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To calculate the shockwave propagation of deep water explosions for different explosives quickly and accurately, a calculation method, based on the Kirkwood‐Bethe theory, was proposed. At the same time, an underwater explosion experiment of the aluminized explosive was carried out in the pressure vessel under high hydrostatic pressure. Then, the calculated results and experimental results were compared for peak pressure, impulse and energy flux density. The results indicated that the proposed method can quickly and accurately determine the shockwave propagation of deep water explosions for the aluminized explosives, with satisfactory agreement with experimental data. Using the proposed method, the shockwave of aluminized explosive under the conditions of different charge weight, different depth and different distance were calculated, the propagation laws of peak pressure, impulse and energy flux density with depth and distance were obtained. The calculation method proposed could be used to calculate shockwave propagation for any kind of explosive, if only knows the parameters of detonation and JWL equation of state. [ABSTRACT FROM AUTHOR]

The increased proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of vascular diseases. The intermediate conductance calcium‐activated potassium (IKCa) channel plays a critical role in VSMC proliferation by raising the intracellular calcium concentration ([Ca2+]i), but the underlying mechanism is still not unclear. Here we investigated the cooperation between IKCa and transient receptor potential canonical 1 (TRPC1) channels in mediating extracellular Ca2+ entry, which in turn activates downstream Ca2+ signalling in the regulation of VSMC proliferation using serum‐induced cell proliferation model. Serum‐induced cell proliferation was accompanied with up‐regulation of IKCa expression and an increase in [Ca2+]i. Serum‐induced cell proliferation and increase in [Ca2+]i were suppressed by IKCa inhibition with TRAM‐34 or IKCa knockdown. Serum‐induced cell proliferation was strongly reduced by the removal of extracellular Ca2+ with EGTA or intracellular Ca2+ with BAPTA‐AM and, additionally, by TRPC1 knockdown. Moreover, the increase in [Ca2+]i induced by serum or by IKCa activation with 1‐EBIO was attenuated by TRPC1 knockdown. Finally, serum induced ERK1/2 activation, which was attenuated by treatment with TRAM‐34 or BAPTA‐AM, as well as TRPC1 knockdown. Consistently, serum‐induced cell proliferation was suppressed by ERK1/2 inhibition with PD98059. Taken together, these results suggest that the IKCa and TRPC1 channels cooperate in mediating Ca2+ influx that activates the ERK1/2 pathway to promote cell proliferation, thus providing new mechanistic insights into VSMC proliferation. [ABSTRACT FROM AUTHOR]

The United States of America (USA) was afflicted by extreme heat in the summer of 2021 and some states experienced a record‐hot or top‐10 hottest summer. Meanwhile, the United States was also one of the countries impacted most by the coronavirus disease 2019 (COVID‐19) pandemic. Growing numbers of studies have revealed that meteorological factors such as temperature may influence the number of confirmed COVID‐19 cases and deaths. However, the associations between temperature and COVID‐19 severity differ in various study areas and periods, especially in periods of high temperatures. Here we choose 119 US counties with large counts of COVID‐19 deaths during the summer of 2021 to examine the relationship between COVID‐19 deaths and temperature by applying a two‐stage epidemiological analytical approach. We also calculate the years of life lost (YLL) owing to COVID‐19 and the corresponding values attributable to high temperature exposure. The daily mean temperature is approximately positively correlated with COVID‐19 deaths nationwide, with a relative risk of 1.108 (95% confidence interval: 1.046, 1.173) in the 90th percentile of the mean temperature distribution compared with the median temperature. In addition, 0.02 YLL per COVID‐19 death attributable to high temperature are estimated at the national level, and distinct spatial variability from −0.10 to 0.08 years is observed in different states. Our results provide new evidence on the relationship between high temperature and COVID‐19 deaths, which might help us to understand the underlying modulation of the COVID‐19 pandemic by meteorological variables and to develop epidemic policy response strategies. Plain Language Summary: The spread of coronavirus disease 2019 (COVID‐19) pandemic has become of unparalleled public health concern from the beginning of 2020, especially in the United States of America (USA). In the summer of 2021, extreme heat swept the United States and some states even underwent the hottest or top‐10 hottest summer on record. The relationships between high temperature and COVID‐19 severity are less discussed compared with other environmental exposures and existing studies show different results. In this research, we focus on COVID‐19 deaths and use epidemiological approach to explore the effects of high temperature during the summer of 2021 in the USA. We find an approximately positive association between daily mean temperature and COVID‐19 mortality nationally. When temperature get to the 90th percentile from the local median, about 11% increase in the next 7‐day cumulative number of COVID‐19 deaths is noticed. Different temperature–mortality responses are observed at the region‐specific level. The findings of our study suggest that with spatial variations, high temperature could be an important factor influencing the COVID‐19 pandemic and might increase the risk of COVID‐19 mortality, which would be a useful supplement to assist policymakers to design COVID‐19 control measures. Key Points: This study explores the relationship between COVID‐19 deaths and temperature by applying a two‐stage epidemiological analytical approach during the summer of 2021 in the Unites StatesThe daily mean temperature is approximately positively correlated with COVID‐19 deaths nationwide, with different shapes of temperature–mortality curves noted at the regional levelEvaluation of temperature‐mortality relationship is important in controlling COVID‐19 severity [ABSTRACT FROM AUTHOR]

