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Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer–immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer–immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies. Lipids regulate cancer immunity cycle by affecting antigen presentation, T-cell priming and activation and T-cell killing of tumor, which in turn promotes immune surveillance escape. [Display omitted] [ABSTRACT FROM AUTHOR]

Compared with a disordered network, the ordered framework is more beneficial to improving the multifunctional properties (including thermal, electrical, and mechanical properties) of epoxy-based composites. However, current methods for building aligned structures are both energy and time-consuming on account of the tedious and lengthy lyophilization process. Herein, a new strategy is proposed to obtain low-density graphene aerogels (GAs) with long-range oriented structures through a lyophilization-free processes. Due to the minimum thermal boundary resistance, the prepared aligned graphene/epoxy composite exhibits an ultrahigh thermal conductivity of ∼11.6 W/(m·K) at a graphene content of 1.84 vol%, i.e., an enhancement efficiency of 3640% per 1 vol%. In addition, the compressive strength of the composite is increased by 2.6 times compared to epoxy (from 0.29 MPa to 0.76 MPa). Because the composite shows a modulus as low as 0.5–1.0 MPa, it has excellent deformability and compression performance. Moreover, the obtained 3-mm-thick composite achieves an electromagnetic interference shielding effectiveness (EMI SE) of 40 dB due to the interconnected graphene network structure, which meets the requirements of commercial EMI shielding applications. Hence, this strategy can be used to synthesize aligned graphene/epoxy composites with excellent multifunctional performances, which can be simultaneously used as elastic thermal interface materials (TIMs) and EMI shielding materials in the fields of advanced electronic packaging. [Display omitted] • Aligned graphene aerogel (GA) was fabricated by a lyophilization-free approach. • The compressive strength of the composite is increased by 2.6 times compared to epoxy (0.29 MPa to 0.76 MPa) and the composite shows a modulus as low as 0.48–1.0 MPa, exhibiting excellent deformability and compression performance. • The vertical pathways and high-quality give composite an ultrahigh thermal conductivity (∼11.6 W/m·K) with ultralow graphene loading (1.84 vol%), i.e., an enhancement efficiency of 3640% per 1 vol%. • The obtained 3-mm-thick composite achieves an electromagnetic interference shielding effectiveness of 40 dB due to the interconnected network structure. [ABSTRACT FROM AUTHOR]

Substantial evidence has linked short-term exposure to ambient fine particulate matter (PM 2.5 ) with increased cardiovascular mortality, however, the specific chemical constituent and emission source responsible for this effect remained largely unclear. A time series Poisson model was employed to quantify the association of cardiovascular mortality with two sets of shipping pollution emission: nickel (Ni), vanadium (V) (the indices of shipping emission) and estimated shipping emission using a source apportionment approach in Guangzhou, China in 2014. We observed that Ni, V, and estimated shipping emission in PM 2.5 were associated with increased cardiovascular mortality, an inter-quartile range (IQR) increase in lag 2 Ni was associated with 4.60% (95% CI: 0.14%, 9.26%) increase in overall cardiovascular mortality, and 13.35% (95% CI: 5.54%, 21.75%) increase in cerebrovascular mortality; each IQR increase of lag 1 V was correlated with 6.01% (95% CI: 1.83%, 10.37%) increase in overall cardiovascular mortality, and 11.02% (95% CI: 3.15%, 19.49%) increase in cerebrovascular mortality; and each IQR increase in lag 1 shipping emission was associated with 5.55% (95% CI: 0.78%, 10.54%) increase in overall cardiovascular mortality, and 10.39% (95% CI: 1.43%, 20.14%) increase in cerebrovascular mortality. The results remained robust to adjustment for PM 2.5 mass and gaseous air pollutants. This study suggests that shipping emission is an important detrimental factor of cardiovascular mortality, and should be emphasized in air pollution control and management in order to protect the public health in Guangzhou, China. [ABSTRACT FROM AUTHOR]

While increasing evidence suggested that PM 2.5 is the most harmful fraction of the particle pollutants, the health effects of coarse particles (PM 10–2.5 ) have been inconclusive, especially on cerebrovascular diseases, we thus evaluated the effects of PM 10 , PM 2.5 , and PM 10–2.5 on stroke mortality in six Chinese subtropical cities using generalized additive models. We also conducted random-effects meta-analyses to estimate the overall effects across the six cities. We found that PM 10 , PM 2.5 , and PM 10-2.5 were significantly associated with stroke mortality. Each 10 μg/m 3 increase of PM 10 , PM 2.5 and PM 10-2.5 (lag03) was associated with an increase of 1.88% (95% CI: 1.37%, 2.39%), 3.07% (95% CI: 2.35%, 3.79%), and 5.72% (95% CI: 3.82%, 7.65%) in overall stroke mortality. Using the World Health Organization's guideline as reference concentration, we estimated that 3.21% (95% CI: 1.65%, 3.01%) of stroke mortality (corresponding to 1743 stroke mortalities, 95% CI: 896, 1633) were attributed to PM 10 , 5.57% (95% CI: 0.50%, 1.23%) stroke mortality (3019, 95% CI: 2286, 3777) were attributed to PM 2.5 , and 2.02% (95% CI: 1.85%, 3.08%) of stroke mortality (1097, 95% CI: 1005, 1673) could be attributed to PM 10-2.5 . Our analysis indicates that both PM 2.5 and PM 10-2.5 are important risk factors of stroke mortality and should be considered in the prevention and control of stroke in the study area. [ABSTRACT FROM AUTHOR]

