Development of a non-intercepting weak beam current measurement electronics for Heavy Ion Accelerator Facility in Lanzhou.

Non-destructive measurements of low-intensity charged particle beams are particularly challenging for beam diagnostics. At the Heavy Ion Accelerator Facility in Lanzhou (HIRFL), beams with weak currents below 1 µA are often provided for experiments. The detection of such low beam current is below the threshold of typical standard beam current transformers. Therefore, a low-intensity monitoring system is developed by using a sensitive capacitive pick-up (PU) and low-noise electronics. This device measures beam currents by digitally analyzing the amplitude of the PU signals using a homodyne detection scheme. During lab tests, the amplitude nonlinearity is <0.5% in the operational range of 1 nA-45 µA and the amplitude resolution is 0.94 nA. At present, four measurement systems for low beam currents are installed at HIRFL for the monitoring of standard operating conditions with low beam currents below 1 µA. After an absolute calibration with a Faraday cup, it can be used for accurate beam intensity measurement with a current resolution of about 1 nA.

Tri-comb generation with a dual-ring structure.

By introducing a third measurement comb with different repetition frequencies (Δ f r e p ), the tri-comb spectroscopy technique overcomes the ambiguity problem of the original dual-comb spectroscopy technique and eliminates physical delay stages in multidimensional coherent spectroscopy. Nowadays, tri-comb generation based on three frequency-stabilized comb lasers is overly complicated and costly for many potential applications. Previous research on single-cavity dual-combs inspired research on single-cavity tri-combs. However, the currently reported tri-comb structures cannot achieve independently controllable pulses. This paper shows a dual-ring tri-comb seed-source structure using wavelength-based multiplexing in one of the rings. The wavelength and power of the output pulse are independently controlled by using the dual-ring structure. The Δ f r e p of wavelength multiplexing-based dual-comb output can be tuned by adjusting the intra-ring polarization controller (PC). In the case of single-wavelength mode-locking, the PC can be adjusted to achieve a wavelength tuning range of nearly 20 nm. The tri-comb source could offer an attractive alternative solution as a low-complexity light source for field-deployable multi-comb metrology applications.

The Effect of Genetic Variation on the Sensitivity to Opioid Analgesics in Patients With Postoperative Pain: An Updated Meta-analysis.

BACKGROUND: Responsiveness to opioid analgesics differs among patients with acute postoperative pain. OBJECTIVE: Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids. STUDY DESIGN: An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain. METHODS: PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021. RESULTS: Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human µ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms. LIMITATIONS: Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis. CONCLUSIONS: In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia. KEY WORDS: Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.

An alternative ZnO with large specific surface area: Preparation, physicochemical characterization and effects on growth performance, diarrhea, zinc metabolism and gut barrier function of weaning piglets.

High-dose ZnO is widely used to prevent diarrhea and promote growth of weaning piglets, which has led to serious problems of animal toxicity, bacterial resistance and environmental pollution. In this study, a novel alternative ZnO (AZO) was prepared and its physicochemical properties were characterized. Animal experiments were further conducted to evaluate the effects of the ZnO forms, the dose of AZO and the combinations with AZO on the growth performance, diarrhea, zinc metabolism and gut barrier function of weaning piglets. The results showed that the AZO, compared with ordinary ZnO (OZO), nano ZnO (NZO) and porous ZnO (PZO), had the largest surface area and reduced the release of Zn2+ into the gastric fluid. AZO showed better antibacterial activity on Escherichia coli K88, Staphylococcus aureus and Salmonella enteritidis but lower cytotoxicity on porcine intestinal epithelial cells. Animal experiments suggested that low-dose AZO, NZO and PZO (300 mg/kg) improved growth performance and reduced diarrhea in weaning piglets as well as high-dose OZO (3000 mg/kg). Notably, low-dose AZO had the lowest diarrhea incidence. Additionally, low-dose AZO in combination with probiotics improved digestibility and digestive enzyme activities. Low-dose AZO in combination with probiotics also upregulated the expression of the intestinal zinc transporter proteins ZIP4 and DMT1, increased zinc bioavailability, reduced faecal zinc emissions, and avoided zinc overload in the liver and oxidative damage caused by high-dose ZnO. Moreover, low-dose AZO in combination with probiotics improved the gut barrier function of weaning piglets by promoting the expression of tight junction proteins, mucins and antimicrobial peptides and increasing gut microbiota diversity and beneficial Lactobacillus. This study proposed a novel strategy to replace high-dose ZnO and antibiotics with low-dose AZO and probiotics in weaning piglets, which effectively improved growth performance and prevented diarrhea while reducing animal toxicity, bacterial resistance, heavy metal residues and zinc emission pollution.

