Search

Introduction Due to individual deviations in tumor tissue uptake, the role of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) in hepatocellular carcinoma (HCC) diagnosis is limited. β-Hydroxy β-methylglutaryl-CoA reductase degradation 1 (HRD1) plays a key role in clearing misfolded proteins. This study is aimed to investigate the role and mechanism of HRD1 in [18F]FDG uptake for the diagnosis of HCC. Methods HRD1 expression level was detected using immunohistochemical (IHC) staining in 9 HCC patients. [18F]FDG PET/CT scans were conducted before treatment. [18F]FDG uptakes in HRD1 overexpressed and knockdown transgenic models were measured by γ-counter and microPET imaging. The GLUT1-HRD1 complex was examined by co-immunoprecipitation and IHC assays. GLUT1 expression in different cell lines, xenograft models and HCC patients was evaluated by Western blot and IHC assays. Results HRD1 was highly expressed in the HCC tumors of patients with low [18F]FDG uptake, while the HRD1 expression was obviously low in the higher [18F]FDG uptake group. Both in vitro and in vivo studies found that HRD1 significantly inhibited [18F]FDG uptake in HCC Huh7 cell lines and animal models. Furthermore, the co-location and interaction of HRD1 with GLUT1 were detected, and the results also indicate that HRD1 could induce the degradation of GLUT1 in vitro and in vivo. Conclusion HRD1 inhibits the high uptake of [18F]FDG in HCC tumor cells by inducing degradation of GLUT1, which leads to decreased diagnostic efficiency of [18F]FDG PET imaging for HCC. Advances in knowledge This study suggests that HRD1 inhibits the high uptake of [18F]FDG in HCC tumor by inducing degradation of GLUT1. Implications for patient care HCC diagnosis with [18F]FDG PET should be accompanied by determination of HRD1 expression, and patients with high tumor HRD1 expression might be unsuitable for [18F]FDG PET.

Currently, mitigating severe particle pollution in autumn and winter is the key to further improving the air quality of China. The source contributions and transboundary transport of fine particles (PM2.5) in pollution episodes are closely related to large-scale or synoptic-scale atmospheric circulation. How to effectively reduce emissions to control haze pollution under different synoptic conditions is rarely reported. In this study, we classify the synoptic conditions over central China from 2013 to 2018 by using Lamb–Jenkinson method and the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) Final (FNL) operational global analysis data. The effectiveness of emission control to reduce PM2.5 pollution during winter haze episodes under potential synoptic controls is simulated by GEOS-Chem model. Among the 10 identified synoptic patterns, four types account for 87 % of the total pollution days. Two typical synoptic modes are characterized by low surface wind speed and stable weather conditions or high relative humidity (A or C type) over central China due to a high-pressure system or a southwest trough and low-pressure system, blocking pollutants dispersion. Sensitivity simulations show that these two heavy pollution processes are mainly contributed by local emission sources with ∼82 % for A type and ∼85 % for C type, respectively. The other two patterns lead to pollution of transport characteristics affected by northerly or southerly winds (NW or SW type), carrying air pollution from northern or southern China to central China. The contribution of pollution transmission from northern and southern China is 36.9 % and 7.6 %, respectively of PM2.5, and local emission sources contribute 41 % and 69 %, respectively. We also estimate the effectiveness of emission reduction in these four typical severe pollution synoptic processes. By only reducing SO2 and NOx emission and not controlling NH3, the enhanced nitrate counteracts the effect of sulfate reduction on PM2.5 mitigation, with a less than 4 % decrease in PM2.5. In addition, to effectively mitigate haze pollution of NW- and SW-type synoptic-controlled episodes, local emission control actions should be in coordination with regional collaborative actions.

Background. Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. Methods. We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. Results. At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. Conclusions. The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. Trial registration. ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov. Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx

BACKGROUND Intimate partner violence (IPV) is an emerging risk factor for HIV infection. Given the high vulnerability of and limited research on transwomen in China, we described IPV, sexual risk behaviors, HIV, and sexually transmitted infection (STIs) testing rates and results, and investigated the pathways that link IPV to HIV infection among this population. METHODS We conducted a cross-sectional survey and collected blood samples for HIV and syphilis testing among transwomen in Shanghai, China (n = 199). With logistic regression, we examined sexual risk behaviors and HIV/STI testing history among participants with and without IPV experience. RESULTS More than half of the respondents reported IPV (57.3%), and the prevalence of unprotected sex ranged from 51.9% (with sex workers) to 87.8% (oral sex); 85.9% had ever tested for HIV and 49.3% for other STIs. Self-reported positivity results were as follows: HIV (2.3%), herpes simplex virus type 2 (8.3%), gonorrhea (18.8%), and syphilis (17.8%). Laboratory-confirmed positivity values were 5.0% for HIV and 6.5% for syphilis. Respondents with a history of IPV were significantly less likely to report HIV testing in the past 12 months (adjusted odds ratio, 0.20; 95% confidence interval, 0.10-0.38). CONCLUSIONS Transwomen self-reported a high prevalence of IPV, which was related to a lower probability of HIV testing. The prevalence of HIV and other STIs was lower than reported in previous studies of Chinese transwomen, whereas the HIV/STI testing rates were higher. Findings suggest transwomen in China are at risk for IPV and need enhanced HIV prevention services to promote HIV testing in an IPV setting.

The importance of regional air pollutant transport modulated by large-scale synoptic circulation has been poorly understood for air pollution. In the present study of 5-year (2015-2019) observation...

As an important issue in atmospheric environment, the contributions of anthropogenic emissions and meteorological conditions to air pollution have been few assessed over the receptor region in regional transport of air pollutants. In this study on observations of environment and meteorology over 2015–2019, the Kolmogorov–Zurbenko (KZ) filter was performed to decompose the PM2.5 variations into multi-time scale components over the Twain-Hu Basin (THB), a receptor region in regional transport of air pollutants in central China, where the short-term, seasonal and long-term components accounted for respectively 47.5 %, 41.4 % and 3.7 % to daily PM2.5 changes. The short-term and seasonal components dominated the day-to-day PM2.5 variations with long-term component determining the change trend of PM2.5 concentrations over recent years. The emission- and meteorology-related long-term PM2.5 components over the THB were identified. The meteorological contribution to PM2.5 declining trend presented the distinct spatial pattern over the THB with northern positive rates up to 61.92 % and southern negative rates down to −24.93 %. The opposite effects of meteorology on PM2.5 pollution could accelerate and offset the effects of emission reductions in the northern and southern THB, which is attributed to the upwind diffusion and downward accumulation of air pollutants over the receptor region in regional PM2.5 transport. It is noteworthy that the increasing conversion efficiencies of SO2 and NO2 to sulfate and nitrate for secondary PM2.5 could offset the effects of PM2.5 emission reduction on air pollution in the THB during recent years, revealing the enhancing contribution of gaseous precursor emissions to PM2.5 concentrations with controlling anthropogenic emissions of PM2.5 and the gaseous precursors over the receptor region in regional transport of air pollutants.