Until menopause, women have a lower propensity to develop metabolic diseases than men, suggestive of a protective role for sex hormones. Although a functional synergy between central actions of estrogens and leptin has been demonstrated to protect against metabolic disturbances, the underlying cellular and molecular mechanisms mediating this crosstalk have remained elusive. By using a series of embryonic, adult-onset, and tissue/cell-specific loss-of-function mouse models, we document an unprecedented role of hypothalamic Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 (Cited1) in mediating estradiol (E2)-dependent leptin actions that control feeding specifically in pro-opiomelanocortin (Pomc) neurons. We reveal that within arcuate Pomc neurons, Cited1 drives leptin's anorectic effects by acting as a co-factor converging E2 and leptin signaling via direct Cited1-ERα-Stat3 interactions. Together, these results provide new insights on how melanocortin neurons integrate endocrine inputs from gonadal and adipose axes via Cited1, thereby contributing to the sexual dimorphism in diet-induced obesity. [Display omitted] • Global and hypothalamic Cited1 loss exacerbates diet-induced obesity in female mice • Cited1 is highly enriched in estradiol-sensitive melanocortin neurons • Hypothalamic Cited1 molecularly links the effects of E2 and leptin on food intake • Cited1 in PomcARC neurons acts as a downstream co-factor for E2-leptin signaling Estradiol regulates energy homeostasis by altering feeding behavior, but how this sex hormone converges with the melanocortin system is not fully understood. Here, González-García et al. discover that Cited1 acts as a crucial hypothalamic co-factor mediating the anti-obesity effects of estradiol through potentiation of leptin's anorectic actions. This neuroendocrine mechanism represents a mode by which melanocortin neurons integrate energy stores with reproductive signals for metabolic adaptation in diet-induced obesity. [ABSTRACT FROM AUTHOR]

Though significant associations between particulate matter (PM) air pollution and cardiovascular diseases have been widely reported, it remains unclear what characteristics, such as particle size and chemical constituents, may be responsible for the effects. A time-series model was applied to examine the cardiovascular effects of particle size (for the period of 2009–2011) and chemical constituents (2007–2010) in Guangzhou, we controlled for potential confounders in the model, such as time trends, day of the week, public holidays, meteorological factors and influenza epidemic. We found significant associations of cardiovascular mortality with PM 10 , PM 2.5 and PM 1 ; the excess risk (ER) was 6.10% (95% CI: 1.76%, 10.64%), 6.11% (95% CI: 1.76%, 10.64%) and 6.48% (95% CI: 2.10%, 11.06%) for per IQR increase in PM 10 , PM 2.5 and PM 1 at moving averages for the current day and the previous 3 days (lag 03 ), respectively. We did not find significant effects of PM 2.5-10 and PM 1-2.5 . For PM 2.5 constituents, we found that organic carbon, elemental carbon, sulfate, nitrate and ammonium were significantly associated with cardiovascular mortality, the corresponding ER for an IQR concentration increase at lag 03 was 1.13% (95% CI: 0.10%, 2.17%), 2.77% (95% CI: 0.72%, 4.86%), 2.21% (95% CI: 1.05%, 3.38%), 1.98% (95% CI: 0.54%, 3.44%), and 3.38% (95% CI: 1.56%, 5.23%), respectively. These results were robust to adjustment of other air pollutants and they remained consistent in various sensitivity analyses by changing model parameters. Our study suggests that PM 1 and constituents from combustion and secondary aerosols might be important characteristics of PM pollution associated with cardiovascular mortality in Guangzhou. [ABSTRACT FROM AUTHOR]

The short-term effects of ambient temperature on mortality have been widely investigated. However, the epidemiological evidence on the long-term effects of temperature on mortality is rare. In present study, we conducted a nationwide quasi-experimental design, which based on a variant of difference-in-differences (DID) approach, to examine the association between long-term exposure to ambient temperature and mortality risk in China, and to analyze the effect modification of population characteristics and socioeconomic status. Data on mortality were collected from 364 communities across China during 2006–2017, and environmental data were obtained for the same period. We estimated a 2.93 % (95 % CI: 2.68 %, 3.18 %) increase in mortality risk per 1 °C decreases in annual temperature, the greater effects were observed on respiratory diseases (5.16 %, 95 % CI: 4.53 %, 5.79 %) than cardiovascular diseases (3.43 %, 95 % CI: 3.06 %, 3.80 %), and on younger people (4.21 %, 95 % CI: 3.73 %, 4.68 %) than the elderly (2.36 %, 95 % CI: 2.06 %, 2.65 %). In seasonal analysis, per 1 °C decreases in average temperature was associated with 1.55 % (95 % CI: 1.23 %, 1.87 %), −0.53 % (95 % CI: −0.89 %, −0.16 %), 2.88 % (95 % CI: 2.45 %, 3.31 %) and 4.21 % (95 % CI: 3.98 %, 4.43 %) mortality change in spring, summer, autumn and winter, respectively. The effects of long-term temperature on total mortality were more pronounced among the communities with low urbanization, low education attainment, and low GDP per capita. In total, the decrease of average temperature in summer decreased mortality risk, while increased mortality risk in other seasons, and the associations were modified by demographic characteristics and socioeconomic status. Our findings suggest that populations with disadvantaged characteristics and socioeconomic status are vulnerable to long-term exposure of temperature, and targeted policies should be formulated to strengthen the response to the health threats of temperature exposure. [Display omitted] • Long-term effect of temperature on health was assessed by a quasi-experiment study. • The decreased summer temperature was associated with decreased mortality risks. • The average winter temperature is negatively correlated with mortality risks. • People with respiratory diseases and the young are more susceptible to temperature. • The temperature risk are more prominent in areas with low socioeconomic status. [ABSTRACT FROM AUTHOR]

Insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) can provide safe and effective control of some major pests, but evolution of resistance by pests diminishes these benefits. Better understanding of the genetics and mechanisms of resistance is urgently needed to improve methods for monitoring, managing, and countering pest resistance to Bt toxins. Here we used CRISPR-mediated knockouts to evaluate the role of five genes encoding candidate Bt toxin receptors in Spodoptera exigua (beet armyworm), a devastating pest of vegetable, field and flower crops. We compared susceptibility to Bt toxins Cry1Ac, Cry1Fa, and Cry1Ca between the parent susceptible strain and each of five strains homozygous for the knockout of one of the candidate genes (SeAPN1, SeCad1, SeABCC1, SeABCC2 or SeABCC3). The results from the 15 pairwise comparisons reveal that SeABCC2 has a major role and SeCad1 a minor role in mediating toxicity of Cry1Ac and Cry1Fa. SeABCC2 also has a minor role in toxicity of Cry1Ca. In addition, the results imply little or no role for the other three candidate receptors in toxicity of Cry1Ac or Cry1Fa; or for the four candidate receptors other than SeABCC2 in toxicity of Cry1Ca. Image 1 • CRISPR-mediated knockouts used to evaluate the role of five genes encoding candidate Bt receptors in Spodoptera exigua. • SeABCC2 has a major role and SeCad1 a minor role in mediating toxicity of Cry1Ac and Cry1Fa. • SeABCC2 also has a minor role in toxicity of Cry1Ca. [ABSTRACT FROM AUTHOR]

The small naphthoquinone molecules modified reduced-graphene oxide with chemical absorption of polysulfides based on the abundant keto functional groups, leads to the significantly improved cycling performance for Li-S batteries. • Organic NQ molecule-decorated rGO was applied as host for Li-S batteries. • Chemical absorption of polysulfides/sulfur can be achieved. • The S/NQ-rGO electrode delivers outstanding electrochemical performance. Graphene-based materials are explored to be promising candidates for lithium-sulfur batteries based on their unique two-dimensional geometry structure and excellent electric conductivity. However, the inferior ability to confine polysulfides results in quick capacity fading and poor cycling stability of graphene-related electrode materials. Herein, small organic naphthoquinone (NQ) molecules with redox active properties are introduced to the reduced graphene oxide (rGO) as an advanced sulfur host to significantly prolong cycle life for Li-S batteries. The effective combination between small NQ organic molecules and rGO successfully leads to the conductive composite network, where the keto groups from NQ play the key role in promoting the chemical absorption of polysulfides/sulfur by forming the S O interaction. Notably, the NQ-rGO composite shows superior lithium polysulfides absorptivity with a sulfur loading of 65.3%. The S/NQ-rGO displays outstanding electrochemical performances for lithium-sulfur batteries, in terms of large reversible capacities with excellent cycling stability (936 mAh g−1 after 200 cycles at 0.1C and 670 mAh g−1 after 500 cycles at 1C) and superior rate ability (525 mAh g−1 at 5C). [ABSTRACT FROM AUTHOR]

