bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monsoon Clouds Control the Summer Surface Energy Balance on East Rongbuk Glacier (6,523 m Above Sea Level), the Northern of Mt. Qomolangma (Everest)
Authors: Liu Weigang , Zhang Dongqi , Qin Xiang , van den Broeke Michiel R. , Jiang Youyan , Yang Diyi , Ding Minghu 
Published: April 2021

AbstractTo identify the atmospheric controls of the summertime glacier surface energy balance in the Himalayas, in situ meteorological data collected at 6,523 m above sea level during May–July 2005 were obtained and analyzed. Our results showed that net shortwave radiation (103 W m−2) and turbulent sensible heat flux (12 W m−2) acted as energy sources, and net longwave radiation (−62 W m−2) and turbulent latent heat flux (−20 W m−2) represented heat sinks. Cloud cover controlled the summer surface energy balance. During the active period of the South Asian Summer Monsoon, the frequent cloud coverage increased the incoming longwave radiation more than it decreased the incident solar radiation. Intensification (weakening) of the South Asian Summer Monsoon strengthened (suppressed) surface melting. The melt energy measured during the nonmonsoon period was small due to the energy consumption associated with glacier volume warming, energy loss from sublimation, and large heat loss through net longwave radiation due to the low amount of incoming longwave radiation caused by the low cloudiness. The comparison of glacier surface energy balances on the Tibetan Plateau shows that on continental glaciers, net radiation is lower and accounts for a smaller contribution to energy sources, and the dominant energy sinks are sublimation and evaporation, rather than melting, which is the primary energy sink for maritime/subcontinental glaciers. This implies an important spatial variability in glacial sensitivity to different climatic conditions on the Tibetan Plateau.
Targeting the glucocorticoid receptor signature gene Mono Amine Oxidase-A enhances the efficacy of chemo- and anti-androgen therapy in advanced prostate cancer
Authors: Puhr Martin , Eigentler Andrea , Handle Florian , Hackl Hubert , Ploner Christian , Heidegger Isabel , Schaefer Georg , Brandt Maximilian P. , Hoefer Julia , Van der Pluijm Gabri , Klocker Helmut 
Published: April 2021

AbstractDespite increasing options for treatment of castration-resistant prostate cancer, development of drug resistance is inevitable. The glucocorticoid receptor (GR) is a prime suspect for acquired therapy resistance, as prostate cancer (PCa) cells are able to increase GR signaling during anti-androgen therapy and thereby circumvent androgen receptor (AR)-blockade and cell death. As standard AR-directed therapies fail to block the GR and GR inhibitors might result in intolerable side effects, the identification of GR signature genes, which are better suited for a targeted approach, is of clinical importance. Therefore, the specific epithelial and stromal GR signature was determined in cancer-associated fibroblasts as well as in abiraterone and enzalutamide-resistant cells after glucocorticoid (GC) treatment. Microarray and ChIP analysis identified MAO-A as a directly up-regulated mutual epithelial and stromal GR target, which is induced after GC treatment and during PCa progression. Elevated MAO-A levels were confirmed in in vitro cell models, in primary tissue cultures after GC treatment, and in patients after neoadjuvant chemotherapy with GCs. MAO-A expression correlates with GR/AR activity as well as with a reduced progression-free survival. Pharmacological MAO-A inhibition combined with 2nd generation AR signaling inhibitors or chemotherapeutics results in impaired growth of androgen-dependent, androgen-independent, and long-term anti-androgen-treated cells. In summary, these findings demonstrate that targeting MAO-A represents an innovative therapeutic strategy to synergistically block GR and AR dependent PCa cell growth and thereby overcome therapy resistance.
FOXO3 is a latent tumor suppressor for FOXO3-positive and cytoplasmic-type gastric cancer cells
Authors: Tsuji Toshikatsu , Maeda Yusuke , Kita Kenji , Murakami Kazuhiro , Saya Hideyuki , Takemura Hirofumi , Inaki Noriyuki , Oshima Masanobu , Oshima Hiroko 
Published: April 2021

