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This study investigated the air pollution characteristics of synoptic-scale circulation in the Beijing megacity, and provided quantitative evaluation of the impacts of circulation patterns on air quality during the 2008 Beijing Summer Olympics. Nine weather circulation types (CTs) were objectively identified over the North China region during 2000–2009, using obliquely rotated T-mode principal component analysis (PCA). The resulting CTs were examined in relation to the local meteorology, regional transport pathways, and air quality parameters, respectively. The FLEXPART-WRF model was used to calculate 48-h backward plume trajectories for each CT. Each CT was characterized with distinct local meteorology and air mass origin. CT 1 (high pressure to the west with a strong pressure gradient) was characterized by a northwestern air mass origin, with the smallest local and southeasterly air mass sources, and CT 6 (high pressure to the northwest) had air mass sources mostly from the north and east. On the contrary, CTs 5, 8, and 9 (weak pressure field, high pressure to the east, and low pressure to the northwest, respectively) were characterized by southern and southeastern trajectories, which indicated a greater influence of high pollutant emission sources. In turn, poor air quality in Beijing (high loadings of PM10, BC, SO2, NO2, NOx, O3, AOD, and low visibility) was associated with these CTs. Good air quality in Beijing was associated with CTs 1 and 6. The average visibilities (with ±1σ) in Beijing for CTs 1 and 6 during 2000–2009 were 18.5 ± 8.3 km and 14.3 ± 8.5 km, respectively. In contrast, low visibility values of 6.0 ± 3.5 km, 6.6 ± 3.7 km, and 6.7 ± 3.6 km were found in CTs 5, 8, and 9, respectively. The mean concentrations of PM10 for CTs 1, 6, 5, 8, and 9 during 2005–2009 were 90.3 ± 76.3 μg m−3, 111.7 ± 89.6 μg m−3, 173.4 ± 105.8 μg m−3, 158.4 ± 90.0 μg m−3, and 151.2 ± 93.1 μg m−3, respectively. Analysis of the relationship between circulation pattern and air quality during the emission control period suggests that CTs are the primary drivers of day-to-day variations in pollutant concentrations over Beijing and its vicinity. During the Olympics period, the frequency of CT 6 was twice that of the mean in August from 2000 to 2009. This CT had northerly transport pathways and favorable meteorological conditions (e.g. frequent precipitation) for clean air during the Olympics. Assuming that relationships between CTs and air quality parameters in the same season are fixed in different years, the relative contributions of synoptic circulation to decreases in PM10, BC, SO2, NO2, NOx, CO, and horizontal light extinction during the Olympics were estimated as 19 ± 14%, 18 ± 13%, 41 ± 36%, 12 ± 7%, 10 ± 5%, 19 ± 11%, and 54 ± 25%, respectively.

Key messageWe identify the largest amount of QTLs for cold tolerance in maize; mainly associated with photosynthetic efficiency, which opens new possibilities for genomic selection for cold tolerance in maize.Breeding for cold tolerance in maize is an important objective in temperate areas. The objective was to carry out a highly efficient study of quantitative trait loci (QTLs) for cold tolerance in maize. We evaluated 406 recombinant inbred lines from a multi-parent advanced generation intercross (MAGIC) population in a growth chamber under cold and control conditions, and in the field at early and normal sowing. We recorded cold tolerance-related traits, including the number of days from sowing to emergence, chlorophyll content and maximum quantum efficiency of photosystem II (Fv/Fm). Association mapping was based on genotyping with near one million single nucleotide polymorphism (SNP) markers. We found 858 SNPs significantly associated with all traits, most of them under cold conditions and early sowing. Most QTLs were associated with chlorophyll and Fv/Fm. Many candidate genes coincided between the current research and previous reports. These results suggest that (1) the MAGIC population is an efficient tool for identifying QTLs for cold tolerance; (2) most QTLs for cold tolerance were associated with Fv/Fm; (3) most of these QTLs were located in specific genomic regions, particularly bin 10.04; (4) the current study allows genetically improving cold tolerance with genome-wide selection.

Key messageA large association panel of 836 maize inbreds revealed a broader genetic diversity of cold tolerance, as predominantly favorable QTL with small effects were identified, indicating that genomic selection is the most promising option for breeding maize for cold tolerance.Maize (Zea mays L.) has limited cold tolerance, and breeding for cold tolerance is a noteworthy bottleneck for reaching the high potential of maize production in temperate areas. In this study, we evaluate a large panel of 836 maize inbred lines to detect genetic loci and candidate genes for cold tolerance at the germination and seedling stages. Genetic variation for cold tolerance was larger than in previous reports with moderately high heritability for most traits. We identified 187 significant single-nucleotide polymorphisms (SNPs) that were integrated into 159 quantitative trait loci (QTL) for emergence and traits related to early growth. Most of the QTL have small effects and are specific for each environment, with the majority found under control conditions. Favorable alleles are more frequent in 120 inbreds including all germplasm groups, but mainly from Minnesota and Spain. Therefore, there is a large, potentially novel, genetic variability in the germplasm groups represented by these inbred lines. Most of the candidate genes are involved in metabolic processes and intracellular membrane-bounded organelles. We expect that further evaluations of germplasm with broader genetic diversity could identify additional favorable alleles for cold tolerance. However, it is not likely that further studies will find favorable alleles with large effects for improving cold tolerance in maize.