Residential coal combustion (RCC) emission exhibited obvious daily variation, while no real-time estimation of air pollutants from RCC has been reported, as the shortages of corresponding activity dataset and emission factors with high time resolution. A real-time monitoring platform for RCC emission was established. Hourly emission factors of 18 typed of TEs from eleven kinds of chunk coals and nine kinds of honeycomb coals burning in China were obtained. The monthly and hourly coal consumption amounts were calculated with reference and our field survey. Then the hourly TEs emission inventories from RCC were established in China. GEOS-Chem and Risk Quotients Models were utilized to map the spatialized health risks of hazardous elements, including the gridded hazard index and carcinogenic risk. The result indicated that the EFs of TEs would be underestimated if the tests only consider flaming conditions. Cu, K, Ca, Zn, and Co were the top five elements from RCC, with corresponding emission amounts as 1397.7, 1054.0, 676.0, 623.5 and 420 tons in 2017, respectively. K, Ti, Fe, Sn, and Sb showed hourly peak values under flaming dominated periods, accounting for 48.2%, 45.9%, 31.8%, 42.8%, and 33.8% of their daily emissions. Other elements (e.g., V, Co, As, Hg and Pb) exhibited higher emissions under smoldering dominated period in nighttime, accounting for 22.2%, 32.9%, 27.6%, 34.7%, and 28.4% of their daily emissions. TEs emission from RCC closely follows the habits of human daily cooking and heating activity. The national HI were lower than the acceptable level (HI ≤ 1) except Sichuan Province (up to 1.2). Higher carcinogenic risks (≥1 × 10-6) occurred in parts of Sichuan, Shanxi, Hunan and Hubei, which were up to 2.0 × 10-5. The high-resolution TEs emission inventories could be useful for future modeling works on the formation and evolution of air pollution and are helpful for human exposure assessment.

Purpose: China recently commenced several pre-exposure prophylaxis (PrEP) projects, but little work has characterized potential users. This study describes awareness of, intention to use, and uptake of PrEP in a sample of men who have sex with men (MSM), a key population experiencing high rates of HIV in China. Methods: Through a cross-sectional survey administered to 708 MSM in four cities, we mapped respondents onto a Motivational PrEP Cascade. We conducted bivariable and multivariable analysis to examine factors associated with progression through the Cascade. Results: Among 45.6% of MSM who were PrEP eligible, 36% were in Contemplation, 9% were in PrEParation, 2% were in PrEP Action and Initiation, and none reached Maintenance and Adherence. We found no association between individual risk factors and progression through the Cascade. In multivariable analysis, friends' positive attitudes toward PrEP, more frequent sexually transmitted infection testing, and higher scores on the perceived PrEP benefits scale were positively associated with entering PrEP Contemplation. Having higher condom use self-efficacy was associated with decreased odds of entering PrEP Contemplation. Having sex with men and women in the past 6 months, having heard of PrEP from medical providers, and knowing a PrEP user were positively associated with entering PrEParation. Conclusion: We found a high proportion of MSM who were PrEP eligible and identified several intervention targets to prepare for PrEP introduction in China: community education to increase accurate knowledge, gain-framed messaging for PrEP and sexual health, and provider trainings to build MSM-competent services that can support shared decision-making for PrEP initiation.

Anthropogenic emission, meteorological conditions, and regional transport are the three major factors influencing heavy air pollution in China. The Hunan and Hubei provinces in the middle Yangtze River region border China's main air pollution areas, serving as the hub of regional transport of air pollutants. The meteorological formation mechanism of regional transport of air pollutants on heavy air pollution in the Hunan and Hubei provinces still remain urgent to be addressed in depth. In this study, multivariate empirical orthogonal function (MV-EOF) analysis was performed to objectively select eight typical heavy pollution events in the two provinces that occured in January 2015–2019. Based on the regional surface environment, meteorological network data, atmospheric sounding data, ERA-interim reanalysis data, and a numerical simulation experiment, this study investigated the pattern of regional transport of air pollutants in the two provinces and its mechanism of regional meteorological conditions. The results showed that transporting air pollutants mainly passed through two transport pathways, namely the Nanxiang Basin-Yunmeng Plain pathway and the Dabie Mountain's Hilly Area-Yunmeng Plain pathway, existing anomalous near-surface northerly winds in the two provinces and their upstream area accompanied by southward penetration of a shallow cold layer, all of which jointly provide a dynamic condition for regional air pollutant transport. The weak cold-air mass degenerated as it passed through the Hunan–Hubei Plain, causing warm air to accumulate in the near-surface layer of the downstream area, where winds slowed down and converged, buffering the air pollutant transport and resulting in pollutants accumulation; the near-surface atmosphere of the Hunan and Hubei provinces was a non-stagnant condition (dry intrusion of cold air, anomalous northerly winds, and positive anomalies of boundary-layer height), which is conducive to the horizontal transport of air pollutants. However, the mid-high layers, characterized by temperature inversion and the presence of a warm lid, had a stable stratification, inhibiting the diffusion of air pollutants to the upper layers; there is an obvious longitudinal vertical circulation above the Hunan–Hubei Plain, which results in the sinking and accumulation of air pollutants, thereby promoting rapid accumulation of air pollutants in the Hunan and Hubei provinces. In addition, extended empirical orthogonal function (EEOF) analysis was performed, revealing a quasi-4-d periodic oscillation pattern of air pollutants transport in the Hunan and Hubei provinces, which provides a reference for early prediction of its regional transport. The findings are of practical value in broadening the scientific understanding of the differences in the formation mechanism of heavy atmospheric pollution between the various regions of China and promoting environmental and ecological protection of the middle Yangtze Basin.

Neuroimaging studies have demonstrated that autism spectrum disorder (ASD) is accompanied by abnormal functional and structural features in specific brain regions of the default mode network (DMN). However, little is known about the alterations of the topological organization and the functional connectivity (FC) of the DMN in ASD patients. Thirty-seven ASD patients and 38 healthy control (HC) participants underwent a resting-state functional magnetic resonance imaging scan. Twenty DMN subregions were specifically selected to construct the DMN architecture. We applied graph theory approaches to the topological configuration and compare the FC patterns of the DMN. We then examined the relationships between the neuroimaging measures of the DMN and clinical characteristics in patients with ASD. The current study revealed that both the ASD and HC participants showed a small-world regimen in the DMN; however there were no significant differences in global network measures. Compared with the HC group, the ASD group exhibited significantly decreased nodal centralities in the bilateral anterior medial prefrontal cortex and increased nodal centralities in the right lateral temporal cortex and the right retrosplenial cortex. Patients with ASD displayed significantly reduced and increased FC within the DMN. Our findings demonstrated that ASD patients showed a pattern of disrupted FC metrics and nodal network metrics in the DMN, which could be a potential biomarker for objective ASD diagnoses and for the level of autism spectrum traits. HIGHLIGHTS: We used graph theoretical approaches and functional connectivity (FC) to investigate the topological configuration and FC patterns of the DMN in ASD. The current study revealed that both ASD and HC participants exhibited small-world regimes in the DMN, however there were no significant differences in global network measures. The ASD group showed abnormal nodal centralities in the bilateral aMPFC, the right LTC and the Rsp of the DMN, and ASD was characterized by altered FC patterns, including decreased and increased FC within the DMN.

