobiidae, endemic to Mountain Maoer in Guangxi province, China. It was first found and reported in 2006 and so far there is a little molecular research about it. The complete mitochondrial genome of H. maoershanensis has been obtained for the first time in this study. The circular genome (16,412 bp in length) consisted of 37 typical animal mitochondrial genes (13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes) and 1 control region. Overall base composition of the complete mitochondrial DNA was 33% A, 32% T, 21% C, and 14% G with AT (65%).

Surface-enhanced Raman scattering of suspended monolayer graphene.

The interactions between phonons and electrons induced by the dopants or the substrate of graphene in spectroscopic investigation reveal a rich source of interesting physics. Raman spectra and surface-enhanced Raman spectra of supported and suspended monolayer graphenes were measured and analyzed systemically with different approaches. The weak Raman signals are greatly enhanced by the ability of surface-enhanced Raman spectroscopy which has attracted considerable interests. The technique is regarded as wonderful and useful tool, but the dopants that are produced by depositing metallic nanoparticles may affect the electron scattering processes of graphene. Therefore, the doping and substrate influences on graphene are also important issues to be investigated. In this work, the peak positions of G peak and 2D peak, the I2D/IG ratios, and enhancements of G and 2D bands with suspended and supported graphene flakes were measured and analyzed. The peak shifts of G and 2D bands between the Raman and SERS signals demonstrate the doping effect induced by silver nanoparticles by n-doping. The I2D/IG ratio can provide a more sensitive method to carry out the doping effect on the graphene surface than the peak shifts of G and 2D bands. The enhancements of 2D band of suspended and supported graphenes reached 138, and those of G band reached at least 169. Their good enhancements are helpful to measure the optical properties of graphene. The different substrates that covered the graphene surface with doping effect are more sensitive to the enhancements of G band with respect to 2D band. It provides us a new method to distinguish the substrate and doping effect on graphene. PACS: 78.67.Wj (optical properties of graphene); 74.25.nd (Raman and optical spectroscopy); 63.22.Rc (phonons in graphene).

Observation of strain effect on the suspended graphene by polarized Raman spectroscopy.

We report the strain effect of suspended graphene prepared by micromechanical method. Under a fixed measurement orientation of scattered light, the position of the 2D peaks changes with incident polarization directions. This phenomenon is explained by a proposed mode in which the peak is effectively contributed by an unstrained and two uniaxial-strained sub-areas. The two axes are tensile strain. Compared to the unstrained sub-mode frequency of 2,672 cm-1, the tension causes a red shift. The 2D peak variation originates in that the three effective sub-modes correlate with the light polarization through different relations. We develop a method to quantitatively analyze the positions, intensities, and polarization dependences of the three sub-peaks. The analysis reflects the local strain, which changes with detected area of the graphene film. The measurement can be extended to detect the strain distribution of the film and, thus, is a promising technology on graphene characterization.

Trichloroethylene causes generalized hypersensitivity skin disorders complicated by hepatitis.

Idiosyncratic generalized skin disorders complicated by hepatitis, which resemble severe drug hypersensitivities, occur sporadically in workers exposed to trichloroethylene (TCE) in China. However, it has been a matter of controversy whether the solvent itself, not its impurities or stabilizers, can cause hypersensitivity reactions or not. This study aimed to characterize the exposure of hospitalized patients and their healthy colleagues. TCE metabolites were measured in urine of 19 hospitalized patients suffering from the disorders. To assess the exposure of patients' healthy colleagues, on-site surveys were conducted in 6 factories where the disorders occurred and in 2 control factories without such occurrences despite TCE use. Urinalysis of the patients detected trichloroacetic acid (TCA) in all of them. Its average concentration in the end-of-shift urine was estimated to be 206 mg/l. On-site survey of healthy exposed workers revealed that the maximum urinary TCA concentrations and the maximum time-weighted average concentrations of personal TCE exposure were 318-1,617 mg/l and 164-2,330 mg/m(3), respectively. There was no common impurity in TCE used in the factories. These results suggested that TCE itself caused the skin hypersensitivity disorders, and that the disorders occurred in factories where TCE metabolites could be extensively accumulated, possibly due to long working hours. Since the lowest TCA concentration in the end-of-shift urine of the patients was estimated to be 72-80 mg/l, it is recommended to control TCE exposure to keep the urinary TCA concentration below 50 mg/l to reduce the disease risk.