bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic Plasticity and Genetic Variation of Leaf Pigment Content in a Southern Beech
Authors: Rios Jorge Andres Arias , Mujtar Veronica Andrea El , Pastorino Mario Juan , Marchelli Paula 
Published: September 2021

Abstract
Physiological, morphological and phenological attributes are potentially adaptive traits that determine functional responses to certain environmental conditions. They are crucial for understanding adaptations to environmental variation along a species natural range. In particular, leaf pigment content can be a good proxy to the physiological and phenological tree state. Our goal was to evaluate the variation in pigment traits among Nothofagus alpina populations in a common garden trail during two years to infer local adaptation and/or phenotypic plasticity. We also aim to analyse the correlation between pigment traits and phenological traits and climatic data from the geographic location of the populations. To comprise the entire range of the species in Argentina, we analysed 400 individuals from eight natural populations coming from four lake watersheds. Pigment traits were estimated using a spectrophotometer and analysed with linear mixed model (LMM). Significant differences among fixed factors (populations - years and watershed – years) were found in chlorophyl a, b, total, carotenoids and anthocyanins concentrations. Higher concentrations were found for 2018, year with the highest number of rainy days and accumulated precipitation. Two populations (Boquete and Tren Tren) were always the most contrasting ones. At population level, the correlation between the means of pigment concentrations and phenological traits was significant in almost all cases. Conversely, the correlation between the means of population pigment concentrations and the main geographic, climatic and bioclimatic variables of the home range were not significant. The significance of the environmental factor (year) in the linear mixed models tested is evidence of phenotypic plasticity of pigment content, suggesting flexibility for acclimatization to moderate inter-annual changes in climatic conditions. The significance of population and watershed and the influence of the family factor on the variance of the pigment traits are evidence of the genetic control as well as the potential adaptive value of leaf pigment content in N. alpina, giving a base for adaptation to a long-lasting change in climate. High correlations between phenological and pigment traits indicate that, in N. alpina, the determination of only one pigment concentration could be used as a proxy of bud burst, senescence and growing degree days.
Dominant Tree Mycorrhizal Associations Affect Soil Nitrogen Transformation Rates Through Mediating Microbial Abundances in a Temperate Forest
Authors: Lin Guigang , Yuan Zuoqiang , Zhang Yansong , Zeng De-Hui , Wang Xugao 
Published: September 2021

Abstract
Tree-fungal symbioses are increasingly recognized to affect soil nitrogen (N) transformations, yet the role of soil microbes in the process is largely unclear. Soil microbes directly interact with trees and are a primary driver of many N transformation processes. Here, we explored the linkage among tree mycorrhizal associations, soil microbes and N transformation rates in a temperate forest of Northeast China. Across a gradient of increasing ectomycorrhizal (ECM) tree dominance, we measured soil acid-base chemistry, bacterial and fungal abundances, N-hydrolyzing enzyme activities, abundances and community composition of ammonia-oxidizing archaea (AOA) and bacteria, and net N mineralization and net nitrification rates. Results showed that soil pH, exchangeable base cations, inorganic N concentrations and N transformation rates decreased with increasing ECM tree dominance. The ECM tree dominance was negatively related to soil bacterial and AOA amoA gene abundances, and positively to soil fungal abundances and β-N-acetylglucosaminidase activities. These shifts in soil microbial abundances and enzyme activities along the mycorrhizal gradient were linked with the increase in soil acidity with increasing ECM tree dominance. Structural equation models revealed that ECM tree dominance was not directly related to N transformation rates, but indirectly to net N mineralization rates via affecting bacterial and fungal abundances, and indirectly to net nitrification rates via influencing AOA amoA gene abundances. Collectively, our results indicate that soil microbes provide a mechanistic link between mycorrhizal associations and soil N transformations, and suggest that shifts in forest mycorrhizal associations under global change could have profound consequences for biogeochemical cycling of temperate forests.
Workpiece Temperature Investigation In Micromilling of Titanium Alloy
Authors: Santos Aline Gonçalves dos , Silva Marcio Bacci da , Oliveira Gustavo Vilela , Jackson Mark James 
Published: September 2021

