bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosome-transmitted LINC00960 and LINC02470 promote the epithelial-mesenchymal transition and aggressiveness of bladder cancer cells
Authors: Huang Cheng-Shuo , Ho Jar-Yi , Chiang Jung-Hwa , Yu Cheng-Ping , Yu Dah-Shyong 
Published: April 2020

Abstract
Background

Exosomes are essential for several tumor progression-related processes, including epithelial-mesenchymal transition (EMT). Long noncoding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive roles of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470; we found that these lncRNAs potently induced EMT during bladder cancer progression.
Methods

Low-grade bladder cancer cells (TSGH-8301) were treated with conditioned media or exosomes derived from high-grade bladder cancer cells (T24 or J82), and the aggressiveness-promoting effects were evaluated. Cell viability, cell migratory/invasive activities and clonogenicity were compared to assess the response to these intercellular transmissions. Exosome-transmitted lncRNA candidates were screened with bioinformatic pipelines, and their expression levels were validated in bladder cancer cells and exosomes. Two novel lncRNAs, LINC00960 and LINC02470, were selected, and their roles and regulatory mechanisms in inducing the aggressiveness of bladder cancer cells were investigated.
Results

Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including β-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells.
Conclusion

Our findings indicate that exosome-transmitted LINC00960 and LINC02470 from high-grade bladder cancer cells promotes the malignant behaviors of recipient low-grade bladder cancer cells and induces EMT by upregulating β-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.
ASXL2 promotes colorectal cancer tumorigenesis by inducing cell proliferation
Authors: Cui Ran , Yang Ludi , Wang Yiwei , Zhong Ming , Yu Minhao , Chen Bo 
Published: April 2020

Abstract
Background: Colorectal cancer is one of the most common malignant tumors worldwide. ASXL2 is an enhancer of trithorax and polycomb gene, which have been proved to act in many tumor types. The role of ASXL2 in the occurrence and development of tumors have been extensively studied in recent years. However the relationship between ASXL2 and the prognosis of CRC is still unclear.Methods: In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemistry (IHC) were used to examine the expression of ASXL2 in CRC tissues. Cells were transfected with siRNAs or lentivirus to regulate the expression of ASXL2. The effects of ASXL2 on proliferation of CRC cells were determined by CCK8 assay.Results: This study demonstrated that ASXL2 was significantly more expressed in CRC specimens relative to the normal adjacent tissues. The upregulation of ASXL2 was related to advanced clinical stages. Patients who exhibited high expression levels of ASXL2 had poorer overall survival, whereas those with low expression of ASXL2 survived longer. Multivariate Cox regression analysis revealed ASXL2 expression could be considered as an independent prognostic factor for CRC. Inhibition or overexpression of ASXL2 markedly influenced the proliferation of CRC cells.Conclusion: These results showed that ASXL2 could induce cell proliferation which is associated with poor prognosis of CRC patients and might be a new therapeutic target for CRC.
The novel MET inhibitor, HQP8361, possesses single agent activity and enhances therapeutic efficacy of osimertinib, against NSCLC cells with acquired resistance to osimertinib due to MET amplification
Authors: Yu Danlei , Li Yiting , Sun Kevin D-H , Gu Jiajia , Chen Zhen , Omonikoko Taofeek K , Ramalingam Suresh S , Sun SHi-Yong 
Published: April 2020

