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Qiongdan Zhang,1,2,* Huizhen Wang,1,2,* Qingyi Liu,1,2 Ni Zeng,1,2 Gang Fu,1,2 Yixing Qiu,1,2 Yupei Yang,1,2 Hanwen Yuan,1,2 Wei Wang,1,2 Bin Li1,2 1TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Wang; Bin Li, Tel +86-136-5743-8606 ; +86-158-7410-0917, Email wangwei402@hotmail.com; libin@hnucm.edu.cnAbstract: Exosomes, small extracellular vesicles derived from cells, are known to carry important bioactive molecules such as proteins, nucleic acids, and lipids. These bioactive components play crucial roles in cell signaling, immune response, and tumor metastasis, making exosomes potential diagnostic biomarkers for various diseases. However, current methods for detecting tumor exosomes face scientific challenges including low sensitivity, poor specificity, complicated procedures, and high costs. It is essential to surmount these obstacles to enhance the precision and dependability of diagnostics that rely on exosomes. Merging DNA signal amplification techniques with the signal boosting capabilities of nanomaterials presents an encouraging strategy to overcome these constraints and improve exosome detection. This article highlights the use of DNA signal amplification technology and nanomaterials’ signal enhancement effect to improve the detection of exosomes. This review seeks to offer valuable perspectives for the enhancement of amplification methods applied in practical cancer diagnosis and prognosis by providing an overview of how these novel technologies are utilized in exosome-based diagnostic procedures. Keywords: tumor, exosomes, nanomaterials, DNA signal amplification

Clarifying how increased atmospheric CO2 concentration (eCO2) contributes to accelerated land carbon sequestration remains important since this process is the largest negative feedback in the coupled carbon–climate system. Here, we constrain the sensitivity of the terrestrial carbon sink to eCO2 over the temperate Northern Hemisphere for the past five decades, using 12 terrestrial ecosystem models and data from seven CO2 enrichment experiments. This constraint uses the heuristic finding that the northern temperate carbon sink sensitivity to eCO2 is linearly related to the site-scale sensitivity across the models. The emerging data-constrained eCO2 sensitivity is 0.64 ± 0.28 PgC yr−1 per hundred ppm of eCO2. Extrapolating worldwide, this northern temperate sensitivity projects the global terrestrial carbon sink to increase by 3.5 ± 1.9 PgC yr−1 for an increase in CO2 of 100 ppm. This value suggests that CO2 fertilization alone explains most of the observed increase in global land carbon sink since the 1960s. More CO2 enrichment experiments, particularly in boreal, arctic and tropical ecosystems, are required to explain further the responsible processes.

Xiaofang Wen,1,&ast; Nan Zeng,1,&ast; Ningbo Zhang,1,2,&ast; Tingting Ou,1 Xiaowei Li,1 Xiaoying Li,1 Wangen Li,1 Kang Xu,3 Tao Du1 1Department of Endocrinology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China; 2Department of Endocrinology, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Du; Kang Xu, Email dutao@gzhmu.edu.cn; xukang@mail.sysu.edu.cnBackground: Although flash continuous glucose monitoring systems (FCGM) accuracy has been extensively studied in diabetes, its accuracy is still not fully evaluated in type 2 diabetes (T2D) patients in real-world settings. In the present study, we aim to assess the effects of diabetes complications and related comorbidities on FCGM accuracy in T2D patients with diabetes complications and related comorbidities in the real world.Methods: FCGM data were collected at eight-time points daily (3 AM, 7 AM, 9 AM, 11 AM, 1 PM, 5 PM, 7 PM, and 9 PM) from 742 patients with T2D and compared with simultaneous fingertip capillary blood glucose (reference blood glucose, REF), and the difference was evaluated using Parkes error grid (PEG), surveillance error grid (SEG), and logistic regression analysis.Results: In total, 25,579 FCGM/REF data pairs were included in the study. The FCGM values were lower than the paired REF values in 75% of the pairs. The maximum bias (− 23.0%) and maximum mean absolute relative difference (24.5%) were observed at 3 AM among eight-time points. SEG analysis also demonstrated the highest percentage of paired readings in moderate and great risk zone (C and D) at 3 AM than PEG analysis (7.33% vs 0.43%, P< 0.001). According to the SEG classification, hypoglycemia, infection, diabetic foot, diabetic ketoacidosis, and hypertension were independent risk factors that impaired FCGM accuracy in patients.Conclusion: FCGM commonly underestimates blood glucose levels. Compared with PEG, SEG analysis seems more conducive to the analysis of FCGM performance. The present data highlights the impairment of diabetes complications and related comorbidities on the FCGM accuracy in T2D patients.Keywords: flash continuous glucose monitoring system, type 2 diabetes, surveillance error grid, Parkes error grid, diabetes complications