Despite abundant evidence on its safety, tolerability and cost-effectiveness, post-exposure prophylaxis (PEP) has not been officially approved for non-occupational use in China. This study aims to assess awareness of, willingness to use, and actual experience with PEP in gay, bisexual and other men who have sex with men (GBM) in China and to explore potential associations between demographic, behavioral, and psychosocial factors and PEP-related outcomes. We recruited a convenience sample through community venue-based strategies, peer referrals, and online advertisement in four cities of China in 2018. We used bivariable and multivariable logistic regression to test associations between potential predictors and PEP outcomes. Over 60% of men reported having heard of PEP prior to the survey, 70% would be willing to use it if exposed to HIV, and 6% reported having used PEP. Awareness of PEP was associated with higher education, more frequent HIV testing, knowing someone who seroconverted in the past two years, having sex with only men in the past six months, and lower perceived risk of HIV infection. PEP willingness was associated with more frequent HIV testing, being worried about becoming HIV infected, prior awareness and favorable attitudes towards PEP among friends. Findings suggest PEP is an underutilized diomedical HIV prevention intervention among GBM in China. Clinical guidance on non-occupational PEP use, as well as communication campaigns targeting social networks of GBM are needed to address barriers to PEP awareness and uptake.

The purinergic P2X7 receptor (P2X7R) is an adenosine triphosphate (ATP) ligand-gated cationic channel receptor. P2X7R is closely associated with various inflammatory, immune, cancer, neurological, musculoskeletal and cardiovascular disorders. P2X7R is an interesting therapeutic target as well as molecular imaging target. This brief digest highlights the radioligands targeting P2X7R recently developed in drug discovery and molecular imaging agent development.

Background In China, addressing disparities in the HIV epidemic among men who have sex with men (MSM) requires targeted efforts to increase their engagement and retention in prevention. In an effort to advance MSM-friendly HIV services within China, and informed by community-based partnerships, we tested whether MSM who have ever versus never disclosed their same-sex behavior to healthcare providers (HCP) differ in sociodemographic and behavioral characteristics as well as the qualities of sexual health services each group would prefer to access. Methods We conducted a cross-sectional survey among HIV-negative MSM who went to MSM-focused voluntary counseling and testing clinics in four cities in China. The survey was anonymous and collected information on sociodemographic characteristics, testing behaviors, sexual-health related behavior, and sexual health service model preferences. Results Of 357 respondents, 68.1% participants had ever disclosed same-sex behavior to HCPs when seeking advice for sexual health. Younger age (aOR = 1.04; 95% CI: 1.01-1.08), and worry of HIV acquisition (aOR = 1.39; 95% CI: 1.05–1.84) were associated with higher odds of past disclosure. The availability of comprehensive sexual health services was one of the most valued characteristics of the ideal sexual health clinic. Those who ever disclosed and never disclosed differed significantly in their ranking of the importance of three out of ten dimensions: sexual health counseling services available (M = 3.99 vs. M = 3.65, p = .002), gay identity support available (M = 3.91 vs. M = 3.62, p = .016) and clinic collaborates with a gay CBO (M = 3.81 vs. M = 3.56, p = .036). Conclusions Our hypothesis that MSM who had disclosed versus never disclosed same-sex behavior would differ in the value they placed on different dimensions of sexual health service was partially borne out. As health authorities in China decide on implementation models for pre-exposure prophylaxis (PrEP) delivery and specifically within which institutions to integrate PrEP services, the preferences of target populations should be considered to develop comprehensive, patient-centric and LGBT-friendly services.

The purpose of this study was to assess the human cancer risk due to the exposure to the soil-bound polycyclic aromatic hydrocarbons (PAHs) from Chengdu Economic Region (CER), western China with the main concern on cancer risk source apportionment. The total concentrations of sixteen PAHs ranged from 12.5 to 75431 ng g–1, with a mean value of 3106 ng g–1, which suggested that the most areas of CER were contaminated. Source apportionment of PAHs was conducted by the positive matrix factorization (PMF) model and the biomass burning contributed most (63.6%) to the total PAHs, followed by petroleum combustion (16.0%), coke source (11.3%), and petrogenic source (9.2%). Results from incremental lifetime cancer risk (ILCR) calculation showed that soil ingestion exerted the highest cancer risk (accounted for 98.1 − 99.3% of the total cancer risk) on human health among three different exposure pathways, followed by dermal contact (0.66 – 1.83%) and inhalation (0.03 – 0.04%). Among different age groups, adult suffered the highest cancer risk via any exposure pathways. Based on PMF and ILCR methods, the cancer risk source apportionment was conducted and the biomass burning showed moderate cancer risk. The petrogenic, coke, and petroleum sources showed low cancer risks to human. To analyze the sensitivity of the parameters used in ILCR calculation, Monte Carlo simulation was employed. The results indicated that the contribution of each source and exposure duration (ED) were the influential parameters on human health associated with soil-bound PAHs. Therefore, much attentions should be paid to biomass burning to avoid cumulative cancer risk.

Intimate partner violence (IPV) and its association with HIV infection among men who have sex men (MSM) in China are not understood. In this study, 732 MSM recruited from Shanghai, China between March and August 2015 were administered with a questionnaire survey and HIV blood testing. IPV victimization was measured by 25 forced-choice items capturing lifetime experience of physical, sexual, psychological, deprivation or neglect, and other forms of violence. Of them, 179 (24.3%) reported having experienced at least one type of IPV victimization. In separate multivariable analyses, sexual violence was associated with age over 35 years (AOR = 0.26, 95% CI: 0.07-1.02), ever had male-to-male commercial sex (AOR = 2.53, 95%CI: 1.19-5.39), and diagnosis of a sexually transmitted infection (STI) (AOR = 2.14, 95%CI: 0.98-4.66). Both psychological violence (AOR = 2.53, 95%CI: 1.25-5.12)and deprivation or neglect violence (AOR = 1.75, 95%CI: 1.14-2.68) were associated with ever had sex with a casual male partner(s). Having experienced at least one type of IPV victimization was significantly associated with ever had sex with a causal partner(s) (AOR = 1.72, 95%CI: 1.15-2.57) and ever had a diagnosis of a STI (AOR = 1.80, 95% CI: 1.12-2.88). HIV infection was marginally associated with having experienced any form of IPV victimization. IPV victimization is common among MSM, especially young MSM, in China, although its association with HIV infection is not conclusive in our sample. Nonetheless, our findings highlight the importance of the needs of individualized IPV interventions for certain target risk groups of MSM.