Burden of lung cancer attributable to household air pollution in the Chinese female population: trend analysis from 1990 to 2019 and future predictions.

This study analyzes the long-term trend of the burden of lung cancer attributable to household air pollution in the Chinese female population, from 1990 to 2019, and make predictions for the next decade. Based the data from the 2019 Global Burden of Diseases (GBD 2019), the joinpoint regression model was used to reflect the temporal trend of the burden of lung cancer attributable to household air pollution, and an autoregressive integrated moving average (ARIMA) model was used to predict the burden of disease over the next decade. From 1990 to 2019, the age-standardized mortality and disability-adjusted life years (DALYs) rates of the Chinese female population were higher than the global rates, and the gap due to residential radon increased over time. The burden of lung cancer attributable to solid fuels has shown a significant downward trend while that due to residential radon has increased slightly overall, but remains lower than the former. The burden of lung cancer increased with age, and the peak age of DALYs rates changed from 70 < 75 years in 1990 to 75 < 80 years in 2019. The model predicted that the burden of lung cancer attributable to solid fuels will gradually decrease over the next decade, whereas the burden of lung cancer due to residential radon will gradually increase and surpass the burden due to solid fuels in 2023. Residential radon will become a more important factor of household air pollution than solid fuels in the next decade for the Chinese female population. Future interventions targeted at household air pollution are needed to reduce the burden of lung cancer.

A new digital beam position and phase measurement implementation based on a field programmable gate array for the high intensity heavy-ion accelerator iLinac.

A new digital beam position and phase measurement (BPM) system was designed for the ion-Linac accelerator at the high intensity heavy ion accelerator facility. The fundamental and second harmonic signals are retrieved from the BPM electrodes to simultaneously calculate their respective beam positions and phases. All data acquisition and digital signal processing algorithm routines are performed in a field programmable gate array (FPGA). The position and phase information are obtained by using the in-phase and quadrature demodulation method. A practical and straightforward method is used to generate the second harmonic reference signal for processing the second harmonic beam signal. The reconfigurable filters are integrated into the FPGA to allow the measurement of short beam pulse length. The laboratory test results show that the achieved phase resolution is better than 0.2° and 0.03° when the input signal is -60 and -45 dBm, respectively. A position resolution better than 30 µm was achieved for an input power level of approximately -60 dBm, and it can reach 7 µm with the input power higher than -45 dBm. The entire execution time of the algorithm is accomplished within 3.4 µs, which provides a sufficient reaction time for the fast beam interlock signal to the machine protection system. The performance of this newly designed prototype BPM electronics was evaluated with the online proton beam.

A Novel Central Camera Calibration Method Recording Point-to-Point Distortion for Vision-Based Human Activity Recognition.

The camera is the main sensor of vison-based human activity recognition, and its high-precision calibration of distortion is an important prerequisite of the task. Current studies have shown that multi-parameter model methods achieve higher accuracy than traditional methods in the process of camera calibration. However, these methods need hundreds or even thousands of images to optimize the camera model, which limits their practical use. Here, we propose a novel point-to-point camera distortion calibration method that requires only dozens of images to get a dense distortion rectification map. We have designed an objective function based on deformation between the original images and the projection of reference images, which can eliminate the effect of distortion when optimizing camera parameters. Dense features between the original images and the projection of the reference images are calculated by digital image correlation (DIC). Experiments indicate that our method obtains a comparable result with the multi-parameter model method using a large number of pictures, and contributes a 28.5% improvement to the reprojection error over the polynomial distortion model.

Development of a diagonal-cut type beam position monitor for the booster ring in the High Intensity Heavy-Ion Accelerator Facility project.

