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The corneal epithelium plays important roles in the maintenance of corneal transparency for good vision, and acts as a protective barrier against foreign insults. Structural and functional changes with aging in the corneal epithelium have been documented. Here we found that transforming growth factor-β (TGF-β) is highly expressed in the elderly donor corneal epithelium, as are senescence-associated genes, such as p16 and p21. In human corneal epithelial cell (HCEC) models, TGF-β induces cellular senescence, characterized by increased SA-β-gal positive cells and elevated expression of p16 and p21. Pharmacological inhibition of TGF-β signaling alleviates TGF-β-induced cellular senescence. In addition, we determined that senescence-associated inflammation was significantly aggravated in TGF-β-induced cellular senescence by detecting the expression of interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNFα). Both genetic and pharmacological approaches revealed that blocking nuclear factor-κB (NF-κB) signaling not only inhibited the production of inflammatory factors, but also rescued the senescent phenotype induced by TGF-β in HCECs. Mechanistically, TGF-β induced an atypical RNA stress responses, leading to accelerated mRNA degradation of IκBα, an inhibitor of NF-κB. Together, our data indicate that TGF-β-driven NF-κB activation contributes to corneal epithelial senescence via RNA metabolism and the inflammation blockade can attenuate TGF-β-induced senescence.

Nonlinear waves are ubiquitous in various physical systems, and they have become one of the research hotspots in nonlinear physics. For the experimental realization, observation and application of nonlinear waves, it is very important to understand the generation mechanism, and determine the essential excitation conditions of various nonlinear waves. In this paper, we first briefly review the experimental and theoretical research progress of nonlinear waves in recent years. Based on the exact nonlinear wave solutions and linear stability analysis results, we systemically discuss how to establish the quantitative relations between fundamental nonlinear waves and modulation instability. These relations would deepen our understanding on the mechanism of nonlinear waves. To solve the excitation conditions degenerations problem for some nonlinear waves, we further introduce the perturbation energy and relative phase to determine the excitation conditions of nonlinear waves. Finally, we present a set of complete parameters that can determine the excitation conditions of nonlinear waves, and give the excitation conditions and phase diagrams of the fundamental nonlinear waves. These results can be used to realize controllable excitation of nonlinear waves, and could be extended to many other nonlinear systems.

To establish an animal model for loaded swimming, so as to investigate the energy metabolism effects of soybean isoflavones (SI) on swimming mice.Thirty male Kunming mice were randomly divided into three groups:normal control, swimming group, and swimming+SI group. The normal control group mice were fed a basic AIN-93M diet, the SI groups were supplied with soybean isoflavones(4 g/kg).Two weeks later, the mice were forced to swim for an hour,and then all the mice were killed, the samples of blood, liver and muscles of hind were collected.The serum contents of lactic acid(Lac), the activities of lactic dehydrogenase (LDH), succinate dehydrogenase (SDH), creatine kinase (CK) and ATPase were measured.Compared with normal control,the serum content of Lac was significantly improved in the group of the swimming control and SI(Soybean isoflavones can improve the energy metabolism,antioxidant capacity of the swimming mice.

Keratoconus (KC) is a complex degenerative disorder of the cornea. Genetic, environmental, and lifestyle factors may all contribute to the pathogenesis of KC. Most of the reported KC-associated SNPs have been detected in Caucasians and Australians. To investigate whether the reported associated SNPs can be found in a Chinese population, we performed a replication study of the significantly associated SNPs.A total of 210 unrelated Chinese KC patients and 191 unrelated controls were included in the present study. SNPs rs4954218 (Near RAB3GAP1 (5')), rs4894535 (FNDC3B), rs2956540 (LOX), rs3735520 (Near HGF (5')), rs1324183 (MPDZ-NF1B), rs1536482 (RXRA-COL5A1), rs7044529 (COL5A1), rs2721051 (Near FOXO1 (3')), rs9938149 (BANP-ZNF469) and rs6050307 (VSX1) were assessed for their association with KC. The genotype of each SNP was detected using the Sequenom MassARRAY-Assay.SNP rs1324183 located in MPDZ-NF1B was associated with an increased risk of KC (OR=3.108, 95% CI=1.366-7.072, p=0.005), and SNP rs2956540 in the LOX gene may confer a reduced risk of KC with a borderline p value in our population (OR=0.664, 95% CI=0.447-0.986, p=0.042). No significant difference was observed between patients and controls in the other eight SNP genotypes and allele frequencies.The replication association of rs1324183 (MPDZ-NF1B) with KC in our population and the results, which are identical to those in different populations, suggest that rs1324183 (MPDZ-NF1B) is a common genetic risk for KC and should be further investigated.

