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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]

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]

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]

[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]

Heavy metals play an important role in inducing fine particulate matter (PM 2.5) related cardiovascular disease (CVD). However, most of the past researches concerned the associations between CVD mortality and the PM 2.5 mass, which may not reveal the CVD mortality risk contributed by heavy metals in PM 2.5. This study explored the correlations between individual heavy metals in PM 2.5 and CVD mortality, identified the heavy metals that significantly contribute to PM 2.5 -related CVD, heart disease (HD), and cerebrovascular disease (CEV) mortality, and attempted to establish corresponding source control measures. Over a 2-year study period, PM 2.5 was sampled daily in Guangzhou, China and analyzed for heavy metals. The airborne pollution and weather data, along with CVD, HD, and CEV mortality, were obtained at the same time. The excess risk (ER) of mortality was linked to the individual heavy metals using a distributed lag non-linear model. PM 2.5 and most heavy metals showed significant correlations with the CVD, HD, and CEV mortality; the largest cumulative ER (LCER) values of CVD mortality associated with an interquartile range increase in the levels of lead, cadmium, arsenic, selenium, antimony, nickel, thallium, aluminum, iron, and PM 2.5 were 2.43%, 2.23%, 1.66%, 2.39%, 1.19%, 1.21%, 2.69%, 3.29%, 1.74%, and 2.40%, respectively. Most heavy metals showed comparable LCER values of HD and CEV mortality. Heavy metals with the addition of PM 2.5 were divided into three groups following their LCER values; lead, cadmium, arsenic, antimony, thallium, zinc, aluminum, and iron, whose contributions were greater than or equal to the average effect of the PM 2.5 components, should be limited on a priority basis. These findings indicated that heavy metals play roles in the CVD, HD, and CEV mortality risk of PM 2.5 , and specific control measures which aimed at the emission sources should be taken to reduce the CVD mortality risk of PM 2.5. [Display omitted] • Daily levels of heavy metals in PM 2.5 were analyzed from a 2-year sampling. • Nine heavy metals in PM 2.5 were significantly associated with CVD mortality. • Precise source control of Pb, Cd, Se, Sb, Tl, Zn, Al, and Fe should be conducted. [ABSTRACT FROM AUTHOR]

Our previously reported carboxyl-containing DPP-4 inhibitors were highly potent but were poorly bioavailable. Esters of the carboxyl analogs exhibited a significant DPP-4 potency loss albeit with enhanced oral absorption. Herein, we described identification and structure–activity relationship (SAR) exploration of a novel series of benzoic acid and ester derivatives as low single-digit nanomolar DPP-4 inhibitors. Importantly, the esters displayed comparable activities to the acids counterparts. Molecular simulation revealed that ester adopts a similar binding mode to acid. Moreover, the selected esters and acids demonstrated high selectivity and low cytotoxicity, as well as good metabolic stability. And more importantly, the esters possessed excellent pharmacokinetic profiles for oral administration. The best compound ester 19b demonstrated long DPP-4 inhibition in vivo, and robustly improved the glucose tolerance in normal and db/db mice while ensuring glucose-lowering potency in chronic treatment. Our results supported that the compound 19b can be served as a potential candidate for the treatment of type 2 diabetes. [Display omitted] • The designed benzoic acid and ester derivatives showed low single-digit nanomolar potency. • Esters displayed comparable activities to the acids counterparts. • Ester possessed excellent pharmacokinetic profiles for oral administration. • Ester 19b demonstrated long in vivo DPP-4 inhibition. • Ester 19b robustly improved the glucose tolerance in normal and db/db mice. [ABSTRACT FROM AUTHOR]