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Xiangjin Gao,1,2,&ast; Xiuqi Zhang,1,&ast; Le Kuai,3,&ast; Qing Yang,4 Huan Li,4 Rui Zhang,1 Bin Li,1 Ruiping Wang1,2 1Clinical Research Center, Shanghai Skin Diseases Hospital, Medical School of Tongji University, Shanghai, People’s Republic of China; 2School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Obstetrics and Gynecology Department, Songjiang Maternal and Child Health-Care Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruiping Wang, Clinical Research Center, Shanghai Skin Diseases Hospital, Medical School of Tongji University, 1278 Baode Road, Jing’an District, Shanghai, 200443, People’s Republic of China, Tel +86-189 1879 1651, Fax +86-21-3680 3000, Email w19830901@126.comObjective: This study was based on a gestational diabetes mellitus (GDM) cohort in Shanghai to examine the association between physical exercise and plasma glucose control among GDM women with and determine what the effects of pre-pregnancy body mass index (BMI).Methods: In this study, GDM was diagnosed if the plasma glucose values at any of the following time points reached the diagnostic threshold: fasting blood glucose (5.1 mmol/L), 1-hour blood glucose (10.0 mmol/L), and 2-hour blood glucose (8.5 mmol/L) by 75 g oral glucose tolerance test (OGTT). Information on GDM women was extracted from the hospital’s health records and prenatal examination forms and was obtained through face-to-face interviews after delivery. A restricted cubic spline curve with four knots was used to flexibly model the relationship between the duration of moderate-intensity physical exercise and the percentage of abnormal plasma glucose among GDM patients with different BMI values. In this study, a P-value less than 0.05 (two-tailed) was considered as statistical significance.Results: Among 1139 GDM women with GDM, the median percentage of abnormal plasma glucose (PG) was 40.0% (interquartile range (IQR): 20.0– 66.7%), and the difference between overweight-obese group and underweight-normal group was statistically significant (50.0% vs 40.0%, P < 0.001). In this study, engaging in more physical exercise during pregnancy contributed to a higher prevalence of satisfactory glycemic control, and women with BMI < 25 kg/m2 should engage in no less than 90 minutes of moderate-intensity physical activity per day to achieve satisfactory glycemic control (prevalence of abnormal PG < 35%). However, over 120 minutes of daily moderate-intensity physical activity is required for GDM women with a BMI ≥ 25 kg/m2 to achieve satisfactory glycemic control.Conclusion: Overweight or obese women with GDM have a higher risk of poor glycemic control and require a longer duration of physical exercise to achieve the same level of blood glucose control.Keywords: gestational diabetes mellitus, plasma glucose control, physical exercise, overweight and obesity

Qi Zheng,1,&ast; Le Kuai,2,&ast; Wencheng Jiang,1,&ast; Yan Qiang,3 Lei Wei,2 Siting Chen,2 Bin Li,1 Ruiping Wang3,4 1Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Clinical Research and Innovation Transformation Center, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 4School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li; Ruiping Wang, Email 18930568129@163.com; w19830901@126.comBackground: Gender difference is prevalent in clinical feature, disease severity for noncommunicable diseases (NCD), but studies on gender disparity in clinical feature, disease severity and NCD comorbidity among psoriasis patients are limited. This cross-sectional study explores gender differences in clinical feature, lifestyle behavior and NCD comorbidity among psoriasis patients.Methods: Psoriasis patients were recruited through cluster survey method in two hospitals, and questionnaire interviews were applied to collect the demographic feature, lifestyle habits, clinical feature and NCD among patients.Results: A total of 2102 psoriasis patients included 1332 males (63.4%), 70% were over 35 years old and approximately 50% of them were overweight or obesity. The median value for psoriasis initiation age and disease duration was 33 years old (34 for male and 32 for female) and 9 years (10 for male and 7 for female), respectively. The psoriasis recurrence was mainly in winter (73.4%) and autumn (34.2%) both for patients. The prevalence of tobacco smoking and alcohol drinking was 31.2% and 12.6%. Male patients had higher prevalence of tobacco smoking (odds ratio (OR) = 13.26, 95% confidence interval (CI): 9.54– 18.44) and alcohol drinking (OR = 14.44, 95% CI: 7.90– 26.40). The prevalence of diabetes, hypertension, hyperlipidemia, and metabolic syndrome were 13.2%, 28.5%, 23.4% and 21.5%, respectively. Male patients had higher prevalence of diabetes (OR = 1.53, 95% CI: 1.16– 2.02), hypertension (OR = 1.87, 95% CI: 1.52– 2.30), hyperlipidemia (OR = 2.34, 95% CI: 1.85– 2.95) and metabolic syndrome (OR = 2.06, 95% CI: 1.63– 2.62) than female patients. The proportions for 4 types of NCDs diagnosed after psoriasis onset were over 58%, which were also higher in males than females.Conclusion: Female patients had shorter disease duration and with less NCD, and male patients had more body weight issue, with fewer sleep time and higher prevalence of tobacco smoking and alcohol drinking and NCDs. We recommend that dermatologist should notice the gender disparity in psoriasis patients, which is helpful for the disease diagnosis and treatment.Keywords: psoriasis, gender disparity, tobacco smoking, alcohol drinking, overweight, metabolic diseases, comorbidity

