bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saccharomyces Cerevisiae Strains Selected from Nature Significantly Increased the Production of 2-Phenylethanol Through Protoplast Fusion
Authors: Lin Lucheng , Xu Zhiwei , Wang Weixia , Wang Kun , Zhu Tingheng 
Published: May 2021

Abstract
Background: 2-Phenylethanol (2-PE) is an aromatic alcohol with rose fragrance, which is widely used as an additive in food, tobacco and daily chemical industries. Yeast is the main microorganism producing natural 2-PE, but it is limited by low production and weak tolerance. Nature and fermented products is a resource treasury of yeasts with excellent traits. Screening strains with good phenotypic traits and conducting breeding by cell fusion for genetic pyramiding is an effective way to improve strains. Results: In this study, 25 strains of 2-PE-producing yeasts were isolated from Chinese brewed samples. Three Saccharomyces cerevisiae strains with good traits in tolerance and 2-PE titre were screened out. The strain LSC-1 produces 2-PE of 3.41 g/L with an increase of 9.3% compared to the industrial strain CWY132. The strain NGER shows good tolerance to 2-PE at the concentration of 3.60 g/L in agar plate, and the thermotolerant strain S.C-1 shows growth ability at 41℃. Two rounds of protoplast fusion were performed with these three parent strains for pyramiding of traits. A fusant strain RH2-16 with high 2-PE titre and increased tolerance was obtained. Using 5g/L L-phenylalanine as the precursor substrate, the maximum titre of 2-PE produced by the RH2-16 strain through fermentation and transformation is 4.31 g/L, and the average titre is 4.04 g/L. The molar conversion rate of L-Phe reached 115% in 36 h. Compared to the parental strain LSC-1 and the industrial strain CWY132, 2-PE titre in RH2-16 increased by 26.4% and 38.1%, respectively.Conclusion: Diversified S. cerevisiae strains with different traits can be isolated from the brewing related samples. Protoplast fusion technology can effectively pyramid excellent genetic traits and breed yeast strains with significantly improved tolerance and 2-PE titre. Our research provided a breeding strategy for S. cerevisiae and a strain for industrial production of 2-PE.
Development and performance of a population-based risk stratification model for COVID-19
Authors: Vela Emili , Carot-Sans Gerard , Clèries Montse , Monterde David , Acebes Xènia , Comella Adrià , Eroles Luís Manuel García , Coca Marc , Valero-Bover Damià , Piera Jordi , Sust Pol Pérez 
Published: May 2021

Abstract
The shortage of recently approved vaccines against the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has highlighted the need for evidence-based tools to prioritize healthcare resources for people at higher risk of severe coronavirus disease 2019 (COVID-19). Current evidence indicates that age is far from accurate in identifying the risk of severe illness; furthermore, the count of individual risk factors has limited applicability to population-based “stratify-and-shield” strategies. We developed a COVID-19 risk stratification system that allows allocating people into four mutually-exclusive risk categories based on multivariate models for hospital admissions, transfer to intensive care unit (ICU), and mortality among the general population. The model was developed using clinical, hospital, and epidemiological data from the entire population of Catalonia (North-East Spain; 7.5 million people) and validated using an independent dataset of 218,329 individuals with PCR-confirmed COVID-19, who were infected after developing the model. This showed high discrimination capacity, with an area under the curve of the receiving operating characteristics of 0.85 (95% CI 0.85–0.85) for hospital admissions, 0.86 (0.86–0.97) for ICU transfers, and 0.96 (0.96–0.96) for deaths. Our results provide clinicians and policymakers with an evidence-based tool for prioritizing COVID-19 healthcare resources other population groups aside from those with higher exposure to SARS-CoV-2 and frontline workers.
Homogenization of Fish Composition Among Mesohabitats Driven by Stream Degradation from Urban Land Use
Authors: Pessoa Leonardo Antunes , Baumgartner Matheus T. , Frota Augusto , Garcia Thiago D. , Pagotto João , Goulart Erivelto 
Published: May 2021