NASA has launched the decade-long Arctic-Boreal Vulnerability Experiment (ABoVE). While the initial phases focus on field and airborne data collection, early integration with modeling activities is important to benefit future modeling syntheses. We compiled feedback from ecosystem modeling teams on key data needs, which encompass carbon biogeochemistry, vegetation, permafrost, hydrology, and disturbance dynamics. A suite of variables was identified as part of this activity with a critical requirement that they are collected concurrently and representatively over space and time. Individual projects in ABoVE may not capture all these needs, and thus there is both demand and opportunity for the augmentation of field observations, and synthesis of the observations that are collected, to ensure that science questions and integrated modeling activities are successfully implemented.

Ni Zeng,1,2 Yueyue Li,2 Qian Wang,3 Yihe Chen,2 Yan Zhang,1 Lanfang Zhang,1 Feng Jiang,4,5 Wei Yuan,1 Dan Luo2 1Department of Dermatology, Affiliated Hospital of Zunyi Medical University,149 Dalian Road, Huichuan District, Guizhou, 563003, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 3Department of Endocrinology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, People’s Republic of China; 4Neonatal Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China; 5Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 21000, People’s Republic of ChinaCorrespondence: Wei YuanDepartment of Dermatology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Guizhou, 563003, People’s Republic of ChinaTel/Fax +86 13655187928Email dryuanweihua@sina.comDan LuoDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of ChinaTel/Fax +86 13655187928Email daniluo2005@163.comPurpose: To identify potential risk factors for herpes zoster infection in type 2 diabetes mellitus in southeast Chinese population.Patients and Methods: We built a model involving 266 herpes zoster patients collecting data from January 2018 to December 2019. The least absolute shrinkage and selection operator (Lasso) predictive model was used to test herpes zoster virus risk using the patient data. Multivariate regression was conducted to decide which variable would be the strongest to decrease the Lasso penalty. The predictive model was tested using the C-index, a calibration plot, and decision curve study. External validity was verified by bootstrapping by counting probabilities.Results: In the prediction nomogram, the prediction variables included age, sex, weight, length of hospital stay, infection, and blood pressure. The C-index of 0.844 (0.798– 0.896) indicated substantial variability and thus the model was adjusted appropriately. A score of 0.825 was achieved somewhere in the above interval. Examination of the decision curve estimated that herpes zoster nomogram was useful when the intervention was determined at the 16 percent of the herpes zoster infection potential threshold.Conclusion: The herpes zoster nomogram combines age, weight, position of the rash, 2-hour plasma glucose, glycosuria, serum creatinine, length of the hospital stay, and hypertension. This calculator can be used to assess the individual herpes zoster risks in patients diagnosed with type 2 diabetes mellitus.Keywords: glycemic status, herpes zoster, nomogram, type 2 diabetes mellitus, infection