The reference standard N-(3-(4-methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)-3-(piperazin-1-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[11C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([11C]9) was prepared from its precursor with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 50-60% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol.

The contributions of emission reduction and meteorological changes to air quality improvement in Hubei Province (HB) have required assessment in recent years. In this study, the WRF-Chem scenario tests were conducted to evaluate the effect of both the emission and meteorological changes on the winter PM2.5 from 2015 to 2019, especially that of regional transport and local emissions on the PM2.5 variations in HB. The results showed that meteorological changes in January 2019 increased the PM2.5 by 24% relative to January 2015, whereas emissions reduced it by 36%, indicating that emission reduction was vital in improving the air quality in HB. However, the meteorological changes increased the concentration of air pollutants by 10–25% relative to January 2018. This led to a rebound of the observed pollutant concentrations in January 2019, highlighting the importance of meteorological conditions on air pollution. Regional transport of air pollutants contributed to the inter-annual increase of wintertime PM2.5 by 78%, driven purely by meteorology from 2015 to 2019. This indicated that regional PM2.5 transport could aggravate PM2.5 levels in winter over HB with the reduction of air pollutant emissions in China. Additionally, the regional transport of air pollutants contributed to the decrease in PM2.5 in HB by 42%, resulting from the non-local emission reduction during COVID-19 lockdown in winter. This indicates the importance of the regional transport of air pollutants in driving regional changes in the atmospheric environment over China.

The brain tumor is one of the most dangerous diseases at present. Accurate diagnosis of brain tumors can contribute to improving the prognosis conditions of patients. Existing methods have some shortcomings, such as manual extraction of features and insufficient amount of data. Since the convolutional neural network (CNN) can extract features automatically, we propose a deep Convolutional Neural Network to diagnose the brain tumors. In this paper, an automatic system based on CNN is proposed to classify three categories of brain Magnetic Resonance Images, including normal images, brain images with meningiomas and brain images with gliomas. Several steps, including image preprocessing, data augmentation and image classification, are applied to the original brain images. And the experiments show that the accuracy of the proposed system on testing set can reach 93.33%, which indicates that our model can achieve a comparable classification result.

In a study of sexually-active HIV-negative men who have sex with men (MSM) in China, we compared behavioral indication for pre-exposure prophylaxis (PrEP) based on risk criteria to self-perception of PrEP candidacy (SPC) and explored factors associated with SPC. Of 708 MSM surveyed, 323 (45.6%) were behaviorally-indicated for PrEP, among whom 42.1% self-perceived as appropriate PrEP candidates. In a multivariable model we found no association between sexual behavior nor HIV risk perception and SPC but found that higher perceived benefits of PrEP, increased frequency of HIV testing, and low condom use self-efficacy were positively-associated with SPC. In a sub-analysis restricted to MSM behaviorally-indicated for PrEP, relationship-factors were also significant. Our findings suggest that PrEP implementers should look beyond risk criteria to consider shared decision-making tools that support individuals to assess whether they are appropriate PrEP candidates based on their existing HIV prevention strategies, sexual health goals, and relationship dynamics.

Compared with the 21-year climatological mean over the same period during 2000–2020, the aerosol optical depth (AOD) and Angstrom exponent (AE) during the COVID-19 lockdown (January 24–February 29, 2020) decreased and increased, respectively, in most regions of Central-Eastern China (CEC). The AOD (AE) values decreased (increased) by 39.2% (29.4%) and 31.0% (45.3%) in Hubei and Wuhan, respectively, because of the rigorous restrictions. These inverse changes reflected the reduction of total aerosols in the air and the contribution of the increase in fine-mode particles during the lockdown. The surface PM2.5 had a distinct spatial distribution over CEC during the lockdown, with high concentrations in North China and East China. In particular, relatively high PM2.5 concentrations were notable in the lower flatlands of Hubei Province in Central China, where six PM2.5 pollution events were identified during the lockdown. Using the observation data and model simulations, we found that 50% of the pollution episodes were associated with the long-range transport of air pollutants from upstream CEC source regions, which then converged in the downstream Hubei receptor region. However, local pollution was dominant for the remaining episodes because of stagnant meteorological conditions. The long-range transport of air pollutants substantially contributed to PM2.5 pollution in Hubei, reflecting the exceptional importance of meteorology in regional air quality in China., Graphical abstract Unlabelled Image, Highlights • Inverse changes in AOD and AE during lockdown were found over CEC. • Pollution events were frequently observed during the strictest lockdown over Hubei. • Air pollution was caused by regional transport of upstream air pollutants to Hubei. • Local pollution was accumulated despite of large reductions in air pollutant emissions.

The purinergic receptor subtype 7 (P2X7R) represents a novel molecular target for imaging neuroinflammation via PET. GSK1482160, a potent P2X7R antagonist, has high receptor affinity, high blood-brain barrier penetration, and the ability to be radiolabeled with 11C. We report the initial physical and biologic characterization of this novel ligand. Methods:11C-GSK1482160 was synthesized according to published methods. Cell density studies were performed on human embryonic kidney cell lines expressing human P2X7R (HEK293-hP2X7R) and underwent Western blotting, an immunofluorescence assay, and radioimmunohistochemistry analysis using P2X7R polyclonal antibodies. Receptor density and binding potential were determined by saturation and association-disassociation kinetics, respectively. Peak immune response to lipopolysaccharide treatment in mice was determined in time course studies and analyzed via Iba1 and P2X7R Western blotting and Iba1 immunohistochemistry. Whole-animal biodistribution studies were performed on saline- or lipopolysaccharide-treated mice at 15, 30, and 60 min after radiotracer administration. Dynamic in vivo PET/CT was performed on the mice at 72 h after administration of saline, lipopolysaccharide, or lipopolysaccharide + blocking, and 2-compartment, 5-parameter tracer kinetic modeling of brain regions was performed. Results: P2X7R changed linearly with concentrations or cell numbers. For high-specific-activity 11C-GSK1482160, receptor density and Kd were 1.15 ± 0.12 nM and 3.03 ± 0.10 pmol/mg, respectively, in HEK293-hP2X7R membranes. Association constant kon, dissociation constant koff, and binding potential (kon/koff) in HEK293-hP2X7R cells were 0.2312 ± 0.01542 min-1⋅nM-1, 0.2547 ± 0.0155 min-1, and 1.0277 ± 0.207, respectively. Whole-brain Iba1 expression in lipopolysaccharide-treated mice peaked by 72 h on immunohistochemistry, and Western blot analysis of P2X7R for saline- and lipopolysaccharide-treated brain sections showed a respective 1.8- and 1.7-fold increase in signal enhancement at 72 h. Biodistribution of 11C-GSK1482160 in saline- and lipopolysaccharide-treated mice at 72 h was statistically significant across all tissues studied. In vivo dynamic 11C-GSK1482160 PET/CT of mice at 72 h after administration of saline, lipopolysaccharide, or lipopolysaccharide + blocking showed a 3.2-fold increase and 97% blocking by 30 min. The total distribution volumes for multiple cortical regions and the hippocampus showed statistically significant increases and were blocked by an excess of authentic standard GSK1482160. Conclusion: The current study provides compelling data that support the suitability of 11C-GSK1482160 as a radioligand targeting P2X7R, a biomarker of neuroinflammation.