Xiaoying Sun,1,2 Liu Liu,1,2 Siting Chen,1,2 Jiao Wang,1,2 Xiaoce Cai,1,2 Jiankun Song,3 Mi Zhou,1,2 Dongjie Guo,1,2 Le Kuai,1,2 Xiaojie Ding,1,2 Bin Li,2,4 Xin Li1,2 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Dermatology of TCM, Shanghai Skin Diseases Hospital, Shanghai, People’s Republic of China; 4Department of Dermatology, Shanghai Skin Diseases Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Xin Li, Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of China, Tel +8613661956326, Email 13661956326@163.com Bin Li, Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of China, Tel +8618930568129, Email 18930568129@163.comBackground: Psoriasis is an immune-mediated chronic systemic inflammatory skin disease whose diagnosis and severity assessment pose challenges for clinicians worldwide. The use of serum biomarkers facilitates the early diagnosis and treatment of psoriasis.Methods: This case–control study compared tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-17, IL-10, and fibrinogen-like protein 1 (FGL1) levels of 139 untreated psoriasis patients and 140 healthy controls. Serum samples were collected, and enzyme-linked immunosorbent assays were performed to quantify their levels. Subgroups were analyzed according to abnormal lipid metabolism status.Results: Compared to controls, patients with psoriasis exhibited lower concentrations of serum TNF-α, IL-17, and FGL1 (P < 0.05). A correlation analysis showed that FGL1 was inversely correlated with high-density lipoprotein cholesterol and IL-17 in the psoriatic state. Stepwise multiple regression analysis revealed that FGL1 and total cholesterol were the independent determinants of Psoriasis Area and Severity Index (PASI) score in psoriasis patients. The area under the receiver operating characteristic curve of FGL1 assessing moderate-to-severe psoriasis and mild psoriasis was 0.70, while the area under the curve (AUC) assessing severe psoriasis and mild-to-moderate psoriasis was 0.67, better than that of IL-17. In addition, FGL1, but not IL-17, was able to identify psoriasis with abnormal lipid metabolism to a certain extent (AUC = 0.60).Conclusion: In conclusion, serum FGL1 may be a promising biomarker for diagnosing and staging psoriasis. It may also be involved in its progression and comorbid abnormal lipid metabolism.Keywords: psoriasis, disease severity, biomarker, fibrinogen-like protein 1, lipid metabolism

For the past decade, observations of carbonyl sulfide (OCS or COS) have been investigated as a proxy for carbon uptake by plants. OCS is destroyed by enzymes that interact with CO2 during photosynthesis, namely carbonic anhydrase (CA) and RuBisCO, where CA is the more important one. The majority of sources of OCS to the atmosphere are geographically separated from this large plant sink, whereas the sources and sinks of CO2 are co-located in ecosystems. The drawdown of OCS can therefore be related to the uptake of CO2 without the added complication of co-located emissions comparable in magnitude. Here we review the state of our understanding of the global OCS cycle and its applications to ecosystem carbon cycle science. OCS uptake is correlated well to plant carbon uptake, especially at the regional scale. OCS can be used in conjunction with other independent measures of ecosystem function, like solar-induced fluorescence and carbon and water isotope studies. More work needs to be done to generate global coverage for OCS observations and to link this powerful atmospheric tracer to systems where fundamental questions concerning the carbon and water cycle remain.

