bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entendendo o paradigma do comportamento e função das células-tronco em microgravidade
Authors:   Carla Viana Dendasck, Santos Enrico Jardim Clemente ,   Anísio Francisco Soares,   Cláudio Alberto Gellis de Mattos Dias,   Josué Ribeiro da Silva Nunes
Published: April 2023

O constante desenvolvimento tecnológico vem ampliando significativamente as perspectivas da humanidade em diferentes áreas do conhecimento. Dentre estas temos a necessidade de nos tornarmos uma raça espacial, de forma que possamos explorar e estabelecer nossa presença em outras luas e planetas, o que tende a resultar na implementação do turismo espacial, por meio de diversos voos tripulados. Entretanto, a fim de alcançar esses objetivos, a vida terrestre precisa superar desafios associados a ambientes que diferem daquelas encontradas na Terra, os quais tendem a ser estressantes para o organismo como a microgravidade (aproximadamente 1×10−6 g), falta de uma atmosfera, mudanças de fluidos, ausência de um campo geomagnético que deflete partículas carregadas, radiação cósmica galáctica (além do Cinturão de Van Allen da Terra), privação de sono e alteração dos ritmos circadianos. Estudos vêm demonstrando que uma longa permanência no espaço pode ter um impacto significativo no organismo, resultando em problemas de saúde como desregulação do sistema imunológico, atrofia muscular, perda óssea devido a um aumento da atividade de reabsorção óssea, problemas cardíacos, motilidade gastrointestinal reduzida, prejuízo no processo de cicatrização de feridas e fraturas ósseas, entre outros (KIRCHEN , 1995; SONNENFELD, 2003; RADEK, 2008; TRAPPE, 2009; SMITH, 2014; BLOOMFIELD, 2016; HUGHSON, 2018). A longo prazo a microgravidade tende a atuar nas células-tronco adultas tecido específicas, de forma a afetar os processos de proliferação e diferenciação influenciando diretamente no mecanismo contínuo de regeneração tecidual. Atualmente as células-tronco são divididas em três tipos distintos os quais são denominados de células-tronco embrionárias (CTEs) isoladas a partir da massa celular interna do blastocisto, células-tronco pluripotentes induzidas (CTPIs) células adultas modificadas geneticamente de forma adquirirem as características das CTEs e as células-tronco adultas (CTAs) isoladas a partir de tecidos maduros como gordua, músculo, medula óssea, polpa dentária, entre outros. As CTAs ainda podem ser subdivididas em células-tronco mesenquimais (CTMs) e células-tronco hematopoiéticas (CTHs). As CTMs, por meio de seus processos de adesão, migração, proliferação e diferenciação, são de fundamental importância para a manutenção da homeostase do organismo o que torna o seu estudo, em condições de microgravidade, de fundamental importância para a exploração espacial (MAZINI, 2019; MATSUO, 2021; HERNANDEZ, 2021).
PAOX1 expression in mixed-substrate continuous cultures of Komagataella phaffii (Pichia pastoris) is completely determined by methanol consumption regardless of the secondary carbon source
Authors: Singh Anamika , Narang Atul 
Published: April 2023

The expression of recombinant proteins by the AOX1 promoter of Komagataella phaffii is typically induced by adding methanol to the cultivation medium. Since growth on methanol imposes a high oxygen demand, the medium is often supplemented with an additional secondary carbon source which serves to reduce the consumption of methanol, and hence, oxygen. Early research recommended the use of glycerol as the secondary carbon source, but more recent studies recommend the use of sorbitol because glycerol represses PAOX1 expression. To assess the validity of this recommendation, we measured the steady state concentrations of biomass, residual methanol, and LacZ expressed from PAOX1 over a wide range of dilution rates (0.02–0.20 h−1) in continuous cultures of the Mut+ strain fed with methanol + glycerol (repressing) and methanol + sorbitol (non-repressing). We find that under these conditions, the specific PAOX1 expression rate (measured as either specific LacZ productivity or specific AOX productivity) is completely determined by the specific methanol consumption rate regardless of the type (repressing/non-repressing) of the secondary carbon source. In both cultures, the specific PAOX1 expression rate is proportional to the specific methanol consumption rate, provided that the latter is below 0.15 g/(gdw-h); beyond this threshold consumption rate, the specific PAOX1 expression rate of both cultures saturates to the same value. Analysis of the data in the literature shows that the same phenomenon also occurs in continuous cultures of Escherichia coli fed with mixtures of lactose plus repressing/non-repressing carbon sources. The specific Plac expression rate is completely determined by the specific lactose consumption rate, regardless of the type of secondary carbon source, glycerol or glucose.
Dose-dependent effect of GFI1 expression in the reconstitution and the differentiation capacity of HSCs
Authors: Xie Xiaoqing , Patnana Pradeep Kumar , Frank Daria , Schütte Judith , Al-Matary Yahya , Künstner Axel , Busch Hauke , Ahmed Helal , Liu Longlong , Engel Daniel R. , Dührsen Ulrich , Rosenbauer Frank , Von Bubnoff Nikolas , Lenz Georg , Khandanpour Cyrus 
Published: April 2023

