bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lycium barbarum glycopeptide targets PER2 to inhibit lipogenesis in glioblastoma by downregulating SREBP1c
Authors: Xia Hechun , Yao Jian , Hui Jianwen , Chen Yanjun , Luo Dongyang , Yan Jiangshu , Zhang Yifan , Lan Yuanxiang , Yan Xiurui , Wang Zhihua , Fan Heng 
Published: October 2022

Abstract
Lycium barbarum polysaccharide (LBP) is a substance with various biological activities extracted from Lycium barbarum. LbGPs are peptidoglycans with a short peptide backbone and a complex, branched glycan moiety, which is further extracted and isolated from LBPs. Previous studies have shown that LbGP can inhibit cancer cell growth, but its specific mechanism is not completely clear. In this study, we found that LbGP could inhibit the proliferation of glioma cells and promote the expression of period 2 (PER2) through the PKA-CREB pathway. In addition, LbGP could inhibit the de novo synthesis of lipids by downregulating SREBP1c and its target genes, which depended on the expression of PER2. Moreover, PER2 negatively regulated the expression of SREBP1c via suppressing PI3K/AKT/mTOR pathway. In summary, LbGP may upregulate the expression of PER2 to reduce the expression of SREBP1c, inhibit lipid synthesis in glioblastoma, and inhibit glioblastoma cell proliferation. This study provides an alternative drug for the treatment of glioma and elucidates its potential mechanism.
Biodegradable PBAT, PBS and PHBV polymers characterization for porous structure: further steps to sustainable plastics
Authors: Lima Guilherme M.R. , Mukherjee Adrivit , Picchioni Francesco , Bose Ranjita K. 
Published: October 2022

Abstract
Plastic pollution is one of the main issues of the modern era. When plastic is wrongly disposed of, it can be found in contaminated water, land, and even in the air. One of the solutions to tackle plastic con-tamination in the world is introducing polymers that require fewermaterials to fulfill the same function in addition to biodegradable and biobased options. Biodegradable polymers tackle end-of-life pollution when wrongly discarded, and biobased polymers use fewer or none fossil-based resources. In this study, we characterize the bioplastics Polybutylene adipate terephthalate (PBAT), Polybutylene succinate(PBS), and Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as further steps to stage the features of promising alternatives to currently utilized plastics. We access the chemical, thermal and mechanical characteristics of commercially available PBAT, PBS, and PHBV polymers.These results help us to understand purity, process behavior, and per-ceive different porous morphology. In addition, we successfully produce porous materials using a green process with carbon dioxide. Because of their respective features, all three polymers resulted in microcellularporous, but PBAT and PBS resulted in closed cells and PHBV opencells. Since each polymer has different thermal properties, the process temperature follows their respective melting temperature.In order to see the morphology of each sample, the porous material was cut and analyzed under a scanning electron microscope (SEM). The possibility to make porous samples with different morphology also adds value to the polymers and introduces new options to fill more applications.
Evaluation of the trueness of intraoral scanning for partial edentulous patients with maxillary defect
Authors: Cao Rongkai , Zhang Shilei , Li Lishan , Xu Hui , Cao Yujie 
Published: October 2022

Abstract
Objectives.
The trueness of intraoral scanning (IOS) for partial edentulous patients with maxillary defect has not been investigated sufficiently. This study aimed to evaluate trueness of digital dental impressions obtained by IOS for partial edentulous patients with maxillary defect by quantitatively comparing liner distance and best-fit algorithm measurement with model scanning.
Materials and Methods.
Three ceramic blocks were pasted on healthy palate mucosa using medical tissue glue in 10 subjects. Digital dental impressions were scanned by IOS and imported into the software. Plaster dental impressions obtained by silicone rubber were also taken and scanned. Linear distance and best-fit algorithm measurement were performed using model scanning as the reference. To examine linear distance, Paired t-test and Analysis of Variance (ANOVA) were applied. The best-fit algorithm measurement of dentition was evaluated with Kolmogorov–Smirnoff test. The level of significance was set to α = .05.
Results.
Paired t-test showed no difference between IOS and model scanning for liner distance in group A and C, while for group B, significant differences were observed (P < 0.05). Results of ANOVA indicated differences among groups (P < 0.05). For best-fit algorithm measurement, Kolmogorov–Smirnoff test showed no significant difference between IOS and model scanning (P = 0.18).
Conclusion.
IOS demonstrated satisfactory results in trueness of digital dental impressions for partial edentulous patients with maxillary defect, while functional impressions were needed in defect or flap areas to better meet clinical requirements.
Clinical Relevance.
The feasibility of digital dental impressions for partially edentulous patients with maxillary defect using IOS was illustrated in this study, which provided references for clinical treatment.
An ancient metalloenzyme evolves through metal preference modulation
Authors: Sendra Kacper , Barwinska-Sendra Anna , Mackenzie Eilidh , Basle Arnaud , Kehl-Fie Thomas , Waldron Kevin 
Published: October 2022