Biomass burning (BB) has significant impacts on air quality, climate and human health. In China, the BB emission has changed substantially over the past decades while the multi-year variation held high uncertainty and the driving forces have addressed little attention. Here, this research aimed to conduct a comprehensive and systematic analysis of BB variation in China and provided precise and targeted BB emission reduction suggestions. The moving of high emission for BB from 2003 to 2014 was clearly identified, by the view of reliable emission estimation and anthropogenic impacts. Multiple satellite products, field survey, time varying biomass loading data and measured emission factors were adopted to better estimating BB emission and reducing the uncertainty. Social-economic analysis was added to assess the anthropogenic impacts on high emission variation quantitatively. Results showed that the cumulative BB emissions of OC, EC, CH4, NOX, NMVOC, SO2, NH3, CO, CO2, PM2.5 and PM10 during 2003-2014 were 1.6 × 104, 5.64 × 103, 3.57 × 104, 1.7 × 104, 5.44 × 104, 2.96 × 103, 6.77 × 103, 6.5 × 105, 1.15 × 107, 5.26 × 104 and 6.04 × 104 Gg, respectively. Crop straw burning (in-field and domestic) in northeast China plain (NEP), north China plain (NCP), northern arid and semiarid region and loess plateau were the key sources, averagely contributed 73% for all the pollutants emission. While domestic straw burning and firewood burning in Sichuan basin (SB), Yunnan-Guizhou plateau and southern China were main contributors, averagely accounting for 70% of all the pollutants emission. On regional level, high emissions were mainly found in SB, NCP and NEP. Temporally, high emissions were mainly found in crop sowing harvesting and heating seasons. From 2003 to 2014, the BB emission for different biomass species has changed significantly in different regions. High emission has gradually moved from SB to NCP and NEP. Firewood burning and domestic straw burning emission decreased by 47% and 14% in SB, respectively. In-field straw burning emission increased by 52% and 231% in NCP and NEP respectively and domestic straw burning emission increased by 62% in NEP. Emissions from heating season have decreased while emissions in corn harvest season were continuously increased. Analysis of Environmental kuznets curve, agricultural productivity level, human burning habits, rural energy structure and local control policies revealed the internal human driving strength of the variation for BB emission. The unbalanced development of social economy and the policy bias were primary drivers of limiting the BB management. BB emission will alleviate in NCP and aggravate in NEP. For the further emission reduction, effective measures for corn sources management, straw returning and rural energy utilization should be systematically considered. This research provides a clear evidence for the multi-year variation pattern of BB emissions, which is critical for pollution prediction, air quality modeling and targeted mitigation strategies for the key regions of China.

After releasing the Air Pollution Prevention Control and Action Plan (APPC) in China since 2013, the role of source emission control strategies and meteorological conditions on the reduction of air pollutants has received wide attention. Using an Aethalometer (AE31), equivalent black carbon (eBC) was monitored for 5.5-year after the APPC at Wuhan, a megacity in Central China, to identify its levels, sources, and variations trends. eBC varied in the range of 0.03–12.3 μg m−3, with the highest and lowest values in January (1.98 ± 1.70 μg m−3) and July (0.87 ± 0.61 μg m−3), respectively. The Kolmogorov-Zurbenk (KZ) filter and multiple-linear-regression were adopted to isolate the impacts of source emission control strategies and meteorological conditions on eBC variation. A long-term linear trend showed that emission-related reduction (7.79% yr−1) rather than meteorology-related reduction (4.51% yr−1) dominated the decreasing of eBC in the past years. Combining the KZ filter and Aethalometer model, the trends of eBC from fossil fuel combustion (eBCff) and biomass burning (eBCbb) were calculated. eBCbb and eBCff both showed decreasing trends with the reduction rates of 7.78% yr−1 and 7.76% yr−1, respectively. Backward trajectory analysis indicated that the air masses transported to the observational site from different regions in China all showed decreasing trend (1.64–18.7% yr−1) for eBC due to both the reduction from eBCbb (5.74–16.0% yr−1) and eBCff (7.38–19.7% yr−1), suggesting the positive role of pollution control measures in migrating air pollution across China.

Wuhan was the first city to adopt the lockdown measures to prevent COVID-19 spreading, which improved the air quality accordingly. This study investigated the variations in chemical compositions, source contributions, and regional transport of fine particles (PM2.5) during January 23–February 22 of 2020, compared with the same period in 2019. The average mass concentration of PM2.5 decreased from 72.9 μg m−3 (2019) to 45.9 μg m−3 (2020), by 27.0 μg m−3. It was predominantly contributed by the emission reduction (92.0%), retrieved from a random forest tree approach. The main chemical species of PM2.5 all decreased with the reductions ranging from 0.85 μg m−3 (chloride) to 9.86 μg m−3 (nitrate) (p, Graphical abstract Unlabelled Image, Highlights • Differences in PM2.5 chemical species and sources since lockdown were reported. • Primary emission reduced while secondary formation enhanced since lockdown. • Emission reduction dominated the improvement of air quality in Wuhan during lockdown.

16α-[18F]Fluoroestradiol ([18F]FES) is the most successful estrogen receptor (ER) targeting radiopharmaceutical to date. [18F]FES has been extensively used for positron emission tomography (PET) to assess the ER expression in breast cancer and to monitor the response of breast cancer to antiestrogen therapy. To address local investigator needs for [18F]FES-PET, we sought to adapt established literature methods to our in-house multi-purpose 18F-radiosynthesis module for [18F]FES production. Here we describe facile fully automated radiosynthesis and quality control (QC) of [18F]FES using our home-built automated multi-purpose 18F-radiosynthesis module. [18F]FES was produced via two-step-one-pot synthesis using cyclic sulfate precursor, and purified by semi-preparative reversed-phase (RP) high performance liquid chromatography (HPLC) with a C18 column followed by solid-phase extraction (SPE) with a C18 Plus Sep-Pak cartridge trap/release formulation. The overall synthesis time was 75–80 min, and the radiochemical yield was 30–35% decay corrected to end of bombardment (EOB), based on H[18F]F. The radiochemical purity was >99%, and the molar activity (Am) was 182–470 GBq/μmol at EOB. The [18F]FES dose meets all QC criteria for clinical use, and is suitable for clinical PET study of breast cancer.