Background & Aims We aimed to identify long noncoding RNAs (lncRNAs) that are up-regulated in gastric cancer tissues from patients and study their function in gastric tumor metastasis. Methods We collected gastric tumor and nontumor tissues from patients in China and analyzed levels of lncRNAs by microarray analysis, proteins by immunohistochemistry, and RNAs by quantitative reverse-transcription polymerase chain reaction; we compared these with survival times of patients and tumor progression. RNA levels were knocked down or knocked out in BGC-823, SGC-7901, and MKN45 cell lines using small interfering or short hairpin RNAs or clustered regularly interspaced short palindromic repeats (ie, CRISPR)/CRISPR associated protein 9 (ie, Cas9) vectors. Genes were overexpressed from transfected plasmids in HGC-27 cells. Cells were analyzed by Northern blot and immunoblot, polysome profiling assay, and cell invasion assay. Cells were injected into the tail veins or spleens of nude mice or SCID mice; lung and liver tissues were collected, and metastases were counted. lncRNAs were cloned by using rapid amplification of complementary DNA ends. Their interactions with other genes were determined by RNA pulldown and mapping assays. Results In microarray analyses, we identified 151 lncRNAs expressed at significantly higher levels in gastric tumor vs nontumor tissues. Levels of an lncRNA that we called gastric cancer metastasis associated long noncoding RNA (GMAN) were increased in gastric tumor tissues, compared with nontumor tissues; its up-regulation was associated with tumor metastasis and shorter survival times of patients. The GMAN gene overlaps with the ephrin A1 gene (EFNA1) and was highly expressed in BGC-823 and MKN45 cells. Knockdown of GMAN in these cells did not affect proliferation, colony formation, or adhesion but did reduce their invasive activity in Transwell assays. Ectopic expression of GMAN increased the invasive activity of HGC-27 cells. BGC-823 and MKN45 cells with knockdown of GMAN formed fewer metastases after injection into tail veins of nude mice. Knockdown or knockout of GMAN also reduced levels of ephrin A1 protein in cells. We found that GMAN promoted translation of ephrin A1 messenger RNA into protein by binding to the antisense GMAN RNA (GMAN-AS)—this antisense sequence is also complementary to that of ephrin A1 mRNA. Levels of ephrin A1 protein were also increased in gastric tumors from patients with metastases than in those without metastases. Knockout of ephrin A1 in BGC-823 cells reduced their invasive activity in Transwell assays and ability to form metastases after injection into SCID mice. Ectopic expression of ephrin A1 in BGC-823 cells with knockdown or knockout of GMAN restored their invasive activities and ability form metastases in nude or SCID mice. A CRISPR/Cas9-based strategy to disrupt the GMAN gene significantly reduced the numbers of metastases formed from SGC-7901 cells in mice. Conclusions We identified an lncRNA, which we call GMAN , that is increased in gastric tumors from patients and associated with survival and formation of metastases. It regulates translation of ephrin A1 mRNA by binding competitively to GMAN-AS. Knockdown or knockout of GMAN or ephrin A1 in gastric cancer cell lines reduces their invasive activity and ability to form metastases after injection into mice. These genes might be targeted to prevent or reduce gastric cancer metastasis. [ABSTRACT FROM AUTHOR]

Abstract The World Health Organization sets up the Ambient Air Quality Guidelines mainly based on short-term and long-term health effects of air pollution. Previous studies, however, have generally revealed a non-threshold concentration-response relationship between air pollution and health, making it difficult to determine a concentration, below which no obvious health effects can be observed. Here we proposed a novel approach based on the concept of "number needed to treat", specifically, we calculated the reduction in air pollution concentrations needed to avoid one death corresponding to different hypothetical concentration standards; the one with the smallest value would be the most practical concentration standard. As an example, we applied this approach to the daily standard of ambient PM 2.5 (particulate matter with aerodynamic diameter ≤2.5 μm) in four Chinese cities. The calculation was based on the association between daily mortality and ambient PM 2.5 , which was examined by a generalized additive model with adjustment of important covariates. Significant associations were observed between PM 2.5 and mortality. Our analyses suggested that it is appropriate to have 50 μg/m3 as the daily standard of ambient PM 2.5 for the study area, compared to the current standard of which were directly adopted from the national standard of 75 μg/m3. This novel approach should be considered when planning and/or revising the ambient air quality guidelines/standards. Highlights • There is limited method for air pollution standard formulation. • The "number needed to treat" was proposed as one potential method. • We examined the acute association between PM 2.5 and mortality in four Chinese cities. • We then calculated the reduction in air pollution concentrations needed to avoid one death. • Finally, we suggested that 50 μg/m3 should be considered as daily standard of ambient PM 2.5 in the study area. Capsule This study proposes a new "number needed to treat" approach to help establish or revise daily ambient air quality standards. [ABSTRACT FROM AUTHOR]

Diamide insecticides selectively activate insect ryanodine receptors (RyRs), inducing uncontrolled release of calcium ions, and causing muscle contraction, paralysis and eventually death. The RyR G4946E substitution associated with diamide resistance has been identified in three lepidopteran pests, Plutella xylostella , Tuta absoluta and Chilo suppressalis . Recently, the T. absoluta RyR G4946V mutation was knocked into the model insect Drosophila melanogaster by CRISPR/Cas9 mediated genome editing and provided in vivo functional confirmation for its role in diamide resistance. In the present study, we successfully introduced the RyR G4946E mutation with CRISPR/Cas9 technology into a lepidopteran pest of global importance, Spodoptera exigua . The genome-edited strain (named 4946E) homozygous for the SeRyR G4946E mutation exhibited 223-, 336- and >1000-fold resistance to chlorantraniliprole, cyantraniliprole and flubendiamide, respectively when compared to the wild type strain (WHS) of S. exigua . Reciprocal crossing experiments revealed that the target-site resistance in strain 4946E underlies an autosomal and almost recessive mode of inheritance for anthranilic diamides, whereas it was completely recessive for flubendiamide. Our results not only provided in vivo functional validation of the RyR G4946E mutation in conferring high levels of resistance to diamide insecticides for the first time in a controlled genetic background of a lepidopteran pest, but also revealed slight differences on the level of resistance between anthranilic diamides (chlorantraniliprole and cyantraniliprole) and flubendiamide conferred by the SeRyR G4946E mutation. [ABSTRACT FROM AUTHOR]