Zhang, Zhiqing, Zhonghai Xiao, Bingnan Deng, Xiaohua Liu, Wei Liu, Hongjing Nie, Xi Li, Zhaoli Chen, Danfeng Yang, and Ruifeng Duan. Therapeutic efficacy of methazolamide against intermittent hypoxia-induced excessive erythrocytosis in rats. High Alt Med Biol 19:69-80, 2018.-This study aimed to determine whether methazolamide is effective for the treatment of chronic mountain sickness. Forty-eight male Wistar rats were randomly divided into eight groups: normoxia control, hypoxia control, hypoxia + acetazolamide (30 mg·kg

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

Resveratrol, as a natural polyphenolic compound, has a wide range of beneficial effects, which includes anti-tumor, cardiovascular protection, anti-oxidant and estrogen-like effects, and so on. Its various physiological properties are closely related to the therapeutic principle for prevention and treatment of high altitude hypoxia injury. Resveratrol may play an important role in relieving or curing high altitude diseases, especially high altitude polycythemia(HAPC). However, the literature about study and application of resveratrol in plateau medicine field is rarely reported up to now. In this review, we summarized the physiological effects of resveratrol, discussed the possible main principle of resveratrol for HAPC therapy, and looked forward to resveratrol's perspective or potential application in high altitude medicine.

OBJECTIVE To explore the relationship between CAR and the development of human lung cancer, as well as to provide the basis for the clinical treatment of lung cancer using an adenovirus vector-based gene therapy. METHODS CAR expression was assessed immunohisto-chemically in tumoral, paraneoplastic and normal samples from 112 lung cancer patients. At the same time, the mRNA and protein expression of CAR in 32 cases were determined by RT-PCR and Western blot. The relationship between CAR expression and clinicopathologic parameters was statistically analyzed. RESULTS There was no expression of CAR in normal lung tissue but a little in paraneoplastic tissue. The positive rate was 43% in squamous cell carcinoma, and 70% in adenocarcinoma. Both were much significantly higher than that in paraneoplastic tissue. The CAR expression level in adenocarcinoma was higher than that in squamous cell cancer. mRNA expression by RT-PCR and protein expression by Western blot were consistent with immunohistochemistry results. CONCLUSION CAR is overexpressed in human lung cancer, especially in adenocarcinoma. This data offer the reliable basis for adenovirus-mediated gene therapy of lung cancer; more important, CAR may take part in the formation or development of lung cancer; this may be exploitable for the development of antibody-directed therapy in human lung cancer.

To investigate the effects of simple hypobaric hypoxia on parameters of hematology and blood rheology in order to establish a rat model of simulated high altitude polycythemia (HAPC) for the study of pathophysiologic mechanisms and medical prevention and treatment of HAPC.Forty-eight male Wistar rats were randomly divided into three normal control groups and three hypoxia model groups. Normal control group rats were bred in normoxia conditions, and hypoxia group rats were subjected to hypoxic exposure for 8 hours per day at simulated 5 500 m high altitude in a hypobaric chamber. After hypoxic exposure for 2, 4, 12 weeks, one group of normal control and hypoxia model rats were killed and blood was collected, respectively. Then parameters of erythrocyte and blood rheology were examined.Mucous membrane of hypoxia model rats showed obviously cyanosis after 2 weeks hypoxic exposure. Hemoglobin concentration of hypoxia model rats were beyond 210 g/L after 2 weeks, 4 weeks and 12 weeks hypoxia exposure and significantly increased than that of normal control rats respectively. Besides, RBC counts, hematocrit, whole blood viscosity, erythrocyte aggregation index of hypoxia model rats were all notably higher than those of normal control rats respectively.A rat model of high altitude polycythemia can be rapidly established by hypobaric hypoxia exposure at simulated 5 500 m high altitude for 8 hours daily.