Abstract
Evolutionary processes create functional diversity of natural proteins, the essential building blocks of all biological systems. Although descriptions of general protein evolution are extensive1, studies of natural proteins sampled across the tree of life and evaluated in a single experimental system are virtually non-existent. Almost half of all enzymes require metals2,3 and metalloproteins tend to optimally utilise the physicochemical properties of a specific metal cofactor. Life must constantly adapt to changes in metal-bioavailability, including exposure of pathogens to nutritional immunity4,5 and biogeological oxygenation of Earth’s atmosphere6,7. These changes can challenge the ability of metalloenzymes to maintain activity and presumptively drive their evolution. Here, we studied metal-preference evolution within the natural diversity of the iron/manganese superoxide dismutase (SodFM) enzyme family, important scavengers of toxic reactive oxygen species. We identified and experimentally verified residues with critically conserved roles in determining metal-preference that, when combined with an understanding of the protein’s evolutionary history, enabled improved prediction of metal-utilisation across the five SodFM subfamilies defined herein. By combining phylogenetics, bioinformatics, biochemistry, and structural biology we demonstrate that SodFM metal-utilisation can be evolutionarily fine-tuned by sliding on a continuous scale between perfect manganese- and iron-specificities. Over the history of life, SodFM metal-preference has been modulated multiple independent times within different evolutionary and ecological contexts and can be changed within short evolutionary timeframes. Our data shed light on the evolutionary mechanisms by which diverse metalloenzyme families can change their metal preference over time in nature or by design in man-made systems.
Clinicopathological features and prognosis of patients with HER2-low breast cancer
Authors: Yang Xin , Li Yao , lu Xu , Ren Xiaotian , Hua Bin 
Published: October 2022

Abstract
Background
Low human epidermal growth factor receptor 2 (HER2) expression is an emerging concept in breast cancer that is defined as immunohistochemistry (IHC) 1 + or IHC 2 + and negative in situ hybridization (ISH) but has been poorly investigated. The aim of our study was to determine the frequency of low HER2 expression among HER2-negative breast cancers and compare the clinicopathological features and prognosis of HER2-low patients with those of HER2-zero patients.
Methods
We collected the data of 684 patients with primary HER2-negative breast cancer who underwent surgery between January 2012 and September 2021 from our self-built database. Clinicopathological features, recurrence-free interval (RFI) and breast cancer-specific survival (BCSS) were compared between HER2-low and HER2-zero (IHC 0) patients.
Results
Among the 684 patients, 512 (74.9%) patients had low HER2 expression, and 172 (25.1%) patients had zero HER2 expression. The average age was 57.7 ± 12.6 years, 472 (69.0%) patients were aged < 65 years, and 212 (31.0%) patients were aged ≥ 65 years. Compared to HER2-zero tumors, HER2-low tumors had a higher proportion of hormone receptor (HR)-positive cases (89.6% vs. 75.6%, P < 0.001) and a lower rate of histological grade III cases (29.4% vs. 38.8%, P < 0.001). Kaplan–Meier analysis showed that low HER2 expression was associated with prolonged RFI in breast cancer patients, especially in HR + breast cancer patients (P = 0.028) and < 65-year-old breast cancer patients (P = 0.000). Multivariate Cox regression analysis showed that low HER2 expression was a low-risk factor for RFI (HR: 0.531, 95% CI: 0.292–0.967, P = 0.038) but had no influence on BCSS (P = 0.272).
Conclusions
HER2-low tumors had a higher proportion of HR positivity and a lower rate of histological grade III than HER2-zero tumors. Low HER2 expression seemed to be a protective factor for RFI, especially in patients with HR + and those younger than 65 years.
Perception and practices of depth of anesthesia monitoring and intraoperative awareness event rate among Jordanian anesthesiologists: a cross-sectional study
Authors: Nawafleh Sager , Alrawashdeh Ahmad , Ababneh Omar , Hani Diab Bani , Bani-Hani Morad , Bataineh Adel , Al-Salameh Faisal , Abuzaid Sajeda , Yasser Omer , Khairallah Khaled , Modanat Zaid Al 
Published: October 2022

