Immune checkpoint blockade therapy has been successful in treating some types of cancers but has not shown clinical benefits for treating leukemia 1 . This result suggests that leukemia exploits unique escape mechanisms. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukemia cells. It remains unknown whether these receptors can initiate immune-related primary signaling in tumor cells. Here we show that LILRB4, an ITIM-containing receptor and a monocytic leukemia marker, supports tumor cell infiltration into tissues and suppresses T cell activity via ApoE/LILRB4/SHP-2/uPAR/Arginase-1 signaling axis in acute myeloid leukemia (AML) cells. Blocking LILRB4 signaling using knockout and antagonistic antibody approaches impeded AML development. Thus, LILRB4 orchestrates tumor invasion pathways in monocytic leukemia cells by creating an immune-suppressive microenvironment. LILRB4 represents a compelling target for treatment of monocytic AML.

BackgroundHeavy fine particulate matter (PM2.5) air pollution occurs frequently in China. However, epidemiological research on the association between short-term exposure to PM2.5 pollution and respiratory disease morbidity is still limited. This study aimed to explore the association between PM2.5 pollution and hospital emergency room visits (ERV) for total and cause-specific respiratory diseases in urban areas in Beijing.MethodsDaily counts of respiratory ERV from Jan 1 to Dec 31, 2013, were obtained from ten general hospitals located in urban areas in Beijing. Concurrently, data on PM2.5 were collected from the Beijing Environmental Protection Bureau, including 17 ambient air quality monitoring stations. A generalized-additive model was used to explore the respiratory effects of PM2.5, after controlling for confounding variables. Subgroup analyses were also conducted by age and gender.ResultsA total of 92,464 respiratory emergency visits were recorded during the study period. The mean daily PM2.5 concentration was 102.1±73.6 μg/m3. Every 10 μg/m3 increase in PM2.5 concentration at lag0 was associated with an increase in ERV, as follows: 0.23% for total respiratory disease (95% confidence interval [CI]: 0.11%-0.34%), 0.19% for upper respiratory tract infection (URTI) (95%CI: 0.04%-0.35%), 0.34% for lower respiratory tract infection (LRTI) (95%CI: 0.14%-0.53%) and 1.46% for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (95%CI: 0.13%-2.79%). The strongest association was identified between AECOPD and PM2.5 concentration at lag0-3 (3.15%, 95%CI: 1.39%-4.91%). The estimated effects were robust after adjusting for SO2, O3, CO and NO2. Females and people 60 years of age and older demonstrated a higher risk of respiratory disease after PM2.5 exposure.ConclusionPM2.5 was significantly associated with respiratory ERV, particularly for URTI, LRTI and AECOPD in Beijing. The susceptibility to PM2.5 pollution varied by gender and age.

SARS-CoV-2 is a spherical, enveloped, single-stranded positive RNA virus with a diameter of 80 nm-160 nm and a genome size of 29.9 kb

Help-seeking is important to access appropriate care and improve mental health. However, individuals often delay or avoid seeking help for mental health problems. Interventions to improve help-seeking have been developed, but their effectiveness is unclear. A systematic review and meta-analysis were therefore conducted to examine the effectiveness of mental health related help-seeking interventions. Nine databases in English, German and Chinese were searched for randomised and non-randomised controlled trials. Effect sizes were calculated for attitudes, intentions and behaviours to seek formal, informal and self-help. Ninety-eight studies with 69 208 participants were included. Interventions yielded significant short-term benefits in terms of formal help-seeking, self-help, as well as mental health literacy and personal stigma. There were also positive long-term effects on formal help-seeking behaviours. The most common intervention types were strategies to increase mental health literacy, destigmatisation (both had positive short-term effects on formal help-seeking behaviours) as well as motivational enhancement (with positive long-term effects on formal help-seeking behaviours). Interventions improved formal help-seeking behaviours if delivered to people with or at risk of mental health problems, but not among children, adolescents or the general public. There was no evidence that interventions increased the use of informal help. Few studies were conducted in low- and middle-income countries (LMICs). This study provides evidence for the effectiveness of help-seeking interventions in terms of improving attitudes, intentions and behaviours to seek formal help for mental health problems among adults. Future research should develop effective interventions to improve informal help-seeking, for specific target groups and in LMICs settings.