A diagonal-cut type beam position monitor (BPM) has been developed for the High Intensity Heavy-Ion Accelerator Facility (HIAF) project at the Institute of Modern Physics. Compared with other types of BPMs, the diagonal-cut type BPM has almost perfect position linearity, i.e., no non-linear correction required, which is advantageous for beams that are transversally large and have a complex charge distribution. The key parameters for the diagonal-cut type BPM have been simulated and optimized in detail and systematically herein. It was found that the crosstalk is improved by ∼10 dB at 160 MHz by insertion of a separate ring between two horizontal or vertical electrodes of the BPM made of stainless steel with vacuum as a dielectric. Furthermore, the longitudinal and transverse numerical simulation to evaluate the beam impedance on the diagonal-cut type BPM has been performed. The results for the crosstalk, position sensitivity, and electrode capacitance to ground obtained from simulations and laboratory measurements agree well. The vacuum of the BPM prototype after baking out at 250 °C for 72 h is better than 1.0 × 10-11 mbar. The simulated and on-line measured BPM output signal magnitude results are consistent with each other. This diagonal-cut type BPM structure will be considered for application to the HIAF project as a priority.

Coupling Removal of P-Chloronitrobenzene and Its Reduction Products by Nano Iron Doped with Ni and FeOOH (nFe/Ni-FeOOH).

The removal of chlorinated pollutants from water by nanoparticles is a hot topic in the field of environmental engineering. In this work, a novel technique that includes the coupling effect of n-Fe/Ni and its transformation products (FeOOH) on the removal of p-chloronitrobenzene (p-CNB) and its reduction products, p-chloroaniline (p-CAN) and aniline (AN), were investigated. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were employed to characterize the nano-iron before and after the reaction. The results show that Fe0 is mainly oxidized into lath-like lepidocrocite (γ-FeOOH) and needle-like goethite (α-FeOOH) after 8 h of reaction. The coupling removal process and the mechanism are as follows: Fe0 provides electrons to reduce p-CNB to p-CAN and then dechlorinates p-CAN to AN under the catalysis of Ni. Meanwhile, Fe0 is oxidized to FeOOH by the dissolved oxygen and H2O. AN is then adsorbed by FeOOH. Finally, p-CNB, p-CAN, and AN were completely removed from the water. In the pH range between 3 and 7, p-CAN can be completely dechlorinated by n-Fe/Ni within 20 min, while AN can be nearly 100% adsorbed by FeOOH within 36 h. When the temperature ranges from 15 °C to 35 °C, the dechlorination rate of p-CAN and the removal rate of AN are less affected by temperature. This study provides guidance on the thorough remediation of water bodies polluted by chlorinated organics.

Burden of lung cancer attributable to household air pollution in the Chinese female population: trend analysis from 1990 to 2019 and future predictions / Carga de doença devida a câncer de pulmão atribuível à poluição do ar domiciliar na população feminina chinesa: análise de tendências de 1990 a 2019 e previsões futuras / Carga de morbilidad del cáncer de pulmón atribuible a la contaminación del aire doméstico en la población femenina china: análisis de tendencias de 1990 a 2019 y predicciones futuras

This study analyzes the long-term trend of the burden of lung cancer attributable to household air pollution in the Chinese female population, from 1990 to 2019, and make predictions for the next decade. Based the data from the 2019 Global Burden of Diseases (GBD 2019), the joinpoint regression model was used to reflect the temporal trend of the burden of lung cancer attributable to household air pollution, and an autoregressive integrated moving average (ARIMA) model was used to predict the burden of disease over the next decade. From 1990 to 2019, the age-standardized mortality and disability-adjusted life years (DALYs) rates of the Chinese female population were higher than the global rates, and the gap due to residential radon increased over time. The burden of lung cancer attributable to solid fuels has shown a significant downward trend while that due to residential radon has increased slightly overall, but remains lower than the former. The burden of lung cancer increased with age, and the peak age of DALYs rates changed from 70 < 75 years in 1990 to 75 < 80 years in 2019. The model predicted that the burden of lung cancer attributable to solid fuels will gradually decrease over the next decade, whereas the burden of lung cancer due to residential radon will gradually increase and surpass the burden due to solid fuels in 2023. Residential radon will become a more important factor of household air pollution than solid fuels in the next decade for the Chinese female population. Future interventions targeted at household air pollution are needed to reduce the burden of lung cancer.