Abstract
The heterogeneity along the course of streams beget habitat features that are highly different and strongly influence the composition of fish assemblages. Stream stretches such as riffles, runs, and pools are particularly distinct in physical structures and water flow, with expected differences in the identity and body shape of the species that occupy these habitat units. However, how land is used in the adjacent areas of these aquatic environments also changes the habitat characteristics and, therefore, the fish composition from each stretch. In this context, we collected data from both rural and urban streams to assess how these land-use types influence the species composition and their body morphology among mesohabitats. Differences in body morphology were evaluated using Analysis of Variance (ANOVA) on the mean of Compression Index (CI) weighted by the species abundance for each sampled site. The differences in species composition were assessed using permutational multivariate analogous (PERMANOVA) and Indicator Value (IndVal). Urban streams showed a significantly decreased fish diversity combined with no differences in body morphology of fish and homogenization of species composition among mesohabitats. Importantly, we could infer that mesohabitats influence the body shape of fish and, consequently, species composition in less disturbed streams. However, the lower fish diversity in more imperiled streams led to the homogenization of fish composition among mesohabitats. These patterns constitute important contributions for evidence-based management and restoration of streams, as the presence of different mesohabitats is not enough to overcome the effects of urbanization on fish assemblages.
Transcriptome Analysis of Walnut Seedling Roots Under Nitrogen Starvation and Excess Nitrogen Stress
Authors: Song Yan , Zhang Rui , Gao Shan , Zhiyong Pan , Guo Zhongzhong , Yu Shangqi , Wang Yu , Jin Qiang , Chen Xiaofei , Zhang Lei 
Published: May 2021

Abstract
Nitrogen is an essential core element in walnut seedling growth and development. However, nitrogen starvation and excessive nitrogen stress can cause stunted growth and development of walnut seedlings, and environmental pollution is also of concern. Therefore, it is necessary to study the mechanism of walnut seedling resistance to nitrogen stress. In this study, morphological and physiological observations and transcriptome sequencing of walnut seedlings under nitrogen starvation and excess nitrogen stress were performed. The results showed that walnut seedlings under nitrogen starvation and excess stress could adapt to the changes in the nitrogen environment by changing the coordination of their root morphology and physiological indexes. Based on an analysis of transcriptome data, 4911 differential genes (DEGs) were obtained (2180 were upregulated and 2731 were downregulated) in a comparison of nitrogen starvation and control groups. A total of 9497 DEGs (5091 upregulated and 4406 downregulated) were obtained in the comparison between the nitrogen overdose and control groups. When these DEGs were analysed, the differential genes in both groups were found to be significantly enriched in the plant’s circadian pathway. Therefore, we selected the circadian rhythm as the core focus for further analysis. We made some discoveries by analysing the gene co-expression network of nitrogen metabolism, circadian rhythm, and hormone signal transduction. (a) Nitrite nitrogen (NO2-) or Glu may act as a nitrogen signal to the circadian clock. (b) Nitrogen signalling may be input into the circadian clock by regulating changes in the abundance of the CRY1 gene. (c) After the nitrogen signal enters the circadian clock, the expression of the LHY gene is upregulated, which causes a phase shift in the circadian clock. (d) The RVE protein may send information about the circadian clock’s response to nitrogen stress back to the nitrogen metabolic pathway via the hormone transduction pathway. In conclusion, various metabolic pathways in the roots of walnut seedlings coordinated with one another to resist the ill effects of nitrogen stress on the root cells, and these coordination relationships were regulated by the circadian clock. This study is expected to provide valuable information on the circadian clock regulation of plant resistance to nitrogen stress.
Hyaluronate – Black Phosphorus Conjugates as a Copper Chelating Agent for Wilson Disease Treatment
Authors: Kim Seong-Jong , Han Hye Hyeon , Hahn Sei Kwang 
Published: May 2021

Abstract
Background: Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods: We developed hyaluronate - black phosphorus (HA-BP) conjugates for capturing copper ions accumulated in the liver for the treatment of WD.Results: HA-BP conjugates showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-BP conjugates to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-BP conjugates.Conclusion: HA-BP conjugates would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.
MiR-23b-3p Targeting NCAPG Promotes Cell Proliferation and Anti-Apoptosis By Regulating PI3K/AKT Signaling Pathway in Colorectal Cancer
Authors: Li Peidong , Wen Jing , Ren Xiru , Zhou Yu , Xue Yuan , Yan ZaiHua , Li Shengjie , Tian Hongpeng , Tang Xuegui , Zhang Guangjun 
Published: May 2021

Abstract
The authors have requested that this preprint be removed from Research Square.
Regulation of CD4+CD25+FOXP3+ Treg Cells in Systemic Lupus Erythematosus (SLE): Association With miRNAs Expression
Authors: El-Maghraby Abeer M. , Ali Yasser B.M. , El-maadawy Eman , Elshal Mohamed F. , Bassyouni Iman H , El-Garawani Islam M , talaat roba 
Published: May 2021

