[Research on the establishment of standard limits for perfluorooctanoic acid and perfluorooctane sulfonate in the "Standards for Drinking Water Quality（GB5749-2022）"in China].

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.

Predictive value of endometrial receptivity evaluated by three-dimensional ultrasound in ectopic pregnancy after in vitro fertilization-embryo transfer.

OBJECTIVE: The aim of this study was to use three-dimensional (3D) ultrasound to detect ultrasound parameters related to the uterine artery and endometrium, evaluate endometrial receptivity, and investigate the predictive value of each parameter for ectopic pregnancy (EP) after in vitro fertilization-embryo transfer (IVF-ET). PATIENTS AND METHODS: Fifty-seven cases of pregnancy following IVF-ET in our institution were collected and split into EP and intrauterine pregnancy (IP) groups based on the location of pregnancy, with 27 cases in EP and 30 cases in IP. Endometrial thickness, type, volume, endometrial blood flow parameters, and uterine artery blood flow parameters were all measured one day before transplantation in both groups, and the differences between the two groups were examined. RESULTS: There were differences in endometrial blood flow typing between the two groups, with type III endometrium accounting for the highest proportion in both; the uterine spiral artery pulsatility index PI was significantly higher in the EP group than in the IP group; there were no statistical differences in uterine volume, uterine artery resistance index mRI, or uterine artery resistance index S/D between the two groups; there were no statistical differences in uterine volume, or uterine artery. CONCLUSIONS: Intracavitary 3D ultrasound can assess endometrial tolerance and may predict pregnancy outcome after IVF-ET.

[Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C].

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.

[Preliminary application of the Asia-Pacific colorectal screening score combined with the quantitative fecal occult blood in colorectal neoplasia screening].

To evaluate the efficacy of the Asia-Pacific colorectal screening (APCS) score combined with the quantitative fecal immunochemical test in colorectal neoplasia screening. Subjects who appointment to receive colonoscopy were recruited from August 2017 to May 2019 in the digestive endoscopy center. Before the colonoscopy, all subjects were scored by the Asia Pacific colorectal cancer screening scoring system and measured by quantitative fecal immunochemical test (QFIT). The detection rates of colorectal neoplasia were compared to evaluate the efficacy of the combined assay in colorectal neoplasia screening between APCS score and QFIT. A total of 1 420 subjects were enrolled in this study, APCS score medium-risk (MR) and high-risk (HR) groups were 847 (59.7%) and 573 (40.4%) and 26 cases (1.8%) of colorectal cancer, 196 cases (13.8%) of advanced adenoma, and 395 cases (27.8%) of non-advanced adenoma were detected. With the combination of APCS score and QFIT, participants were classified into 4 groups high-risk with positive QFIT result group G1, high-risk with negative QFIT result group G2, medium-risk with positive QFIT group G3, medium-risk negative QFIT group G4. The prevalence of colorectal neoplasia was 64.3%, 16.4%, 55.0%, and 9.8%, respectively. The prevalence of advanced neoplasia in high-risk with QFIT results was significantly higher than that in other 3 groups. HR and positive QFIT were the indicators for further colonoscopy, and MR with FIT negative group could postpone colonoscopy and conduct annual QFIT follow-up. The combination of APCS score and QFIT for colorectal neoplasia screening can reduce unnecessary colonoscopy, improve colonoscopy compliance and screening efficiency, and has important clinical significance and promotion value in colorectal tumor screening.

FOXN2 suppresses the proliferation and invasion of human hepatocellular carcinoma cells.

OBJECTIVE: The aim of this study was to explore the roles of FOXN2 (Fork head Box N2) in mediating the proliferation and invasion of hepatocellular carcinoma (HCC) cells. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to determine expression of FOXN2 in HCC tissues and cells. Transfection of plasmid containing FOXN2 was used to exogenously overexpress FOXN2 in vitro. Cell Counting Kit-8 (CCK-8) assay and transwell assay were applied to detect the proliferation and invasion of HCC cells, respectively. RESULTS: FOXN2 expression decreased significantly in both HCC tissues and cells (p<0.05). Upregulation of FOXN2 significantly inhibited the proliferation and invasion of HCC cells (p<0.05). CONCLUSIONS: FOXN2 acts as a regulator in the progression of HCC. Our findings suggest that FOXN2 may be a novel therapeutic monitoring and prognosis biomarker in HCC.

[Analysis of diagnosis and treatment of 100 patients with Hürthle cell adenoma].