Abstract
Background The oncogenic protein, MET (or c-MET), is involved in the positive regulation of cell survival and proliferation and in mediating acquired resistance to EGFR-TKIs including AZD9291 (osimertinib). Thus, MET inhibition is a promising strategy for overcoming acquired EGFR-TKI resistance due to MET amplification. HQP8361 (MK8033) is a novel and selective MET kinase inhibitor that has completed a phase I clinical trial. The current study focuses on determining the activity and mechanism of action of HQP8361 as a single agent and in combination with AZD9291 against human NSCLC cells, particularly EGFR-mutant NSCLCs with acquired resistance to AZD9291. Methods Drug effects on cell growth in vitro were evaluated by measuring cell number alterations and colony formation and in vivo with mouse xenogtaft models, respectively. Apoptosis was assessed with annexin V/flow cytomentry and protein cleavage. Protein alterations were detected with Western blotting. Protein degradation was determined by comparing protein half-lives and inhibiting proteasome. Gene overexpression and knockout were achieved with lentiviral infection and CRISPR/Cas9, respectively. Significance of differences between two tested groups was analyzed with two-sided unpaired Student's t tests. Results The majority of human NSCLC cell lines tested, including those harboring EGFR-activating mutations with acquired resistance to AZD9291, had very low or undetectable levels of MET and p-MET and were insensitive to HQP8361. However, AZD9291-resistant (AR) cell lines derived from the EGFR-mutant HCC827 cell line possessed high levels of MET and p-MET and responded to HQP8361 single agent and particularly to the combination of HQP8361 and AZD9291. The HQP8361 and AZD9291 combination synergistically decreased the survival of these HCC827/AR cell lines with enhanced induction of apoptosis that involved alteration of Bim and Mcl-1 levels via modulating their degradation. Moreover, the combination also very effectively inhibited the growth of HCC827/AR xenografts in nude mice. Conclusions These preclinical findings support the potential of HQP8361 in the treatment of NSCLCs with MET amplification or highly activated MET protein and, when combined with AZD9291, in overcoming acquired resistance to EGFR-TKIs due to MET amplification.
Herd immunity is not a realistic exit strategy during a COVID-19 outbreak
Authors: Slot Ed , Hogema Boris M. , Reusken Chantal B.E.M. , Reimerink Johan H. , Molier Michel , Karregat Jan H.M. , IJlst Johan , Novotný Věra M.J. , Lier René A.W. van , Zaaijer Hans L. 
Published: April 2020

Abstract
The world is combating an ongoing COVID-19 pandemic1-4. Health-care systems, society and the economy are impacted in an unprecedented way. It is unclear how many people have contracted the causative coronavirus (SARS-CoV-2) unknowingly. Therefore, reported COVID-19 cases do not reflect the true scale of outbreak5-9. Natural herd immunity has been suggested as a potential exit strategy during COVID-19 outbreaks, which may arise when 50-67% of a community has been infected10. Here we present the prevalence and distribution of antibodies to SARS-CoV-2 in a healthy adult population of a highly affected country using a novel immunoassay, indicating that one month into the outbreak (i) the seroprevalence in the Netherlands is 2.7% with substantial regional variation, (ii) the hardest-hit areas show a seroprevalence of up to 9.5%, (iii) the seroprevalence is sex-independent throughout age groups (18-72 years), (iv) antibodies are significantly more often detected in younger people (18-30 years), and (v) the number of immune individuals in the current epidemic stage is far below the herd immunity threshold. This study provides vital information on the extent of virus spread in a country where social distancing is in place, concluding that herd immunity to SARS-CoV-2 is not a realistic short-term exit strategy option.
Association between drought and agricultural productivity using remote sensing data: a case study of Gujarat state of India
Authors: Sur Koyel , Lunagaria M. M. 
Published: April 2020

Abstract
Drought is a complex hazard which directly affects the water balance of any region. It impacts agricultural, ecological and socioeconomical spheres. It is a global concern. The occurrence of drought is triggered by climatic phenomena which cannot be eliminated. However, its effect can be well managed if actual spatio-temporal information related to crop status influenced by drought is available to decision-makers. This study attempted to assess the efficiency of remote sensing products from space sensors for monitoring the spatio-temporal status of meteorological drought in conjunction with impact on vegetation condition and crop yield. Time series (2000–2019) datasets of the Tropical Rainfall Measuring Mission (TRMM) were used to compute Standardized Precipitation Index (SPI) and MODIS (MODerate resolution Imaging Spectroradiometer) was used to compute Vegetation Condition Index (VCI). Association between SPI and VCI was explored. YAI was calculated from the statistical data records. Final observations are that the agricultural crop yield changed as per the climate variability specific to location. The study indicates drought indices derived from remote sensing give a synoptic view because of the course resolution of the satellite images. It does not reveal the precise relationship to the small-scale crop yield. Remote sensing can be an effective way to monitor and understand the dynamics of the drought and agriculture pattern over any region.
The effect of atmospheric rivers on cold-season heavy precipitation events in Iran
Authors: Esfandiari Neda , Lashkari Hassan 
Published: April 2020