AbstractFOXO3 is a member of the FOXO transcription factors thought to play a tumor-suppressor role in gastrointestinal cancer, while tumor-promoting function of FOXO3 has also been reported. These results suggest a context-dependent function of FOXO3 in tumor development. However, the relationship between the FOXO3 expression pattern and its role in tumorigenesis has not been elucidated. We examined the FOXO3 expression in 65 human primary gastric cancer and patient-derived xenograft tissues by immunohistochemistry and identified three subtypes according to subcellular localization: FOXO3-nuclear accumulated (FOXO3-Nuc), FOXO3-nuclear/cytoplasmic or cytoplasmic distributed (FOXO3-Cyt), and FOXO3-negative. In the FOXO3-Cyt gastric cancer cells, the expression of the constitutive active mutant FOXO3 (Act-ER FOXO3) induced the nuclear accumulation of FOXO3 and significantly suppressed colony formation and proliferation. The inhibition of the PI3K-AKT pathway by inhibitor treatment also suppressed the proliferation of FOXO3-Cyt gastric cancer cells, which was associated with the nuclear accumulation of endogenous FOXO3. Furthermore, the expression of Act-ER FOXO3 by an endogenous promoter significantly suppressed gastric tumorigenesis in Gan mice, a model of gastric cancer. Finally, treatment of FOXO3-Cyt human gastric cancer-derived organoids with an AKT inhibitor significantly suppressed the survival and proliferation. These results indicate that FOXO3 is a latent tumor suppressor for FOXO3-Cyt-type gastric cancer cells and that activation of the PI3K-AKT pathway protects this type of gastric cancer cell from FOXO3-mediated growth suppression via constitutive nuclear export. Thus, the inhibition of the PI3K-AKT pathway and nuclear translocation of endogenous FOXO3 may have therapeutic applications in the treatment of FOXO3-positive and cytoplasmic-type gastric cancer.
Patent ductus arteriosus, tracheal ventilation, and the risk of bronchopulmonary dysplasia
Authors: Clyman Ronald I. , Hills Nancy K. , Cambonie Gilles , Debillon Thierry , Ligi Isabelle , Gascoin Geraldine , Patkai Juliana , Beuchee Alain , Favrais Geraldine , Durrmeyer Xavier , Flamant Cyril , Rozé Jean Christophe 
Published: April 2021

Abstract
Background
An increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days.

Goal
To examine the interaction between prolonged exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants <28 weeks gestation.

Study Design
Predefined definitions of prolonged ventilation (≥10 days), hsPDA (≥14 days), and BPD (room air challenge test at 36 weeks) were used to analyze deidentified data from the multicenter TRIOCAPI RCT in a secondary analysis of the trial.

Results
Among 307 infants who survived >14 days, 41 died before 36 weeks. Among survivors, 93/266 had BPD. The association between BPD and hsPDA depended on the length of intubation. In multivariable analyses, prolonged hsPDA shunts were associated with increased BPD (odds ratio (OR) (95% confidence interval (CI)) = 3.00 (1.58–5.71)) when infants required intubation for ≥10 days. In contrast, there was no significant association between hsPDA exposure and BPD when infants were intubated <10 days (OR (95% CI) = 1.49 (0.98–2.26)). A similar relationship between prolonged hsPDA and length of intubation was found for BPD/death (n = 307): infants intubated ≥10 days: OR (95% CI) = 2.41 (1.47–3.95)); infants intubated <10 days: OR (95% CI) = 1.37 (0.86–2.19)).

Conclusions
Moderate-to-large PDAs were associated with increased risks of BPD and BPD/death—but only when infants required intubation ≥10 days.

Impact

Infants with a moderate-to-large hsPDA that persist beyond 14 days are only at risk for developing BPD if they also receive prolonged tracheal ventilation for ≥10 days.

Infants who receive less ventilatory support (intubation for <10 days) have the same incidence of BPD whether the ductus closes shortly after birth or whether it persists as a moderate-to-large shunt for several weeks.