BackgroundResearch on the relationship between metabolic syndrome (MetS), its components and eating speed is limited in China. The present study aimed to clarify the association between MetS, its components and eating speed in a Beijing adult population.MethodsThis cross-sectional study included 7972 adults who were 18–65 years old and who received health check-ups at the Beijing Physical Examination Center in 2016. Logistic regression was conducted to explore the associations between MetS, its components and eating speed.ResultsThe prevalence of MetS in this population was 24.65% (36.02% for males and 10.18% for females). Eating speed was significantly associated with a high risk for MetS, elevated blood pressure, and central obesity for both genders. Eating speed was associated with a high risk for elevated triglycerides and with a reduction in high-density lipoprotein in males, and eating speed was associated with a high risk for elevated fasting plasma glucose in females. Compared with slow eating speed, the multivariate-adjusted odds ratios of medium eating speed and fast eating speed for MetS were 1.65 (95% confidence interval 1.32–2.07) and 2.27 (95% confidence interval 1.80–2.86) for all subjects, 1.58 (95% confidence interval 1.21–2.07) and 2.21 (95% confidence interval 1.69–2.91) for males, and 1.75 (95% confidence interval 1.15–2.68) and 2.27 (95% confidence interval 1.46–3.53) for females, respectively.ConclusionsEating speed is positively associated with MetS and its components. Future recommendations aiming to prevent MetS and its components may focus on eating speed.Electronic supplementary materialThe online version of this article (10.1186/s12889-018-5784-z) contains supplementary material, which is available to authorized users.

ObjectiveLimited information is available regarding spatiotemporal variations of particles with median aerodynamic diameter < 2.5 μm (PM2.5) at high resolutions, and their relationships with meteorological factors in Beijing, China. This study aimed to detect spatiotemporal change patterns of PM2.5 from August 2013 to July 2014 in Beijing, and to assess the relationship between PM2.5 and meteorological factors.MethodsDaily and hourly PM2.5 data from the Beijing Environmental Protection Bureau (BJEPB) were analyzed separately. Ordinary kriging (OK) interpolation, time-series graphs, Spearman correlation coefficient and coefficient of divergence (COD) were used to describe the spatiotemporal variations of PM2.5. The Kruskal-Wallis H test, Bonferroni correction, and Mann-Whitney U test were used to assess differences in PM2.5 levels associated with spatial and temporal factors including season, region, daytime and day of week. Relationships between daily PM2.5 and meteorological variables were analyzed using the generalized additive mixed model (GAMM).ResultsAnnual mean and median of PM2.5 concentrations were 88.07 μg/m3 and 71.00 μg/m3, respectively, from August 2013 to July 2014. PM2.5 concentration was significantly higher in winter (P < 0.0083) and in the southern part of the city (P < 0.0167). Day to day variation of PM2.5 showed a long-term trend of fluctuations, with 2–6 peaks each month. PM2.5 concentration was significantly higher in the night than day (P < 0.0167). Meteorological factors were associated with daily PM2.5 concentration using the GAMM model (R 2 = 0.59, AIC = 7373.84).ConclusionPM2.5 pollution in Beijing shows strong spatiotemporal variations. Meteorological factors influence the PM2.5 concentration with certain patterns. Generally, prior day wind speed, sunlight hours and precipitation are negatively correlated with PM2.5, whereas relative humidity and air pressure three days earlier are positively correlated with PM2.5.