Abstract
Background
Intraoperative awareness is the second most common complication of surgeries, and it negatively affects patients and healthcare professionals. Based on the limited previous studies, there ‎is a wide variation in the incidence intraoperative awareness and in the practices and attitudes of depth of anesthesia (DoA) monitoring among healthcare systems and anesthesiologists. This study aimed to evaluate the Jordanian anesthesiologists’ practice and attitudes toward DoA monitoring and their estimation of the incidence of ‎intraoperative awareness.
Methods
A descriptive cross-sectional survey of the Jordanian anesthesiologists working in public, private, and university hospitals was utilized using questionnaire ‎developed based on previous studies. Practice and attitude in using DoA monitors were evaluated. Anesthesiologists were asked to best estimate the number of anesthesia procedures and frequency of intraoperative awareness events in the year before. Percentages and 95% Confidence Intervals (95%CI) were reported and compared between groups using chi-square tests.‎
Results
A total of 107 physicians participated and completed the survey. About one-third of the participant (34.6%; 95% CI 26.1–44.2) had never used a DoA monitor and only 6.5% (96% CI ) reported using it as a “daily practice”. The use of a DoA monitor was associated with experience and type of health sector. However, 81.3% (95% CI 66.5–83.5) believed that currently available DoA monitors are effective for DoA monitoring, and only 4.7% (95%CI ‎1.9–10.8‎) reported it as being “invalid”. Most participants reported that the main purpose of using the DoA monitor was to prevent awareness (86.0%; 95%CI 77.9–91.4), guide the delivery of anesthetics (63.6%; 95%CI 53.9–72.2), and reduce recovery time (57%; 95%CI 47.4–66.1). The event rate of intraoperative awareness was estimated at 0.4% among participated anesthesiologists. Most of participants’ hospitals lacked policy intended to prevent intraoperative awareness.
Conclusions
Most anesthesiologists believed in the role of DoA monitors in preventing intraoperative awareness, however, their attitudes and knowledge are inadequate, and few use DoA monitors in routine practices. In Jordan, large efforts are needed to regulate the use of DoA monitoring and reduce the incidence of intraoperative awareness.
PIM2 kinase regulates the expression of TIGIT and energy metabolism on NK cell in multiple myeloma patients
Authors: Liu ZhaoYun , Wang Hao , Li YiMan , Meng NanHao , Liu Hui , Ding Kai , Fu Rong 
Published: October 2022

Abstract
Background: PIM2 kinase play a vital role in the generation of plasma cell and bone loss in multiple myeloma(MM), which highly related to the tumor progression and as a potential therapy target in MM. In immune cell,PIM2 kinase involved in the regulation of lymphocyte like T cell and B cell, However, its role in NK cells remains unclear.
Methods: Single-cell RNA sequencing data were analysed the expression of PIM2 kinase in NK cells from MM patients and healthy donors.Immune checkpoint expression, cell apoptosis, and NK cell function had been evaluated through flow cytometry.Then, NCBI, UCSC, JASPAR and GEPIA database were used to predict promoter of TIGIT.NK-92 cells with ETS-1 knockdown were established by using sh-RNA. Kinase functional assay (ADP-Glo) were used to confirm PIM2 inhibitor from 160 kinds of natural flavonoids compound.Samples treated with or without drugs were analyzed using mass spectrometry and RNA-seq. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR) were measured by assay kit.
Result: The PIM2 kinase was highly expressed in the NK cells from MM patients based on single-cell sequencing analysis and confirmed in clinical sample by PCR and flow cytometry.Inhibition of PIM2 kinase can increase the function of NK cells and down regulation TIGIT expression. Mechanism, we confirmed that ETS-1 which was directly binding to the promoter of TIGIT was up-regulated by PIM2 kinase, which can lead the strengthened transcription of TIGIT on NK cells.Furthermore, two novel natural flavonoids compound named Kaempferol and Quercetin dihydrate as PIM2 kinase inhibitors exhibiting higher efficiency at low dose in MM cells,while influence the expression of TIGIT and energy metabolism on NK-92 cells. For in vitro experiment,PIM2 kinase inhibitors can activate NK cell killing function and decrease TIGIT expression,while promoted the apoptosis of MM cells irrespective of adding BMSCs or not in co-culture systems BMSCs.
Conclusion: PIM2 kinase involved in the regulation of NK cell.Inhibiting PIM2 kinase could down-regulate the expression of TIGIT and improve energy metabolism to enhance NK cell anti myeloma cell.
KGCNA-CNN-BiLSTM：Knowledge graph and hybrid neural networks for drugs association prediction
Authors: Liu Shuang , Zhu Xiaomin 
Published: October 2022