Ni Zeng,1,2 Liwen Ma,3 Yuxin Cheng,1 Qingyue Xia,1 Yueyue Li,1 Yihe Chen,1 Zhiyu Lu,1 Qian Lu,1 Feng Jiang,4 Dan Luo1 1Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 3Department of Dermatology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 4Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of ChinaCorrespondence: Dan LuoDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, People’s Republic of ChinaEmail daniluo2005@163.comFeng JiangDepartment of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People’s Republic of ChinaEmail dxyjiang@163.comObjective: In this research, we studied the genes associated with ferroptosis to develop a prognostic model and find out an association with tumor immune microenvironment in skin cutaneous melanoma (SKCM) patients.Methods: To find SKCM-related ferroptosis genes, we used Cox regression and LASSO approach on 60 genes related to ferroptosis and SKCM-related RNA-seq. Following that, a ferroptosis-related gene signature was created. Time-dependent ROC curve and Kaplan–Meier analysis were calculated to determine its capability of prediction. Besides, several assessments were used to evaluate overall survival (OS), accompanied by the creation of a nomogram for the clinicopathologic factors and the ferroptosis-related gene signature we established. We also investigated the relationship between ferroptosis-related gene signature with three immune checkpoints and immune cell infiltration.Results: Our prognostic model included two genes (ALOX5, CHAC1). In both TCGA and GEO cohorts, OS was lower in high-risk category. Using our gene signature, we can reliably predict OS. Additionally, our gene signature can predict immune cell infiltration and SKCM immunotherapy response.Conclusion: Our gene signature has shown to be a reliable predictor of OS, reflect the immune microenvironment, and predict the effectiveness of immunotherapy for SKCM patients.Keywords: skin cutaneous melanoma, SKCM, ferroptosis, immune microenvironment, immune checkpoint

Terrestrial ecosystems play a vital role in regulating the accumulation of carbon (C) in the atmosphere. Understanding the factors controlling land C uptake is critical for reducing uncertainties in projections of future climate. The relative importance of changing climate, rising atmospheric CO2, and other factors, however, remains unclear despite decades of research. Here, we use an ensemble of land models to show that models disagree on the primary driver of cumulative C uptake for 85% of vegetated land area. Disagreement is largest in model sensitivity to rising atmospheric CO2 which shows almost twice the variability in cumulative land uptake since 1901 (1 s.d. of 212.8 PgC vs. 138.5 PgC, respectively). We find that variability in CO2 and temperature sensitivity is attributable, in part, to their compensatory effects on C uptake, whereby comparable estimates of C uptake can arise by invoking different sensitivities to key environmental conditions. Conversely, divergent estimates of C uptake can occur despite being based on the same environmental sensitivities. Together, these findings imply an important limitation to the predictability of C cycling and climate under unprecedented environmental conditions. We suggest that the carbon modeling community prioritize a probabilistic multi-model approach to generate more robust C cycle projections.

Accomplishing the objective of the current climate policies will require establishing carbon budget and flux estimates in each region and county of the globe by comparing and reconciling multiple estimates including the observations and the results of top-down atmospheric carbon dioxide (CO2) inversions and bottom-up dynamic global vegetation models. With this in view, this study synthesizes the carbon source/sink due to net ecosystem productivity (NEP), land cover land use change (E LUC), fires and fossil burning (E FIRE) for the South Asia (SA), Southeast Asia (SEA) and South and Southeast Asia (SSEA = SA + SEA) and each country in these regions using the multiple top-down and bottom-up modeling results. The terrestrial net biome productivity (NBP = NEP - E LUC - E FIRE) calculated based on bottom-up models in combination with E FIRE based on GFED4s data show net carbon sinks of 217 ±147, 10 ±55, and 227 ±279 TgC yr-1 for SA, SEA, and SSEA. The top-down models estimated NBP net carbon sinks were 20 ±170, 4 ±90 and 24 ±180 TgC yr-1. In comparison, regional emissions from the combustion of fossil fuels were 495, 275, and 770 TgC yr-1, which are many times higher than the NBP sink estimates, suggesting that the contribution of the fossil fuel emissions to the carbon budget of SSEA results in a significant net carbon source during the 2000s. When considering both NBP and fossil fuel emissions for the individual countries within the regions, Bhutan and Laos were net carbon sinks and rest of the countries were net carbon source during the 2000s. The relative contributions of each of the fluxes (NBP, NEP, E LUC, and E FIRE, fossil fuel emissions) to a nation's net carbon flux varied greatly from country to country, suggesting a heterogeneous dominant carbon fluxes on the country-level throughout SSEA.