OBJECTIVE: To summarize and analyze the clinical data and prognosis of the patients with Hürthle cell tumor (HCT) in order to raise the clinicians' awareness of the disease. METHODS: The clinical data on patients with histopathologically proven HCT, without other thyroid carcinomas, were collected retrospectively in Peking University First Hospital from January 2001 to February 2017. All the patients underwent surgery due to thyroid nodules. The follow-up information was also collected. RESULTS: A total of 100 patients were enrolled in the current study. All of them were diagnosed with Hürthle cell adenoma (HCA). There were 77 females and 23 males, with the male-to-female ratio of 1 : 3.3. The average age of these patients was (52±14) years at the time of operation. Fifty-one patients were found their thyroid nodules accidentally by ultrasonography during their health check-ups. 69.4% of the 49 symptomatic patients presented with painless cervical nodules. 83.0% HCA patients were combined with multinodular goiters (MNGs). 88.4% (76/86) patients were euthyroid and 53.8% (21/39) had increasing thyroglobulin levels. The mean longest diameter of HCAs was (3.2±1.5) cm (range: 0.9-7.3 cm) on ultrasonography. There were a series of sonographic features of HCA, such as larger, solidity, hypoecho, a smooth outline, intranodular vascularization, perinodular vascularization, absence of calcification in nodules and absence of enlarged cervical lymph nodes. Compared with the histological diagnosis, the diagnostic accuracy by frozen section (FS) during operation was 97.4%. Twenty-nine patients were followed up with an average period of (49.2±22.1) months and none of them had local recurrence or cervical lymph node metastasis. Six patients accepted thyroid hormone replacement treatment and one had thyrotoxicosis due to over-dose. CONCLUSION: HCA is more common in women. It is often found accidentally by ultrasonography during their health check-ups or presented with painless cervical nodules. It is combined with MNG frequently. HCA exhibits numerous sonographic features but not unique. FS during operation is a reliable method to identify HCA with high diagnostic accuracy. Patients with thyroid hormone administration should be monitored for thyroid function after thyroid surgery.

[The optimal thresholds of the quantitative fecal immunochemical test for opportunistic screening of colorectal neoplasia].

Objective: To investigate the significance of quantitative fecal immunochemical test (FIT) for opportunistic screening of colorectal neoplasia, and to propose the most optimal thresholds to improve the screening level of early colorectal neoplasia. Methods: The opportunistic screening participants were recruited from the Department of Gastroenterology & GI Endoscopy Center of the Seventh Medical Center of PLA General Hospital, and stool sample was collected before colonoscopy and the quantitative FIT was analyzed by OC-MICRO analysator for each patient. We assessed test performance in detecting colorectal neoplasia (advanced adenoma and CRC)with different thresholds on sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: A total of 1 448 objects were enrolled in this study, including 714 male (49.3%)and 734 female (50.7%).All participants were classified according to the result of colonoscopy and pathology, and 242 cases of colorectal neoplasia were found, containing 157 advanced adnoma and 85 colorectal cancer. The FIT threshold increased from 50 µg/L to 200 µg/L, while the positivity rate dropped from 11.5% to 8.6% and the sensitivity in detecting colorectal neoplasia dropped from 47.9% to 38.8%. However, the specificity increased from 96.8% to 98.2% and the positive predictive value increased from 82.3% to 87.0%.The miss rate of colorectal cancer increased from 11.8% (n=10) to 17.6% (n=15) along with the increase in FIT thresholds, but the miss rate of 100 µg/L and 150 µg/L was the same as 12.9% (n=11). Conclusions: Quantitative FIT,which is simple and fast,with the threshold of 100 µg/L for opportunistic screening, has a high sensitivity and specificity for the diagnosis of colorectal neoplasia,and is an important index in screening and diagnosis of colorectal neoplasia.

[Association of sleep with anxiety in the elderly aged 60 years and older in China].