Although the effect of ambient temperature on cardiovascular disease (CVDs) has been well explored, studies using years of life lost (YLLs) as the outcome especially evaluating the average life loss per death attributable to temperatures were rare. We examine the associations between ambient temperature and YLLs of CVDs, and further quantify temperature-related life loss per death. Daily YLL rates were calculated using death data from 364 locations across China during 2006–2017, and meteorological data were collected for the same period. A distributed-lag nonlinear model and meta-regression were applied to examine the relationships between temperature and YLL rates of CVDs. Subgroup analyses by age, gender, region, and cause-specific CVDs were investigated. The total YLLs and average YLLs per death attributable to temperature were further quantified to assess life loss caused by non-optimal temperature. Both high and low temperatures significantly increased YLL rates of CVDs, with greater effects for cold than heat. Cerebrovascular diseases (CEDs) account for the largest proportion (47.17%) of total YLLs of CVDs attributable to non-optimal temperature. On average, life loss per CVD death attributable to non-optimal temperatures was 1.51 (95% eCI: 1.33, 1.69) years, with 1.07 (95% eCI: 1.00, 1.15) years from moderate cold. Average life losses per death were observed higher for males (1.71, 95% eCI: 1.43, 1.99), younger population (3.82, 95% eCI: 2.86, 4.75), central China (1.62; 95% eCI: 1.41, 1.83) and hemorrhagic stroke (2.86, 95% eCI: 2.63, 3.10) than their correspondents. We found that non-optimal temperature significantly aggravated premature death of CVD, with CEDs being the most affected, and most of temperature-related life loss of CVD was attributed to moderate cold. Our findings imply that peoples with CEDs in moderate cold days are vulnerable populations, which may contribute to a better understanding the adverse effects and pathogenesis of temperature on CVDs. Unlabelled Image • This study examines the health effects of non-optimal temperature, and quantify temperature-related life loss per death. • Life loss per CVD death attributable to non-optimal temperatures was 1.51. • Most of temperature-related life loss of CVD was attributed to moderate cold. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs) are functional RNA molecules that play crucial regulatory roles in many fundamental biological processes. The dysregulation of ncRNAs is significantly associated with the progression of human cancers, including gastric cancer. In this review, we have summarized the oncogenic or tumor-suppressive roles and the regulatory mechanisms of lncRNAs, miRNAs, circRNAs and piRNAs, and have discussed their potential as biomarkers or therapeutic targets in gastric cancer. [ABSTRACT FROM AUTHOR]

Previous research has reported the effects of long-term fine particulate matter (PM 2.5) pollution on years of life lost (YLL), but these effects may not represent the full impact. This study aims to estimate potential benefits in life time from adhering to daily ambient PM 2.5 concentration standards/guidelines. This study evaluated the relationship between daily ambient PM 2.5 level and YLL using a two-stage approach with generalized additive models and meta-analysis. Potential life expectancy gains were then estimated by presuming that daily PM 2.5 levels were in compliance with the Chinese and WHO standards. In addition, the attributable fraction of YLL due to excess PM 2.5 exposure was also calculated. During 2013–2016, 459,468 non-accidental deaths were recorded in the six cities of Pearl River Delta, China. Each 10 μg/m3 increment in four-day average (lag 03) level of PM 2.5 was related to an increment of 13.31 [95% confidence interval (CI): 5.74, 20.87] years of life lost. Implementation of the WHO guidelines might avoid 180,980.83 YLLs (95% CI: 78,116.07, 283,845.60), which corresponded to 0.39 (95% CI: 0.17, 0.62) years of increased life time per death. Additionally, an estimated 0.15% (95% CI: 0.06%, 0.23%) or 2.04% (95% CI: 0.88%, 3.20%) of YLLs could be attributed to PM 2.5 exposures higher than the Chinese or WHO guidelines, respectively. This study suggests that people might live longer by controlling daily PM 2.5 concentration and highlights the need to adopt stricter standards in China. • We estimated the life time gain by attaining daily PM 2.5 standards. • Life time might increase by 0.39 years for each death by attaining WHO's guideline. • Up to 2.04% of YLL could be ascribed to PM 2.5 exposure higher than WHO's guideline. • More ambitious target for PM 2.5 control should be employed to improve public health. [ABSTRACT FROM AUTHOR]

Phased arrays are increasingly employed in clinical high-intensity focused ultrasound (HIFU) systems for treatment of uterine fibroids. However, the electronic steering range of current phased arrays is insufficient to cover a symptomatic uterine fibroid. This study proposes a method to augment the focal steering range for HIFU treatment of uterine fibroids. Geometric focus can be shifted by tilting HIFU phased array around two orthogonal axes with a rotating platform, and both rotating angles can be adjusted up to 15° with tilt radius of 277 mm according to the shift of geometric focus. A three-layer (skin, fat and muscle) tissue model was used as the beam propagation path. The acoustic fields with and without tilting HIFU phased array were characterized by numerical simulation and hydrophone measurement. Focal accuracy was evaluated in phantoms and targeting areas were ablated in in vivo pigs' thighs. In combination with the electronic focal steering, the steering range in the focal plane has been augmented to ±53 mm from ±6 mm. In the phantoms, the mean focal error has been increased from 0.2 mm to 0.9 mm with the geometric focus shift ranged from 10 mm to 40 mm. In vivo experimental results have proved that it is safe and effective to ablate the 25 mm × 25 mm square area. Tilting the HIFU phased array is feasible to safely augment the focal steering range, which can potentially improve the efficacy of HIFU treatment. [ABSTRACT FROM AUTHOR]

