Emergence, Pattern, and Frequency of Spontaneous Waves in Spreading Epithelial Monolayers.

A striking phenomenon of collective cell motion is that they can exhibit a spontaneously emerging wave during epithelia expansions. However, the fundamental mechanism, governing the emergence and its crucial characteristics (e.g., the eigenfrequency and the pattern), remains an enigma. By introducing a mechanochemical feedback loop, we develop a highly efficient discrete vertex model to investigate the spatiotemporal evolution of spreading epithelia. We find both numerically and analytically that expanding cell monolayers display a power-law dependence of wave frequency on the local heterogeneities (i.e., cell density) with a scaling exponent of -1/2. Moreover, our study demonstrates the quantitative capability of the proposed model in capturing distinct X-, W-, and V-mode wave patterns. We unveil that the phase transition between these modes is governed by the distribution of active self-propulsion forces. Our work provides an avenue for rigorous quantitative investigations into the collective motion and pattern formation of cell groups.

Effects of chronic exposure to Aspergillus fumigatus on epidermal growth factor receptor expression in the airway epithelial cells of asthmatic rats.

Epidemiologic studies suggest that increased concentrations of airborne spores of Aspergillus fumigatus closely relate to asthma aggravation. Chronic exposure to A. fumigatus aggravates airway inflammation, remodeling, and airway hyperresponsiveness in asthmatic rats. The effects of chronic exposure to A. fumigatus on epidermal growth factor receptor (EGFR) expression in the airway epithelial cells of asthmatic rats remain unclear. This study aimed to investigate the effects of chronic exposure to A. fumigatus on injury and shedding of airway epithelium, goblet cell metaplasia, and EGFR expression in the airway epithelial cells of asthmatic rats. A rat model of chronic asthma was established using ovalbumin (OVA) sensitization and challenge. Rats with chronic asthma were then exposed to long-term inhalation of spores of A. fumigatus, and the dynamic changes in injury and shedding of airway epithelium, goblet cell metaplasia, and EGFR expression were observed and analyzed. Chronic exposure to A. fumigatus could aggravate airway epithelial cell damage, upregulate the expression of EGFR and its ligands EGF and TGF-α, promote goblet cell metaplasia, and increase airway responsiveness in rats with asthma. Chronic exposure to A. fumigatus upregulates the expression of EGFR and its ligands in asthmatic rats. The EGFR pathway may play a role in asthma aggravation induced by exposure to A. fumigatus.

Chronic Aspergillus fumigatus exposure upregulates the expression of mucin 5AC in the airways of asthmatic rats.

BACKGROUND: Airway mucus hypersecretion is associated with increased morbidity and mortality in patients with asthma. Chronic Aspergillus fumigatus (A. fumigatus) exposure leads to aggravation of airway inflammation and remodeling, including goblet cell hyperplasia (GCH) and mucus hypersecretion in a rat model of asthma. The effects of chronic A. fumigatus exposure on the expression of airway mucin 5AC (MUC5AC) are unknown. METHODS: The rat model of chronic asthma was set up by systemic sensitization and repeated challenge to ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. The changes of MUC5AC expression, the extent of GCH, and airway hyperreactivity (AHR) were measured after exposure to the fungus. RESULTS AND CONCLUSIONS: Chronic exposure to A. fumigatus upregulates the expression of MUC5AC, and induces GCH in the airways of asthma rats, and the remodeling changes of the airway epithelium was positively correlated with AHR. Upregulation of MUC5AC and induction of GCH may be mechanisms by which chronic A. fumigatus exposure promotes the progression of asthma.

[Different prevalence of impaired glucose tolerance between hyperinsulinemic and normoinsulinemic subjects].

OBJECTIVE: To study the impact of different insulin levels on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM), through analysis of different glycometabolism condition among quinquagenarian population. METHODS: Subjects enrolled were Beijing habitants who received annual physical examination [including oral glucose tolerance test (OGTT)] in the Chinese PLA General Hospital from 2005 - 2007. According to the OGTT results, the subjects were divided into three groups, including normal glucose tolerance-non-hyperinsulinemia group (NGT-NHIns), IGT-hyperinsulinemia group (IGT-HIns) and IGT-non-hyperinsulinemia group (IGT-NHINS). The prognosis between the year 2009 and 2010 of the three groups was observed. Hyperinsulinemia was diagnosed with fasting serum insulin ≥ 15 mU/L and/or 2-hour serum insulin ≥ 80 mU/L after glucose loading. RESULTS: The rate of case number of conversion to T2DM in IGT-NHIns group (42/133) was higher than that in IGT-HIns group (24/154) or NGT-NHIns group (12/126). The HOMA insulin resistance index (HOMA-IR) of individuals with IGT-NHIns was lower than that of IGT-HIns [0.96 (0.40, 3.53) vs 2.04 (0.59, 23.20), P < 0.05], while whole body insulin sensitivity index (WBISI) was higher than that of IGT-HIns [7.48 (3.20, 31.35) vs 3.28 (0.86, 7.67), P < 0.05]. Modified ß-cell function index (MBCI) and insulin secretion index (ISI) in IGT-NHIns was poorer than that of IGT-HIns respectively [2.57 (0.58, 10.98) vs 5.17 (1.04, 65.09); 7.66 (0.99, 28.40) vs 17.56 (4.18, 96.46), all P values < 0.01]. CONCLUSIONS: The risk of IGT-NHIns progressing into T2DM is higher than that of IGT-HIns. For the prevention of T2DM, individuals with IGT-NHIns should be paid more attention than keeping an eye on IGT-HIns patients. Early control of risk factors could protect ß cell function and prevent the progression to T2DM.