Abstract
Atmospheric rivers (ARs) as massive and concentrated water vapour paths can have a critical impact on extreme events in arid and semi-arid areas. This study investigated the effect of ARs on heavy precipitation events during the cold, rainy months (November–April) in Iran for 11 years. The results showed that 107 ARs had an influence on heavy precipitation, which providing partial moisture for Iran's precipitation. On average, 11 heavy precipitation days were linked to the presence of ARs in the six cold months of each year. During the study period, ARs accounted for almost 20–50% of the country's total heavy precipitation monthly. Although most ARs entered the country from the south through coastal areas, the western part of Iran, especially elevated stations along the western slope of the Zagros Mountains, received the highest heavy precipitation. Accordingly, about 66% of ARs directly originated from the Red Sea and the Gulf of Aden. Moreover, December experienced the highest frequency of ARs linked to heavy precipitation during the statistical period.
Hydrogeochemical evolution under a changing environment: a case study in Jilin, China
Authors: Li Mingqian , Xiao Changlai , Liang Xiujuan , Cao Yuqing , Hu Shuya 
Published: April 2020

Abstract
Groundwater is an important component of the global water cycle, and acts as a receptor and information carrier of global environmental changes. Therefore, it is of great importance to research the chemical evolution of groundwater under a changing environment. Historical data shows that groundwater hydrochemical types are becoming more complicated, groundwater quality is deteriorating and the scope of pollution is expanding. This is attributed to an increasingly dry climate and the gradual deterioration of the original ecological environment, together with the unreasonable groundwater exploitation and intense agricultural activities of the past 30 years. Climate change and human activities are intertwined, and are responsible for changing the original groundwater system and forming a new evolutionary system.
Multi-grained cascade forest for effluent quality prediction of papermaking wastewater treatment processes
Authors: Xin Chen , Shi Xueqing , Wang Dongsheng , Yang Chong , Li Qian , Liu Hongbin 
Published: April 2020

Abstract
The real time estimation of effluent indices of papermaking wastewater is vital to environmental conservation. Ensemble methods have significant advantages over conventional single models in terms of prediction accuracy. As an ensemble method, multi-grained cascade forest (gcForest) is implemented for the prediction of wastewater indices. Compared with the conventional modeling methods including partial least squares, support vector regression, and artificial neural networks, the gcForest model shows prediction superiority for effluent suspended solid (SSeff) and effluent chemical oxygen demand (CODeff). In terms of SSeff, gcForest achieves the highest correlation coefficient with a value of 0.86 and the lowest root-mean-square error (RMSE) value of 0.41. In comparison with the conventional models, the RMSE value using gcForest is reduced by approximately 46.05% to 50.60%. In terms of CODeff, gcForest achieves the highest correlation coefficient with a value of 0.83 and the lowest root-mean-square error value of 4.05. In comparison with the conventional models, the RMSE value using gcForest is reduced by approximately 10.60% to 18.51%.
Chemical precipitation of heavy metals from wastewater by using the synthetical magnesium hydroxy carbonate
Authors: Zhang Yue , Duan Xiumei 
Published: April 2020