Ting Guo,1– 3,* Qinxue Shen,1– 3,* Zhiguo Zhou,4 Jinhua Li,1– 3 Wei Guo,1– 3 Wenlong He,1– 3 Yunnian Wang,5 Zhi Xiang,6 Peng Huang,7 Nanyang Zeng,8 Qingwu Qin,1– 3 Ping Chen,1– 3 Hong Luo,1– 3 Hong Peng1– 3 1Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, People’s Republic of China; 2Research Unit of Respiratory Disease, Central-South University, Changsha, Hunan, People’s Republic of China; 3The Respiratory Disease Diagnosis and Treatment Center of Hunan Province, Changsha, Hunan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Hospital of Changsha, Changsha, Hunan, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, The Traditional Chinese Medicine Hospital of Liling, Zhuzhou, Hunan, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Huaihua, Huaihua, Hunan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, The Central Hospital of Zhuzhou, Zhuzhou, Hunan, People’s Republic of China; 8Department of Infectious Disease, The Lvkou People’s Hospital of Zhuzhou, Zhuzhou, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong PengDepartment of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central-South University, No. 139 Renmin Middle Road, Changsha, Hunan 410011, People’s Republic of ChinaTel +86 13807494486Email penghong66@csu.edu.cnPurpose: To summarize the clinical features and effective therapy of severe COVID-19 patients.Patients and Methods: In this retrospective, multicenter study, the medical records of COVID-19 patients in Hunan, from January 21, 2020 to February 19, 2020 were reviewed.Results: Of the 350 COVID-19 patients, 13.7% were severe cases. On admission, compared with non-severe patients, more severe patients had a neutrophil/lymphocyte ratio > 3 (58.3% vs 33.8%, P=0.001), D-dimer > 1 mg/L (41.7% vs 13.6%, P< 0.0001), higher level of CRP (39.1 mg/L, IQR18.1– 75.9 vs 13.4 mg/L, IQR5.0– 32.8, P< 0.0001), and multiple pneumonia on CT (77.1% vs 18.2%, P< 0.0001). All severe patients received oxygen support. 95.8% of them received antivirals, and the most frequent therapy was lopinavir and ritonavir plus human interferon-α 2b. Moxifloxacin was used in 70.8% severe patients. The total dosage of methylprednisolone sodium succinate was 640 mg (IQR 360– 960) in severe patients, and the duration of use was 8.5 days (IQR 6.8– 11.3). The total dosage of immunoglobulin was 80 g (IQR, 60– 140) in severe patients, and the duration was 8.0 days (IQR, 6.0– 11.5). As of March 15, 2020, 95.8% of the severe patients had been discharged and only two deaths occurred.Conclusion: The rate of severe cases and mortality of COVID-19 in Hunan are lower than those in Wuhan. In addition to antivirals and oxygen support, timely interventions including corticosteroids, immunoglobulin, and antibiotics, contribute to improving the prognosis of severe COVID-19 patients.Keywords: coronavirus disease 2019, SARS-CoV-2, severe disease, corticosteroid, immunoglobulin

We examined the net terrestrial carbon flux to the atmosphere (FTA) simulated by nine models from the TRENDY dynamic global vegetation model project for its seasonal cycle and amplitude trend during 1961-2012. While some models exhibit similar phase and amplitude compared to atmospheric inversions, with spring drawdown and autumn rebound, others tend to rebound early in summer. The model ensemble mean underestimates the magnitude of the seasonal cycle by 40g% compared to atmospheric inversions. Global FTA amplitude increase (19g±g8g%) and its decadal variability from the model ensemble are generally consistent with constraints from surface atmosphere observations. However, models disagree on attribution of this long-term amplitude increase, with factorial experiments attributing 83g±g56g%, ĝ'3g±g74 and 20g±g30g% to rising CO2, climate change and land use/cover change, respectively. Seven out of the nine models suggest that CO2 fertilization is the strongest control - with the notable exception of VEGAS, which attributes approximately equally to the three factors. Generally, all models display an enhanced seasonality over the boreal region in response to high-latitude warming, but a negative climate contribution from part of the Northern Hemisphere temperate region, and the net result is a divergence over climate change effect. Six of the nine models show that land use/cover change amplifies the seasonal cycle of global FTA: some are due to forest regrowth, while others are caused by crop expansion or agricultural intensification, as revealed by their divergent spatial patterns. We also discovered a moderate cross-model correlation between FTA amplitude increase and increase in land carbon sink (R2 Combining double low line g0.61). Our results suggest that models can show similar results in some benchmarks with different underlying mechanisms; therefore, the spatial traits of CO2 fertilization, climate change and land use/cover changes are crucial in determining the right mechanisms in seasonal carbon cycle change as well as mean sink change.