O objetivo do texto foi analisar a tendência a longo prazo da carga da doença devida a câncer de pulmão atribuível à poluição atmosférica domiciliar na população feminina chinesa de 1990 a 2019 e fazer previsões para a próxima década. Com base nos dados da Carga Global de Doenças 2019 (GBD 2019), o modelo de regressão joinpoint foi utilizado para refletir a tendência temporal da carga da doença devida a câncer de pulmão atribuível à poluição atmosférica domiciliar e um modelo autorregressivo de média móvel integrada (ARIMA), para prevê-la na próxima década. Entre 1990 e 2019, as taxas de mortalidade padronizada por idade e esperança de vida corrigida pela incapacidade (DALYs) da população feminina chinesa foram maiores do que as taxas globais e a diferença devido à exposição residencial a radônio aumentou ao longo do tempo. A carga da doença atribuível a combustíveis sólidos mostrou uma tendência significativa à queda, enquanto aquela devida à exposição residencial a radônio aumentou ligeiramente no geral, mas permanece menor que a primeira. A carga da doença aumentou com a idade, e a idade máxima das taxas de DALYs passou de 70 < 75 anos em 1990 para 75 < 80 anos em 2019. Nosso modelo previu que a carga da doença atribuível aos combustíveis sólidos diminuirá gradualmente na próxima década, enquanto a carga da doença devida ao radônio aumentará paulatinamente e superará a carga devida aos combustíveis sólidos em 2023. A exposição residencial ao radônio se tornará um fator mais importante à poluição atmosférica domiciliar para a população feminina chinesa do que os combustíveis sólidos na próxima década. Futuras intervenções direcionadas à poluição atmosférica domiciliar são necessárias para reduzir a carga do câncer de pulmão.

El objetivo fue analizar la tendencia a largo plazo de la carga de morbilidad del cáncer de pulmón atribuible a la contaminación del aire doméstico en la población femenina china de 1990 a 2019 y hacer predicciones para la próxima década. Según los datos de la Carga Global de Enfermedad de 2019 (GBD 2019), se utilizó el modelo de regresión joinpoint para reflejar la tendencia temporal de la carga de morbilidad pulmonar atribuible a la contaminación del aire doméstico y un modelo autorregresivo integrado de media móvil (ARIMA) para predecir la carga de morbilidad durante la próxima década. De 1990 a 2019, las tasas de mortalidad estandarizadas por edad y años de vida ajustados por discapacidad (AVAD) de la población femenina china fueron más altas que las tasas mundiales, y la brecha debida al radón residencial aumentó con el tiempo. La carga de morbilidad atribuible a los combustibles sólidos mostró una significativa tendencia decreciente, mientras que la del radón residencial aumentó ligeramente, pero en niveles inferiores a la anterior. La carga de morbilidad aumentó con la edad, y las tasas de edad máxima de AVAD cambiaron de 70 < 75 años en 1990 a 75 < 80 años en 2019. El modelo predijo que la carga de morbilidad atribuible a los combustibles sólidos disminuirá gradualmente durante la próxima década, mientras que la carga de morbilidad por radón residencial aumentará gradualmente y superará la carga debida a los combustibles sólidos en 2023. El radón residencial se convertirá en un factor más importante de contaminación del aire doméstico que los combustibles sólidos en la próxima década para la población femenina china. Se necesitan intervenciones futuras dirigidas a la contaminación del aire doméstico para reducir la carga del cáncer de pulmón.