Abstract
Various genetic factors are controlling regulatory cells T (Treg) cell function, such as miRNAs. Interfering in the miRNA synthesis pathway in Treg cells could result in loss of Tregs' regulatory function, leading to the promotion of inflammatory settings and autoimmunity. This study was designed to investigate the role of miRNA in regulating Treg cells in SLE patients. Treg's frequency was determined using flow cytometry in 100 SLE patients’ and100 healthy controls. Expression of miR-21, miR-24, miR125, miR-146a, miR-148a, and miR-155 was estimated in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction (qRT-PCR). The ROC curve evaluated the diagnostic role of miRNAs in SLE. A significant elevation (p<0.001) in Treg cells in SLE patients than controls was observed, with a maximum increase inactive SLE cases. SLE patients exhibit a significant increase in miR-21 (p<0.01), miR-148a (p<0.001), miR-146a (p<0.05) and miR-155 (p<0.001) and significant reduction in miR-24 (p<0.001). An insignificant decrease in miR-125 was observed in SLE patients. The best sensitivity and specificity were detected in miR-148a (88%, 70%) at a cutoff value of 1. 065. Tregs were positively correlated with miR-21(r=0.333, p<0.05), miR-146a (r=0.589, p<0.01) and miR-148a (r=0.309, p<0.05). In conclusion, this research provides a piece of novel information regarding Treg cells' in SLE patients. Our results pointed to the substantial role of miRNAs in controlling Treg cells in lupus. To validate our interesting results, more researches are needed.
Comparison of Prevalence of Degenerative Findings on Lumbar MRI among Sciatica Patients classified using the McKenzie Method.
Authors: Kilpikoski Sinikka , Suominen Eetu , Repo Jussi , Häkkinen Arja H , Kyrölä Kati , Kautiainen Hannu , Ylinen Jari 
Published: May 2021

Abstract
The authors have requested that this preprint be removed from Research Square.
Efficacy of Dipeptidyl Peptidase-4 Inhibitors on Leptin in type 2 Diabetes Mellitus: A Meta-Analysis
Authors: wei xin , bai yu , wang zhuo , zheng xiaohong , jin zening , liu xin 
Published: May 2021

Abstract
Background: Dipeptidyl peptidase-4 inhibitors (DPP-4i) provide a unique anti-hyperglycemic effect through regulating incretin peptides in type 2 diabetes mellitus (T2DM) patients that are inadequately controlled with insulin therapy. The aim of this study was to investigate the impact of DPP-4i on leptin concentrations in subjects with T2DM. Methods: Randomized controlled trials (RCTs) with comparators were identified through systematically searching PubMed, Embase, and Cochrane library. Quantitative analysis was performed with a fixed or random-effects model according to heterogeneity. Publication bias was evaluated by using the standard methods for sensitivity analysis. Results: Ten trials with 698 patients with T2DM were included. Pooled analysis demonstrated that DPP-4i did not significantly change leptin concentrations (1.31 ng/mL, 95% CI, -0.48 to 3.10). DPP-4i exerted no stronger effect on modulating leptin levels compared to active comparators (0.21 ng/mL, 95% CI, -1.37 to 1.78). Meta-analysis was powerful and stable after sensitivity analysis.Conclusions: DDP-4i did not modulate leptin concentrations and exerted no stronger effect than traditional antidiabetic agents.
Functional Outcomes Following Fixation of an Ultra-distal Radius Fracture with Two Commonly used Volar Locking Plates: A Retrospective Cohort Study
Authors: Huang Yin-Ming , Chen Chun-Yu , Lin Kai-Cheng , Tarng Yih-Wen , Liao Ching-Yi , Chang Wei-Ning 
Published: May 2021