Abstract
Heavy metal pollution has become one of the most serious environmental problems today. The preparation of magnesium hydroxy carbonate from low-grade magnesite, and the chemical precipitation of heavy metal wastewater with magnesium hydroxy carbonate as precipitating agent were undertaken. The removal efficiencies of heavy metals were improved by increasing the dose of magnesium hydroxy carbonate, and the applicable dose of magnesium hydroxy carbonate was 0.30 g for 50 mL of the wastewater (6,000 mg/L). The precipitation reactions proceeded thoroughly within 20 min. At this time, the removal efficiencies of heavy metals were above 99.9%. The final pH value was 7.1, the residual VO2+, Cr3+ and Fe3+ concentrations were 0.01, 0.05 and 1.12 mg/L, respectively, which conformed to the limit of discharge set by China (0.5–2.0 mg/L, GB 8978–1996). The precipitate was mainly composed of Fe2O3, V2O5 and Cr2O3, which can be recycled as secondary raw material for metallurgical industry. The treatment of the heavy metal wastewater with magnesium hydroxy carbonate was successful in decreasing the concentrations of VO2+, Cr3+ and Fe3+ in wastewater.
Synthesis, Cr(VI) removal performance and mechanism of nanoscale zero-valent iron modified potassium-doped graphitic carbon nitride
Authors: Guo Jing , Chen Tao , Zhou Xiaohui , Xia Wenning , Zheng Tao , Zhong Chubin , Liu Yaochi 
Published: April 2020

AbstractA novel composite (nZVI@K-GCN) was firstly synthesized by liquid phase reducing nanoscale zero-valent iron (nZVI) on potassium-doped graphitic carbon nitride (K-GCN). The results of Fourier transform infrared (FTIR) spectrometry, X-ray diffraction (XRD), scanning electron microscopy (SEM) and Brunauer–Emmett–Teller (BET) suggested that nZVI@K-GCN possessed abundant active functional groups such as terminal amino-groups (-NH or -NH2 groups) and -OH, and the specific surface area and pore volume from BET of nZVI@K-GCN were 4.7 times and 3.7 times higher than that of graphitic carbon nitride (GCN), respectively. These properties showed that the composite was especially suitable for heavy metal treatment. The application of the composite in the removal of chromium(VI) from aqueous solution showed that the maximum adsorption capacity of nZVI@K-GCN towards Cr(VI) was 68.6 mg/g at 308 K when the initial concentration of Cr(VI) was 30 mg/L, and more than 99% removal was obtained at pH = 3. This adsorption was an endothermic and spontaneous process. XPS patterns and batch experiments proved that complexation, electrostatic attraction and reduction precipitation were the main adsorption mechanism for Cr(VI) on nZVI@K-GCN.
Hepatocellular Carcinoma in Non Alcoholic Fatty Liver Disease
Authors: Tovoli Francesco , Ferri Silvia , Piscaglia Fabio 
Published: April 2020

Background:
Non-alcoholic fatty liver disease (NAFLD) is a global epidemic involving 20-40% of the
general population. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma (HCC) worldwide.
Knowledge about NAFLD-HCC peculiar features is needed to understand this emerging disease better.

Objective:
To review the current literature about the epidemiological, pathogenic and clinical features characterising
the NAFLD and distinguishing it from HCC of other etiologies.

Methods:
A systematic review of the literature (PubMed and Medline) using the following string ("Non-alcoholic
Fatty Liver Disease"[Mesh] and "Carcinoma, Hepatocellular"[Mesh]). Particular relevance was given to papers
published in the last five years as well as previously published manuscript very relevant to this topic according to
the experience of the authors.

Results:
A total of 244 original papers in humans in English literature were analysed. Inherent difficulties in the
identification of high-risk subjects and the possibility of occurrence in non-cirrhotic livers are peculiar characteristics
of NAFLD-HCC hampering surveillance programs. The consequently delayed diagnosis limits access to
surgical procedures and impacts on survival. After correction for tumour burden, however, the survival is not
different from that of viral HCC, suggesting that NAFLD-HCC is not intrinsically a more aggressive malignancy.