We present two new products from near-infrared Greenhouse Gases Observing Satellite (GOSAT) observations: Lowermost tropospheric (LMT, from 0 to 2.5km) and upper tropospheric-stratospheric (U, above 2.5km) carbon dioxide partial column mixing ratios. We compare these new products to aircraft profiles and remote surface flask measurements and find that the seasonal and year-to-year variations in the new partial column mixing ratios significantly improve upon the Atmospheric CO2 Observations from Space (ACOS) and GOSAT (ACOS-GOSAT) initial guess and/or a priori, with distinct patterns in the LMT and U seasonal cycles that match validation data. For land monthly averages, we find errors of 1.9, 0.7, and 0.8ppm for retrieved GOSAT LMT, U, and XCO2; for ocean monthly averages, we find errors of 0.7, 0.5, and 0.5ppm for retrieved GOSAT LMT, U, and XCO2. In the southern hemispheric biomass burning season, the new partial columns show similar patterns to MODIS fire maps and MOPITT multispectral CO for both vertical levels, despite a flat ACOS-GOSAT prior, and a CO-CO2 emission factor comparable to published values. The difference of LMT and U, useful for evaluation of model transport error, has also been validated with a monthly average error of 0.8 (1.4)ppm for ocean (land). LMT is more locally influenced than U, meaning that local fluxes can now be better separated from CO2 transported from far away.

We introduce a retrieval algorithm to estimate lower tropospheric methane (CH4) concentrations from the surface to 1 km with uncertainty estimates using Hyperspectral Thermal Emission Spectrometer (HyTES) airborne radiance measurements. After resampling, retrievals have a spatial resolution of 6 × 6 m2. The total error from a single retrieval is approximately 20 %, with the uncertainties determined primarily by noise and spectral interferences from air temperature, surface emissivity, and atmospheric water vapor. We demonstrate retrievals for a HyTES flight line over storage tanks near Kern River Oil Field (KROF), Kern County, California, and find an extended plume structure in the set of observations with elevated methane concentrations (3.0 ± 0.6 to 6.0 ± 1.2 ppm), well above mean concentrations (1.8 ± 0.4 ppm) observed for this scene. With typically a 20 % estimated uncertainty, plume enhancements with more than 1 ppm are distinguishable from the background values with its uncertainty. HyTES retrievals are consistent with simultaneous airborne and ground-based in situ CH4 mole fraction measurements within the reported accuracy of approximately 0.2 ppm (or ∼8 %), due to retrieval interferences related to air temperature, emissivity, and H2O.

Quantifying the carbonyl sulfide (OCS) land/ocean fluxes contributes to the understanding of both the sulfur and carbon cycles. The primary sources and sinks of OCS are very likely in a steady state because there is no significant observed trend or interannual variability in atmospheric OCS measurements. However, the magnitude and spatial distribution of the dominant ocean source are highly uncertain due to the lack of observations. In particular, estimates of the oceanic fluxes range from approximately 280 Gg S yr-1 to greater than 800 Gg S yr-1, with the larger flux needed to balance a similarly sized terrestrial sink that is inferred from NOAA continental sites. Here we estimate summer tropical oceanic fluxes of OCS in 2006 using a linear flux inversion algorithm and new OCS data acquired by the Aura Tropospheric Emissions Spectrometer (TES). Modeled OCS concentrations based on these updated fluxes are consistent with HIAPER Pole-to-Pole Observations during 4th airborne campaign and improve significantly over the a priori model concentrations. The TES tropical ocean estimate of 70±16GgS in June,when extrapolated over the whole year (about 840 ± 192 Gg S yr-1), supports the hypothesis proposed by Berry et al. (2013) that the ocean flux is in the higher range of approximately 800 Gg S yr-1.

Summary: Regulatory T (Treg) cells play a critical regulatory role in the immune system by suppressing excessive immune responses and maintaining immune balance. The effective migration of Treg cells is crucial for controlling the development and progression of inflammatory diseases. However, the mechanisms responsible for directing Treg cells into the inflammatory tissue remain incompletely elucidated. In this study, we identified BAF60b, a subunit of switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complexes, as a positive regulator of Treg cell migration that inhibits the progression of inflammation in experimental autoimmune encephalomyelitis (EAE) and colitis animal models. Mechanistically, transcriptome and genome-wide chromatin-landscaped analyses demonstrated that BAF60b interacts with the transcription factor RUNX1 to promote the expression of CCR9 on Treg cells, which in turn affects their ability to migrate to inflammatory tissues. Our work provides insights into the essential role of BAF60b in regulating Treg cell migration and its impact on inflammatory diseases.