Chemoresistance is the major obstacle in multiple myeloma (MM) management. We previously showed that macrophages protect myeloma cells, on a cell contact basis, from melphalan or dexamethasone-induced apoptosis in vitro . In this study, we found that macrophage-mediated myeloma drug resistance was also seen with purified macrophages from myeloma patients’ bone marrow (BM) in vitro and was confirmed in vivo using the human myeloma-SCID (severe combined immunodeficient) mouse model. By profiling differentially regulated and paired plasma membrane protein genes, we showed that PSGL-1 (P-selectin glycoprotein ligand-1)/selectins and ICAM-1/CD18 played an important role in macrophage-mediated myeloma cell drug resistance, as blocking antibodies against these molecules or genetic knockdown of PSGL-1 or ICAM-1 in myeloma cells repressed macrophages’ ability to protect myeloma cells. Interaction of macrophages and myeloma cells via these molecules activated Src and Erk1/2 kinases and c-myc pathways and suppressed caspase activation induced by chemotherapy drugs. Thus, our study sheds new light on the mechanism of drug resistance in MM and provides novel targets for improving the efficacy of chemotherapy in patients.

Activation of cyclin E1, a key regulator of the G1/S cell-cycle transition, has been implicated in many cancers including hepatocellular carcinoma (HCC). Although much is known about the regulation of cyclin E1 expression and stability, its post-transcriptional regulation mechanism remains incompletely understood. Here, we report that nuclear factor 90 (NF90), a double-stranded RNA (dsRNA) binding protein, regulates cyclin E1 in HCC. We demonstrate that NF90 is upregulated in HCC specimens and that suppression of NF90 decreases HCC cell growth and delays G1/S transition. We identified cyclin E1 as a new target of NF90 and found a significant correlation between NF90 and cyclin E1 expression in HCC. The mRNA and protein levels of cyclin E1 were downregulated upon NF90 knockdown. Suppression of NF90 caused a decrease in the half-life of cyclin E1 mRNA, which was rescued by ectopic expression of NF90. Furthermore, NF90 bound to the 3’ untranslated regions (3’UTRs) of cyclin E1 mRNA in vitro and in vivo . Knockdown of NF90 also inhibited tumor growth of HCC cell lines in mouse xenograft model. Moreover, we showed that inhibition of NF90 sensitized HCC cells to the cyclin-dependent kinase 2 (CDK2) inhibitor, roscovitine. Taken together, downregulation of NF90 in HCC cell lines can delay cell-cycle progression, inhibit cell proliferation, and reduce tumorigenic capacity in vivo . These results suggest that NF90 has an important role in HCC pathogenesis and that it can serve as a novel therapeutic target for HCC.

Yi Q, Ma J, Kang K, Gu Z. Int J Nanomedicine. 2018;13:653-667. The authors have advised that the Figure 4 caption on page 661 needs correction and the HE image of the Saline group in Figure 9 on page 666 was incorrectly placed due to an oversight during the process of compiling the data into a figure. This error resulted in its duplication with the HE image of the DOX/Z-NCs group in the same figure. The updated Figure 4 caption should read as follows. Figure 4 Flow cytometry results of time-dependent DOX signal changes.Notes: The experimental procedure commenced with a long duration of 24 hours (B), followed subsequently by a period of 2 hours (A), and both segments terminated simultaneously at the zero-hour mark. To ensure comparability between data from the two time points, a control group consisting of untreated cells (without any DOX-containing formulations) was utilized. The correct Figure 9 is as follows. Figure 9 HE staining of tissues of major organs (heart, liver, spleen, lung, kidney; ×100).Abbreviations: DOX, doxorubicin; DOX·HCl, doxorubicin hydrochloride; FA, folic acid; HE, Hematoxylin and Eosin; NCs, nanocapsules.Notes: For the DOX·HCl group: black arrows point out granular degeneration of the cardiac muscles and the black line marks laminar necrosis of liver cells. For the saline group: the black arrows point out diffuse hepatic necrosis and nucleus dissolution necrosis in the liver and inflammatory cell infiltration in the lung; the blue arrows point out tumor cell metastasis into the lung. Scale bar measures 100 μm. The authors apologise for these errors.