The willingness for dietary and behavioral changes in frontline epidemic prevention workers after experiencing the outbreak of COVID-19 in China: a cross-sectional study.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) has had a massive impact on public health, resulting in sudden dietary and behavioral habit changes. Frontline epidemic prevention workers play a pivotal role against COVID-19. They must face high-risk infection conditions, insufficient anti-epidemic material supplies, mental pressure, and so on. COVID-19 seriously affects their dietary and behavioral habits, and poor habits make them more susceptible to COVID-19. However, their baseline dietary and behavioral habits before COVID-19 and their willingness to change these habits after the outbreak of COVID-19 remain unclear for these workers in China. This study aimed to explore the baseline dietary and behavioral habits of frontline workers and their willingness to change these habits after the outbreak of the epidemic; in addition, susceptible subgroups were identified by stratified analyses as targets of protective measures to keep them from being infected with COVID-19. METHODS: A cross-sectional study was conducted through an online questionnaire using a sample of 22,459 valid individuals living in China, including 9402 frontline epidemic prevention workers. RESULTS: Before COVID-19, 23.9% of the frontline epidemic prevention workers reported a high-salt diet, 46.9% of them reported a high frequency of fried foods intake, and 50.9% of them smoked cigarettes. After the outbreak of COVID-19, 34.6% of them expressed a willingness to reduce salt intake, and 43.7% of them wanted to reduce the frequency of pickled vegetables intake. A total of 37.9% of them expressed a willingness to decrease or quit smoking, and 44.5% of them wanted to increase sleep duration. Significant differences in the baseline dietary and behavioral habits and the willingness to change their habits were observed between frontline epidemic prevention workers and other participants. Among the frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19, frontline epidemic prevention experience was a promoting factor for adopting worse dietary and behavioral habits, including those in the high-salt intake subgroup (OR, 2.824; 95% CI, 2.341-3.405) and the 11-20 cigarettes/day subgroup (OR, 2.067; 95% CI, 1.359-3.143). CONCLUSIONS: The dietary and behavioral habits of frontline epidemic prevention workers were worse than that those of other participants before COVID-19. They had a greater willingness to adopt healthy dietary and behavioral habits after experiencing the outbreak of COVID-19. However, frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19 continued in engage in these poor habits. Dietary and behavioral intervention policies should be drafted to protect their health, especially frontline epidemic prevention workers with poor habits at baseline.

Responses to child sexual assaults and associated factors among parents of young children / 中国学校卫生

Objective@#To analyze the possible responses of parents of young children to Child sexual assault (CSA) and the potential influencing factors, so as to provide evidence for prevention programs of CSA.@*Methods@#Part of the data from "2016-2020 Child Injury Prevention Project" was used to analyze responses to CSA among parents of children younger than 3rd grade in primary school by chi square test and Logistic regression analysis.@*Results@#A total of 4 072 parents were included in the analysis. Among them, 86.8% of parents chose "to solve problems together", 51.0% of parents taking children to a "psychologist", 4.9% of parents "scolding children for being too careless", 2.9% of parents "letting child not disclose abuse" and 6.5% of parents chose "other" coping methods. Parents with foreign nationality [OR(95%CI)=2.58(1.25-5.15)] and lower education level (OR=0.26-0.64) tend to "blame" their children. Mothers [(OR(95%CI)=0.54(0.33-0.90)], higher parental education level (OR=0.27-0.72) were more reluctant to encourage their children to keep quiet. Mothers [OR(95%CI)=1.73(1.32-2.27)], older children (OR=1.33-1.78) and parents with higher education level (OR=1.65-2.99) tend to "accompany". Parents aged 30 or more, and from high school/technical school/technical secondary school tend to take their children to see a "psychologist" [OR(95%CI)=1.39(1.14-1.71), 1.79(1.26-2.53)].@*Conclusion@#Parents universally pay attention to the physical and mental health of children after CSA, but some parents still take negative coping methods, e.g. "blame" and "not disclose". Parenting educational level, duration of parent-child communication and age of children are primary factors associated with parental responses to child sexual assault. This study suggests that prevention secondary injury following child sexual assault should be farther strengthened, while fully considering the characteristics of the educated objects.

The association between subjective impact and the willingness to adopt healthy dietary habits after experiencing the outbreak of the 2019 novel coronavirus disease (COVID-19): a cross-sectional study in China.

To investigate the associations between subjective perception of impacts and willingness to change dietary habits in China after experiencing the outbreak of the 2019 novel coronavirus disease (COVID-19), an online questionnaire survey was carried out and 22,459 respondents in mainland China participated in the study, with an average age of 27.9±7.8 years old. Of them, 84.5% self-reported epidemic concern (middle or above), and 60.2%, 66.3% and 66.8% self-reported impact (middle or above) on psychology, life, work respectively. 31.9%, 46.0% and 41.0% of respondents reported their willingness to reduce their dietary intakes of salt, fried foods, and sugary foods, respectively. The stratified analysis of multinomial logistic regression models showed that, respondents with higher psychological impact were more likely to increase their dietary intake of salt, fried foods, sugary foods. Except as aforesaid, most respondents with higher epidemic concerns and higher impacts on psychology, life, work were more likely to reduce eating salt, fried foods, sugary foods. After the epidemic, early stage of positive improvement to a proper diet was observed, whereas the opposite tendency was also found in some respondents with higher impact on psychology. Thus, there is an urgent need for health care and lifestyle intervention policies for different subgroups.