[Effects of chronic Aspergillus fumigatus exposure on the expression of mucin 5AC in the airways of asthmatic rats].

OBJECTIVE: To explore the effects of chronic Aspergillus fumigatus (Af) exposure on the expression of mucin 5AC (MUC5AC) in the airways of asthmatic rats. METHODS: Fifty-six male Wistar rats were randomly divided into 8 groups: chronic asthma (group A), chronic asthma plus Af spores inhalation for 1 week (group B), 3 weeks (group C) and 5 weeks (group D), chronic asthma plus saline inhalation for 5 weeks (group E), OVA-sensitized and-saline-challenged group (group F) and OVA-sensitized and-saline-challenged plus Af spores inhalation for 5 weeks (group G) (each n = 8). The airway resistance (Raw) and the change rate of Raw after acetylcholine provocation were detected using a computerized system. The level of MUC5AC mRNA in the lung tissue was measured by RT-PCR, and the expression of MUC5AC in airway epithelial cells were demonstrated by immunohistochemistry. The concentration of IL-13 in BALF was measured by ELISA. The extent of goblet cell hyperplasia was evaluated on periodic acid-Schiff stain (PAS) lung sections. RESULTS: In group B, C, and D, the level of MUC5AC mRNA (MUC5AC mRNA/ß-actin mRNA) (1.9 ± 0.4, 2.3 ± 0.6, 2.9 ± 0.8, respectively), the integrated optical density (value A) of MUC5AC positive stain in airway epithelial cells (278 ± 58, 566 ± 64, 891 ± 80, respectively), the concentration of IL-13 in BALF (µg/L) (96 ± 16, 136 ± 22, 197 ± 34, respectively), and the ratio of goblet cell area to epithelial cell area(%) (16 ± 5, 23 ± 7, 36 ± 9, respectively), were higher than those in group A, E, F and G (all P < 0.05). The change rate of Raw(%) in group C and D (61.91 ± 5.26 and 84.69 ± 6.38) were higher than that in group A, E, F and G (all P < 0.05). The level of MUC5AC mRNA and the value A of MUC5AC were positively correlated with the ratio of goblet cell area to epithelial cell area (r = 0.578, P < 0.05;r = 0.614, P < 0.05, respectively) and the change rate of Raw (r = 0.638, P < 0.05;r = 0.564, P < 0.05, respectively) in group B, C and D. CONCLUSION: Chronic Aspergillus fumigatus exposure upregulated the expression of MUC5AC in the airway epithelial cells and induced goblet cell hyperplasia, resulting in increased airway hypersensitivity in rats with chronic asthma.

[The quantitative classification and survey of sanitation of urban secondary water supply in Haidian district of Beijing].

OBJECTIVE: To investigate the sanitary status of urban secondary water supply facilities in Haidian district of Beijing. METHODS: Adopting the quantitative classification table drafted by the Bureau for Sanitation Inspection and Supervision of Haidian district, we carried quantitative classification (A, B, C grade) on all 1725 secondary water supply facilities in Haidian district for two times. At the same time, we collected 20 residential areas with stratified random sampling method. As the public points in the first quantitative classification, the effect of level publicity on changing the sanitary grade of the secondary water supply facilities were observed. RESULTS: In the first two times of quantitative classification, A-level and B-level secondary water supply facilities took up 81.04% (1398/1725) and 89.04% (1536/1725) of all secondary water supply facilities respectively; the ratio of effective sanitary permits achieved 86.14% (1486/1725) and 92.35% (1593/1725) respectively; and the ratio of effective water quality test reports achieved 86.60% (1494/1725) and 97.10% (1675/1725) respectively. There were 52 secondary water supply facilities in 20 collected areas, including 8 A-level, 27 B-level and 17 C-level secondary water supply facilities before level publicity, and 19, 29 and 4 after level publicity. The impact of level publicity on changing the sanitary grade of the secondary water supply facilities was statistically significant (χ(2) = 12.60, P = 0.002). CONCLUSION: The city secondary water supply facilities in Haidian district are overall in good sanitary conditions. Quantitative classification and level publicity can effectively improve the sanitary status of secondary water supply facilities.