Surface ozone is damaging to human health and crop yields. When evaluating global air pollution risk, gridded datasets with high accuracy are desired to reflect the local variations in air pollution concentrations. Here, a cluster‐enhanced ensemble machine learning method was used to develop a new 0.5‐degree monthly surface ozone data set during 2003–2019 by combining numerous informative variables. The overall accuracy of our data set is 91.5% (90.8% for space and 92.3% for time). Historically, populations in South Asia, North Africa and Middle‐East, and High‐income North America are exposed to the highest ozone concentrations. Globally, the population weighted ozone concentration in the peak season is 47.07 ppbv. Our results highlight that ozone pollution is intensifying in some regions, and implicate air quality management is crucial to secure human health from air pollution. Plain Language Summary: Surface ozone is one of the most hazardous air pollutants to human health and plants. However, estimation of global surface ozone is still limited. Here, by using state‐of‐the‐art machine learning techniques, we fuse satellite, chemical transport model outputs, atmospheric reanalyses, and emission data with surface observations to construct a full coverage and long‐time period surface ozone data set. We demonstrate that surface population weighted ozone concentration in North America and Europe has decreased from 2003 to 2019, while ozone pollution in East Asia has intensified during 2016–2019. We also show at least 37% of the world's population is exposed to ozone greater than the World Health Organization's interim target one of 50 ppbv (MDA8) in the peak season. Our results could help identify the key regions for improving global air quality and offers an insightful data set for human health assessments and air quality management. Key Points: A cluster‐enhanced ensemble machine learning method can predict global surface ozone with high accuracyPopulations in South Asia, North Africa and Middle‐East, and High‐income North America are exposed to the highest MDA8 during 2003–2019At least 37% of world's population is exposed to greater than 50 ppbv MDA8 in peak seasons [ABSTRACT FROM AUTHOR]

Vascular stiffening, an early and common characteristic of cardiovascular diseases (CVDs), stimulates vascular smooth muscle cell (VSMC) proliferation which reciprocally accelerates the progression of CVDs. However, the mechanisms by which extracellular matrix stiffness accompanying vascular stiffening regulates VSMC proliferation remain largely unknown. In the present study, we examined the role of the intermediate‐conductance Ca2+‐activated K+ (IKCa) channel in the matrix stiffness regulation of VSMC proliferation by growing A7r5 cells on soft and stiff polydimethylsiloxane substrates with stiffness close to these of arteries under physiological and pathological conditions, respectively. Stiff substrates stimulated cell proliferation and upregulated the expression of the IKCa channel. Stiff substrate‐induced cell proliferation was suppressed by pharmacological inhibition using TRAM34, an IKCa channel blocker, or genetic depletion of the IKCa channel. In addition, stiff substrate‐induced cell proliferation was also suppressed by reducing extracellular Ca2+ concentration using EGTA or intracellular Ca2+ concentration using BAPTA‐AM. Moreover, stiff substrate induced activation of extracellular signal‐regulated kinases (ERKs), which was inhibited by treatment with TRAM34 or BAPTA‐AM. Stiff substrate‐induced cell proliferation was suppressed by treatment with PD98059, an ERK inhibitor. Taken together, these results show that substrates with pathologically relevant stiffness upregulate the IKCa channel expression to enhance intracellular Ca2+ signaling and subsequent activation of the ERK signal pathway to drive cell proliferation. These findings provide a novel mechanism by which vascular stiffening regulates VSMC function. [ABSTRACT FROM AUTHOR]