Biomedical knowledge is typically organized in a relational scheme, such as chemical-disease relation, gene-disease relation, and gene-pathway relation. Biomedical scientists heavily rely on search engines to acquire up-to-date relational knowledge from massive biomedical articles. The navigation efficiency of the retrieval process, however, is significantly restricted by keyword matching techniques unaware of the biomedical relations of these keywords in articles. To bridge the gap between existing retrieval techniques and practical access demands for relational knowledge, we present a novel framework, Biomedical Relation-Aware Document Ranking (BioRADR), capable of retrieving articles expressing specific relations with respect to the queried entity pair. Based on a deep neural network, BioRADR can be trained from large-scale data automatically annotated via distant supervision, and empirical evaluation reveals that it outperforms the strongest baseline by over 8 points in NDCG@1. We implement an online system (http://bioradr.ai.thunlp.org/) based on BioRADR, enabling more efficient relation-oriented retrieval of biomedical articles.

Abstract The histone acetyltransferase p300/CBP is composed of several conserved domains, among which, the TAZ2 domain is known as a protein-protein interaction domain that binds to E1A and various transcription factors. Here we show that TAZ2 has a HAT autoinhibitory function. Truncating p300/CBP at TAZ2 leads to hyperactive HAT and elevated histone H3K27 and H3K18 acetylation in cells. Mechanistically, TAZ2 cooperates with other HAT neighboring domains to maintain the HAT active site in a ‘closed’ state. Truncating TAZ2 or binding of transcription factors to TAZ2 induces a conformational change that ‘opens’ the active site for substrate acetylation. Importantly, genetic mutations that lead to p300/CBP TAZ2 truncations are found in human cancers, and cells with TAZ2 truncations are vulnerable to histone deacetylase inhibitors. Our study reveals a function of the TAZ2 domain in HAT autoinhibitory regulation and provides a potential therapeutic strategy for the treatment of cancers harboring p300/CBP TAZ2 truncations.

For the effective, convenient and unified management of materials about military logistics, this paper studies and designs a monitoring system for monitoring the presence of items. The system uses the motherboard of Raspberry Pi to collect the level signal of the infrared sensor about the presence of the items and the images taken by camera of the items. Then it converts the data into the general data frame, and sends the frame to the data processing module through the source-specific multicast. Finally, the image recognition based on the convolutional neural network is used to judge the correctness of the item, and display its status in real time through the monitoring interface. It has been verified that the system can ensure the real time of data acquisition and the accuracy of identifying items. It has strong practicability.

With the rapid development of civil aviation industry, more and more tasks are required to fuel the aircraft. At present, the aircraft refueling task is mainly assigned to the refueling personnel by the dispatcher of the fuel supplier, one by one, according to the flight refueling information, after receiving the task, the refueling operator drives the refueling vehicle to the aircraft for refueling operation. The realization of electronic, information and big data analysis technology has gradually opened up the information channel of refueling system. Based on a large number of multi-dimensional data, according to the characteristics of aircraft refueling operation, an intelligent dispatching method for aircraft refueling vehicle is provided, which can automatically assign refueling tasks, avoid flight delays and the resulting serious waste of resources and can reduce the workload of the dispatcher. Through the intelligent dispatch, refueling resources can be reasonably allocated to ensure the timely refueling of aircraft and smooth completion of flight support tasks.

As the core basic equipment of the industrial control system, PLC is widely used in important national infrastructure and various industrial control fields. It is the top priority to realize the transformation from made in China to intelligent manufacturing in China to control the industrial site independently, safely, stably and reliably. In this context, domestic PLC has a strong and rapid development momentum, especially in high-end application fields such as aerospace, national defense and military industry. There is an urgent demand for domestic high-performance PLC products. Due to the late development and less application of domestic large-scale PLC, how to evaluate the performance of domestic PLC and whether it can meet the industrial field application is lack of unified standards and evaluation methods. In view of this problem, a set of comprehensive test platform for domestic high-performance PLC is designed. Two mainstream domestic PLCs are selected for quantitative comparison of horizontal parameters with a foreign mainstream product. The key performance indicators and evaluation methods of high-end PLC are proposed. By building a hardware in the loop virtual industrial scene, the ability of PLC to meet the application is tested and compared. The effectiveness of the test platform is verified through a test example, which provides a basis for the evaluation of domestic high-performance PLC Choose to provide reference, promote the normalization, standardization and scale of domestic PLC, and help the high-quality development of Industry 4.0.