Experimental studies have indicated that alterations in the gut microbiota might play a role in the pathway of diabetes induction resulting from particulate matter pollution with aerodynamic diameters < 2.5 μm (PM 2.5). However, few human studies have examined such experimental findings. Here, we examine the mediating effects of gut microbial dysbiosis on the associations between PM 2.5 and particulate matter pollution with aerodynamic diameters < 1 μm (PM 1) on diabetes using the Guangdong Gut Microbiome Project (GGMP) dataset. A multistage cluster sampling method was employed to recruit adult participants from communities in Guangdong. Each participant was interviewed using a questionnaire, fasting blood and stool samples were collected, and the exposure to air pollutants was assessed using a spatiotemporal land-use regression model. The mediation analysis was conducted to estimate the associations among air pollutants, gut microbiota diversity and diabetes. Both PM 2.5 and PM 1 were positively associated with the risks of impaired fasting glucose (IFG) or type 2 diabetes and negatively associated with alpha diversity indices of the gut microbiota. The mediation analyses indicated that the associations of PM 2.5 and PM 1 with the risk of type 2 diabetes were partially mediated by the decrease in gut microbiota diversity. Moreover, we found that 79 (PM 2.5 on IFG), 84 (PM 2.5 on type 2 diabetes), 83 (PM 1 on IFG) and 89 (PM 1 on type 2 diabetes) bacterial taxa could partially mediate the associations of PM 2.5 and PM 1 with IFG and type 2 diabetes, respectively. The relative abundance of most Firmicutes , Proteobacteria and Verrucomicrobia bacteria were negatively associated with particulate matter (PM) concentrations and the risks of diabetes. Long-term exposure to PM may increase the risk of diabetes, and alterations in the gut microbiota partially explained these associations. Unlabelled Image • Long-term exposure to PM may increase the risks of IFG and T2DM, and decrease the diversity of gut microbiota. • The alternations of gut microbiota diversity could partially mediate the associations of PM with diabetes risk. • Bacterial taxa could partially mediate the effects of PM 2·5 and PM 1 on IFG and T2DM. [ABSTRACT FROM AUTHOR]

• The tumor immune microenvironment in uncommon EGFR -mutated NSCLC was determined. • Uncommon EGFR -mutant tumors had a high frequency of PD-L1 and CD8 dual positivity. • Uncommon EGFR -mutated NSCLC had preliminary therapeutic sensitivity to PD-1 blockade. The efficacy of immunotherapy in epidermal growth factor receptor (EGFR) -activating non-small cell lung cancer (NSCLC) is limited. However, a series of patients with uncommon EGFR alterations was reported to derive clinical benefit from PD-1 blockade. To characterize the tumor immune microenvironment, we retrospectively evaluated tumor PD-L1 expression and T cells infiltration among NSCLC patients with uncommon EGFR mutations. Immunohistochemistry was used to analyze the expression of PD-L1 and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs). Chi-square test and Cox proportional hazards regression were conducted to investigate the correlations between the immune microenvironment features and clinicopathological variables and survival, as well as to explore the potential of immunotherapy in this patient population. Among 600 NSCLC patients with EGFR alterations, we identified 49 (8.2 %) bearing uncommon mutations, including G719X, L861Q, S768I, and Ex20 ins. In total, 49.0 % (24/49) of these patients showed positive PD-L1 expression in tumor cells, markedly higher than the proportion in patients with classic sensitive mutations (19del and L858R, 12.2 % [67/551], P < 0.05). Furthermore, PD-L1 expression was associated with relatively short overall survival (OS; 15.2 vs 29.3 months, P = 0.006) and was identified as an independent predictor of OS (hazard ratio=2.57, 95 % confidence interval: 1.03–7.12, P = 0.045). Additionally, PD-L1 positivity was predominantly observed among tumors with CD8+ TILs infiltration (P = 0.001). Uncommon EGFR -mutant tumors had a high frequency (36.7 %) of concurrent PD-L1 expression and abundant CD8 + TILs infiltration. Moreover, this dual-positive group exhibited the most unfavorable prognosis (P = 0.023). Notably, patients with PD-L1 and CD8 dual positivity showed a favorable response to PD-1 inhibitors. High rates of concomitant PD-L1 expression and CD8 + TILs within the tumor microenvironment were observed in NSCLC patients with uncommon EGFR mutations. Further investigations are needed to confirm the therapeutic sensitivity to PD-1 blockade in this subgroup. [ABSTRACT FROM AUTHOR]