Objective: To investigate the relationship of sleep duration and sleep quality with anxiety in the elderly aged 60 years and older in China. Methods: The elderly aged 60 years and older were selected from the China Short-term Health Effects of Air Pollution Study conducted between July 18, 2017 and February 7, 2018. Multivariate logistic regression models were used to analyze the association of sleep duration and sleep quality with anxiety. Results: A total of 3 897 elderly aged 60 years and older were included in the study. The age of the elderly was (73.4±8.0) years old. Among the elderly surveyed, 6.5% were defined with anxiety, and 18.7% reported poor sleep quality. Multivariate logistic regression models showed shorter sleep duration was the risk factor for anxiety in the elderly that after adjusting for factors such as general demographics, socioeconomic factors, lifestyle, health status, social support and ambient fine particulates exposure. Compared with the elderly with 7 hours of sleep duration daily, the OR (95%CI) of anxiety for those with sleep duration ≤ 6 hours was 2.09 (1.49-2.93). Compared with those with good sleep quality, the OR (95%CI) of anxiety for those with poor sleep quality was 5.12 (3.88-6.77). We also found statistically significant correlations of the scores of subscales of Pittsburgh sleep quality index with anxiety, in which the effects of sleep disturbance, subjective sleep quality and daytime dysfunction scores were most obvious, the ORs (95%CI) were 4.63 (3.55-6.04), 2.75 (2.33-3.23) and 2.50 (2.19-2.86), respectively. Subgroup analysis showed that the association of sleep duration and sleep quality with anxiety was more obvious in males and in those aged <80 years. Conclusion: Shorter sleep duration and poor sleep quality are associated with anxiety in the elderly in China.

[Influencing factors for depressive symptoms in the elderly aged 65 years and older in 8 longevity areas in China].

Objective: To analyze influencing factors for depressive symptoms in the elderly aged 65 years and older in 8 longevity areas in China. Methods: We recruited 2 180 participants aged 65 years and older in 8 longevity areas from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey in 2017. Multivariate logistic regression analysis was performed to evaluate the relationships of socio-demographic characteristics, behavioral lifestyle, chronic disease prevalence, functional status, family and social support with depressive symptoms in the elderly. Results: The detection rate of depression symptoms was 15.0% in the elderly aged 65 years and older in 8 longevity areas of China, and the detection rate of depression symptoms was 11.5% in men and 18.5% in women. Multivariate logistic regression analysis results showed that the detection rate of depressive symptoms was lower in the elderly who had regular physical exercises (OR=0.44, 95%CI: 0.26-0.74), frequent fish intakes (OR=0.57, 95%CI: 0.39-0.83), recreational activities (OR=0.65, 95%CI: 0.44-0.96), social activities (OR=0.28, 95%CI: 0.11-0.73) and community services (OR=0.68, 95%CI: 0.50-0.93). The elderly who were lack of sleep (OR=2.04, 95%CI: 1.49-2.80), had visual impairment (OR=1.54, 95%CI: 1.08-2.18), had gastrointestinal ulcer (OR=2.97, 95%CI: 1.53-5.77), had arthritis (OR=2.63, 95%CI: 1.61-4.32), had higher family expenditure than income (OR=1.80, 95%CI: 1.17-2.78) and were in poor economic condition (OR=4.58, 95%CI: 2.48-8.47) had higher detection rate of depressive symptoms. Conclusion: The status of doing physical exercise, fish intake in diet, social activity participation, sleep quality or vision, and the prevalence of gastrointestinal ulcers and arthritis were associated with the detection rate of depressive symptoms in the elderly.

[Prediction of 6-year incidence risk of chronic kidney disease in the elderly aged 65 years and older in 8 longevity areas in China].

Objective: To establish a prediction model for 6-year incidence risk of chronic kidney disease (CKD) in the elderly aged 65 years and older in China. Methods: In this prospective cohort study, we used the data of 3 742 participants collected during 2008/2009-2014 and during 2012-2017/2018 from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey. Two follow up surveys for renal function were successfully conducted for 1 055 participants without CKD in baseline survey. Lasso method was used for the selection of risk factors. The risk prediction model of CKD was established by using Cox proportional hazards regression models and visualized through nomogram tool. Bootstrap method (1 000 resample) was used for internal validation, and the performance of the model was assessed by C-index and calibration curve. Results: The mean age of participants was (80.8±11.4) years. In 4 797 person years of follow up, CKD was found in 262 participants (24.8%). Age, BMI, sex, education level, marital status, having retirement pension or insurance, hypertension prevalence, blood uric acid, blood urea nitrogen and total cholesterol levels and estimated glomerular filtration rate in baseline survey were used in the model to predict the 6-year incidence risk of CKD in the elderly. The corrected C-index was 0.766, the calibration curve showed good consistence between predicted probability and observed probability in high risk group, but relatively poor consistence in low risk group. Conclusion: The incidence risk prediction model of CKD established in this study has a good performance, and the nomogram can be used as visualization tool to predict the 6-year risk of CKD in the elderly aged 65 years and older in China.