Abstract
The study of the micromachining process of titanium alloys has been intensified due to a greater need to develop microcomponents applied to the medical area. However, the investigation of the behavior of process variables is still incipient, complex and challenging. Heat and temperature distribution, for example, are important aspects for any machining process. Thus, the main objective of this work is to investigate the temperature during the micro-milling of the Ti-6Al-4V alloy, by means of an experimental study combined with numerical simulation. To carry out the tests, AlCrN coated carbide end mill tool was used for machining micro slots. During machining, the workpiece temperature is measured using T-type thermocouples welded to the workpiece surface, aligned with the tool path. The temperature distribution was also obtained by numerical simulation using the commercial software Third Wave AdvantEdge, version 7.4015. The experimental results showed that the temperature on the surface of the specimen increases from the up-milling side to the down milling side. In addition, the temperature has a tendency to increase with tool wear. However, the simulation data showed that the temperature is higher in the center of the channel, the position with the highest undeformed chip thickness.
Pharmacokinetics of a retrograde infusion of Paclitaxel into the thoracic duct in a porcine model
Authors: Saito Akira , Kimura Natsuka , Kaneda Yuji , Ohzawa Hideyuki , Miyato Hideyo , Yamaguchi Hironori , Lefor Alan Kawarai , Nagai Ryozo , Sata Naohiro , Kitayama Joji , Aizawa Kenichi 
Published: September 2021

Abstract
Gastrointestinal cancer with massive nodal metastases is a lethal disease. In this study, using a porcine model, we attempted to infuse the anti-cancer drug, Paclitaxel (PTX), into the thoracic duct to examine the efficiency of drug delivery to intra-abdominal lymph nodes. We established a technical method to catheterize the thoracic duct in the necks of pigs. Serum, liver, and spleen concentrations of PTX were significantly lower after thoracic duct (IT) infusion than after intravenous (IV) administration. Approximately 12–24 h after infusion, PTX concentrations in abdominal lymph nodes tended to be higher with IT than with IV infusion; however, increased levels of PTX were much lower than expected. Unexpectedly, concentrations of PTX in urine were much higher after IT administration than after IV administration, demonstrating that most PTX administered via the thoracic duct was promptly excreted from the kidneys. These findings suggest that infusion of anti-cancer drugs into the thoracic duct will not produce clinical benefits for patients with extensive lymphatic metastases in abdominal malignancies.
Alternative Splicing Related Genetic Variants in lncRNA BCLETare Associated with Bladder Cancer Risk in the Chinese Population
Authors: Liu Hanting , Wang Xi , Guo Zheng , Sun Guanting , Lv Qiang , Qin Chao , Yuan Lin , Wang Yunyan , Du Mulong , Wang Meilin , Chu Haiyan , Zhang Zhengdong 
Published: September 2021

Abstract
Background: Although thousands of alternative splicing related single nucleotide polymorphisms (AS-SNPs) have been uncovered in human tumors, the potential function of AS-SNPs involved in bladder cancer is rarely reported. Here we identified bladder cancer risk-associated AS-SNPs and revealed its underlying causal mechanism in bladder carcinogenesis.Methods: Variants with annotation of “splice-3” or “splice-5” were extracted as AS-SNPs through the database of Single Nucleotide Polymorphism (dbSNP). Two-stage case-control studies comprising 1,630 cases and 2,504 controls were conducted to assess the association between the AS-SNPs and bladder cancer risk. A series of experiments including luciferase reporter assays, RNA immunoprecipitation, and malignant phenotype were performed to comprehensively investigate the genetic and epigenetic biological effects of AS-SNPs in the development of bladder cancer.Results: We identified the potential causal variant rs558814 A>G located in intron of lncRNA BCLET (Bladder Cancer Low-Expressed Transcript) was significantly associated with a reduced risk of bladder cancer [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.76 to 0.92, P = 3.26 × 10−4]. The SNP rs558814 exerted transcriptional activity regulatory effect and thus facilitated the expression of BCLET transcripts including BCLET-long and BCLET-short. In addition, both BCLET transcripts overexpression remarkably inhibited in vitro and in vivo bladder cancer phenotypes including cell proliferation, clone formation, invasion, migration and apoptosis. Mechanistically, lncRNA BCLET bound to MSANTD2 mRNA, masked splicing site of MSANTD2 mRNA, and thereby facilitated the expression of MSANTD2-004 transcript, which lacks the first exon and remarkably inhibited the progression of bladder cancer.Conclusions: Our findings not only revealed the important role of AS related genetic variants rs558814 and its associated gene BCLET in bladder cancer progression, but also provided the perspective to understand the etiology and pathology of cancers from the alternative splicing regulation mechanism.
NDRG2 Inhibits Pyruvate Carboxylase-Mediated Anaplerosis and Combines with Glutamine Blockade To Inhibit The Growth of Glioma
Authors: Wang Jiancai , Sun Xiang , Wang Jiayuan , Zhang Kun , Yuan Yiyi , Yao Libo , Li Xia , Shen Lan 
Published: September 2021