Identification and Analysis of p53-Regulated Enhancers in Hepatic Carcinoma.

Enhancers can act as cis-regulatory elements to control transcriptional regulation by recruiting transcription factors (TFs) in a distance and orientation-independent manner. However, it is still unclear how p53 participates in the enhancer network as TF in hepatic carcinoma under the condition of DNA damage. A total of 14,286 active enhancers were identified through the integration of stable and unstable enhancer RNAs (eRNAs) captured by CAGE and GRO-seq, respectively. Furthermore, 218 p53-bound enhancers (Enhp53) were identified by analyzing p53 ChIP-seq in HepG2 cells after DNA damage. The results showed that the enhancer expression and histone markers of enhancers (H3K4me1, H3K4me2, H3K4me3, H3K9ac, and H3K27ac) revealed significantly higher level on Enhp53 than Enhno-p53 which suggested that p53 participated in regulating enhancer activity and chromatin structure. By analyzing 124 TFs ChIP-seq from ENCODE, 93 TFs were found significantly enriched on Enhp53 such as GATA4, YY1, and CTCF, indicating p53 may co-regulate enhancers with TFs participation. Moreover, significantly differentially expressed 438 miRNAs and 1,264 mRNAs were identified by analyzing small RNA-seq and RNA-seq, and 26 Enhp53-miRNAs and 145 Enhp53-mRNA interactions were identified by the integration of 3D genome data and genomic distance. The functional enrichment analysis showed that these miRNA targets and mRNAs were significantly involved in tumor biological processes and signaling pathways such as DNA replication, p53 signaling pathway, hepatitis B, focal adhesion, etc. The above results indicated that p53 participated in regulating enhancer network in hepatic carcinoma and Enhp53 exhibited significantly different characteristics with Enhno-p53.

Genome-Wide Identification and Analysis of Enhancer-Regulated microRNAs Across 31 Human Cancers.

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner, and dysregulation of target genes could lead to various diseases, such as cancer. Recent studies have shown that enhancers can regulate microRNAs (miRNAs) and participate in their biological synthesis. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited a significant cancer type-specific feature trend at the tissue level rather than at the single-cell level, and there was a noteworthy positive correlation between the expression of the miRNA and the number of enhancers regulating the same miRNA in most cancers. Furthermore, we found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of enhancer RNAs (eRNAs) whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, guanine-cytosine (GC) content, and histone modification signatures. Notably, GC content, H3K4me1, and H3K36me3 were present differently between distal and proximal regulation, suggesting that they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507 ∼ miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on the enhancer affected the expression of the TNFRSF18 gene as a tumor suppressor.

Cadmium Exposure and Osteoporosis: A Population-Based Study and Benchmark Dose Estimation in Southern China.

This study aimed to assess the association between osteoporosis and long-term environmental Cd exposure through diet in southern China. A total of 1116 subjects from a Cd-polluted area and a non-Cd-polluted area were investigated. All subjects met the criteria of having been living in the investigated area for more than 15 years and lived on a subsistence diet of rice and vegetables grown in that area. Besides bone mineral density, the levels of urinary markers of early renal impairment, such as urinary N-acetyl-ß-D-glucosaminidase (NAG), α1 -microglobulin, ß2 -microglobulin, and urinary albumin, were also determined. Urinary Cd concentrations of all studied subjects ranged from 0.21 to 87.31 µg/g creatinine, with a median of 3.97 µg/g creatinine. Multivariate linear regression models indicated a significant negative association of urinary Cd concentrations with bone mineral density. In logistic regression models, both categorical and continuous urinary Cd concentrations were positively associated with osteoporosis. Subjects in the second, third, and fourth quartiles of urinary Cd concentration had greater odds of osteoporosis compared with subjects in the first quartile (odds ratio [OR] = 3.07, 95% confidence interval [CI], 1.77 to 5.33; OR = 4.63, 95% CI, 2.68 to 7.98; OR = 9.15, 95% CI, 5.26 to 15.94, respectively). Additional adjustment for levels of urinary markers did not attenuate the associations. No evidence existed of an interaction between urinary Cd concentration and renal function using levels of urinary markers, and estimated glomerular filtration rate (eGFR). In all subjects, the benchmark dose and benchmark dose lower bound were 1.14 (0.61) and 2.73 (1.83) µg/g creatinine, with benchmark response set at 5% and 10%, respectively. The benchmark dose of urinary Cd was lower in women than in men. This study demonstrated an inverse association between the body burden of Cd and osteoporosis. The toxic effect of Cd on bone may occur in parallel to nephrotoxicity. © 2017 American Society for Bone and Mineral Research.