Prevalence of bovine tuberculosis in the Aksu Region of Xinjiang, China, between 1985 and 2016 / Prevalência de tuberculose bovina na região Aksu de Xinjiang, China, entre 1985 e 2016

Prevalence of bovine tuberculosis infection in cattle in Aksu Prefecture determined by intradermal tuberculin skin test (TST), between 1985 and 2016. Cattle were analyzed according to region, feeding pattern, herds and age. A total of 890,009 cattle were tested, with overall bovine tuberculosis prevalence of 0.13% (1172/890009). Statistically significant difference was found in feeding pattern and herds. Prevalence in cows (0.19%, 615/327022) was higher than that in beeves (P< 0.01, OR= 1.903, 95% CI = 1.696 to 2.134). Significant difference (P< 0.01; OR= 2.238, 95%; CI= 1.937 to 2.585) was evident for rates for bovine tuberculosis in the peasant household (0.12%, 942/802343) and farm groups (0.26%, 230/87666). The overall prevalence of bTB was decreased in the Aksu Prefecture, especially the positive rate was under 0.1% in 2010s. We concluded that the control measures forbovine tuberculosis in the Aksu region cattle herds are effective.(AU)

Prevalência de infecção por tuberculose bovina em gado na prefeitura de Aksu determinada por teste cutâneo tuberculínico (TST) entre 1985 e 2016 foi avaliada. O gado foi analisado de acordo com região, padrão alimentar, rebanho e idade. Um total de 890009 animais foram testados, com prevalência de 0,13% de tuberculose bovina (1172/890009). Diferença estatisticamente significativa foi encontrada em padrão alimentar e rebanhos. Prevalência em vacas (0,19%, 615/327022) foi mais alta que em bois (P< 0,01, OR= 1,903, 95% CI = 1,696 a 2,134). Diferenças significativas (P< 0,01; OR= 2,238, 95%; CI= 1,937 a 2,585) foram evidentes em taxas para tuberculose bovina em casas de camponeses (0,12%, 942/802343) e grupos de fazendeiros (0,26%, 230/87666). A prevalência de bTB caiu na prefeitura Aksu, a taxa positiva se encontrava abaixo de 0.1% a partir de 2010. Conclui-se que as medidas de controle para tuberculose bovina na região de Aksu foram eficazes.(AU)

Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium.

The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.

Intra-articular corrective osteotomies combined with the Ilizarov technique for the treatment of deformities of the knee.

AIMS: To present our experience of using a combination of intra-articular osteotomy and external fixation to treat different deformities of the knee. PATIENTS AND METHODS: A total of six patients with a mean age of 26.5 years (15 to 50) with an abnormal hemi-joint line convergence angle (HJLCA) and mechanical axis deviation (MAD) were included. Elevation of a tibial hemiplateau or femoral condylar advancement was performed and limb lengthening with correction of residual deformity using a circular or monolateral Ilizarov frame. RESULTS: At a mean follow-up of 2.8 years (1.5 to 4.1), the mean HJLCA improved from 15.6° (10° to 23°) pre-operatively to 0.4° (0° to 2°). The mean MAD improved from 70.0 mm (20.1 to 118.5) pre-operatively to 9.1 mm (3 to 15). The mean tibiofemoral angle improved from 31.0° (8° to 54°) pre-operatively to 4.9° (2° to 8°). The mean limb-length discrepancy decreased from 6.3 cm (2.9 to 13.6) pre-operatively to 1.1 cm (0 to 5). All osteotomies and distraction zones healed without complications. CONCLUSION: The use of intra-articular corrective osteotomies combined with the Ilizarov technique allowed correction of deformities of the knee joint with satisfactory HJLCA and overall mechanical axis in six patients with a good functional and cosmetic outcome in the short term. Cite this article: Bone Joint J 2017;99-B:204-10.

Raman-shifted wavelength-selectable pulsed fiber laser with high repetition rate and high pulse energy in the visible.

A high-pulse-energy, diffraction-limited, wavelength-selectable, visible source, based on Raman frequency shifting of a frequency-doubled Yb-doped fiber laser, has been studied. The relative length-scaling laws of Raman gain and self-phase modulation push the design towards short fiber lengths with large core size. It is experimentally demonstrated that the Raman clean-up effect in a graded-index multi-mode fiber is not sufficient to obtain diffraction-limited beam quality in the short fiber length. Thus, a large-core photonic crystal fiber is used to maintain diffraction-limited performance and output pulse energies of ~1 µJ, at a 1-MHz repetition rate and 1.3-ns pulse-width are successfully achieved. This step-tunable visible source should find applications in photoacoustic microscopy.