Abstract
Background

Due to the rapid proliferation, cancer cells have increased anabolic biosynthesis, which requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the catalysis of pyruvate carboxylase (PC) and glutaminase (GLS) respectively. In GLS-suppressed cancer cells, the PC-mediated pathway for anaplerosis is crucial to maintain cell growth and proliferation. Here, we investigated the regulatory role and molecular mechanism of the tumor suppressor NDRG2 in PC and PC-mediated anaplerosis.
Methods

We first evaluated the correlation between PC and NDRG2 in glioma cell lines and human glioma tissue microarrays. The interaction between PC and NDRG2 was tested by tandem affinity purification-mass spectrometry (TAP-MS) and coimmunoprecipitation (Co-IP). We then detected the effect of NDRG2 on PC-mediated anaplerosis by gas chromatography-mass spectrometry (GC-MS). Preclinical evaluation of NDRG2 alone or combined with a glutaminase inhibitor was conducted in glioma cells and xenograft mouse tumors.
Results

NDRG2 interacted with PC and induced the degradation of PC in glutamine-deficient glioma cells. NDRG2 also inhibited the activity of PC and PC-mediated anaplerosis. As a result, NDRG2 significantly inhibited the malignant growth and proliferation of glioma cells in combination with a glutamine antagonist. In addition, NDRG2 more significantly inhibited the protein level of PC in IDH1(R132H)-mutant glioma cells than in wild-type glioma cells.
Conclusions

These findings indicate that the molecular mechanism of NDRG2 inhibits PC-mediated anaplerosis and collaborates with glutamine antagonist to inhibit the malignant proliferation of glioma cells, thus providing a theoretical and experimental basis for targeting anaplerosis in glioma therapy.
Online self-evaluation: the EFL writing skills in focus
Authors: Al-Mwzaiji Khaled Nasser Ali , Alzubi Ali Abbas Falah 
Published: September 2021

Abstract
Students need more independent roles to evaluate their learning performance, especially in the absence of teachers’ feedback due to some constraints such as technology and poor experience. This study investigates the potential of online self-evaluation on students’ writing skills in English as a foreign language (EFL). It examines the Preparatory Year (PY) students’ most improved EFL writing areas and perceptions when they use online self-evaluation in writing. In this quasi-experiment, two groups of PY EFL writing program students participated in the study for one semester 2020–2021. A mixed-method design was applied: Self-monitoring checklists, self-evaluation questionnaires, achievement tests, and students’ portfolios. Findings revealed that most of the learners’ mistakes were in punctuation marks, capitalization, informal language, and subject-verb agreement. It was also perceived that learners were doing fine about where and how they should be. The study proved that the students’ self-evaluation and performance in writing correlated significantly; however, the effect size was low. Based on the research findings, it is recommended that training programs on strategy are to be boosted, especially in institutions where learners receive less feedback.
Lin28 Enhances Glucose Metabolism in Human Placental Mesenchymal Stem Cells during Hypoxia via the PI3K-Akt Pathway
Authors: Zhou Xi , Li Junbo , Wang Jin , Yang Huifang , Wang Jingzeng , Xie Xiaoyun , Chen Zhishui , Zhang Bo 
Published: September 2021