Global environmental change is rapidly altering the dynamics of terrestrial vegetation, with consequences for the functioning of the Earth system and provision of ecosystem services. Yet how global vegetation is responding to the changing environment is not well established. Here we use three long-term satellite leaf area index (LAI) records and ten global ecosystem models to investigate four key drivers of LAI trends during 1982-2009. We show a persistent and widespread increase of growing season integrated LAI (greening) over 25% to 50% of the global vegetated area, whereas less than 4% of the globe shows decreasing LAI (browning). Factorial simulations with multiple global ecosystem models suggest that CO2 fertilization effects explain 70% of the observed greening trend, followed by nitrogen deposition (9%), climate change (8%) and land cover change (LCC) (4%). CO2 fertilization effects explain most of the greening trends in the tropics, whereas climate change resulted in greening of the high latitudes and the Tibetan Plateau. LCC contributed most to the regional greening observed in southeast China and the eastern United States. The regional effects of unexplained factors suggest that the next generation of ecosystem models will need to explore the impacts of forest demography, differences in regional management intensities for cropland and pastures, and other emerging productivity constraints such as phosphorus availability.

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates as well as consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2, and land-cover change (some including nitrogen-carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2005-2014), EFF was 9.0 ± 0.5 GtC yrg'1, ELUC was 0.9 ± 0.5 GtC yrg'1, GATM was 4.4 ± 0.1 GtC yrg'1, SOCEAN was 2.6 ± 0.5 GtC yrg'1, and SLAND was 3.0 ± 0.8 GtC yrg'1. For the year 2014 alone, EFF grew to 9.8 ± 0.5 GtC yrg'1, 0.6 % above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2 % yrg'1 that took place during 2005-2014. Also, for 2014, ELUC was 1.1 ± 0.5 GtC yrg'1, GATM was 3.9 ± 0.2 GtC yrg'1, SOCEAN was 2.9 ± 0.5 GtC yrg'1, and SLAND was 4.1 ± 0.9 GtC yrg'1. GATM was lower in 2014 compared to the past decade (2005-2014), reflecting a larger SLAND for that year. The global atmospheric CO2 concentration reached 397.15 ± 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in EFF will be near or slightly below zero, with a projection of g'0.6 [range of g'1.6 to +0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of EFF and assumed constant ELUC for 2015, cumulative emissions of CO2 will reach about 555 ± 55 GtC (2035 ± 205 GtCO2) for 1870-2015, about 75 % from EFF and 25 % from ELUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quéré et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP-2015).

