Human/mouse CD137 agonist, JNU-0921, effectively shrinks tumors through enhancing the cytotoxicity of CD8+ T cells in cis and in trans.

Agonistic antibodies against CD137 have been demonstrated to completely regress established tumors through activating T cell immunity. Unfortunately, current CD137 antibodies failed to benefit patients with cancer. Moreover, their antitumor mechanisms in vivo remain to be determined. Here, we report the development of a small molecular CD137 agonist, JNU-0921. JNU-0921 effectively activates both human and mouse CD137 through direct binding their extracellular domains to induce oligomerization and signaling and effectively shrinks tumors in vivo. Mechanistically, JNU-0921 enhances effector and memory function of cytotoxic CD8+ T cells (CTLs) and alleviates their exhaustion. JNU-0921 also skews polarization of helper T cells toward T helper 1 type and enhances their activity to boost CTL function. Meanwhile, JNU-0921 attenuates the inhibitory function of regulatory T cells on CTLs. Our current work shows that JNU-0921 shrinks tumors by enhancing the cytotoxicity of CTLs in cis and in trans and sheds light on strategy for developing CD137 small molecular agonists.

The global burden and associated factors of ovarian cancer in 1990-2019: findings from the Global Burden of Disease Study 2019.

BACKGROUND: Ovarian cancer (OC) is a major cause of cancer-related deaths among women. The aim of this study was to estimate and report data on the current burden of ovarian cancer worldwide over the past 30 years. METHOD: Based on the data provided by GBD 2019, we collected and interpreted the disease data of ovarian cancer by incidence, mortality, disability-adjusted life-years (DALYs), and used corresponding age-standardized rates as indicators. Also, we categorized the data by attributed risk factors and captured deaths due to high fasting plasma glucose, occupational exposure to asbestos and high body-mass index, respectively. All outcomes in the study were reported using mean values and corresponding 95% uncertainty intervals (95% UI). RESULTS: Globally, there were 294422 (260649 to 329727) incident cases in 2019, and the number of deaths and DALYs were 198412 (175357 to 217665) and 5.36 million (4.69 to 5.95). The overall burden was on the rise, with a percentage change of 107.8% (76.1 to 135.7%) for new cases, 103.8% (75.7 to 126.4%) for deaths and 96.1% (65.0 to 120.5%) for DALYs. Whereas the age-standardized rates kept stable during 1990-2019. The burden of ovarian cancer increased with age. and showed a totally different trends among SDI regions. Although high SDI region had the declining rates, the burden of ovarian cancer remained stable in high-middle and low SDI regions, and the middle and low-middle SDI areas showed increasing trends. High fasting plasma glucose was estimated to be the most important attributable risk factor for ovarian cancer deaths globally, with a percentage change of deaths of 7.9% (1.6 to 18.3%), followed by occupational exposure to asbestos and high body mass index. CONCLUSIONS: Although the age-standardized rates of ovarian cancer didn't significantly change at the global level, the burden still increased, especially in areas on the lower end of the SDI range. Also, the disease burden due to different attributable risk factors showed heterogeneous, and it became more severe with age.

[Characteristics of haze and its impact factors in four megacities in China during 2006-2009].

The meteorological and environmental data including visibility, SO2, NO2 and PM10 were collected in four major megacities (Beijing, Shanghai, Guangzhou and Chengdu) in the years 2006-2009. Based on the data, seasonal and annual variations of the haze frequency and the key impact factors were discussed. The results indicated that the highest frequencies of haze occurred in summer, winter, spring and autumn for Beijing, Shanghai, Guangzhou and Chengdu, respectively. The trends of haze frequency decreased in Beijing and Guangzhou, while increased in Shanghai and Chengdu during the studied period. The PM10 concentration and relative humidity were the key factors for visibility degradation in the four megacities. The variation of visibility was sensitive to relative humidity in Beijing, to PM10 in Shanghai and Guangzhou, and to both in Chengdu.

[Characterization and reconstruction of aerosol light scattering coefficient at Chengdu during biomass burning and dust storm period in spring].

Aerosol samples for PM2.5 were collected from 19 April to 17 May in 2009 at Chengdu. The concentrations of organic carbon, element carbon, water-solubility ions, crustal elements and levoglucosan of all particle samples were determined by thermal/ optical carbon analyzer,ion chromatography, X-ray fluorescence spectrometer and high performance anion exchange chromatography, respectively. In-situ scattering coefficients (b(sp)) and meteorological parameters for this period were also conducted. Ambient scattering coefficients were reconstructed by IMPROVE formula and compared with measured scattering coefficients. The results showed that the average mass concentration of PM2.5 and measured b(sp) were 133.2 microg x m(-3) and 530 Mm(-1), respectively. Levoglucosan and crustal elements were good traces for biomass burning and dust storm events, respectively. The calculated b'sp was 504 Mm(-1) during campaigning period. The major contributors to scattering coefficients included: (NH4)2SO4 (26%), NH4NO3 (15%), OM (53%), FS (4%) and CM (2%), respectively. The calculated b'sp was 575 Mm(-1) and the dominant species were FS (17%) and CM (21%) during dust storm period (DS). The calculated b'sp was 635 Mm(-1) and OM contributed 62% during biomass burning (BB) period.