[The application of Delphi method in improving the score table for the hygienic quantifying and classification of hotels].

OBJECTIVE: By means of Delphi method and expert panel consultations, to choose suitable indicators and improve the score table for classifying the hygienic condition of hotels so that it can be widely used at nationwide. METHODS: A two-round Delphi consultation was held to choose suitable indicators among 78 experts from 18 provinces, municipalities and autonomous regions. The suitable indicators were selected according to the importance recognized by experts. RESULTS: The average length of service in public health of the experts was (21.08 +/- 5.78) years and the average coefficient of experts' authorities C(r) was 0.89 +/- 0.07. The response rates of the two-round consultation were 98.72% (77/78) and 100.00% (77/77). The average feedback time were (8.49 +/- 4.48) d, (5.86 +/- 2.28) d, and the difference between two rounds was statistically significant (t = 4.60, P < 0.01). Kendall's coefficient were 0.26 (chi(2) = 723.63, P < 0.01), 0.32 (chi(2) = 635.65, P < 0.01) and opinions among experts became consistent. The score table for the hygienic quantifying and classification of hotels was composed of three first-class indicators (hygienic management, hygienic facilities and hygienic practices) and 36 second-class indicators. The weight coefficients of the three first-class indicators were 0.35, 0.34, 0.31. CONCLUSION: Delphi method might be used in a large-scale consultation among experts and be propitious to improve the score table for the hygienic quantifying and classification.

[Health care status of female workers exposed to occupational hazards in Haidian district of Beijing].

OBJECTIVE: To investigate the health care status of female workers exposed to occupational hazards in Haidian district of Beijing and improve the labor protection of female workers. METHODS: A questionnaire provided by National Center for Women and Children's Health of Chinese CDC was used in the survey conducted to collect information about health care status of female workers in 141 factories with occupational hazards including chemical poisons and physical factors (noise, libration, microwave, high frequency and low temperature). RESULTS: 141 factories were investigated, including 53 state-owned enterprises, 21 collective enterprises, 46 joint-stock enterprises, and 21 non-public enterprises. 12 251 female workers were surveyed, 10.19% (1249/12 251) of whom were exposed to occupational hazards. Of 141 factories studied, 16.31% (23/141) had no labor protection management organization.27.66% (39/141) did not provide pre-employment physical examination service to female workers.48.94% (69/141) didn't establish labor protection system for female workers in menstrual period. While, 21.28% (30/141) of the studied institutes deducted some salaries in the pregnancy, and 32.62% (46/141) deducted their wages during the puerperal period. 2.13% (3/141) arranged female workers in the posts which are forbidden by law (continuous heavy work load operation).9.93% (14/141) arranged pregnant female workers on the post forbidden by law.31.91% (45/141) and 33.33% (47/141) would deduct the time of prenatal medical examination and lactation from their working hours, respectively.39.01% (55/141) didn't afford the cost of fertility. 68.09% (96/141) had annual gynecological examination.45 factories were collected occupational examination reports, accounted for 31.91% (45/141). No female workers were found suffering from occupational disease. Of the 1865 occupational hazard factor monitoring points in 34 factories, there were 155 monitoring points, which were all noise monitoring points, did not meet the standard. CONCLUSION: The current health-care status of female workers is not optimistic. It is necessary to consistently improve health care legislations, establish coordinated management mechanism and strengthen the publicity of policy to protect female workers.

Association between polymorphisms of DNA repair gene XRCC1 and DNA damage in asbestos-exposed workers.