GFI1 is a transcriptional repressor and plays a pivotal role in regulating the differentiation of hematopoietic stem cells (HSCs) towards myeloid and lymphoid cells. Serial transplantation of Gfi1 deficient HSCs repopulated whole hematopoietic system but in a competitive setting involving wild-type HSCs, they lose this ability. The underlying mechanisms to this end are poorly understood. To better understand this, we used different mouse strains that express either loss of both Gfi1 alleles (Gfi1-KO), with reduced expression of GFI1 (GFI1-KD) or wild-type Gfi1/GFI1 (Gfi1-/GFI1-WT; corresponding to the mouse and human alleles). We observed that loss of Gfi1 or reduced expression of GFI1 led to a two to four fold lower number of HSCs (defined as Lin−Sca1+c-Kit+CD150+CD48−) compared to GFI1-WT mice. To study the functional influence of different levels of GFI1 expression on HSCs function, HSCs from Gfi1-WT (expressing CD45.1 + surface antigens) and HSCs from GFI1-KD or -KO (expressing CD45.2 + surface antigens) mice were sorted and co-transplanted into lethally irradiated host mice. Every 4 weeks, CD45.1+ and CD45.2 + on different lineage mature cells were analyzed by flow cytometry. At least 16 weeks later, mice were sacrificed, and the percentage of HSCs and progenitors including GMPs, CMPs and MEPs in the total bone marrow cells was calculated as well as their CD45.1 and CD45.2 expression. In the case of co-transplantation of GFI1-KD with Gfi1-WT HSCs, the majority of HSCs (81% ± 6%) as well as the majority of mature cells (88% ± 10%) originated from CD45.2 + GFI1-KD HSCs. In the case of co-transplantation of Gfi1-KO HSCs with Gfi1-WT HSCs, the majority of HSCs originated from CD45.2+ and therefore from Gfi1-KO (61% ± 20%); however, only a small fraction of progenitors and mature cells originated from Gfi1-KO HSCs (&lt;1%). We therefore in summary propose that GFI1 has a dose-dependent role in the self-renewal and differentiation of HSCs.
Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer
Authors: James Christopher , Gomez Kayeromi , Desai Shalin , Patel Hiten D. , Rac Goran , Doshi Chirag P. , Dornbier Ryan , Bajic Petar , Halverson Thomas , Gupta Gopal N. , Quek Marcus L. , Gorbonos Alex , Flanigan Robert , Wolfe Alan J. 
Published: April 2023

IntroductionIntravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC.MethodsPatients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated.ResultsAcross the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P&lt;0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort.ConclusionIVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.
Study on the process of cardiomyocyte apoptosis after pulsed field ablation
Authors: Fan Shaobo , Jia Fenglin , Cui Yingjian , Wu Dongyan , He Le , Zhang Fan , Xue Zhixiao , Xu Xinyu , Lu Fengmin , Ma Wei , Su Siying , Chen Yanpeng , Liu Zhenxu 
Published: April 2023

BackgroundThe development of pulsed field ablation (PFA) as a new technique for pulmonary vein isolation (PVI) has been advancing rapidly in recent years. My team's previous work has shown the safety and long-term efficacy of bipolar asymmetric pulses in animal experiments. However, in ongoing clinical trials, we have observed that atrial fibrillation (AF) recurs in some patients after surgery, but the rhythm returns to normal without surgical intervention after seven days, and there is no recurrence in the follow-up.Based on this observation, we have proposed the hypothesis that myocardial cell apoptosis may play a role in AF recurrence after PFA. Our team has designed animal experiments to verify this hypothesis and further investigate the process of PFA-induced cardiomyocyte apoptosis.MethodsPulse field ablation was performed on 15 dogs and the animals were dissected at various time points after the operation (immediately, 3 days, 7 days, 30 days, and 150 days). To obtain ablation voltage maps, electroanatomic mapping was performed before and after ablation and before dissection. The ablation area was also subjected to HE and TUNEL staining to analyze apoptosis and pathological results.ResultsThe edge area of the ablation in the pulmonary vein (PV) demonstrated continuous dynamic changes from 0 to 2 h after the operation and a slight expansion of the ablation range was observed in the long-term follow-up. Myocardial intima hyperplasia was observed from 0 to 7 days. Local apoptosis was detected from 0 to 2 h and massive, concentrated apoptosis was observed at 3 days. No recurrence of apoptosis was seen at 7 days, 30 days, and 150 days.ConclusionsThe results of this study showed that after pulse field ablation (PFA), the central ablation area of the canine heart experienced immediate cardiomyocyte death. Meanwhile, cardiomyocytes in the edge ablation area underwent apoptosis, which began from 0 to 2 h post-operation and ended between 3 and 7 days. This process occurred simultaneously with intimal thickening.In the long-term follow-up group, there was no recovery of isolation and no recurrence of cardiomyocyte apoptosis, and no change was observed in the endomyocardial intima.
Crustal thickness of the Jiaodong Peninsula in the Mesozoic: Implications for the destruction of the North China Craton
Authors: Dong Leilei , Bai Xin , Song Mingchun , Wang Runsheng 
Published: April 2023