Associations between Urinary Excretion of Cadmium and Renal Biomarkers in Nonsmoking Females: A Cross-Sectional Study in Rural Areas of South China.

OBJECTIVES: The aim of this study was to systematically evaluate the relationship between urinary excretion of cadmium (U-Cd) and biomarkers of renal dysfunction. METHODS: One hundred eighty five non-smoking female farmers (aged from 44 to 71 years) were recruited from two rural areas with different cadmium levels of exposure in southern China. Morning spot urine samples were collected for detecting U-Cd, urinary creatinine (U-cre), ß2-microglobulin (ß2-MG), α1-microglobulin (α1-MG), metallothionein (MT), retinol binding protein (RBP), albumin (AB), N-acetyl-ß-D-glucosaminidase (NAG), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) and kidney injury molecule-1 (KIM-1). Spearman's rank correlation was carried out to assess pairwise bivariate associations between continuous variables. Three different models of multiple linear regression (the cre-corrected, un-corrected and cre-adjusted model) were used to model the dose-response relationships between U-Cd and nine urine markers. RESULTS: Spearman's rank correlation showed that NAG, ALP, RBP, ß2-MG and MT were significantly associated with U-Cd for both cre-corrected and observed data. Generally, NAG correlated best with U-Cd among the nine biomarkers studied, followed by ALP and MT. In the un-corrected model and cre-adjusted model, the regression coefficients and R² of nine biomarkers were larger than the corresponding values in the cre-corrected model, indicating that the use of observed data was better for investigating the relationship between biomarkers and U-Cd than cre-corrected data. CONCLUSIONS: Our results suggest that NAG, MT and ALP in urine were better biomarkers for long-term environmental cadmium exposure assessment among the nine biomarkers studied. Further, data without normalization with creatinine show better relationships between cadmium exposure and renal dysfunction.

[Long-term effect of cadmium exposure on residents' renal dysfunction: An epidemiologic study].