Early PDA closure may be unnecessary in infants who require short durations of intubation since the PDA does not seem to alter the incidence of BPD in infants who require intubation for <10 days.
Circ-ITCH sponges miR-214 to promote the osteogenic differentiation in osteoporosis via upregulating YAP1
Authors: Zhong Da , Xu Gan-Zhe , Wu Ju-Zhi , Liu Hua , Tang Ju-Yu , Wang Cheng-Gong 
Published: April 2021

AbstractOsteoporosis is the most prevailing primary bone disease and a growing health care burden. The aim of this study was to clarify the functional roles and mechanisms of the circ-ITCH regulating osteogenic differentiation of osteoporosis. Circ-ITCH and yes-associated protein 1 (YAP1) levels were downregulated, but the miR‐214 level was upregulated in osteoporotic mice and patients. Knockdown of circ-ITCH inhibited the alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) during osteogenic induction. Furthermore, miR-214 was a target of circ-ITCH, knockdown of miR-214 could impede the regulatory effects of sh-circ-ITCH on osteogenic differentiation. Moreover, miR-214 suppressed hBMSCs osteogenic differentiation by downregulating YAP1. Finally, in vivo experiments indicated that overexpression of circ-ITCH could improve osteogenesis in ovariectomized mice. In conclusion, circ-ITCH upregulated YAP1 expression to promote osteogenic differentiation in osteoporosis via sponging miR-214. Circ-ITCH could act as a novel therapeutic target for osteoporosis.
SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance
Authors: Li Jing , Wu Ruiqin , Yung Mingo M. H. , Sun Jing , Li Zhuqing , Yang Hai , Zhang Yi , Liu Stephanie S. , Cheung Annie N. Y. , Ngan Hextan Y. S. , Braisted John C. , Zheng Wei , Wei Huiqiang , Gao Yingtang , Nemes Peter , Pei Huadong , Chan David W. , Li Yiliang , Zhu Wenge 
Published: April 2021

AbstractThe JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.
EBV-LMP1 promotes radioresistance by inducing protective autophagy through BNIP3 in nasopharyngeal carcinoma
Authors: Xu San , Zhou Zhuan , Peng Xingzhi , Tao Xuxiu , Zhou Peijun , Zhang Kun , Peng Jinwu , Li Dan , Shen Liangfang , Yang Lifang 
Published: April 2021

AbstractStudies have indicated that dysfunction of autophagy is involved in the initiation and progression of multiple tumors and their chemoradiotherapy. Epstein–Barr virus (EBV) is a lymphotropic human gamma herpes virus that has been implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). EBV encoded latent membrane protein1 (LMP1) exhibits the properties of a classical oncoprotein. In previous studies, we experimentally demonstrated that LMP1 could increase the radioresistance of NPC. However, how LMP1 contributes to the radioresistance in NPC is still not clear. In the present study, we found that LMP1 could enhance autophagy by upregulating the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3). Knockdown of BNIP3 could increase the apoptosis and decrease the radioresistance mediated by protective autophagy in LMP1-positive NPC cells. The data showed that increased BNIP3 expression is mediated by LMP1 through the ERK/HIF1α signaling axis, and LMP1 promotes the binding of BNIP3 to Beclin1 and competitively reduces the binding of Bcl-2 to Beclin1, thus upregulating autophagy. Furthermore, knockdown of BNIP3 can reduce the radioresistance promoted by protective autophagy in vivo. These data clearly indicated that, through BNIP3, LMP1 induced autophagy, which has a crucial role in the protection of LMP1-positive NPC cells against irradiation. It provides a new basis and potential target for elucidating LMP1-mediated radioresistance.
LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma
Authors: Hou Xiukun , Shi Xianle , Zhang Wei , Li Dapeng , Hu Linfei , Yang Jihong , Zhao Jingzhu , Wei Songfeng , Wei Xi , Ruan Xianhui , Zheng Xiangqian , Gao Ming 
Published: April 2021

AbstractPapillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial–mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs.
Fluid as a critical biomarker in neovascular age-related macular degeneration management: literature review and consensus recommendations
Authors: Kodjikian Laurent , Parravano Mariacristina , Clemens Andreas , Dolz-Marco Rosa , Holz Frank G. , Munk Marion R. , Nicolò Massimo , Ricci Federico , Silva Rufino , Talks S. James , Verma Rohini Kumar , Zarranz-Ventura Javier , Zweifel Sandrine A. 
Published: April 2021

AbstractCurrent guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD. However, few guidelines distinguished between types of fluid when providing recommendations. A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews. Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes. Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (T&E) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity.
Research advances in and prospects of ornamental plant genomics
Authors: Zheng Tangchun , Li Ping , Li Lulu , Zhang Qixiang 
Published: April 2021