Sepia ink oligopeptide (SIO) is a tripeptide extracted from Sepia ink. To test the hypothesis that SIO inhibits prostate cancer by inducing apoptosis, the effects of SIO on the proliferation of three human prostate cancer cell lines were examined using a CCK-8 assay. SIO significantly inhibited the proliferation of DU-145, PC-3 and LNCaP cells in a time- and dose-dependent manner. Flow cytometry studies showed that exposing DU-145, PC-3 and LNCaP cells to 5, 10, or 15 mg/mL SIO for 24 h increased the percentage of the early-stage apoptotic cells from 11.84% to 38.26% (DU-145), 22.76% to 39.96% (PC-3) and 5.05% to 16.11% (LNCaP), respectively. In addition, typical morphologic changes were observed in the cells with acridine orange/ethidium bromide staining. SIO treatment induced strong S and G2/M phase cell cycle arrest in a dose-dependent manner in DU-145 and LNCaP. In contrast, SIO treatment induced strong Sub G1 and G0/G1 phase cell cycle arrest in a dose-dependent manner in PC-3. SIO exposure for 24 h decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the apoptogenic protein Bax. Moreover, the Bax/Bcl-2expression ratio was increased. Concurrently, the expression of caspase-3 was upregulated. These data support our hypothesis that SIO has anticarcinogenic properties.

better organic active layer materials, such as those star materials of P3HT (2005 by Kim et al.), [2c] DR3TBDTT (2013 by Chen et al.), [2e] ITIC (2015 by Zhan et al.), [2f ] PM6 (2015 by Hou et al.), [2g] Y6 (2019 by Zou et al.), [2h] D18 (2018 by Ding et al.). [2i] Especially in 2019, the rapidly developing OSCs stepped into a new era of PCE exceeding 15% due to the emergence of a super-star acceptor Y6. [2g] As we all known that two determining factors for PCE of OSCs are the active layer materials and its morphology. Therefore, there have been main two approaches for higher performance, one is to get better molecules, and the latter one is to achieve better morphology. While we are always exploring more efficient active layer materials, the journey has been long and challenging. Therefore, it would be much easier to tune the morphology for better performance using some existing materials to achieve their best intrinsic performance. Up to now, tremendous efforts in tuning morphology have been made in the Y6 analogs-based OSCs, such as more suitable coating solvent, [3] solvent [4] or low boiling point solid additives, [5] post treatments of thermal or solvent annealing, [6] rendering the PCE over 18%. [7] In spite of the impressive PCE achieved, the continuously increasing performance of Y6 analogs-based OSCs indicates that the intrinsic best performance might not have been achieved.The above strategies of morphology regulation, such as more suitable coating solvent, solvent or low boiling point solid additives, post treatments of thermal or solvent annealing, can adapt a favorable morphology upon the quick solvent volatile process or post-treatment process by controlling the crystallization and phase separation process. In addition, a multicomponent strategy, which introduces a guest component into the host systems in OSCs, has been proved as an effective way to further improve the device performance recently. [7a,8] The application of a multicomponent strategy can break the limits of light absorption of the existing host systems, optimize the morphology and energy level alignment for the active layer, and thus improve the efficiency of OSC devices. Thus, a feasible multicomponent strategy based on a state-of-the-art system is expected to guide superior device performances. In the past decade, the numerous oligomer-like donors-based organic A wide bandgap oligomer-like donor CNS-6-8 is synthesized and incorporated into the host PM6:Y6:PC 71 BM system to tune the morphology of the active layer for better device performance. Due to the good miscibility of CNS-6-8 with both host donor (PM6) and acceptors (Y6 and PC 71 BM), an optimized morphology is achieved with the appropriate phase separation size and enhanced crystallinity, which ultimately leads to more efficient exciton dissociation, charge transport, and lower nonradiative energy loss. As a result, the quaternary device achieves an improved efficiency of 18.07%, with a simultaneously increased open circuit voltage of 0.868 V, fill factor of 78....