Rubber under-ballast mats (UBM) commonly used in metro traffic in China are applied in high-speed railway ballastless tracks as the isolation layer to improve the operating conditions of high-speed trains. Due to the different operating conditions between the high-speed railway and the metro traffic, the rubber UBM, used as the isolation layer in ballastless tracks, needs to be investigated furtherly. In this paper, a finite element analysis of the China Railway Track System (CRTS) III ballastless track was initially carried out, and the stress state and distribution of the rubber UBM used as the isolation layer were obtained at the service condition. Furthermore, the static, dynamic and fatigue tests of the rubber UBM samples were designed and carried out based on the analysis results. The main conclusions are as follows: under normal service conditions, the stress level of the rubber UBM is low, and it can be considered that the rubber UBM is still in the stage of linear elasticity. The material properties of the rubber UBM can be characterized by the equivalent elastic modulus, which has been determined to be 0.6 MPa by the experimental research. Furthermore, the dynamic characteristic of the rubber isolation layer exhibits a hysteresis phenomenon. The equivalent dynamic stiffness is larger than the equivalent static stiffness due to the viscoelastic characteristics of rubber material. The rubber UBM has large internal friction, high energy absorption rate and good damping performance characterized by its large loss factor. In addition, following the application of 3,000,000 repeated load, which is 1.5 times of a train axle load, the equivalent static stiffness only changes by 2%, indicating that the rubber UBM used as an isolation layer can maintain good mechanical performance under repeated loading. As such, the appropriate selection of rubber UBMs for the isolation layer in ballastless tracks can be made following the analysis and investigation of its performance characteristics.

O-(2-[18F]Fluoroethyl)- l -tyrosine ([18F]FET) has become one of the most successful amino acid tracers for human brain tumor imaging with positron emission tomography (PET). Facile fully automated radiosynthesis and quality control (QC) of [18F]FET using our home-built automated multi-purpose 18F-radiosynthesis module are described. [18F]FET was produced in 75–80 min overall synthesis time with 20–25% radiochemical yield decay corrected to end of bombardment (EOB), based on H[18F]F. The radiochemical and enantiomeric purities were >99%, and the molar activity (Am) was 189–411 GBq/μmol at EOB. The [18F]FET dose meets all QC criteria for clinical use, and is suitable for clinical PET study of brain tumor.

We studied the dynamic properties of the blood oxygenation level-dependent (BOLD) time series of patients diagnosed with schizophrenia both at resting state and during working memory tasks, by computing a key measure from complexity science, the Hurst exponent (H), using Adaptive Fractal Analysis (AFA). 44 participants meeting the DSM-IV criteria for schizophrenia and 77 healthy controls underwent fMRI scanning at 3.0 T at resting state and during Paired associate Memory Task and Spatial Working Memory Task. Mean H for all the 116 brain regions extracted from Anatomical Automatic Labeling (AAL) template as well as the whole brain were generated and analyzed for each subject based on voxel by voxel time series. At resting state, 103 of 116 brain regions showed significantly reduced H, suggesting overwhelmingly less persistent spontaneous brain activity in patients with schizophrenia at whole brain level and region level. While performing working memory task, only prefrontal cortex (PFC), anterior cingulate cortex (ACC) presented significantly lower H. Either resting state or working memory tasks, H of healthy controls showed wide variation from region to region, while patients with schizophrenia were the opposite. The result provides evidence that brain activity of schizophrenia is associated with weaker persistence and more randomness in signal patterns compared to healthy controls at resting state; PFC and ACC are critical area for working memory; schizophrenia is characterized by limited resource allocation capability.

Aerosol acidity affects the chemical transformation of aerosols and subsequent haze formation. High resolution (1-h) observation of water-soluble inorganic ions in fine particles, gaseous pollutants, and meteorological parameters was conducted from September 2015 to August 2016 at Wuhan, a megacity of Central China with high relative humidity and ambient temperature, compared with north Chinese cities. By adopting thermodynamic model ISOROPPIA-II, the aerosol acidity for different time scales, pollution episodes, and air mass directions was calculated. Aerosols in Wuhan were moderate acidic, with pH averaged as 3.30 ± 0.49. The aerosol acidity was higher in July (pH as 2.64 ± 0.31), September (pH as 2.75 ± 0.30) and August (pH as 2.79 ± 0.29), and lower in January (pH as 3.77 ± 0.28) and March (pH as 3.70 ± 0.16). It decreased with the air pollution increasing, with the pH values of 3.07 ± 0.45, 3.63 ± 0.27 and 3.84 ± 0.22 for clean, transition and polluted episodes, respectively. The air masses in Wuhan transported from North China exhibited higher aerosol acidity, with pH averaged as 3.17–3.22. The unique environmental and meteorological conditions (high humidity, annual averaged RH as 0.74 ± 0.13) lead to excess ammonium (on average of 6.06 ± 4.51 μg m−3) and abundant aerosol water content (AWC, on average of 71.0 ± 82.8 μg m−3) in Wuhan, which can explain the lower PM2.5 acidity in Wuhan than other megacities of China. At lower AWC level (less than ~ 15 μg m−3), the particle pH showed a decreasing trend with AWC increased. When the AWC continuous increased from ~ 15 to ~ 380 μg m−3, there was an obvious increase of particle pH. Then no significant growth of pH was found when AWC was higher than ~ 380 μg m−3. With atmospheric RH increasing, the aerosol pH exhibited decreasing trend firstly and then increased, with the turning point RH as about 0.48. There was a logarithmic growth of aerosol pH with total NHx (NH3 + NH4+) increasing. From the fitted logarithmic curve, the aerosol pH of Wuhan was at the range of pH rapid growth stage with NHx increasing, indicating that the control of ammonia emission in Wuhan could be an effective way to reduce the aerosol pH and further mitigate air pollution. This paper firstly obtained the aerosol acidity properties at a megacity under abundant ammonium and high humidity with high time-resolution, which is an important supplementary for the current aerosol acidity research around the world.