Wenping Mao,1,2 Jing Wang,1,2 Liming Zhang,1,2 Ying Wang,1,2 Wenjun Wang,1,2 Na Zeng,3 Jun Zhang,1,2 Qian li,1,2 Fengwei Jiao,1,2 Jie Li,1,2 Na Cui,1,2 Song Mi,1,2 Yi Xue,1,2 Zhaomei Wang,1,2 Sun Ying,4 Kewu Huang1,2 1Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2Beijing Institute of Respiratory Medicine, Beijing 100020, People’s Republic of China; 3Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People’s Republic of China; 4Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, People’s Republic of ChinaCorrespondence: Kewu HuangDepartment of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, People’s Republic of ChinaTel + 86-10-85231167Email kewuhuang@126.comPurpose: We hypothesized that increased level of serum β 2-microglobulin (β 2M) is an independent factor associated with higher mortality in hospitalized patients with exacerbated chronic obstructive pulmonary disease (COPD).Patients and Methods: We retrospectively analyzed 488 hospitalized patients with exacerbated COPD as the first diagnosis at Beijing Chao-Yang hospital, P. R. China between December 31st, 2012 and December 28th, 2017. Concentrations of serum β 2M and other clinical indexes were measured or collected on admission, and all patients were followed up to 90 days. The relationship between β 2M and 30- and 90-day all-cause mortality was explored by Cox regression analysis adjusted for age, C-reactive protein values, N-terminal pro-brain natriuretic peptide/100, respiratory failure [RF, defined as partial arterial oxygen pressure (PaO2) < 60 mmHg on room air or PaO2 over the fraction of inspired oxygen (PaO2/FiO2) < 300], eosinopenia, consolidation, and acidaemia.Results: Median concentrations of β 2M were significantly higher in non-survivals compared to survivals within 30 days (4.11 mg/L (IQR 3.10– 6.60) vs 2.79mg/L (IQR 2.13– 3.76), P < 0.001) and 90 days (3.79 mg/L (IQR 2.61– 6.69) vs 2.79 mg/L (IQR 2.13– 3.73), P < 0.001). Serum levels of β 2M were correlated with 30-day and 90-day mortality in overall exacerbated COPD patients, with hazard ratios (HRs) of 1.09 (95% CI 1.04– 1.14, P = 0.001) and 1.09 (95% CI 1.05– 1.14, P < 0.001). In exacerbated COPD patients without RF and with RF, the HRs were 1.06 (95% CI 0.995– 1.137, P = 0.069) and 1.14 (95% CI 1.02– 1.27, P = 0.021) for 30-day mortality, 1.09 (95% CI 1.02– 1.15, P = 0.010) and 1.14 (95% CI 1.03– 1.26, P = 0.014) for 90-day mortality, respectively.Conclusion: Our data showed that concentrations of serum β 2M were associated with an increased risk of mortality, suggesting that β 2M might be a valuable predictor of poor prognosis for hospitalized patients with exacerbated COPD.Keywords: β 2-microglobulin, COPD, exacerbation, predictor, prognosis

Lei Jin,1,2,* Xue-Mei Ma,1,2,* Ting-Ting Wang,1,2 Yao Yang,1,2 Nan Zhang,2,3 Na Zeng,2,4 Zhi-Gang Bai,1,2 Jie Yin,1,2 Jun Zhang,1,2 Guo-Qian Ding,1,2 Zhong-Tao Zhang1,2 1Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2National Clinical Research Center for Digestive Diseases, Beijing, People’s Republic of China; 3Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Clinical Epidemiology and EBM Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Qian Ding; Zhong-Tao Zhang Email dingguoqian@gmail.com; zhangzhongtao@ccmu.edu.cnPurpose: The present study aimed to investigate the impact of psoralen on miR-196a-5p expression and function, and to reveal the mechanism underlying miR-196a-5p-mediated inhibition and the reversal of cisplatin (DDP) resistance.Methods: Serum samples were collected from 50 patients with gastric cancer (GC), and the association between miR-196a-5p expression and the response to chemotherapy was assessed. A DDP-resistant GC cell line was also established to determine the effects of miR-196a-5p and psoralen on DDP resistance. MGC803 cells were transfected with miR-196a-5p mimic and inhibitor vectors for the overexpression and downregulation of miR-196a-5p, respectively.Results: Clinical data analysis showed that the lower expression levels of miR-196a-5p were significantly associated with chemoresistance in patients with GC. Upregulation of miR-196a-5p significantly enhanced the anti-proliferative effect, apoptosis and sensitivity to DDP by regulating the protein expression levels of HOXB7, HER2, Bcl-2 and G1/S-specific cyclin-D1 (CCND1). Furthermore, psoralen reversed miR-196a-5p-induced DDP resistance and reduced the expression levels of HOXB7, HER2, Bcl-2 and CCND1.Conclusion: miR-196a-5p may be a novel biomarker of chemotherapeutic success in patients with GC and may also influence the sensitivity of GC cells to DDP. Moreover, psoralen can increase chemotherapeutic sensitivity by upregulating miR-196a-5p and then downregulating HOXB7-HER2 signaling axis.Keywords: miR-196a-5p, psoralen, chemoresistance, cisplatin, gastric cancer, HOXB7