To investigate the expression of 14-3-3ε in esophageal squamous cell carcinoma (ESCC) and relationship of 14-3-3ε and clinicopathological factors of ECSS patients.The 14-3-3ε expression in tumors and adjacent normal epithelia from 72 ESCC patients was detected by immunohistochemical staining. Correlations of 14-3-3ε expression or their subcellular localization and clinicopathological factors were analyzed using Chi-squared test. Survival curves were generated according to the Kaplan-Meier method, and the statistical analysis was performed by Log-rank test.The expression of 14-3-3ε protein was significantly up-regulated in tumors with 77.8% positive and 27.8% strong positive staining, compared with paired adjacent normal epithelia with 43.1% positive and only 2.8% strong positive staining (P0.01). In a total of 56 positive staining tumors, 14-3-3ε was detected in cytoplasm of 37 (66.1%), in nucleus of 4 (7.1%), in both cytoplasm and nucleus of 15 (26.8%) cases. Whereas, in a total of 31 positive staining normal epithelia, 14-3-3ε was detected in cytoplasm of 0, in nucleus of 13 (41.9%), in both cytoplasm and nucleus of 18 (58.1%) cases (P0.01). Statistical analysis revealed that strong 14-3-3ε expression was correlated with lymph node metastasis (P = 0.028) and lower 5-year survival (P = 0.018). The survival curves calculated by Kaplan-Meier method further showed that the patients with strong 14-3-3ε expression had a shorter survival than patients with negative or weak 14-3-3ε expression (Log-rank, P = 0.031). No correlation was found between subcellular localization of 14-3-3ε in tumor cells and clinicopathologic factors and prognosis of ESCC patients.The 14-3-3ε expression is significantly up-regulated in ESCCs. It was usually located in cytoplasm of tumor cells, but nucleus of normal epithelia. Strong expression of 14-3-3ε in tumors is associated with lymph node metastasis and considered as an poor prognostic factor for ESCC.

To investigate the expression and relationship of Rho-associated protein kinase 2 (ROCK2) and clinical characteristics in esophageal squamous cell carcinoma (ESCC).Immunohistochemistry was performed to assay the expression of ROCK2 in tumor tissues and adjacent normal epithelium from 118 ESCC patients in tissue microarray. The relationship between ROCK2 level and clinicopathologic profiles such as age, gender, location, smoking, differentiation degree, T stage, lymph node metastasis and TNM stage were analyzed.The ROCK2 expression was up-regulated in 54 of 118 (45.76%) ESCC tissues. The up-regulated expression of ROCK2 was observed in 55.74% (34/61) ESCC tissues of patients under 61 years old. And it was significantly higher than that in 35.09% (20/57) of patients over 61 years old (χ(2) = 5.062, P = 0.024). In addition, the rate of up-regulation of ROCK2 was significantly higher in high-grade differentiation group (58.70%, 27/46) than that in moderate-grade and low-grade differentiation group (37.50%, 27/72) (χ(2) = 5.080, P = 0.024).The up-regulated expression of ROCK2 is correlated with patient age and differentiation grade of ESCC.

To investigate the expression and relationship of receptor for activated C kinase 1 (RACK1) and clinical characteristics in esophageal squamous cell carcinoma (ESCC).Western Blotting was conducted to detect the RACK1 expression in ESCC cell lines. Immunohistochemistry was performed to assay the expression of RACK1 and Ki67 in tumor tissues and adjacent normal epithelium from 113 ESCC patients in tissue microarray. The relationship between the RACK1 level and such clinicopathologic profiles as age, gender, location, smoking, differentiation degree and TNM (tumor, node, metastasis) stage were analyzed.The expression of RACK1 protein was significantly down-regulated in ESCC tissues as compared with the normal adjacent epithelium (χ(2) = 63.363, P0.01). An upregulated expression of RACK1 was observed in 72.5% (29/40) ESCC tissues of patients without a smoking history. And it was significantly higher than that in 46.6% (34/73) of patients with a smoking history (χ(2) = 7.040, P = 0.008). In addition, the rate of up-regulated of RACK1 was significantly higher in stage I and II group (63.8%, 44/69) than that in stage III group (43.2%, 19/44) (χ(2) = 4.616, P = 0.032). Moreover, the ESCC tissues with a higher Ki67 score showed a lower level of RACK1 than that with a lower Ki67 score (χ(2) = 8.261, P = 0.016).The expression of RACK1 is down-regulated in ESCC tissues and associated with smoking. The expression of RACK1 was associated with smoking, TNM staging and Ki67 score of ESCC.