The North China Craton underwent extensive and widespread crustal reworking (or decratonization) during the Mesozoic. However, how the decratonization operated is not well understood. Zircon compositions are widely used by the scientific community to reconstruct crustal thicknesses. In this study, we sampled 13 magmatic rocks in the Jiaodong Peninsula and used zircon Eu/Eu* to constrain the crustal thickness of the Jiaodong area and reveal decratonization processes in the Mesozoic time. The reconstructed crustal thickness using zircon Eu/Eu* is approximately 70 km in the Jurassic, and this value is 89 km at around 130 Ma, after which the crustal thickness drops to 30–40 km at ca. 110 Ma. These results are generally compatible with or slightly higher than the calculation results using a whole-rock La/Yb proxy for the Jurassic and ∼130 Ma rocks. Crustal thickness estimated using a whole-rock La/Yb proxy for the ∼110 Ma rocks is thicker than 70 km, which is not consistent with the geological facts and the result given by zircon proxy. The whole-rock proxy failed in estimating crustal thickness because of amphibole fractionation for the ∼110 Ma rocks. The crustal thickening from Jurassic to ∼130 Ma was probably related to the westward subduction of the Paleo-Pacific slab. The thinning of the crust from 130 to 110 Ma is not a rapid process but occurs more slowly than expected, which might be explained by the chemical erosion process rather than a mechanical delamination model. The chemical erosion was most likely induced by a rollback of the subducting slab and an upwelling of the asthenosphere.
Dyslipidemia and serum cystatin C levels as biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus
Authors: Dejenie Tadesse Asmamaw , Abebe Endeshaw Chekol , Mengstie Misganaw Asmamaw , Seid Mohammed Abdu , Gebeyehu Natnael Atnafu , Adella Getachew Asmare , Kassie Gizchew Ambaw , Gebrekidan Amanuel Yosef , Gesese Molalegn Mesele , Tegegne Kirubel Dagnaw , Anley Denekew Tenaw , Feleke Sefineh Fenta , Zemene Melkamu Aderajew , Dessie Anteneh Mengist , Moges Natnael , Kebede Yenealem Solomon , Bantie Berihun , Adugna Dagnew Getnet 
Published: April 2023

BackgroundDiabetic nephropathy is a leading cause of end-stage renal disease. The diagnostic markers of nephropathy, including the presence of albuminuria and/or a reduced estimated glomerular filtration rate, are not clinically ideal, and most of them are raised after a significant reduction in renal function. Therefore, it is crucial to seek more sensitive and non-invasive biomarkers for the diagnosis of diabetic nephropathy.Objective of the studyThis study aimed to investigate the serum cystatin C levels and dyslipidemia for the detection of diabetic nephropathy in patients with type 2 diabetes mellitus.MethodologyA hospital-based comparative cross-sectional study was conducted from December 2021 to August 2022 in Tikur, Anbessa specialized teaching hospital with a sample size of 140 patients with type2 diabetes mellitus. Socio-demographic data was collected using a structured questionnaire, and 5 mL of blood was collected from each participant following overnight fasting for biochemical analyses.ResultsIn type 2 diabetes patients with nephropathy, we found significant lipoprotein abnormalities and an increase in serum cystatin C (P &lt; 0.001) compared to those without nephropathy. Serum cystatin C, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, low density lipoprotein, very low-density lipoprotein, high density lipoprotein, and duration of diabetes were identified as being significantly associated with diabetic nephropathy (P &lt; 0.05) in multivariable logistic regression analysis. The mean values of total cholesterol levels, triglyceride levels, and high-density lipoprotein cholesterol levels were also found to be significantly higher (P &lt; 0.05) in females as compared to male type-2 diabetic patients. The fasting blood glucose levels and lipid profiles of the participants were found to be significantly associated with serum cystatin C levels.ConclusionThe present study found significant serum cystatin C and lipoprotein abnormalities in T2DM patients with diabetic nephropathy when compared with those without diabetic nephropathy, and these lipoprotein abnormalities were significantly associated with serum cystatin C levels.
Association of miR-196a2 and miR-27a polymorphisms with gestational diabetes mellitus susceptibility in a Chinese population
Authors: Zeng Qiaoli , Zou Dehua , Liu Na , Wei Yue , Yang Jing , Wu Weibiao , Han Fengqiong , He Rongrong , Guo Runmin 
Published: April 2023