AbstractThe term ‘ornamental plant’ refers to all plants with ornamental value, which generally have beautiful flowers or special plant architectures. China is rich in ornamental plant resources and known as the “mother of gardens”. Genomics is the science of studying genomes and is useful for carrying out research on genome evolution, genomic variations, gene regulation, and important biological mechanisms based on detailed genome sequence information. Due to the diversity of ornamental plants and high sequencing costs, the progress of genome research on ornamental plants has been slow for a long time. With the emergence of new sequencing technologies and a reduction in costs since the whole-genome sequencing of the first ornamental plant (Prunus mume) was completed in 2012, whole-genome sequencing of more than 69 ornamental plants has been completed in <10 years. In this review, whole-genome sequencing and resequencing of ornamental plants will be discussed. We provide analysis with regard to basic data from whole-genome studies of important ornamental plants, the regulation of important ornamental traits, and application prospects.
Molecular and physiological characterization of the effects of auxin-enriched rootstock on grafting
Authors: Zhai Longmei , Wang Xiaomin , Tang Dan , Qi Qi , Yer Huseyin , Jiang Xiangning , Han Zhenhai , McAvoy Richard , Li Wei , Li Yi 
Published: April 2021

AbstractsGrafting is a highly useful technique, and its success largely depends on graft union formation. In this study, we found that root-specific expression of the auxin biosynthetic gene iaaM in tobacco, when used as rootstock, resulted in more rapid callus formation and faster graft healing. However, overexpression of the auxin-inactivating iaaL gene in rootstocks delayed graft healing. We observed increased endogenous auxin levels and auxin-responsive DR5::GUS expression in scions of WT/iaaM grafts compared with those found in WT/WT grafts, which suggested that auxin is transported upward from rootstock to scion tissues. A transcriptome analysis showed that auxin enhanced graft union formation through increases in the expression of genes involved in graft healing in both rootstock and scion tissues. We also observed that the ethylene biosynthetic gene ACS1 and the ethylene-responsive gene ERF5 were upregulated in both scions and rootstocks of the WT/iaaM grafts. Furthermore, exogenous applications of the ethylene precursor ACC to the junction of WT/WT grafts promoted graft union formation, whereas application of the ethylene biosynthesis inhibitor AVG delayed graft healing in WT/WT grafts, and the observed delay was less pronounced in the WT/iaaM grafts. These results demonstrated that elevated auxin levels in the iaaM rootstock in combination with the increased auxin levels in scions caused by upward transport/diffusion enhanced graft union formation and that ethylene was partially responsible for the effects of auxin on grafting. Our findings showed that grafting success can be enhanced by increasing the auxin levels in rootstocks using transgenic or gene-editing techniques.
Overexpression of MdATG8i improves water use efficiency in transgenic apple by modulating photosynthesis, osmotic balance, and autophagic activity under moderate water deficit
Authors: Jia Xin , Mao Ke , Wang Ping , Wang Yu , Jia Xumei , Huo Liuqing , Sun Xun , Che Runmin , Gong Xiaoqing , Ma Fengwang 
Published: April 2021

AbstractWater deficit is one of the major limiting factors for apple (Malus domestica) production on the Loess Plateau, a major apple cultivation area in China. The identification of genes related to the regulation of water use efficiency (WUE) is a crucial aspect of crop breeding programs. As a conserved degradation and recycling mechanism in eukaryotes, autophagy has been reported to participate in various stress responses. However, the relationship between autophagy and WUE regulation has not been explored. We have shown that a crucial autophagy protein in apple, MdATG8i, plays a role in improving salt tolerance. Here, we explored its biological function in response to long-term moderate drought stress. The results showed that MdATG8i-overexpressing (MdATG8i-OE) apple plants exhibited higher WUE than wild-type (WT) plants under long-term moderate drought conditions. Plant WUE can be increased by improving photosynthetic efficiency. Osmoregulation plays a critical role in plant stress resistance and adaptation. Under long-term drought conditions, the photosynthetic capacity and accumulation of sugar and amino acids were higher in MdATG8i-OE plants than in WT plants. The increased photosynthetic capacity in the OE plants could be attributed to their ability to maintain optimal stomatal aperture, organized chloroplasts, and strong antioxidant activity. MdATG8i overexpression also promoted autophagic activity, which was likely related to the changes described above. In summary, our results demonstrate that MdATG8i-OE apple lines exhibited higher WUE than WT under long-term moderate drought conditions because they maintained robust photosynthesis, effective osmotic adjustment processes, and strong autophagic activity.