To investigate the expression and relationship of activated Cdc42-associated kinase 1 (ACK1) and the clinical characteristics of esophageal squamous cell carcinoma (ESCC).The ACK1 expression in ESCC cell lines was detected by Western blot. Immunohistochemistry was performed to assay the expression level of ACK1 protein in tumor tissues and adjacent normal epithelium from 105 ESCC patients in tissue microarray and 45 patients in normal tissue slices. Semi-quantitative RT-PCR(reverse transcription-polymerase chain reaction)was performed to determine the expression level of ACK1 mRNA in 45 pairs of ESCC frozen tissues.The expression level of ACK1 protein was significantly up-regulated in 48.6% ESCC tissues as compared with the normal adjacent epithelium in tissue microarray. The overexpression of ACK1 was significantly correlated with the lymph node metastasis and TNM stage of ESCC patients. The results of normal tissue slices were consistent with those of tissue microarray. Furthermore the overexpression of ACK1 was associated with a poor survival of ESCC patients (P = 0.030). The elevated mRNA level of ACK1 in ESCC tissues was correlated with the lymph node metastasis and TNM stage of ESCC patients. And a significant correlation was observed between protein and mRNA level of ACK1 (P = 0.021).The up-regulated expressions of ACK1 protein and mRNA are correlated with the progression and prognosis of ESCC.

An effective and fast RNA isolation method of activated sludge was established and five different methods were compared based on RNA yield, purity, integrity, RT-PCR amplification of 16S rRNA genes and subsequent terminal restriction fragment length polymorphism (T-RFLP) analysis. That is, the precipitated activated sludge was washed with TENP and PBS buffer, followed by using lysozyme and TRIzol to direct lysis of microbial cells, chloroform to remove protein and most of the DNA from bacterial lysate, isopropanol to precipitate nucleic acid and DNase I to hydrolyze residual DNA. To further purify RNA, RNA purifying column was utilized. The results demonstrated that the extraction method, with the aid of TRIzol and RNA purification kit, can effectively extract high-quality RNA. It not only means low degradability and high quantity, purity and diversity, but also the genes of 16S rRNA and amoA can be amplified by RT-PCR. Compared with other methods, it showed great advantage of low cost and high efficiency and can be applied to RNA extraction of activated sludge in a large number. Furthermore, T-RFLP results indicated that the community composition as well as the abundance of individual members was affected by the kind of RNA extraction methods. This work established a rapid and effective method to extract high-quality RNA from activated sludge and would show great potential for monitoring microbial changes and studying metabolism and community array of activated sludge.

To investigate the mRNA and proten expression of coxsackievirus and adenovirus receptor (CAR) in the corresponding normal lung tissue, para-neoplastic tissue and lung cancer tissue, and the correlation of CAR expression with the carcinogenesis as well as the expression difference in various clinicopathologic parameters.The expression of CAR mRNA and protein in the samples from 32 lung cancer patients was determined by RT-PCR and Western blot, respectively.The expression level of CAR mRNA and protein in normal lung tissue, paraneoplastic tissue and cancer tissue were 1.000 +/- 0.012, 1.048 +/- 0.035, 1.282 +/- 0.072, and 0.902 +/- 0.038, 0.944 +/- 0.042, 1.08 +/- 0.052, respectively, with a statistical significance among the groups (P = 0.022, P = 0.007, P = 0.009, P = 0.027). There was a statistically significant positive correlation between expression of CAR mRNA and that of CAR protein (r = 0.448, P = 0.026). The expression levels of CAR were significantly different among different pathological types (P = 0.012), with a high level of CAR in all 7 bronchiolo-alveolar carcinoma (BAC, P = 0.029). However, there was no statistical significance in other clinicopathologic parameters (P0.05), including gender, age, smoking or not, tumor size, with or without lymph node metastasis and TNM stage.The expression of CAR mRNA and protein in cancer tissue samples are significantly higher than that in the normal and paraneoplastic samples, indicating that CAR might play a crucial role in the carcinogenesis. It may become a new potential prognostic marker for lung cancer patients.