The COVID‐19 epidemic has substantially limited human activities and affected anthropogenic emissions. In this work, daily NOx emissions are inferred using a regional data assimilation system and hourly surface NO2 measurement over China. The results show that because of the coronavirus outbreak, NOx emissions across the whole mainland China dropped sharply after 31 January, began to rise slightly in certain areas after 10 February, and gradually recover across the country after 20 February. Compared with the emissions before the outbreak, NOx emissions fell by more than 60% and ~30% in many large cities and most small to medium cities, respectively. Overall, NOx emissions were reduced by 36% over China, which were mainly contributed by transportation. Evaluations show that the inverted changes over eastern China are credible, whereas those in western China might be underestimated. These findings are of great significance for exploring the reduction potential of NOx emissions in China. Plain Language Summary: In this study, we quantitatively estimate the impact of the COVID‐19 lockdown on NOx emissions over China based on nationwide surface hourly NO2 monitoring data. We find that NOx emissions dropped sharply after 31 January and began to gradually recover after 20 February across the country; NOx emissions fell by more than 60% in many large cities and decreased by ~30% in most small to medium cities. Across the whole mainland China, NOx emissions were reduced by 36% due to the COVID‐19 lockdown. Key Points: The spatiotemporal variations of NOx emissions across mainland China during COVID‐19 well inferred from surface NO2 observationsNOx emissions fell by more than 60% in many large cities and by 36% across the whole mainland China due to the lockdownNOx emissions dropped sharply after 31 January and began to gradually recover after 20 February across the country [ABSTRACT FROM AUTHOR]

The host immune response is a fundamental mechanism for attenuating cancer progression. Here we report a role for the DNA demethylase and tumor suppressor TET2 in host anti‐tumor immunity. Deletion of Tet2 in mice elevates IL‐6 levels upon tumor challenge. Elevated IL‐6 stimulates immunosuppressive granulocytic myeloid‐derived suppressor cells (G‐MDSCs), which in turn reduce CD8+ T cells upon tumor challenge. Consequently, systematic knockout of Tet2 in mice leads to accelerated syngeneic tumor growth, which is constrained by anti‐PD‐1 blockade. Removal of G‐MDSCs by the anti‐mouse Ly6g antibodies restores CD8+ T‐cell numbers in Tet2−/− mice and reboots their anti‐tumor activity. Importantly, anti‐IL‐6 antibody treatment blocks the expansion of G‐MDSCs and inhibits syngeneic tumor growth. Collectively, these findings reveal a TET2‐mediated IL‐6/G‐MDSCs/CD8+ T‐cell immune response cascade that safeguards host adaptive anti‐tumor immunity, offering a cell non‐autonomous mechanism of TET2 for tumor suppression. Synopsis: TET2 restrains IL‐6 expression under tumor challenge, thereby restricting G‐MDSCs expansion to promote adaptive anti‐tumor immunity. This mechanism of TET2 function in tumor suppression might have potential therapeutic implications for cancer immunotherapy. Whole‐body deletion of Tet2 impairs anti‐tumor immune responses and increases syngeneic tumor burden in mice.Tet2 deficiency enhances G‐MDSCs expansion in mice, and depletion of G‐MDSCs rescues the impaired anti‐tumor immune response of Tet2−/− mice.Anti‐IL‐6 treatment inhibits G‐MDSCs overexpansion and restores anti‐tumor immune responses inTet2−/− mice. [ABSTRACT FROM AUTHOR]

China has implemented active clean air policies in recent years, and the spatiotemporal patterns of major pollutant emissions have changed substantially. In this study, we construct a regional air pollution data assimilation system based on the WRF/CMAQ model and ensemble Kalman filter algorithm to quantitatively optimize gridded CO emissions using hourly surface CO measurements over China. The Multi‐resolution Emission Inventory of China CO emission inventories in December 2012 and 2016 are treated as prior emissions, and the CO emissions in December 2013 and 2017 are optimized using the CO observations of December of 2013 and 2017, respectively. The results show that in both periods, assimilation of CO observations significantly improves the CO simulations and emission estimates. Assimilation increases the CO emissions in most areas of mainland China, especially in northern China, and the spatial patterns of the increases in the two periods are similar. Overall, the posterior CO emissions in December 2017 are 17% lower than those in December 2013. Large emission decreases are mainly found in most key urban areas and developed regions, and emission increases are mainly located in their surrounding areas and certain central and western regions, which might reflect the emission migration from developed regions or urban areas to developing regions or surrounding areas. These changes are not found in the prior emissions but are basically consistent with the emission control strategies and industrial transformation and upgrade phenomena in recent years, indicating that our CO assimilation system could successfully capture the temporal and spatial variations. Plain Language Summary: CO emissions over China in December 2013 and 2017 were optimized using surface hourly CO observations, and the emission changes between these two periods were presented. We found that there were large emission decreases in key urbans and developed regions, and increases in their surrounding areas and some central and western regions, which were basically consistent with the emission control strategies and industrial transformation in recent years, might reflect the emission migration. Key Points: A regional air pollution data assimilation system based on WRF/CMAQ and EnKF is constructedOverall, the CO emissions are reduced by 17% between December 2013 and 2017 over the whole mainland of ChinaThe emissions migration is found in the posterior emissions but not shown in the prior emissions [ABSTRACT FROM AUTHOR]