Conclusions:
A great deal of effort is needed to improve the clinical outcome of NAFLD-HCC, especially in
terms of prevention, surveillance protocols, and identification of drug modifying the natural history of the underlying
liver disease. The outcome of these efforts will significantly impact global HCC-related costs and mortality.
Curcumin Nanoemulsions Stabilized with Modified Phosphatidylcholine on Skin Carcinogenesis Protocol
Authors: Agame-Lagunes Beatriz , Alegria-Rivadeneyra Monserrat , Quintana-Castro Rodolfo , Torres-Palacios Cristobal , Grube-Pagola Peter , Cano-Sarmiento Cynthia , Garcia-Varela Rebeca , Alexander-Aguilera Alfonso , García Hugo Sergio 
Published: April 2020

Background:
Cancer is one of the main causes of death by disease; several alternative treatments have
been developed to counteract this condition. Curcumin (diferuloylmethane), extracted from the rhizome of Curcuma
longa, has antioxidant, anti-inflammatory, and anti-cancer properties; however, it has low water solubility and poor
intestinal absorption. Carrier systems, such as nanoemulsions, can increase the bioavailability of lipophilic bioactive
compounds.

Objective:
To evaluate the effect of curcumin nanoemulsions prepared with lecithin modified with medium-chain
fatty acids as an emulsifier, on the expression of the Cdk4, Ccne2, Casp8 and Cldn4 genes involved in the carcinogenesis
process in K14E6 transgenic mice.

Methods:
The emulsifier was prepared by interesterification of medium-chain fatty acids, pure lecithin, and immobilized
phospholipase-1 on Duolite A568. An Ultraturrax homogenizer and a Branson Ultrasonic processor were used
for the preparation of nano-emulsions, and a Zetasizer evaluated the particle size. qRT-PCR analysis was performed
to quantify the cancer-related genes expressed in the K14E6 mice. The development and evolution of skin carcinogenesis
were assessed through histological analysis to compare cell morphology.

Results:
Ca 59% of the MCFA were incorporated via esterification into the PC within 12 hours of the reaction. An
emulsifier yield used to formulate the NE of 86% was achieved. Nanoemulsions with a particle size of 44 nm were
obtained. The curcumin nano-emulsion group had a 91.81% decrease in the tumorigenesis index and a reduction in
tumor area of 89.95% compared to the sick group. Histological analysis showed that the group administered with free
curcumin developed a microinvasive squamous cell carcinoma, as opposed to the group with nanoemulsion which
presented only a slight inflammation. In gene expression, only a significant difference in Cdk4 was observed in the
nanoemulsion group.
Anti-IL-6 Therapies for Neuromyelitis Optica Spectrum Disorders: A Systematic Review of Safety and Efficacy
Authors: Lotan Itay , McGowan Richard , Levy Michael 
Published: April 2020

Background:Neuromyelitis Optica Spectrum Disorder (NMOSD) is a chronic autoimmune disease of the central nervous system that causes recurrent attacks of optic neuritis, myelitis, and brainstem symptoms, resulting in severe neurological disability. Preventive treatment with immunosuppressive agents reduces relapse rate and improves long-term prognosis. In recent years, the potential therapeutical effect of new agents has been investigated. Two of these, the anti-interleukin 6 (IL-6) agents tocilizumab and satralizumab, have been studied in active NMOSD.Objective:To systematically review the current data regarding the efficacy and safety of anti-IL-6 agents in NMOSD.Result:Fourteen case reports and 5 case series of intravenous tocilizumab have shown beneficial clinical and paraclinical effects compared to commonly used therapies, and another case series of subcutaneous tocilizumab has shown it is as effective as the IV formulation. A phase 2 comparative trial has shown tocilizumab IV to be more effective than azathioprine for relapse prevention. A phase 3 trial of subcutaneous satralizumab versus placebo, has shown a lower risk of relapse in the sartralizumab-treated group, both as add-on therapy to stable immunosuppressant and as monotherapy. Tocilizumab also reduced pain severity in two trials and fatigue scores in one trial, but satralizumab did not significantly improve pain and fatigue. Adverse events with both agents were relatively mild and comparable to placebo and azathioprine.Conclusions:The anti-Il-6 agents tocilizumab and satralizumab show promising results in active NMOSD. Further randomized, larger-scale trials are needed to better define the role of these agents in the growing arsenal of NMOSD treatments.