Under great efforts in fighting against serious haze problem of China since 2013, decreasing of air pollutants especially for fine particles (PM2.5) has been revealed for several key regions. This study tried to answer whether the reduction of PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) was coincident with PM2.5 because of long-term pollution control measures (PCM), and to assess source-oriented health risks associated with inhalation exposure to PAHs. Field measurements were carried out before and after the publishing of local air pollution protection plan for Nanjing, a mega-city in east China. Results indicated that the air quality was substantially improving, with a significant reduction in annual average PM2.5 by 34%, and moreover, PM2.5-bound PAHs significantly reduced by 63% (p

China's 30-year economic boom has created a unique social and economic market for commercial sex, as well as for a workforce of migrant women from rural China. This qualitative study explores the impact of the rapidly changing social and economic environment on migration patterns, knowledge of sexually transmitted infections (STIs), STI risk behaviours and health beliefs among female streetwalkers in Shanghai. Qualitative data were collected in 2010 through semi-structured in-depth interviews with 16 streetwalkers to characterise their migration passages, sexual health and behaviours, and peer networks. Many streetwalkers reported histories of childhood impoverishment, of family or partner violence or trauma, of migration consistent with the timeline and routes of economic development and of a scarcity in health, social or economic support. Their knowledge of the prevention and treatment of HIV and STIs was limited. They had little bargaining power on condom use and the majority resorted to vaginal douching and self-management with antibiotics as preventative measures. The study identifies streetwalkers' perspectives on the changing environment, their options and actions and, finally, HIV/STI risks that were unique to this hidden population.

P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a specific P2X4 receptor antagonist, as a scaffold. 5-(3-Hydroxyphenyl)-1-[11C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[11C]Me-5-BDBD analog, [11C]9) and 5-(3-Bromophenyl)-1-[11C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[11C]Me-5-BDBD, [11C]8c) were prepared from their corresponding desmethylated precursors with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 30-50% decay corrected radiochemical yields with 370-1110GBq/µmol specific activity at EOB. 5-(3-[18F]Fluorophenyl)-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one ([18F]F-5-BDBD, [18F]5a) and 5-(3-(2-[18F]fluoroethoxy)phenyl)-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one ([18F]FE-5-BDBD, [18F]11) were prepared from their corresponding nitro- and tosylated precursors by nucleophilic substitution with K[18F]F/Kryptofix 2.2.2 and isolated by HPLC-SPE in 5-25% decay corrected radiochemical yields with 111-740GBq/µmol specific activity at EOB. The preliminary biological evaluation of radiolabeled 5-BDBD analogs indicated these new radioligands have similar biological activity with their parent compound 5-BDBD.

The reference standards 4a-b, 6a-b, 7a-c, and desmethylated precursors 9a-b, 10a-b, 8a-c were synthesized from 4-methoxyaniline, ethyl 2-chloro-acetoacetate and substituted benzene-1,2-diamines with 3, 5, 6 steps in 61-67%, 34-41%, 23-31%, and with 4, 6, 7 steps in 49-57%, 28-35%, 20-27% overall chemical yield, respectively. The target tracers [(11)C]4a-b, [(11)C]6a-b, [(11)C]7a-c were synthesized from their corresponding precursors with [(11)C]CH3OTf through O-[(11)C]methylation and isolated by simplified SPE in 40-60% decay corrected radiochemical yields at EOB, with 185-370 GBq/μmol specific activity at EOS.

Seven cases of avian influenza A H7N9 virus infection were reported from February to April 2017 in Changsha City. Viral genome was acquired by RT-PCR, aligned with other H7N9 viruses using Clustal W, and phylogenetic trees were constructed using the neighbor-joining method. Our results showed the representativeness of H7N9 virus infections in Middle Yangtze River City. The hemagglutinin segment contained Thr160Ala, Gly186Val and Gln226Leu substitutions, which are associated with increased binding affinity in humans. Phylogenetic analysis indicated that H7N9 viruses had an avian origin, and belonged to the Yangtze River Delta lineage. The proportion of PB2 Ala588Val substitutions in viruses revealed a significantly increasing in recent years, from 0.8 % (1 of 128 cases) to 84.9 % (275 of 324 cases). The data indicate that H7N9 viruses may be more capable of infecting mammals, even though they are still considered low pathogenic avian influenza virus. Hence, the prevalence and genetic evolution of this virus should be closely monitored to prevent more severe human pandemics.

N -Desmethyl-loperamide and loperamide were synthesized from α,α-diphenyl-γ-butyrolactone and 4-(4-chlorophenyl)-4-hydroxypiperidine in five and four steps with 8% and 16% overall yield, respectively. The amide precursor was synthesized from 4-bromo-2,2-diphenylbutyronitrile and 4-(4-chlorophenyl)-4-hydroxypiperidine in 2 steps with 21–57% overall yield. [ 11 C] N -Desmethyl-loperamide and [ 11 C]loperamide were prepared from their corresponding amide precursor and N -desmethyl-loperamide with [ 11 C]CH 3 OTf through N -[ 11 C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20–30% and 10–15% radiochemical yields, respectively, based on [ 11 C]CO 2 and decay corrected to end of bombardment (EOB), with 370–740 GBq/μmol specific activity at EOB.

The reference standard MK-1064 {5″-chloro-N-((5,6-dimethoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} was synthesized from methyl 2-chloro-5-iodonicotinate and 5-(chloropyridin-3-yl)boronic acid in 4 steps with 33% overall chemical yield. The precursor desmethyl-MK-1064 {5″-chloro-N-((5-hydroxy-6-methoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} for radiolabeling was synthesized from 2-bromopyridin-3-ol and 5″-chloro-[2,2':5',3″-terpyridine]-3'-carboxylic acid in 6 steps with 17% overall chemical yield. The target tracer [(11)C]MK-1064 {5″-chloro-N-((5-[(11)C]methoxy-6-methoxypyridin-2-yl)methyl)-[2,2':5',3″-terpyridine]-3'-carboxamide} was prepared by O-[(11)C]methylation of its corresponding precursor desmethyl-MK-1064 with [(11)C]CH3OTf under basic condition and isolated by a simplified solid-phase extraction (SPE) method in 50-60% decay corrected radiochemical yields based on [(11)C]CO2 at end of bombardment (EOB). The overall synthesis time from EOB was 23min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185-555GBq/μmol.

Little is known about the acceptance and actual uptake of pre-exposure prophylaxis (PrEP) and associated factors in men who have sex with men (MSM) in China. This study is the baseline survey of an intervention study designed to evaluate the effectiveness of tenofovirdisoproxil fumarate (TDF) on a daily use for human immunodeficiency virus (HIV) prevention among MSM in Shanghai, China. From October 2012 to December 2013, a total of 1,033 MSM in Shanghai were recruited by local district Centers for Disease Control and Prevention (CDC) and a MSM community-based non-governmental organization (NGO). Among them, 197 (19.1%) participants expressed willingness to use the TDF group at baseline survey, but only 26 (2.5%) participated in the TDF group and took TDF one tablet a day. Higher willingness to use PrEP was associated with being 45 years or older, non-local residents, having more male sex partners in the past 6 months and not using condom at last anal sex with man. Acutal uptake of PrEP was associated with having ≥ 11 male sex partners in lifetime and reporting no female sex partners in lifetime. Reasons for not participating in TDF group among those who expressed willingness to use PrEP at baseline survey included loss of contact, ineligiblity because of abnormal results for liver or renal function tests, change of mind, and HIV seroconversion before uptake of PrEP. Our findings suggest that promotion of PrEP in MSM remains challenging at current circumstancein China. Future research is needed to solicit effective education and intervention programs to promote acceptance of PrEP among Chinese MSM.