Abstract
Mesenchymal stem cells (MSCs) are widely used to treat and prevent liver ischemia–reperfusion injury (LIRI), which commonly occurs after liver surgery. Lin28 is an RNA-binding protein crucial for early embryonic development, stem cell differentiation/reprogramming, tumorigenesis, and metabolism. However, whether Lin28 can enhance metabolism in human placental MSCs (PMSCs) during hypoxia to improve the protective effect against LIRI remains unclear. First, a Lin28 overexpression construct was introduced into PMSCs; glucose metabolism, the expression of glucose metabolism - and PI3K-AKT pathway-related proteins, and the levels of microRNA Let-7 family members were examined using a glucose metabolism kit, western blots, and real-time quantitative PCR, respectively. Next, treatment with an AKT inhibitor was performed to understand the association of Lin28 with the PI3K-Akt pathway. Subsequently, AML12 cells were co-cultured with PMSCs to construct an in vitro model of PMSC protecting liver cells from hypoxia injury. Finally, C57BL/6J mice were used to establish a partial warm hepatic ischemia–reperfusion model in vivo. Lin28 increased the glycolysis capacity of PMSCs, allowing these cells to produce more energy under hypoxic conditions. Lin28 also activated PI3K-Akt signaling under hypoxic conditions, and AKT inhibition attenuated the effects of Lin28. In addition, Lin28 overexpression was found to protect cells against LIRI-induced liver damage, inflammation, and apoptosis and attenuate hypoxia-induced hepatocyte injury. Inconclusion, Lin28 enhances glucose metabolism under hypoxic conditions in PMSCs, thereby providing protective effects against LIRI via the activation of the PI3K-Akt signaling pathway. Our study first reported the application of gene-modified mesenchymal stem cell-based therapy in LIRI.
Evaluation of Rhomboid Intercostal Block in Video-assisted Thoracic Surgery: Comparing three Concentrations of Ropivacaine
Authors: Liu Fen , Deng Wei , Zhou Qing-he , Jiang Chen-Wei 
Published: September 2021

Abstract
Background: Ultrasound-guided rhombic intercostal block (RIB) is a novel regional block that provides analgesia for patients who have received video-assisted thoracoscopic surgery (VATS). The anesthetic characteristics of ultrasound-guided RIB with different concentrations of ropivacaine are not known. This research primarily hypothesizes that ultrasound-guided RIB, given in combination with the same volume of different concentrations of ropivacaine, would improve the whole quality of recovery-40 (QoR-40) among patients with VATS.Approaches: This double-blinded, single-center, prospective, and controlled trial randomized 100 patients undergoing VATS to receive RIB. One hundred patients who have received elective VATS and satisfied inclusion standards were fallen into four groups randomly: control group with no RIB and R0.2%, R0.3%, and R0.4%; they underwent common anesthesia plus the RIB with ropivacaine at 0.2%, 0.3%, and 0.4% in a volume of 30mL.Outcomes: Groups R0.2%, R0.3%, and R0.4% displayed great diversities in the overall QoR-40 scores and QoR-40 dimensions (in addition to psychological support) by comparing with the control group (Group C) (p<0.001 for all contrasts). Group R0.3% and R0.4% displayed great diversities in the overall QoR-40 scores and QoR-40 dimensions (in addition to psychological support) by comparing with the R0.2% group (p<0.001 for all contrasts). The overall QoR-40 scores and QoR-40 dimensions (physical comfort [p=0.585]) did not vary greatly between the Group R0.3% and R0.4% (p>0.05 for all contrasts). Group R0.2%, R0.3% and R0.4% showed significant differences in numerical rating scales (NRS) score region under the curve (AUC) at rest and on movement in 48 hours when compared with the Group C (p<0.001 for all contrasts). Group R0.3% and R0.4% displayed great diversities in NRS score AUC at rest and on movement in 48 hours when compared with the R0.2% group (p<0.001 for all contrasts). The NRS mark AUC at rest and on movement in 48 hours did not vary greatly between the Group R0.3% and R0.4% (p>0.05 for all contrasts).Conclusion: It was found that a dose of 0.3% ropivacaine is the best concentration for RIB for patients undergoing VATS. Through growing ropivacaine concentration, the analgesia of the RIB was not improved greatly.Trial registration number: ChiCTR2100046254
m6A related exosome gene siganture in colon cancer identifies distinct microenvironment characterization and immunotherapeutical responses
Authors: Zheng Junjie , Chen Daiwei , Zhang Cuiyu , Ji Yuge , Liu Yanting , Fan Xiaohua , Li Jingxin 
Published: September 2021