Abstract
Introduction: The volar locking plate has been widely used for unstable distal radius fractures to provide early recovery of wrist function. Volar plate prominence to the watershed line has been reported to be related to flexor tendon irritation, and avoid implant prominence in this area was suggested. On the other hand, ultra-distal radius fracture patterns required the plate to cross the watershed line, making conflict over plate positioning on ultra-distal radius fractures. This study compared functional outcomes in patients with ultra-distal radius fractures treated with two different implants.Materials and Methods: A retrospective study was conducted, all patients who received a Synthes 2.4mm LCP or an Acumed Acu-Loc VLP between January 2015 and December 2018 were reviewed. The ultra-distal fracture pattern was the most distal horizontal fracture line within 10 mm of the lunate fossa's joint line. The primary outcomes including patient-reported pain scores, range of motion, and grip strength were assessed. Secondary outcomes included patient-based subjective satisfaction scores of the injured wrist and hand function. The Mayo Wrist Score and the requirement for a secondary procedure related to hardware complications were also recorded. Results: Forty-two patients met our inclusion criteria. Twenty-one patients were treated with the Synthes 2.4 mm LCP, and 21 patients with the Acumed Acu-Loc VLP. The primary outcome revealed that post-operative range of motion (P = 0.016) and gripping strengths (P = 0.014) were significantly improved in the Acu-Loc VLP group. The MAYO wrist score in the Acu-Loc VLP group was also significantly better (P = 0.006). Conclusions: Despite advances in implant designs, flexor tendon irritation or rupture is still a complication following distal radius's volar plating. We believe the Acumed Acu-Loc VLP design provided better functional outcomes than the Synthes 2.4 mm LCP if appropriately and carefully placed into its designed-for position. This positioning results in promising patient satisfaction when treating ultra-distal radius fractures.
Normal Tension Primary Ppen-Angle Glaucoma with Progressive Synechial Angle Closure in Senior Chinese
Authors: Fan Zhigang , Zhao Zhenni , Yu Xiaowei , Zhang Dandan , Sun Nannan , Zhang Jiamin 
Published: May 2021

Abstract
Background: This study is to address a unique subtype of combined-mechanism glaucoma (CMG), normal tension glaucoma (NTG) with progressive synechial angle closure in the Chinese senior population, whose clinical course and treatment targets are quite different from classic primary angle-closure glaucoma (PACG). Methods: In this retrospective study, 12 patients with NTG plus primary angle closure suspect or primary angle closure were included in the CMG group, and 12 classic PACG patients with matched extent of glaucomatous optic neuropathy (GON) were included in the control (PACG) group. Clinical features and detailed histories of disease development were investigated and compared between these two groups.Results: There were 6 females and 6 males in CMG group, 3 males and 9 females in PACG group. No statistical significances were found in age (63.42 ± 5.90 vs. 59.42 ± 7.47 years), preoperative intraocular pressure (20.75 ± 5.06 vs. 21.25 ± 4.47 mmHg), anterior chamber depth (ACD) (1.98 ± 0.28 vs. 1.94 ± 0.21mm), mean deviation of visual field (24.37 ± 6.54 vs. 22.01 ± 0.85 dB), average retinal nerve fiber layer thickness (48.00 ± 14.00 vs. 57.25 ± 14.10 μm), cup-to-disc (C/D) ratio (0.89 ± 0.07 vs. 0.87 ± 0.07) and axial length (22.69 ± 0.76 vs. 22.47 ± 0.69 mm) between the two groups (P > 0.05). The extent of synechial angle closure in PACG group was more extensive than that in CMG group, as evaluated by the number of “clock hours” (3.96 ± 1.14 vs. 9.38 ± 1.99, P < 0.05), although the severity of GON was comparable.Conclusion: If NTG develops with synechial angle closure, it might be misdiagnosed as PACG. We need to recognize and scrutinize this specific subtype of CMG, which is very common in the Chinese senior population, but widely neglected. In contrast to classic PACG, treatment targets in NTG with progressive synechial angle closure is primarily in consistent with those in NTG.
Tanshinone IIA Affects the Malignant Growth of Cholangiocarcinoma Cells by Inhibiting the PI3K-Akt-mTOR Pathway
Authors: Liu Huayuan , Liu Caiyun , Wang Mengya , Sun Dongxu , Zhu Pengcheng , Zhang Ping , Tan Xueying , Shi Guangjun 
Published: May 2021