Using metal additive manufacturing processes can make up for traditional forging technologies when forming complex-shaped parts. At the same time, metal additive manufacturing has a fast forming speed and excellent manufacturing flexibility, so it is widely used in the aerospace industry and other fields. The fatigue strength of metal additive manufacturing is related to the microstructure of the epitaxially grown columnar grains and crystallographic texture. The crystal plasticity finite element method is widely used in the numerical simulation of the microstructure and macro-mechanical response of materials, which provides a strengthening and toughening treatment and can reveal the inner rules of material deformation. This paper briefly introduces common metal additive manufacturing processes. In terms of additive manufacturing fatigue, crystal plasticity simulations are summarized and discussed with regard to several important influencing factors, such as the microstructure, defects, surface quality, and residual stress.

Innate lymphoid cells (ILCs) have been identified as a heterogeneous population of lymphocytes that mirrors the cytokine and transcriptional profile of adaptive T cells. The dynamic balance between key transcription factors determines the heterogeneity, plasticity, and functions of ILC subsets. The transcription factor ThPOK is highly conserved in biological evolution and exerts pivotal functions in the differentiation of T cells. However, the function of ThPOK in ILC3s has not been identified. Here, we found that ThPOK regulated the homeostasis of ILC3s, as mice lacking ThPOK showed decreased NKp46+ ILC3s and increased CCR6- NKp46- ILC3s. ThPOK-deficient mice were more sensitive to S. typhimurium infection due to the impaired IFN-γ secretion of NKp46+ ILC3s. Furthermore, ThPOK participates in ILC3-mediated control of C. rodentium infection by negatively regulating IL-17A secretion. ThPOK preserves the identity of NKp46+ ILC3s by repressing RORγt, which indirectly releases T-bet expression. On the molecular level, ThPOK directly binds to Rorc and Il23r to restrain their expression which further modulates IL-17A secretion. Collectively, our analysis revealed a critical role of ThPOK in the homeostasis and functions of ILC3 subsets.

In order to improve the reliability of the acquisition/output link in the PLC control system, the design principle of the redundant system is analyzed, combined with the field application environment and actual needs, a distributed I/O redundancy method based on domestic PLC is developed. The article introduces the digital input/output and analog input/output redundancy schemes respectively for the type of data collected. This method takes the self-diagnosis results of the self-diagnosis periodically during operation as the basis for redundant diagnosis, combined with the user-configured redundancy scheme to improve accuracy of collecting/outputting data. It can be known from experiments and on-site base application that this method improves the reliability of the PLC control system and can ensure that the PLC system operates stably, efficiently and safely for a long time.

Aiming at the requirements of the design parameters temperature, humidity and air volume of the fairing air conditioner in a launch site, the implementation plan of the traditional fairing air conditioning system was investigated. In this paper, from the aspects of information security and reliability, a redundant automatic control system for air conditioning with fairing based on domestic PLC was proposed. In this regard, the article introduces the functions of domestic super Yu PLC components, redundant unit system scheme, and builds the system architecture and control scheme from the hardware and software aspects. Through on-site experimental debugging, the feasibility and stability of the fairing air conditioning control system are verified, and it has obvious advantages such as safety and reliability. It solves the problem of zero application of domestic PLC in the fairing air conditioning system and is a high reliability fairing air conditioning system design plan.

Chromosomal NUP98-PHF23 translocation is associated with an aggressive form of AML. Here, the authors report the molecular mechanisms by which NUP98-PHF23 recognizes the histone mark H3K4me3 and provide evidence of a direct link between the association of NUP98-PHD finger chimeras with H3K4me3-rich regions and leukemic transformation.

Abstract Background Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated. Methods To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM. Results We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure. Conclusions Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.