IntroductionMiR-196a2 and miR-27a play a key role in the regulation of the insulin signaling pathway. Previous studies have indicated that miR-27a rs895819 and miR-196a2 rs11614913 have a strong association with type 2 diabetes (T2DM), but very few studies have investigated their role in gestational diabetes mellitus (GDM).MethodsA total of 500 GDM patients and 502 control subjects were enrolled in this study. Using the SNPscan™ genotyping assay, rs11614913 and rs895819 were genotyped. In the data treatment process, the independent sample t test, logistic regression and chi-square test were used to evaluate the differences in genotype, allele, and haplotype distributions and their associations with GDM risk. One-way ANOVA was conducted to determine the differences in genotype and blood glucose level.ResultsThere were obvious differences in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP) and parity between GDM and healthy subjects (P &lt; 0.05). After adjusting for the above factors, the miR-27a rs895819 C allele was still associated with an increased risk of GDM (C vs. T: OR=1.245; 95% CI: 1.011-1.533; P = 0.039) and the TT-CC genotype of rs11614913-rs895819 was related to an increased GDM risk (OR=3.989; 95% CI: 1.309-12.16; P = 0.015). In addition, the haplotype T-C had a positive interaction with GDM (OR=1.376; 95% CI: 1.075-1.790; P=0.018), especially in the 18.5 ≤ pre-BMI &lt; 24 group (OR=1.403; 95% CI: 1.026-1.921; P=0.034). Moreover, the blood glucose level of the rs895819 CC genotype was significantly higher than that of the TT and TC genotypes (P &lt; 0.05). The TT-CC genotype of rs11614913-rs895819 showed that the blood glucose level was significantly higher than that of the other genotypes.DiscussionOur findings suggest that miR-27a rs895819 is associated with increased GDM susceptibility and higher blood glucose levels.
Spatial heterogeneity and Immune infiltration of cellular lysosomal pathways reveals a new blueprint for tumor heterogeneity in esophageal cancer
Authors: Wei Jinxing , Wu XiaoMing , Wang Shuohao , Liu Siqing , Gao Xia 
Published: April 2023

BackgroundEsophageal squamous cell carcinoma (ESCC) is a common Malignant tumor of digestive tract which have a potential association with lysosomal pathway. The purpose of this study was to explore the correlation between lysosome pathway and immune infiltration of ESCC.MethodsThe cell type annotation of ESCC patients and the distribution of their gene markers were analyzed by single cell data. They were also grouped according to the expression of lysosomal pathways. Gene set variation analysis (GSVA) enriched pathway scoring, Cellchat cell communication was performed to demonstrate the tumour-associated pathway scores and interactions of different cell populations. Relevant differential genes were screened, prognostic risk markers were constructed and direct associations of lysosomal pathway-related gene risk scores with immune infiltration and tumour treatment drug sensitivity were assessed by algorithms. In cellular experiments, qPCR and flow cytometry were used to assess the role of the lysosomal pathway gene-MT1X on tumour cell development.ResultsESCC single cell data were annotated into 7 Cluster clusters by t-sne downscaling analysis. Cellchat analysis revealed that the “MIF” cellular communication network is the main communication mode of the lysosomal pathway in ESCC cells. The lysosomal pathway genetic risk model was found to be significantly different from ESCC prognosis in both the training and validation groups. The lysosome pathway gene risk model was associated with treatment resistance in ESCC patients using oncopredict R package. The correlation between the expression of lysosomal-DEG and tumour immune infiltration and immune cell types by the MCPcounter method. Cellular assays showed that the lysosomal pathway gene MT1X was less expressed in oesophageal cancer cells than in normal oesophageal epithelial cells. Knockdown of MT1X significantly promoted the growth rate of oesophageal cancer cells.ConclusionBased on the single cell sequencing technology and transcriptomic analysis, we confirmed that there is a close association between the lysosomal pathway and the immune infiltration and treatment sensitivity of ESCC, which may be a potential target for a new direction of ESCC therapy.