OBJECTIVE: To compare the asbestos-induced DNA damage and repair capacities of DNA damage between 104 asbestos-exposed workers and 101 control workers in Qingdao City of China and to investigate the possible association between polymorphisms in codon 399 of XRCC1 and susceptibility to asbestosis. METHODS: DNA damage levels in peripheral blood lymphocytes were determined by comet assay, and XRCC1 genetic polymorphisms of DNA samples from 51 asbestosis cases and 53 non-asbestosis workers with a similar asbestos exposure history were analyzed by PCR/RFLP. RESULTS: The basal comet scores (3.95 +/- 2.95) were significantly higher in asbestos-exposed workers than in control workers (0.10 +/- 0.28). After 1 h H2O2 stimulation, DNA damage of lymphocytes exhibited different increases. After a 4 h repair period, the comet scores were 50.98 +/- 19.53 in asbestos-exposed workers and 18.32 +/- 12.04 in controls. The residual DNA damage (RD) was significantly greater (P<0.01) in asbestos-exposed workers (35.62%) than in controls (27.75%). XRCC1 genetic polymorphism in 104 asbestos-exposed workers was not associated with increased risk of asbestosis. But compared with polymorphisms in the DNA repair gene XRCC1 (polymorphisms in codon 399) and the DNA damage induced by asbestos, the comet scores in asbestosis cases with Gln/Gln, Gln/Arg, and Arg/Arg were 40.26 +/- 18.94, 38.03 +/- 28.22, and 32.01 +/- 11.65, respectively, which were higher than those in non-asbestosis workers with the same genotypes (25.58 +/- 11.08, 37.08 +/- 14.74, and 29.38 +/- 10.15). There were significant differences in the comet scores between asbestosis cases and non-asbestosis workers with Gln/Gln by Student's t-test (P<0.05 or 0.01). The comet scores were higher in asbestosis workers with Gln/Gln than in those with Arg/Arg and in non-asbestosis workers exposed to asbestos, but without statistically significant difference. CONCLUSIONS: Exposure to asbestos may be related to DNA damage or the capacity of cells to repair H2O2-induced DNA damage. DNA repair gene XRCC1 codon 399 may be responsible for the inter-individual susceptibility in DNA damage and repair capacities.

[The relation of asbestosis to human 8-oxoguanine DNA glycosidase polymorphism and DNA damage in peripheral lymphocytes].

OBJECTIVE: To explore the relation of asbestosis to human 8-oxoguanine DNA glycosidase (hOGG1) genotype and DNA damage, the investigation of hOGG1 polymorphism distribution and DNA strand breakages in peripheral lymphocytes was carried on in occupational population. METHODS: A total 101 asbestos-exposed workers and 141 controls were investigated. The DNA damage level was obtained by single cell gel electrophoresis (SCGE) and hOGG1 Ser326Cys polymorphism by PCR-RELP. RESULTS: (1) A significant increase in the exposed group was observed in comet scores at basal (34.8 +/- 16.8), H2O2-induced (136.7 +/- 36.0) and 4 hours after repair (51.0 +/- 18.7) as compared with the control group (P < 0.01). And the scores in H2O2-induced (147.0 +/- 30.8) and 4 hours after repair (56.9 +/- 21.4) were significantly higher in asbestosis workers than in non-asbestosis ones (125.7 +/- 38.2 and 44.9 +/- 15.4, P < 0.01). (2) There was no differences of the genotype distribution between the asbestos group and the control group (chi(2) = 0.22, P = 0.89). A significant difference in the distribution of this polymorphism (Ser/Ser, Ser/Cys, Cys/Cys) between asbestosis group (25.5%, 51.0%, 23.5%) and the non-asbestosis group (48.0%, 36.0%, 16.0%) was observed (chi(2) = 6.023, P < 0.05). The comet scores at H2O2-induced and 4 hours after repair were higher in asbestosis subjects than in non-asbestosis ones (P < 0.05). (3) After adjusting ages, sex, smoking and drinking status, the odds ratios of the Cys allele for asbestosis were 0.66 (95% CI = 0.38 - 1.13) in the exposed subjects. CONCLUSION: The results suggested that the asbestos occupational exposure might induce DNA damage and the augment on susceptivity of H2O2 oxidation and the fall of the capacity of repairing DNA damage might be one of the mechanisms to induce asbestosis among subjects with the Cys allele.

[Expression, purification and identification of recombinant human lymphotoxin alpha deletant (rhLT-alphaDeltaN27)].

AIM: To construct prokaryotic expression vector of recombinant human lymphotoxin alpha deletant (rhLT-alphaDeltaN27) and express the protein in E.coli. METHODS: The rhLT-alphaDeltaN27 gene was amplified by RT-PCR using total RNA extracted from Jurkat cells,cloned into prokaryotic expression vector pET-23b, and transformed into E.coli BL21(DE3). The recombinant protein was expressed after IPTG induction and purified by DEAE Sepharose FF and Phenyl-Sepharose FF. RESULTS: The recombinant protein was expressed as inclusion bodies with the yield of more than 30% of total bacterial protein. After purification, the purity of rhLT-alphaDeltaN27 was 99%, and the biological activity was more than 8x10(7) U/mg. Other characteristics of rhLT-alphaDeltaN27, such as relative molecular mass(M(r)), pI and N-terminal amino acid sequence, all corresponded to theoretical prediction. CONCLUSION: The expression vector of rhLT-alphaDeltaN27 gene was constructed, and the recombinant protein was expressed in E.coli successfully.A method of for purifying rhLT-alphaDeltaN27 was established.