Abstract Background Small cell lung cancer (SCLC) is one of the deadliest malignancies and accounts for nearly 15% of lung cancers. Previous study had revealed the genomic characterization of SCLC in Western patients. However, little is known about that in Chinese SCLC patients. Methods Formalin‐fixed paraffin‐embedded tumor tissues and matched blood samples from 122 Chinese SCLC patients were collected for next generation sequencing to detect 450 cancer‐related genes. All pathological diagnoses were confirmed by independent pathologists. Results The most frequently altered genes were TP53 (93.4%), RB1 (78.7%), LRP1B (18.9%), KMT2D (15.6%), FAT1 (11.5%), KMT2C (11.5%), SPTA1 (11.5%), STK24 (11.5%), FAM135B (10.7%), and NOTCH1 (10.7%). The gene fusion/rearrangement detection rate was 16.4%, and mostly occurred in chromosomes 7 and 17. The rate of co‐occurring mutations of TP53 and RB1 in these Chinese SCLC patients was 74.6%, and lower than the reported Western patients (90.9%, P = 0.007). The most common gene mutations (83.6%) were found in cell cycle signaling pathway in Chinese SCLC patients. Mutation of Wnt and Notch signaling pathways in the Chinese cohort were lower than Western cohort (P = 0.0013 and 0.0068). A significant association was found between high tumor mutation burden and mutations involved in FAT1, TP53, SPTA1, KEAP1, KMT2D, MAGI2, NOTCH2, NOTCH3, FLT1, KDM6A, and FAT4. Conclusions In this study, we characterized the genomic alterations profile of Chinese SCLC patients. Compared with westerners, the genetic alterations of Chinese SCLC patients presented different patterns. Our data might provide useful information in targeted therapy and drug development for Chinese SCLC patients.

Background: KRAS-mutant lung adenocarcinomas (LUADs) are heterogeneous and frequently occur in smokers. The heterogeneity of KRAS-mutant LUAD has been an obstacle for the drug discovery. Methods: We integrated multiplatform datatypes and identified two corresponding subtypes in the patients and cell lines. We further characterized the features of these two subtypes and performed drug screening to identify subtype-specific drugs. Finally, we used the defining features of the KRAS subtypes for drug sensitivity prediction. Findings: Patient-Subtype 1 (PS1) was characterized by increased smoking-related mutational signature activity, a low tumor-infiltrating lymphocyte (TIL)-associating score and STK11/KEAP1 co-mutations. Patient-Subtype 2 (PS2) was characterized by an increased smoking-related methylation signature activity, a high TIL-associating score and increased KRAS dependency. The cell line subtypes faithfully recapitulated all the patients' features. Drug screening of the two cell line subtypes yielded several potential candidates, such as cytarabine and enzastaurin for Cell-line-Subtype 1 (CS1) and a BTK inhibitor QL-XII-61 for Cell-line-Subtype 2 (CS2). The defining features, such as smoking-related methylation signature, were significantly associated with the sensitivity to several drugs. Interpretation: The heterogeneity of KRAS-mutant LUAD is associated with smoking-related genomic and epigenomic aberration along with other features such as immunogenicity, KRAS dependency and STK11/KEAP1 co-mutations. These features might be used as biomarkers for drug sensitivity prediction. Fund: This research was funded by the Young Scientists Fund of the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province, China and the Education and Research Foundation for Young Scholars of Education Department of Fujian Province, China. Keywords: KRAS-mutant lung adenocarcinoma, KRAS subtypes, TIL-associating score, Smoking-related methylation signature, Smoking-related mutational signature, Drug sensitivity prediction

We present a description of the Tropospheric Emission Spectrometer (TES) carbonyl sulfide (OCS) retrieval algorithm, along with evaluation of the biases and uncertainties against aircraft profiles from the HIPPO campaign and data from the NOAA Mauna Loa site. In general, the OCS retrievals (1) have less than 1.0 degree of freedom for signals (DOFs), (2) are sensitive in the mid-troposphere with a peak sensitivity typically between 300 to 500 hPa, (3) but have much smaller systematic errors from temperature, CO2 and H2O calibrations relative to random errors from measurement noise. Here we estimate the monthly means from TES measurements averaged over multiple years so that random errors are reduced and useful information about OCS seasonala latitudinal variability can be derived. With this averaging, TES OCS data are found to be consistent (within the calculated uncertainties) with NOAA ground observations and HIPPO aircraft measurements. TES OCS data also captures the seasonal and latitudinal variations observed by these in situ data. [ABSTRACT FROM AUTHOR]