Highlights • DS-GPA and Lung-molGPA could predict outcomes of NSCLC patients with brain metastases. • Lung-molGPA demonstrated discriminatory capability in patients with gene variations. • A modified Lung-molGPA index was developed. Abstract Objectives The Lung-molGPA index is based on the original diagnosis-specific graded prognostic assessment (DS-GPA) and incorporates recently reported gene alteration data, predicting the outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases (BM). However, the prognostic values of both DS-GPA and Lung-molGPA remain undetermined, especially for patients with different molecular types. Materials and Methods A total of 1184 NSCLC patients with BM were analyzed for clinical factors and outcomes at Zhejiang Cancer Hospital, China. All prognostic factors were weighted for significance by hazard ratios. The applicability of DS-GPA and Lung-molGPA were reappraised in NSCLC patients with BM and various genetic profiles. Additionally, a modified Lung-molGPA was newly developed for NSCLC patients with gene variations. Results NSCLC patients in the present study had a median survival time of 14.0 months from BM diagnosis. Both the DS-GPA and Lung-molGPA models could effectively predict the outcomes of NSCLC patients with BM (P < 0.001), and the Lung-molGPA model appeared to deliver more accurate predictions. Furthermore, Lung-molGPA scores demonstrated discriminatory capability in patients with gene variations (P < 0.001), and no significant difference was reached in wild-type patients (P = 0.133). Regarding oncogene-positive NSCLC patients with BM, a modified Lung-molGPA index was established based on the prognostic factors with a C-index of 0.73 (95% CI: 0.68-0.80) to accurately calculate survival probability (P < 0.001). Conclusions In the era of precision medicine, Lung-molGPA accurately predicted the prognosis of NSCLC patients with mutant genotypes and BM, although it did not perform well in wild-type patients. Thus, it is worthwhile to explore the prognostic model for patients with positive driving genes. [ABSTRACT FROM AUTHOR]

Background Daily mean concentration cannot fully address the hourly variations of air pollution within one day. As such, we proposed a new indicator, daily exceedance concentration hours (DECH), to explore the acute cardiovascular effects of ambient PM 2.5 (particles with aerodynamic diameters less than 2.5 μm). The DECH in PM 2.5 was defined as daily total concentration-hours > 25 μg/m 3 . Methods A generalized additive model with a quasi-Poisson link was applied to estimate the associations between day-to-day variation in PM 2.5 DECH and day-to-day variation in cardiovascular mortality in six subtropical cities in Guangdong Province, China. Results The analysis revealed significant associations between PM 2.5 DECHs and cardiovascular mortality. A 500 μg/m 3 ∗ h increase in PM 2.5 DECHs at lag 03 was associated with an increase of 4.55% (95% confidence interval (CI): 3.59%, 5.52%) in cardiovascular mortality, 4.45% (95% CI: 2.81%, 6.12%) in ischemic cardiovascular mortality, 5.02% (95% CI: 3.41%, 6.65%) in cerebrovascular mortality, and 3.00% (95% CI: 1.13%, 4.90%) in acute myocardial infarction mortality. We further observed a greater mortality burden using PM 2.5 DECHs than daily mean PM 2.5 (6478 (95% CI: 5071, 7917) VS 5136 (95% CI: 3990, 6305)). Conclusion This study reveals that PM 2.5 DECH is one important exposure indicator of ambient PM 2.5 to measure its cardiovascular mortality effects in Pearl River Delta region; and that using daily mean concentration could under-estimate the mortality burden compared with this new indicator. [ABSTRACT FROM AUTHOR]

Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754 nm and particle size of 115 ± 15 nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10–15 nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50 mg MSNs, ratio of MSNs to lipid (w/w) = 1:1.11, and ratio of lipid to CHO (w/w) = 3.93:1. The average experimental EE Tax , EE Cur and stability score value were (77.48 ± 2.73) %, (30.70 ± 3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect. [ABSTRACT FROM AUTHOR]

[Display omitted] • The effects of CPPU on metabolism and nutrients of kiwifruit were investigated. • 29 key metabolites were correlated with CPPU controlling kiwifruit development. • Response of kiwifruits to CPPU was dynamic, and related network was established. • The negative effects on nutrient substances became mild at harvest. • CPPU promoted kiwifruit development with more sucrose and fewer organic acids. Forchlorfenuron (CPPU) is a plant growth regulator widely applied on kiwifruit to improve yield, however, there are rarely reports on its effects on the nutrients of kiwifruits. Based on UHPLC-Q-TOF-MS, the effects of CPPU on metabolism profile and nutrient substances of two kiwifruit varieties during development were investigated by non-targeted metabolomics. A total of 115 metabolites were identified, and 29 differential metabolites were confirmed and quantified using certified reference standards. Metabolic profile indicated that CPPU promoted kiwifruit development during the main expansion stages at the molecular level, and the effects varied slightly for different varieties. In the early and middle stages of kiwifruit development, the anthocyanin, flavone and flavonol biosynthesis were down-regulated in both varieties, and flavanols biosynthesis was down-regulated only in Hayward variety. Arginine biosynthesis was down-regulated at all stages till the harvest. Although the synthesis of these nutrient substances in kiwifruits was mostly down-regulated by CPPU, the negative effects became mild at harvest time, and positively, the significant increase of sucrose and decrease of organic acids at harvest time could help to improve the taste of kiwifruits. [ABSTRACT FROM AUTHOR]