This paper summarizes the results of an intercomparison project with Earth System Models of Intermediate Complexity (EMICs) undertaken in support of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5). The focus is on long-term climate projections designed to 1) quantify the climate change commitment of different radiative forcing trajectories and 2) explore the extent to which climate change is reversible on human time scales. All commitment simulations follow the four representative concentration pathways (RCPs) and their extensions to year 2300. MostEMICs simulate substantial surface air temperature and thermosteric sea level rise commitment following stabilization of the atmospheric composition at year-2300 levels. The meridional overturning circulation (MOC) is weakened temporarily and recovers to near-preindustrial values in most models for RCPs 2.6-6.0. The MOC weakening is more persistent for RCP8.5. Elimination of anthropogenic CO2 emissions after 2300 results in slowly decreasing atmospheric CO2 concentrations. At year 3000 atmospheric CO2 is still at more than half its year-2300 level in all EMICs forRCPs 4.5-8.5. Surface air temperature remains constant or decreases slightly and thermosteric sea level rise continues for centuries after elimination ofCO2 emissions in allEMICs.Restoration of atmosphericCO2 fromRCPto preindustrial levels over 100-1000 years requires large artificial removal of CO2 from the atmosphere and does not result in the simultaneous return to preindustrial climate conditions, as surface air temperature and sea level response exhibit a substantial time lag relative to atmospheric CO2. © 2013 American Meteorological Society.

Hao Wang,1,* Caishuang Pang,2,* Ni Zeng,1 Chun Wan,1 Yongchun Shen,1 Fuqiang Wen1 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Chengdu, China; 2Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, China *These authors contributed equally to this work Background: The gene polymorphism of interleukin-6 (IL-6) has been shown to be implicated in tuberculosis susceptibility in many studies, but with conflicting results. This study aimed to provide more accurate estimation of the relationship between IL-6 gene polymorphism and tuberculosis risk through a meta-analysis Method: A literature search was performed in PubMed, EMBASE, and other databases. Data were retrieved, and pooled odds ratio (OR) with 95% CI were calculated. Statistical analyses were performed by using STATA 12.0. Results: Twelve publications with 2635 cases and 3049 controls were included. The pooled analysis demonstrated significant evidence of association between IL-6 (-174G/C) and low risk of tuberculosis in dominant model (CC+GC vs GG: OR =0.693, 95% CI 0.581–0.826, p

Xerocomoideae is an ecologically and economically important Boletaceae subfamily (Boletales) comprising 10 genera. Although many studies have focused on Xerocomoideae in China, the diversity, taxonomy and molecular phylogeny still remained incompletely understood. In the present study, taxonomic and phylogenetic studies on Chinese species of Xerocomoideae were carried out by morphological examinations and molecular phylogenetic analyses. Eight genera in Xerocomoideae, viz. Aureoboletus, Boletellus, Heimioporus, Hemileccinum, Hourangia, Phylloporus, Pulchroboletus, and Xerocomus were confirmed to be distributed in China; 97 species of the subfamily were accepted as being distributed in China; one ambiguous taxon was tentatively named Bol. aff. putuoensis; two synonyms, viz. A. marroninus and P. dimorphus were defined. Among the Chinese accepted species, 13 were newly described, viz. A. albipes, A. conicus, A. ornatipes, Bol. erythrolepis, Bol. rubidus, Bol. sinochrysenteroides, Bol. subglobosus, Bol. zenghuoxingii, H. squamipes, P. hainanensis, Pul. erubescens, X. albotomentosus, and X. fuscatus, 36 known species were redescribed, and the other 48 species were reviewed. Keys to accepted species of Aureoboletus, Boletellus, Heimioporus, Hemileccinum, Hourangia, Phylloporus, and Xerocomus in China were also provided. [ABSTRACT FROM AUTHOR]