Monitoring the global distribution and long-term variations of CO2 sources and sinks is required for characterizing the global carbon budget. Total column measurements are useful for estimating regional-scale fluxes; however, model transport remains a significant error source, particularly for quantifying local sources and sinks. To improve the capability of estimating regional fluxes, we estimate lower tropospheric CO2 concentrations from groundbased near-infrared (NIR) measurements with space-based thermal infrared (TIR) measurements. The NIR measurements are obtained from the Total Carbon Column Observing Network (TCCON) of solar measurements, which provide an estimate of the total CO2 column amount. Estimates of tropospheric CO2 that are co-located with TCCON are obtained by assimilating Tropospheric Emission Spectrometer (TES) free tropospheric CO2 estimates into the GEOS-Chem model.We find that quantifying lower tropospheric CO2 by subtracting free tropospheric CO2 estimates from total column estimates is a linear problem, because the calculated random uncertainties in total column and lower tropospheric estimates are consistent with actual uncertainties as compared to aircraft data. For the total column estimates, the random uncertainty is about 0.55 ppm with a bias of -5.66 ppm, consistent with previously published results. After accounting for the total column bias, the bias in the lower tropospheric CO2 estimates is 0.26 ppm with a precision (one standard deviation) of 1.02 ppm. This precision is sufficient for capturing the winter to summer variability of approximately 12 ppm in the lower troposphere; double the variability of the total column. This work shows that a combination of NIR and TIR measurements can profile CO2 with the precision and accuracy needed to quantify lower tropospheric CO2 variability. [ABSTRACT FROM AUTHOR]

The article discusses a study on the use of Aura TES and TCCON instruments for profiling tropospheric carbon dioxide. The study aims to improve the capability of estimating regional fluxes and estimates near-surface carbon dioxide values from ground-based near infrared (NIR) measurements with space-based thermal infrared (TIR) measurements. It reveals the consistency of calculated random uncertainties in total column and boundary layer with actual uncertainties as compared to aircraft data.

Brown adipose tissue (BAT) has attracted considerable research interest because of its therapeutic potential to treat obesity and associated metabolic diseases. Augmentation of brown fat mass and/or its function may represent an attractive strategy to enhance energy expenditure. Using high-throughput phenotypic screening to induce brown adipocyte reprogramming in committed myoblasts, we identified a retinoid X receptor (RXR) agonist, bexarotene (Bex), that efficiently converted myoblasts into brown adipocyte-like cells. Bex-treated mice exhibited enlarged BAT mass, enhanced BAT function, and a modest browning effect in subcutaneous white adipose tissue (WAT). Expression analysis showed that Bex initiated several “browning” pathways at an early stage during brown adipocyte reprogramming. Our findings suggest RXRs as new master regulators that control brown and beige fat development and activation, unlike the common adipogenic regulator PPARγ. Moreover, we demonstrated that selective RXR activation may potentially offer a therapeutic approach to manipulate brown/beige fat function in vivo.

The traditional sample preparation methods are pressed powder pellets and glass melting to determine major components for sulfide ores by X-ray Fluorescence Spectrometry. However, for high sulfur geological samples, the preparation method of pressed powder pellet has mineralogical effects and particle size effects, and the glass melting method has the disadvantage of being corrosive to precious metal crucibles. Development of a simple sample preparation method for principal components analysis is essential to meet the requirements for exploration of mineral deposits. In this paper a method is presented to determine Cu, Pb, Zn contained in sulfide ores. This method utilizes Polarized Energy Dispersive X-ray Fluorescence Spectrometry (PE-EDXRF) along with nitric acid and fluoric acid digestion, and is calibrated by standard solution. The accuracy and precision of the method were examined by analyzing reference materials GBW 07162 to GBW 07168. The test results indicate that the relative standard deviations (RSD, n=6) of the most elemental components are less than 5%, when the concentrations of copper, zinc and lead are more than 1%. The results are in good agreement with certified values of reference materials. The impact of matrix effects such as particle size effect and mineral effect on analytical elements has been eliminated by digestion sample and direct solution inlet. The problem of calibrating concentrations that were short of standard materials has been solved with the matrix matching. The technology of PE-EDXRF provides a new means of ore analysis in the laboratory and a new technical support for PE-EDXRF field analysis for high sulfide samples.