Abstract
Background

Gradually, more researches pay attention to the potential relationship between N6-methyladenosine (m6A) modification of RNA and immunity in tumor microenvironment (TME). Therefore, they developed unique scoring modes through detecting level of m6A in various tumors to learn immune phenotypes. Nevertheless, direct detection always is harmful even fatal to patients. Recent studies demonstrated that exosomes in body fluid would deliver RNA with m6A modification from tumors.
Methods

Through analyzing datasets from 1066 colon cancer samples, m6A-related exosome genes modification patterns which based on 59 m6A-related exosome genes was classified. Then we used MREGS to calculate modification patterns of each tumor with PCA algorithm.
Results

In accordance with 59 m6A-related exosome gene, we indicated that there were distinguishing characteristics of TME cell infiltration in three different m6A-related exosome gene modification patterns. Three immune cell infiltration profiles (immune-inflamed, immune-desert and immune-excluded) were pronouncedly relevant with the identified patterns in aspects of immune activation, EMT- and TGFβ-related pathways and activity of stroma in TME. We also discovered that tumor molecular subtypes, genetic aberrant expression and patients’ outcomes could be evaluated by identified modification patterns. Furthermore, patients in lower MREGS group, featured as prolonged lifespan and advantageous immune activation, was associated with high tumor mutation burden (TMB) and good prognosis with anti-PDL1 immune therapy.
Conclusion

Detecting the level of m6A methylation of exosomes in patients’ serum, MREGS could be utilized for assessing m6A-related exosome gene modification patterns of each patient and their own matching characteristics of TME cell infiltration, and next ascertain immunological classifications of tumors and assist clinicians to tailor optimal treatment for patients.
ANXA1 Induces Oxaliplatin Resistance of Gastric Cancer through Autophagy by Targeting PI3K/AKT/mTOR
Authors: Ren Jun , Hu Qing Zhi , Niu Ming Geng , Xia Jie , Wang Xing , Hong Qi Run , Gu Wei Jia , Ke Chongwei 
Published: September 2021

Abstract
Background: Resistance to oxaliplatin (OXA) is a major cause of recurrence in gastric cancer (GC) patients. ANXA1 has been found to participate in the regulation of diverse cellular functions in a variety of cell types including anti-inflammatory processes. We aimed to investigate the role of ANXA1 in autophagy and chemoresistance of GC cells. Methods: To identify the genes that regulate oxaliplatin resistance, we used RNA-seq to profile gene expression within oxaliplatin resistant GC and parental cells. Immunohistochemical and RT-qPCR was performed to detect ANXA1 expression in tissues of 2 cohorts of GC patients who received OXA-based chemotherapy. The chemoresistant effects of ANXA1 were assessed by cell viability, apoptosis, and autophagy assays. The effects of ANXA1 on autophagy were assessed by mRFP-GFP-LC3 and western blot. Gene set enrichment analysis (GSEA) and western blot was performed to detect the activity of PI3K/AKT/mTOR signaling under the regulation of ANXA1.Results: Based on RNA-seq profiling, ANXA1 was selected as a candidate that was upregulated in oxaliplatin resistant GC cells. Furthermore, we discovered that ANXA1 is upregulated in chemo-resistant GC tissues. Knockdown of ANXA1, via inhibiting autophagy, enhanced the sensitivity of OXA-resistant GC cells to OXA in vitro and in vivo. Mechanically, we identified that PI3K/AKT/mTOR signaling pathway was activated in the ANXA1 stably knockdown AGS/OXA cells, which leads to the down-regulation of autophagy.Conclusions: ANXA1 functions as a chemoresistant gene in GC cells by targeting the PI3K/AKT/mTOR signaling pathway and might be a prognostic predictor for GC patients who receive OXA-based chemotherapy.