Abstract
Purpose: In the present study, we aimed to find the target of Tanshinone IIA (Tan-IIA) in Cholangiocarcinoma by network pharmacology-based prediction and investigate the possible mechanism through experimental verification. Methods: In this study, we combined Tan-IIA-specific and Cholangiocarcinoma-specific targets with protein-protein interactions (PPI) to construct a Tan-IIA targets-Cholangiocarcinoma network, and network pharmacology approach was applied to identify potential targets and mechanisms of Tan-IIA in the treatment of Cholangiocarcinoma. The anti-cancer effects of Tan-IIA were investigated by using subcutaneous tumorigenic model in nude mice and in the human Cholangiocarcinoma cell lines in vitro. Results: Our results showed that Tan-IIA treatment considerably suppressed the proliferation and migration of Cholangiocarcinoma cells while inducing apoptosis of Cholangiocarcinoma cells. Western blot results demonstrated that the expression of PI3K, p-Akt, p-mTOR, and mTOR were inhibited by Tan-IIA. Meanwhile, After treatment with Tan-IIA, the level of Bcl2 was downregulated and cleaved caspase-3 expression increased. Further studies revealed that the anticancer effects of Tan-IIA were severely mitigated by pretreatment with a PI3K agonist.Conclusion: Our research provides a new anticancer strategy and strengthens support for the use of Tan-IIA as an anticancer drug for the treatment of CCA.
GLS1 Promotes The Malignant Progression of Osteosarcoma
Authors: TONG ZENG , Lei Peng , JUNQIANG YIN , WEIHAI LIU , DI ZHANG , ZEPEI FAN , HAIBAO CHEN , JINNAN SHEN , SONG JIN 
Published: May 2021

Abstract
Background: Osteosarcoma (OS) is the most frequent and high-grade young malignant bone tumor. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy and chemotherapy. Metabolic reprogramming currently is recognized as one of the hallmarks of cancer. Glutaminase 1(GLS1) has been associated with progression of tumor cell through CDK4 signaling pathway.Methods: In the study, Western blot was used to detect the expression of GLS1 protein in tumor and adjacent normal tissues of osteosarcoma patients, and Western blot was used to detect the expression of GLS1 protein in osteosarcoma cell lines. GLS1 siRNA was transfected into osteosarcoma U2OS cells. Western blot was used to detect the expression of GLS1 protein. MTT and clone formation assay were used to detect cell proliferation. Transwell chamber assay was used to detect migration and invasion. Western blot was used to detect the expression of CDK4 protein in GLS1 knockdown U2OS cells. CB-839 was used to treat U2OS cells. The IC50 value of CB-839 was detected by MTT. The proliferation and migration of CB-839 were detected by clone formation, scratch test, RNA seq sequencing, q-PCR and Western blot.Results: (1) GLS1 was highly expressed in osteosarcoma tissues and cell lines; (2) After transfection, compared with the control group, GLS1 protein expression and CDK4 protein expression of U2OS cells in the knockdown group were significantly down regulated. In vitro experiments showed that the proliferation, migration and invasion of U2OS cells were significantly down regulated; (3) CB-839 promoted apoptosis and inhibited the proliferation and migration of osteosarcoma cells by acting on upstream transcription factors EGR1 and FOXO1. Conclusion: GLS1 can promote the proliferation, migration and invasion of osteosarcoma cells by affecting the cell cycle of CDK4 signaling pathway, and can be used as a potential prognostic indicator and therapeutic target for osteosarcoma patients.
Analysis of Imaging and Pathological Features in 12 Cases of Schwannomatosis and Literature Review
Authors: Kang Cheng-wei , Wu Li-xue , Pu Xiao-bing , Dong Chang-chao Dong , Tan Gang , Yan Zhao-kui , Shen Jiang , Liu Lei 
Published: May 2021

Abstract
Objective We analyzed US, CT, and MR images plus the pathological characteristics of 12 patients with pathologically confirmed schwannomatosis to explore the relationship between imaging and pathology.Method A retrospective analysis was undertaken over a 10-year period (01/01/2000-31/12/2019) of 12 patients undergoing Imaging and pathological examination for schwannomatosis, and the relevant literature was reviewed.Results The median age at diagnosis was 39.4 years (range, 22–56 years). We included the mean diameter of 36 lesions (5.10 ± 0.84 cm; range, 0.5–9.1 cm) in the focal observation. US showed that the mass boundary was clear, and most of the masses were low echo. CT showed that tumors were low density; the plain-scan CT value was 22–35 HU and enhancement amplitude 10–30 HU. MRI showed that most of the tumors were low or medium signal on T1-weighted image (T1WI) and high signal on T2WI; enhancement could be homogeneous or inhomogeneous. We could see the cellular Antoni A and myxoid Antoni B areas of the microscopic morphology. According to the proportions of the two areas, masses could be divided into four types: I, II, III and IV. Immunohistochemical (IHC) staining showed that the expression of S-100 protein was diffusely positive (36/36).Conclusions Imaging examination in schwannomatosis is helpful for localization and characterization of focus, as well as observation of the relationship between the tumor and the surrounding tissue structure. However, the specific diagnosis should also be based on pathological manifestations, IHC results and genetic analysis. Characteristics of mass imaging correlate with pathological changes in the mass.