Compared with daily mean concentration of air pollution, hourly peak concentration may be more directly relevant to the acute health effects due to the high concentration levels, however, few have analyzed the acute mortality effects of hourly peak levels of air pollution. We examined the associations of hourly peak concentration of fine particulate matter air pollution (PM 2.5 ) with mortality in six cities in Pearl River Delta, China. We used generalized additive Poisson models to examine the associations with adjustment for potential confounders in each city. We further applied random-effects meta-analyses to estimate the regional overall effects. We further estimated the mortality burden attributable to hourly peak and daily mean PM 2.5 . We observed significant associations between hourly peak PM 2.5 and mortality. Each 10 μg/m3 increase in 4-day averaged (lag 03 ) hourly peak PM 2.5 corresponded to a 0.9% [95% confidence interval (CI): 0.7%, 1.1%] increase in total mortality, 1.2% (95% CI: 1.0%, 1.5%) in cardiovascular mortality, and 0.7% (95% CI: 0.2%, 1.1%) in respiratory mortality. We observed a greater mortality burden using hourly peak PM 2.5 than daily mean PM 2.5 , with an estimated 12915 (95% CI: 9922, 15949) premature deaths attributable to hourly peak PM 2.5 , and 7951 (95% CI: 5067, 10890) to daily mean PM 2.5 in the Pearl River Delta (PRD) region during the study period. This study suggests that hourly peak PM 2.5 might be one important risk factor of mortality in PRD region of China; the finding provides important information for future air pollution management and epidemiological studies. [ABSTRACT FROM AUTHOR]

We evaluated the safety and efficacy of a live attenuated influenza vaccine (LAIV) product in ferrets. The BCHT LAIV product was significantly less virulent than wild-type H1N1 virus, when evaluated by comparing virus shedding and histopathologic lesions. The data indicated strong evidence for an attenuated phenotype of LAIV. Furthermore, the vaccine induced robust humoral immune responses in seronegative ferrets, and protected ferrets against development of fever, weight loss and turbinate inflammatory lesions after challenging with H3N2 wide-type influenza virus. Thus, the BCHT LAIV product was safe in healthy seronegative ferrets and protected ferrets against infection of H3N2 influenza virus. [ABSTRACT FROM AUTHOR]

Background Epidemiological studies have reported significant association between ambient fine particulate matter air pollution (PM 2.5 ) and mortality, however, few studies have investigated the relationship of mortality with PM 2.5 and associated mortality burden in China, especially in a multicity setting. Methods We investigated the PM 2.5 -mortality association in six cities of the Pearl River Delta region from 2013 to 2015. We used generalized additive Poisson models incorporating penalized smoothing splines to control for temporal trend, temperature, and relative humidity. We applied meta-analyses using random-effects models to pool the effect estimates in the six cities. We also examined these associations in stratified analyses by sex, age group, education level and location of death. We further estimated the mortality burden (attributable fraction and attributable mortality) due to ambient PM 2.5 exposures. Results During the study period, a total of 316,305 deaths were recorded in the study area. The analysis revealed a significant association between PM 2.5 and mortality. Specifically, a 10 μg/m 3 increase in 4-day averaged (lag 03 ) PM 2.5 concentration corresponded to a 1.76% (95% confidence interval (CI): 1.47%, 2.06%) increase in total mortality, 2.19% (95% CI: 1.80%, 2.59%) in cardiovascular mortality, and 1.68% (95% CI: 1.00%, 2.37%) in respiratory mortality. The results were generally robust to model specifications and adjustment of gaseous air pollutants. We estimated that 0.56% (95% CI: 0.47%, 0.66%) and 3.79% (95% CI: 3.14%, 4.45%) of all-cause mortalities were attributable to PM 2.5 using China's and WHO's air quality standards as the reference, corresponding to 1661 (95% CI: 1379, 1946) and 11,176 (95% CI: 9261, 13,120) attributable premature mortalities, respectively. Conclusion This analysis adds to the growing body of evidence linking PM 2.5 with daily mortality, and mortality burdens, particularly in one Chinese region with high levels of air pollution. [ABSTRACT FROM AUTHOR]

Various edible berries widely accessible in nature in Northeast China are poorly exploited. The compositions and contents of anthocyanins in black ( Padus maackii , Padus avium , Lonicera caerulea , and Ribes nigrum ) and red ( Ribes rubrum , Sambucus williamsii , Rubus idaeus , and Ribes procumbens ) wild berries in Northeast China were firstly characterized by HPLC–DAD/ESI-MS 2 . Twenty-three anthocyanins were detected and identified. Cyanidin glycosides were dominant in both berries. Six anthocyanins were reported for the first time in P . avium , R . rubrum , and Sambucus . Total anthocyanin content (TAC) ranged from 10 mg/100 g fresh weight (FW) ( R . procumbens ) to 1058 mg/100 g FW ( P . maackii ) among berries. The TACs and antioxidant activities assessed by DPPH and FRAP assays were much higher in black than in red berries. Black–red berries, especially P . maackii and P . avium , can be used in developing functional foods and in improving breeding programs. [ABSTRACT FROM AUTHOR]