Abstract

Drug association (DDIs) prediction is also called drug interaction prediction, which refers to the interactions between drug and drug that lead to unexpected side effects when two or more drugs are taken simultaneously or successively. Previous studies on DDIs prediction using methods such as molecular representation and network embedding were extremely complex, expensive and time-consuming, and were limited in acquiring rich neighborhood information about drug entities and their surroundings during the forecasting process. A drug linkage prediction method based on knowledge graphs and hybrid neural networks was proposed based on the deficiencies of the above methods. This method is mainly based on methods such as knowledge graphs, graph convolutional network, Convolutional-BiLSTM network and attention mechanisms to solve the limitations in acquiring rich neighborhood information about KG entities during the forecasting process. It transforms drug linkage prediction research into a link prediction problem and views drug relationships with known interactions as edges in the interaction graph. It can effectively discover interactions of unknown drugs; meanwhile, performance comparisons are performed with existing DDIs prediction methods. The results show that higher performance is achieved in terms of indicators such as ACC and F1 values, which validate the effectiveness of the model. Finally, future directions in this field are proposed based on an analysis and summary of challenges faced by current DDIs predictions.
Genome-wide analysis of the KANADI gene family and its expression patterns under different nitrogen treatments in Populus trichocarpa
Authors: Niu Minghui , Zhang Heng , Li Xiangyang , Hu Zhibao , Zhang Hongjiao , Xu Zhiru , Qu Chunpu , Liu Guanjun 
Published: October 2022

Abstract
Background KANADI(KAN) was a plant-specific gene that controlled the polarity development of lateral organs. It mainly acted on the abaxial characteristics of plants to make the lateral organs asymmetrical. However, it had not been identified in woody plants.
Methods and Results In this study, the members of the KAN gene family in Populus trichocarpawere identified and analyzed using the bioinformatics method. The results showed that a total of 8 KAN family members were screened out, and each member contained the unique GARP domain and conserved region of the family proteins. Phylogenetic analysis and their gene structures revealed that all KANgenes from P. trichocarpa, Arabidopsis thaliana, and Nicotiana benthamiana could be divided into four subgroups, while the eight genes in P.trichocarpa were classified into three subgroups, respectively. The analysis of tissue-specific expression indicated that PtKAN1 was highly expressed in young leaves, PtKAN6 was highly expressed in young leaves and mature leaves, PtKAN2, PtKAN5, and PtKAN7 were highly expressed in nodes and internodes, PtKAN8was highly expressed in roots, and PtKAN3 and PtKAN4 showed low expression levels in all tissues. Among them, PtKAN2and PtKAN6, and PtKAN4 and PtKAN5 might have functional redundancy. Under high nitrogen concentrations, PtKAN2 and PtKAN8were highly expressed in mature stems and leaves, respectively, while PtKAN4, PtKAN5, and PtKAN7 were highly expressed in roots.
Conclusions This study laid a theoretical foundation for further study of the KANgene-mediated nitrogen effect on root development.
Hybrid graphene electrode for diagnosis and treatment of epilepsy in free-moving animal models
Authors: Ahn Jong-Hyun , Lim Jeongsik , lee sangwon , Kim Jejung , Hong Jeonghoon , Lim Sooho , Kim Kyungtae , Kim Jeongwoo , Yang Sungchil , Yang Sunggu 
Published: October 2022