OBJECTIVE: To study long-term effect on renal function exposed to environmental cadmium. METHODS: Stratified random sampling and cluster sampling method of epidemiological investigations were carried out in northern Guangdong province between April, 2011 and August, 2012. A total of 167 residents who lived in high cadmium exposure area for more than 15 years, aged above 40 were selected in exposed group. Moreover, A total of 145 residents who had similar living and economic conditions and lived in local for more than 15 years, aged above 40 were selected in control group. We used health questionnaires and medical examinations in order to acquire their health status. Home-harvested rice and vegetables were collected using quartering method for detection of cadmium level. Urine specimens of residents were collected for detection of cadmium level and creatinine as well as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase (NAG), ß2-microglobulin (ß2-MG), and retinol binding protein(RBP), respectively. The analysis of spearman rank correlation and multiple regression were used to investigate the relationships between age, urinary cadmium levels and renal injury biomarkers. RESULTS: The cadmium levels in rice and vegetables of exposed group were 0.75 and 0.10 mg/kg, both were significantly higher than 0.07 and 0.01 mg/kg in the control group (Z values were -6.32 and -7.84, all P values < 0.001). The urinary cadmium level of exposed group was 8.29 µg/g · cr, which was higher than that of the control group 2.03 µg/g · cr with significant difference (Z value was -11.39, P < 0.001). After stratified the total population by age, the urinary cadmium level in 40-49 years, 50-59 years and ≥ 60 years subgroups were 7.22, 8.71, and 13.10 µg/g · cr, which both were significantly higher than 1.80, 2.04, and 2.05 µg/g · cr in the control group (Z values were -5.22, -7.41, and -7.14, all P values < 0.001). After stratified the total population by gender, the urinary cadmium level of male and female were 5.12 and 12.36 µg/g · cr, which both were significantly higher than 1.79 and 2.16 µg/g · cr in the control group (Z values were -7.68 and -9.03, all P values < 0.001). Comparing the differences of renal dysfunction biomarkers (NAG, ß2-MG, RBP) between two groups. The level of urinary ß2-MG and RBP of exposed group were 0.21 and 0.04 µg/g · cr, which were higher than 0.05 and 0.00 µg/g · cr of the control group with significant difference (Z value was -7.08 and -9.65, all P values < 0.001). Pearson correlation analysis showed that NAG, ß2-MG and RBP were positively correlated with urinary cadmium and age, the correlation coefficients were 0.57, 0.49, 0.21 and 0.22, 0.26, 0.23 respectively (all P values < 0.001). After adjusting the effect of age, it was appeared that urinary cadmium levels contributed most to the alteration of NAG, ß2-MG and RBP, the standardized regression coefficients were 0.57, 0.49 and 0.20 (all P values < 0.001), and suggested that the cadmium body burden was one of the most important factors for renal dysfunction. CONCLUSION: Residents, who had cadmium contaminated rice and vegetables for a long time, would take the risk of increasing body burden of cadmium and urinary early biomarkers of renal tubular injury that referred to occurrence of renal dysfunction.

Overexpression of Six1 leads to retardation of myogenic differentiation in C2C12 myoblasts.

The Six1 homeoprotein belongs to the Six (sine oculis) transcription factor family, the members of which are known to act as master regulators of development. Six1 is essential for promoting myogenesis during mammalian somitogenesis. Previous studies have shown that Six1 participates in later steps of myogenic differentiation by enhancing early activation of myogenin via binding to the Mef3 site of the myogenin promoter. In the present study, however, we show that overexpression of Six1 via retroviral infection suppresses the expression of myogenin and myosin in C2C12 myoblasts, consequently retarding myogenic differentiation without affecting cell proliferation or expression of Mef2 and Mef3. These findings further demonstrate the functional role of Six1 in myogenesis.

Increased expression and altered subcellular distribution of PKC-δ and PKC-ɛ in pulmonary arteries exposed to hypoxia and 15-HETE.

15-hydroxyeicosatetraenoic acid (15-HETE), a product of arachidonic acid (AA) catalyzed by 15-lipoxygenase (15-LOX), is an important mediator of hypoxic pulmonary vasoconstriction (HPV). We have previously reported that 15-HETE-induced pulmonary vasoconstriction occurs via protein kinase C (PKC) pathway, however, the role of PKC isoforms involved in 15-HETE-induced pulmonary vasoconstriction remains poorly understood. To examine the potential role of PKC-δ and PKC-ɛ isoforms that appear to be involved in 15-HETE-induced pulmonary artery (PA) contraction, a combination of immunofluorescence, western blotting, semi-quantitative PCR and functional contractile tension approaches on rat PA rings were utilized. We found that 15-HETE activates the translocation of PKC-δ and PKC-ɛ from the cytoplasm to the membranes of pulmonary arterial smooth muscle cells (PASMCs). However, the alteration was significantly reversed by nordihydroguairetic acid (NDGA), a 15-LOX inhibitor which blocked the formation of endogenous 15-HETE. Both endogenous and exogenous 15-HETE enhanced the expression of PKC-δ and PKC-ɛ in PASMCs exposure to hypoxia. The PKC inhibitor Gö6983 and rottlerin (PKC-δ selective), and the inhibitor selective for PKC-ɛ peptide significantly attenuated constriction effect of 15-HETE on isolated PA rings of rats maintained for 9 days in hypoxic environments (FiO(2)=0.12) compared with siblings rats under normoxia. Thus, these findings indicate that PKC-δ and PKC-ɛ contributing to hypoxic pulmonary artery contraction elicited by 15-HETE.