Steroid sulfatase (STS) catalyzes the hydrolysis of steroid sulfates to estrones, the main source of estrogens in tumors. Carbonic anhydrase II (CAII) is highly expressed in red blood cells through a coordination of the monoanionic form of the sulfamate moiety to the zinc atom in the enzyme active site, and CAII is highly expressed in several tumors. 2-Methoxy-3,17β-O,O-bis(sulfamoyl)estradiol (5) is a dual-function STS-CAII inhibitor inhibited STS with 39 nM IC(50) value selectively over CAII with 379 nM IC(50) value. This compound exhibited potent antiproferative activity with mean graph midpoint value of 87 nM in the NCI 60-cell-line panel, and antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model as well. The compound has been recently developed as a multitargeted anticancer agent. Both STS and CAII are over-expressed in cancers and have become attractive targets for cancer treatment and molecular imaging of cancer. Here we report the first design and synthesis of 2-[(11)C]methoxy-3,17β-O,O-bis(sulfamoyl)estradiol ([(11)C]5) as a new potential imaging agent for biomedical imaging technique positron emission tomography (PET) to image STS in cancers. The authentic standard 5 was synthesized from 17β-estradiol by published procedures in 5 steps with 40% overall chemical yield. The precursor 2-hydroxy-3,17β-O,O-bis(sulfamoyl)estradiol (14a) for radiolabeling was synthesized from 17β-estradiol in 10 steps with 5% overall chemical yield. The target tracer [(11)C]5 was prepared from the precursor 14a with [(11)C]CH(3)OTf through O-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) purification in 40-50% radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.

The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[(11)C]methoxyphenoxy)-2-methylpropanamide ([(11)C]8a), (S)-2-hydroxy-3-(2-[(11)C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([(11)C]8 e), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-[(11)C]methoxyphenoxy)-2-methylpropanamide ([(11)C]8c) and (S)-2-hydroxy-3-(4-[(11)C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([(11)C]8 g), were prepared by O-[(11)C]methylation of their corresponding precursors, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-hydroxyphenoxy)-2-methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methylpropanamide (9 c) and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9 d), with [(11)C]CH(3)OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5% (n = 5) radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5).

Background YKL-40 is a new biomarker with diagnostic value in many different cancers. Whether it may serve as a biomarker for hepatocellular carcinoma (HCC) is still unclear. This study aimed to examine the expression of YKL-40 in the serum and liver tissues of HCC patients and in HCC cell lines, in comparison with that in non-HCC liver disease patients and non-tumor hepatic cell lines, respectively. Methods Immunohistochemical staining was used to detect YKL-40 protein expression in liver biopsy specimens from 8 HCC patients. ELISA was used to assess the serum YKL-40 level in 90 HCC patients, 90 inactive HBsAg carrier (IHC) patients with normal liver functions, and 90 liver cirrhosis patients. Real-time PCR was used to determine the YKL-40 mRNA expression in three HCC cell lines and two non-tumor hepatic cell lines. Results Immunohistochemical staining of liver biopsy specimens from HCC patients showed that the YKL-40 protein expression in tumor tissue was higher than that in adjacent normal tissues. ELISA revealed that the YKL-40 serum level in the HCC group was significantly higher than that in the IHC group, but not significantly different from that in the cirrhosis group. Real-time PCR showed that YKL-40 mRNA levels in HCC cell lines were significantly higher than those in non-tumor hepatic cells. Conclusions YKL-40 is highly expressed in HCC at the molecular, cellular and tissue levels. However, it may not serve as a serum biomarker for HCC because measurement of the serum YKL-40 level cannot distinguish HCC from cirrhosis.

Purpose In studies where [11C]raclopride (RAC) positron emission tomography (PET) is used to assess changes in striatal dopamine, it is important to control for cognitive states, such as drug craving, that could alter dopamine levels. In cigarette smokers, transdermal nicotine patches (TNP) can control nicotine craving, but the effects of nicotine patches on RAC binding are unknown. Thus, we sought to determine the test-retest reliability of RAC binding in the presence of nicotine patches.

The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [(11)C]4a-c and [(11)C]8a-d, were prepared by O-[(11)C] methylation of their corresponding precursors using [(11)C]CH(3)OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 52 ± 2% (n = 5) and 57 ± 3% (n = 5) radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5). The IC(50) values to block COX-2 for known compounds celecoxib (4d), 4a and 4c were 40, 290 and 8 nM, respectively, and preliminary findings from in vitro biological assay indicated that the synthesized new compounds 4b and 8a-d display similar strong inhibitory effectiveness in the MDA-MB-435 human cancer cell line in comparison with the parent compound 4d. These results encourage further in vivo evaluation of carbon-11-labeled celecoxib derivatives as new potential PET radiotracers for imaging of COX-2 expression in cancer.

Anand A, Barkay G, Dzemidzic M, Albrecht D, Karne H, Zheng Q-H, Hutchins GD, Normandin MD, Yoder KK. Striatal dopamine transporter availability in unmedicated bipolar disorder. Bipolar Disord 2011: 13: 406–413. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Dopamine transmission abnormalities have been implicated in the etiology of bipolar disorder (BPD). However, there is a paucity of receptor imaging studies in BPD, and little information is available about the dopamine system in BPD. Reuptake of synaptic dopamine by the dopamine transporter (DAT) is the principal mechanism regulating dopamine neurotransmission, and is often used as a marker for presynaptic dopamine function. This positron emission tomography (PET) study investigated whether DAT availability differed between BPD and healthy control subjects. Methods: A total of 11 unmedicated BPD patients in either the euthymic or depressed phase and 13 closely matched healthy subjects underwent PET imaging with the DAT-selective radiotracer [11C]CFT and a structural magnetic resonance imaging (MRI) scan. Striatal binding potential (BPND) was estimated using the multilinear reference tissue model. Region of interest and analyses were conducted to test for differences in [11C]CFT BPND between groups. Results: Unmedicated BPD subjects had significantly lower DAT availability relative to healthy controls in bilateral dorsal caudate. Conclusions: The results of this study support the hypothesis that there are abnormalities in the dopaminergic system in BPD, and suggest that DAT availability may be related to the neuropathology of BPD. Future studies are needed to determine if DAT availability cycles with disease phase.