Abstract
Various electrophysiological and imaging techniques have been studied for the diagnosis and treatment of epilepsy. In particular, electrocorticography (ECoG) provides valuable information that can guide clinical treatment in patients with epilepsy. To date, it is necessary to define the clinical benefits of ECoG in free-moving animals for the treatment of epilepsy. Here, we present the results of simultaneous recordings of multiple cortical sites and responsive neurostimulations for epilepsy treatment carried out in free-moving rats. In this study, we developed a high-density, flexible electrode array comprising graphene/Au/graphene which stably wraps onto the cortex surface of living rat’s brain, exhibiting superior signal-to-noise ratio. The hybrid graphene multichannel electrode successfully detected brain signals with high-throughput spatiotemporal resolution and substantially suppressed pilocarpine-induced epileptic discharges and behavior. The simultaneous recording and neurostimulation in awake animals can lead to a fundamental change in the approaches used for the treatment of medically intractable epilepsy.
Kiss and spit metabolomics highlights the role of host purine metabolism during pathogen infection
Authors: Gallego-Lopez Gina , Olson William , Perdomo Andres Tibabuzo , Stevenson David , Amador-Noguez Daniel , Lawrence Grant , Leahy James , Knoll Laura 
Published: October 2022

Abstract
Intracellular bacteria and protists are auxotrophic for many metabolites and must rely on the host cell to supply these nutrients. The mechanisms of how pathogens manipulate host metabolism to their benefit are not understood. These questions are difficult to address for intracellular pathogens because one cannot easily distinguish the origin of the metabolite as host or pathogen derived. The obligate intracellular parasite Toxoplasma gondii manipulates the host cell by a pre-invasion process called “kiss and spit”, where the contents of the parasite rhoptry organelles are secreted into the host cytoplasm before invasion occurs. Here, we demonstrated that rhoptry contents from kiss and spit altered metabolite abundance in nucleotide synthesis, the pentose phosphate pathway, glycolysis, and amino acid synthesis. An increase in 2,3-bisphosphoglycerate (2,3-BPG) abundance led us to investigate the activation of host cytosolic nucleosidase II (cN-II) to provide purines for the parasite.
Frailty knowledge level and its influencing factors among older adults in China
Authors: Zhou Tian , Qu Zhe , Ge Song , Wu Xiang , Zhang Xiao , Wang Aming , Tang Xianping 
Published: October 2022

Abstract
Background

Raising older adults’ frailty knowledge level and encouraging them to actively engage in the prevention and treatment of frailty is important to promote healthy aging. This study aimed to investigate frailty knowledge level and its influencing factors among community-dwelling older adults in China.

Methods

This cross-sectional study included a total of 734 community-dwelling older adults in China. A self-designed questionnaire was used to assess their frailty knowledge level. Logistic regression and decision tree analysis were used to examine the association between the following factors and frailty knowledge level: gender, age, residential area, co-residence, marital status, education level, monthly income, pension insurance, smoking status, drinking status, exercise status, body mass index, type of chronic disease, number of oral medications, nutritional status, cognitive status, depression, social activity, social isolation, and frailty.

Results

Most of the participants (mean age 72.01, standard deviation 9.45) were female (51.1%) and living with a spouse (76.4%). They knew little about frailty and had misunderstandings about frailty. Nearly half of them made a wrong judgment on their frailty status (42.50%). Most participants expected to obtain frailty knowledge in the community (33.92%). Those who were female, lived in rural areas, lived alone, had not attended school, had a monthly income < 3,000RMB, were at risk for malnutrition, were depressed, and were socially isolated were more likely to lack knowledge on frailty. In contrast, those with advanced age and were at pre-frailty or frailty stage were significantly more knowledgeable about frailty. The group that was least knowledgeable about frailty was those who had never attended school or primary school and had loose friend ties (1.3%).

Conclusion

Frailty knowledge level among older adults in China is low, especially among those at high risk for frailty. Therefore, it is crucial to develop tailored measures to raise frailty knowledge level among older adults in China.