Understanding hydraulic fracturing: a multi-scale problem.

Despite the impact that hydraulic fracturing has had on the energy sector, the physical mechanisms that control its efficiency and environmental impacts remain poorly understood in part because the length scales involved range from nanometres to kilometres. We characterize flow and transport in shale formations across and between these scales using integrated computational, theoretical and experimental efforts/methods. At the field scale, we use discrete fracture network modelling to simulate production of a hydraulically fractured well from a fracture network that is based on the site characterization of a shale gas reservoir. At the core scale, we use triaxial fracture experiments and a finite-discrete element model to study dynamic fracture/crack propagation in low permeability shale. We use lattice Boltzmann pore-scale simulations and microfluidic experiments in both synthetic and shale rock micromodels to study pore-scale flow and transport phenomena, including multi-phase flow and fluids mixing. A mechanistic description and integration of these multiple scales is required for accurate predictions of production and the eventual optimization of hydrocarbon extraction from unconventional reservoirs. Finally, we discuss the potential of CO2 as an alternative working fluid, both in fracturing and re-stimulating activities, beyond its environmental advantages.This article is part of the themed issue 'Energy and the subsurface'.

Activation of type 5 metabotropic glutamate receptor promotes the proliferation of rat retinal progenitor cell via activation of the PI-3-K and MAPK signaling pathways.

The metabotropic glutamate receptor 5 (mGluR5) regulates neurogenesis in the brain, but the effect of mGluR5 on retinal progenitor cells (RPCs) remains unknown. In this study, we found that mGluR5 promoted the proliferation of rat RPCs with activation of the phosphatidylinositol-3-kinase (PI-3-K) and mitogen-activated protein kinase (MAPK) signaling pathways in vitro. The mGluR5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) increased the cellular viability in a concentration- and time-dependent manner, whereas the mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine hydrochloride (MTEP) had the opposite effect, as shown by 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTT) assay. Treatment with DHPG (100 µM) also promoted the proliferation of RPCs, as indicated by 5-Bromo-2-deoxyUridine (BrdU) staining and flow cytometry, and likewise, MTEP (100 µM) and mGluR5 knockdown abolished the action of mGluR5 activity. Western blot demonstrated that the activation of mGluR5 enhanced the expression of Cyclin D1 and the phosphorylation level of PKC however, MTEP or mGluR5 knockdown also abrogated the effect of DHPG on RPCs. Furthermore, we found that activation of the extracellular signal-regulated protein kinase (ERK) and protein kinase B (AKT) signaling pathways was involved in the proliferation of RPC. After DHPG treatment, the levels of both p-ERK1/2 and p-AKT increased in a time-dependent manner. Then we used MTEP, mGluR5 knockdown, the ERK1/2 inhibitor U0126 and the AKT inhibitor LY294002 to pretreat the cells, and all of them clearly eliminated the influence of DHPG. These results demonstrated that mGluR5 regulates neurogenesis in RPCs through the MAPK and PI-3-K signaling pathways, and these findings may motivate a pharmacological study investigating a potential mechanism for the treatment of retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).

Lattice Boltzmann modeling of self-propelled Leidenfrost droplets on ratchet surfaces.

In this paper, the self-propelled motion of Leidenfrost droplets on ratchet surfaces is numerically investigated using a thermal multiphase lattice Boltzmann model with liquid-vapor phase change. The capability of the model for simulating evaporation is validated via the D(2) law. Using the model, we first study the performances of Leidenfrost droplets on horizontal ratchet surfaces. It is numerically shown that the motion of self-propelled Leidenfrost droplets on ratchet surfaces is owing to the asymmetry of the ratchets and the vapor flows beneath the droplets. It is found that the Leidenfrost droplets move in the direction toward the slowly inclined side from the ratchet peaks, which agrees with the direction of droplet motion in experiments [Linke et al., Phys. Rev. Lett., 2006, 96, 154502]. Moreover, the influences of the ratchet aspect ratio are investigated. For the considered ratchet surfaces, a critical value of the ratchet aspect ratio is approximately found, which corresponds to the maximum droplet moving velocity. Furthermore, the processes that the Leidenfrost droplets climb uphill on inclined ratchet surfaces are also studied. Numerical results show that the maximum inclination angle at which a Leidenfrost droplet can still climb uphill successfully is affected by the initial radius of the droplet.