Nan Zeng, Zan Gao College of Education and Human Development, School of Kinesiology, University of Minnesota, Minneapolis, MN, USA Abstract: Although exergaming has been used as a physical activity modality among various populations, the evidence regarding its effectiveness on health-related outcomes in overweight/obese individuals remains unclear. The current study systematically reviewed literature and summarized findings of exergame-based interventions in overweight/obese populations with the goal of clarifying the current perspectives on exergaming and obesity. The initial search yielded 202 articles from six databases; 12 studies were included after evaluating for inclusion criteria and removing duplicates. Among these studies, seven were randomized controlled trials, two were control trials, and three were comparison studies. Overall, exergaming has the potential to attenuate weight gain and shows promise when used for physical activity and physical fitness promotion. Further, exergame play is positively associated with psychological well-being, but its effects on physiological outcomes are inconclusive. Finally, effects of exergaming on energy intake are not clear. Existing evidence supports that exergaming may elicit some health benefits in people who are overweight or/and obese. The limited number of available randomized controlled trials, however, restrict the ability to draw a conclusion that exergaming can trigger a change in all health-related outcomes. More research is warranted to make definitive conclusions regarding the effects of exergaming on health-related outcomes in such populations. Keywords: active video game, weight loss, children and adolescents, systematic review

Ni Zeng,1,3,* Xiaoling Gao,2,* Quanyin Hu,1 Qingxiang Song,2 Huimin Xia,1 Zhongyang Liu,1 Guangzhi Gu,1 Mengyin Jiang,1,4 Zhiqing Pang,1 Hongzhuan Chen,2 Jun Chen,1 Liang Fang3 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 2Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, 3Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 4School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong People's Republic of China, *These authors contributed equally to this workBackground: Lipid-based liquid crystalline nanoparticles (LCNPs) have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized.Methods: In this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a "ball-like"/"hexagonal" morphology.Results: Cellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and to fuse with the cell membrane. An in vivo pharmacokinetic study showed that the oral bioavailability of paclitaxel-loaded LCNPs (13.16%) was 2.1 times that of Taxol® (the commercial formulation of paclitaxel, 6.39%).Conclusion: The findings of this study suggest that this LCNP delivery system may be a promising candidate for improving the oral bioavailability of poorly water-soluble agents.Keywords: soy phosphatidylcholine, glycerol dioleate, liquid crystalline nanoparticles, paclitaxel, cellular interaction

Gang Wang1,2, Jun Jie Wang1, Guang Yi Yang1, Shi Ming Du1, Nan Zeng2, Dong Sheng Li3, Rui Ming Li3, Ji Yan Chen1, Jin Bo Feng3, Shen Hao Yuan1, Fang Ye11Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, 2Department of Pharmacy, Chendu Traditional Chinese Medical University, Chendu City, Sichuan Province, 3Hubei Provincial Key Laboratory of Embryo Stem Cells, Shiyan City, Hubei Province, People's Republic of ChinaBackground: Quercetin has been shown to induce apoptosis in a number of cancer cell lines, but a quercetin-loaded nanoliposomal formulation with enhanced antitumor activity in C6 glioma cells and its effect on cancer cell death has not been well studied. The aim of this study was to examine if quercetin-loaded liposomes (QUE-NL) has enhanced cytotoxic effects and if such effects involve type III programmed cell death in C6 glioma cells.Methods: C6 glioma cells were treated with QUE-NL and assayed for cell survival, apoptosis, and necrosis. Levels of reactive oxygen species production and loss of mitochondrial membrane potential (ΔΨm) were also determined by flow cytometry assay to assess the effects of QUE-NL. ATP levels and lactate dehydrogenase activity were measured, and Western blotting was used to assay cytochrome C release and caspase expression.Results: QUE-NL induced type III (necrotic) programmed cell death in C6 glioma cells in a dose-dependent and time-dependent manner. High concentrations of QUE-NL induced cell necrosis, which is distinct from apoptosis and autophagy, whereas liposomes administered alone induced neither significant apoptosis nor necrosis in C6 glioma cells. QUE-NL-induced ΔΨm loss and cytochrome C release had no effect on caspase activation, but decreased ATP levels and increased lactate dehydrogenase activity indicated that QUE-NL stimulated necrotic cell death.Conclusion: C6 glioma cells treated with QUE-NL showed a cellular pattern associated with necrosis without apoptosis and was independent of caspase activity. Nonapoptotic cell death induced by high concentrations of QUE-NL for controlling caspase-independent type III programmed cell death may provide the basis for novel therapeutic approaches to overcome avoidance of apoptosis by malignant cells.Keywords: quercetin, liposome, type III programmed cell death, reactive oxygen species, ATP, mitochondria, C6 glioma cells