Escape behaviors help animals avoid harm from predators and other threats in the environment. Successful escape relies on integrating information from multiple stimulus modalities (of external or internal origin) to compute trajectories toward safe locations, choose between actions that satisfy competing motivations, and execute other strategies that ensure survival. To this end, escape behaviors must be adaptive. When a Drosophila melanogaster larva encounters a noxious stimulus, such as the focal pressure a parasitic wasp applies to the larval cuticle via its ovipositor, it initiates a characteristic escape response. The escape sequence consists of an initial abrupt bending, lateral rolling, and finally rapid crawling. Previous work has shown that the detection of noxious stimuli primarily relies on class IV multi-dendritic arborization neurons (Class IV neurons) located beneath the body wall, and more recent studies have identified several important components in the nociceptive neural circuitry involved in rolling. However, the neural mechanisms that underlie the rolling-escape sequence remain unclear. Here, we present both functional and anatomical evidence suggesting that bilateral descending neurons within the subesophageal zone of D. melanogaster larva play a crucial role in regulating the termination of rolling and subsequent transition to escape crawling. We demonstrate that these descending neurons (designated SeIN128) are inhibitory and receive inputs from a second-order interneuron upstream (Basin-2) and an ascending neuron downstream of Basin-2 (A00c). Together with optogenetic experiments showing that co-activation of SeIN128 neurons and Basin-2 influence the temporal dynamics of rolling, our findings collectively suggest that the ensemble of SeIN128, Basin-2, and A00c neurons forms a GABAergic feedback loop onto Basin-2, which inhibits rolling and thereby facilitates the shift to escape crawling.

Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs), induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4+ T-cell response. Similarly, genetically depleting MФs in myeloma-bearing MMDTR mice retarded myeloma growth in vivo. Furthermore, the combination of CSF1R blockade and chemotherapy such as bortezomib or melphalan displayed an additive therapeutic efficacy against established myeloma. Finally, a fully human CSF1R blocking mAb, similar to its murine counterpart, was able to inhibit the differentiation, proliferation and survival of human MФs. Thus, this study provides the first direct in vivo evidence that MΦs and MAMs are indeed important for myeloma development and progression. Our results also suggest that targeting MAMs by CSF1R blocking mAbs may be promising methods to (re)sensitize myeloma cells to chemotherapy and promote anti-myeloma immune responses in patients.

Immunomodulatory drugs (IMiDs) are effective therapeutic agents with direct inhibitory effects on malignant B- and plasma-cells and immunomodulatory effects on the T-cell activation. This dual function of IMiDs makes them appealing candidates for combination with a cancer vaccine. We investigated the immune stimulatory effects of lenalidomide, administrated to mice in doses, which provided comparable pharmacokinetics to human patients, on the potency of a novel fusion DNA lymphoma vaccine. The combination was curative in the majority of mice with 8d pre-established syngeneic A20 lymphomas compared with vaccine or lenalidomide alone and induced immune memory. In vivo depletion experiments established the requirement for effector CD8 + and CD4 + T cells in protective immunity. Unexpectedly, lenalidomide alone was also associated with reduced numbers of systemic myeloid-derived suppressor cell (MDSC) and regulatory T cell (Treg) in tumor-bearing but not naïve mice, an effect that was independent of simple tumor burden reduction. These results confirm and extend results from other models describing the effect of lenalidomide on enhancing T-cell immunity, highlight the potency of this effect, and provide a rationale for clinical application. Independently, a novel mechanism of action reversing tumor-induced immune suppression by MDSC is suggested.

Carbon transport in river systems is an important component of the global carbon cycle. Most rivers of the world act as atmospheric CO2 sources due to high riverine CO2 partial pressure (pCO2). By determining the pCO2 from alkalinity and pH, we investigated its spatial and temporal variation in the Yellow River watershed using historical water chemistry records (1950s-1984) and recent sampling along the mainstem (2011-2012). Except the headwater region where the pCO2 was lower than the atmospheric equilibrium (i.e. 380 μatm), river waters in the remaining watershed were supersaturated with CO2. The average pCO2 for the watershed was estimated at 2810 ± 1985 μatm, which is 7-fold the atmospheric equilibrium. As a result of severe soil erosion and dry climate, waters from the Loess Plateau in the middle reaches had higher pCO2 than that from the upper and lower reaches. From a seasonal perspective, the pCO2 varied from about 200 μatm to > 30 000 μatm with higher pCO2 usually occurring in the dry season and lower pCO2 in the wet season (at 73% of the sampling sites), suggesting the dilution effect of water. While the pCO2 responded exponentially to total suspended solids (TSS) export when the TSS concentration was less than 100 kg m-3, it decreased slightly and remained stable if the TSS concentration exceeded 100 kg m-3. This stable pCO2 is largely due to gully erosion that mobilizes subsoils characterized by low organic carbon for decomposition. In addition, human activities have changed the pCO2 dynamics. Particularly, flow regulation by dams can diversely affect the temporal changes of pCO2, depending on the physiochemical properties of the regulated waters and adopted operation scheme. Given the high pCO2 in the Yellow River waters, large potential for CO2 evasion is expected and warrants further investigation.