Gene and protein expression in the oxaliplatin-resistant HT29/L-OHP human colon cancer cell line.

Oxaliplatin (L-OHP) is one of the most commonly used anticancer drugs in adjuvant treatment of colon cancer after complete resection of the primary tumor and treatment of metastatic colorectal cancer. Cancer cells eventually become resistant to L-OHP, which diminishes its curative effect. However, the mechanism of action of L-OHP remains unknown. In this study, an L-OHP-resistant human colon cancer cell line, HT29/L-OHP, was established by gradually increasing the dose of L-OHP in culture. The expression levels of the tumor susceptibility gene 101 (tsg101) and the TSG101 protein in HT29 and HT29/L-OHP cell lines were examined by reverse transcription-polymerase chain reaction and western blot analysis. In addition, the expression levels of several apoptosis-regulating protein markers were determined using immunohistochemistry-staining assays. We found that the expression of tsg101 mRNA and of TSG101 protein were significantly higher in the HT29/L-OHP cell line than in its parent, HT29 (P < 0.05). In addition, the expression of multiple apoptosis-regulating protein markers were significantly increased (P < 0.05) in the HT29/L-OHP cell line. These data suggest that these markers could be useful as predictive markers for evaluating and comparing the efficacy and molecular pharmacology of chemotherapeutics.

Tandem overexpression of five human factors renders murine hepatocytes susceptible to hepatitis C virus.

Development of mouse model of hepatitis C virus (HCV) infection has great significance in drug screening and vaccine research. The barriers of interspecies transmission of HCV are increasingly better understood. Human factors, namely low-density lipoprotein receptor (hLDLR), CD81 (hCD81), scavenger receptor class B type I (hSCARB1), occludin (hOCLN) and claudin 1 (hCLDN1) are all required for rendering mouse hepatocytes permissive to HCV. With the aim to humanize mouse hepatocytes we constructed two recombinant vectors tandemly expressing the first three and the last two HCV entry factors mentioned above, respectively. Cotransfection of mouse hepatocytes with these vectors made them permissive to HCV binding and entry. Tandem overexpression of hLDLR, hSCARB1, hCD81, hCLDN1 and hOCLN is a novel approach to tailoring mouse hepatocytes to HCV binding and entry which can be further used to establish a mouse model of HCV infection as a basis for developing antiviral drugs and vaccines.

A long noncoding RNA critically regulates Bcr-Abl-mediated cellular transformation by acting as a competitive endogenous RNA.

Aberrant expression of long noncoding RNAs (lncRNAs) is associated with various human cancers. However, the role of lncRNAs in Bcr-Abl-mediated chronic myeloid leukemia (CML) is unknown. In this study, we performed a comprehensive analysis of lncRNAs in human CML cells using an lncRNA cDNA microarray and identified an lncRNA termed lncRNA-BGL3 that acted as a key regulator of Bcr-Abl-mediated cellular transformation. Notably, we observed that lncRNA-BGL3 was highly induced in response to disruption of Bcr-Abl expression or by inhibiting Bcr-Abl kinase activity in K562 cells and leukemic cells derived from CML patients. Ectopic expression of lncRNA-BGL3 sensitized leukemic cells to undergo apoptosis and inhibited Bcr-Abl-induced tumorigenesis. Furthermore, transgenic (TG) mice expressing lncRNA-BGL3 were generated. We found that TG expression of lncRNA-BGL3 alone in mice was sufficient to impair primary bone marrow transformation by Bcr-Abl. Interestingly, we identified that lncRNA-BGL3 was a target of miR-17, miR-93, miR-20a, miR-20b, miR-106a and miR-106b, microRNAs that repress mRNA of phosphatase and tensin homolog (PTEN). Further experiments demonstrated that lncRNA-BGL3 functioned as a competitive endogenous RNA for binding these microRNAs to cross-regulate PTEN expression. Additionally, our experiments have begun to address the mechanism of how lncRNA-BGL3 is regulated in the leukemic cells and showed that Bcr-Abl repressed lncRNA-BGL3 expression through c-Myc-dependent DNA methylation. Taken together, these results reveal that Bcr-Abl-mediated cellular transformation critically requires silence of tumor-suppressor lncRNA-BGL3 and suggest a potential strategy for the treatment of Bcr-Abl-positive leukemia.