bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modular biosynthesis of plant hemicellulose and its impact on yeast cells
Authors: Robert Madalen , Waldhauer Julian , Stritt Fabian , Yang Bo , Pauly Markus , Voiniciuc Cătălin 
Published: June 2021

Abstract
Background
The carbohydrate polymers that encapsulate plants cells have benefited humans for centuries and have valuable biotechnological uses. In the past 5 years, exciting possibilities have emerged in the engineering of polysaccharide-based biomaterials. Despite impressive advances on bacterial cellulose-based hydrogels, comparatively little is known about how plant hemicelluloses can be reconstituted and modulated in cells suitable for biotechnological purposes.

Results
Here, we assembled cellulose synthase-like A (CSLA) enzymes using an optimized Pichia pastoris platform to produce tunable heteromannan (HM) polysaccharides in yeast. By swapping the domains of plant mannan and glucomannan synthases, we engineered chimeric CSLA proteins that made β-1,4-linked mannan in quantities surpassing those of the native enzymes while minimizing the burden on yeast growth. Prolonged expression of a glucomannan synthase from Amorphophallus konjac was toxic to yeast cells: reducing biomass accumulation and ultimately leading to compromised cell viability. However, an engineered glucomannan synthase as well as CSLA pure mannan synthases and a CSLC glucan synthase did not inhibit growth. Interestingly, Pichia cell size could be increased or decreased depending on the composition of the CSLA protein sequence. HM yield and glucose incorporation could be further increased by co-expressing chimeric CSLA proteins with a MANNAN-SYNTHESIS-RELATED (MSR) co-factor from Arabidopsis thaliana.

Conclusion
The results provide novel routes for the engineering of polysaccharide-based biomaterials that are needed for a sustainable bioeconomy. The characterization of chimeric cellulose synthase-like enzymes in yeast offers an exciting avenue to produce plant polysaccharides in a tunable manner. Furthermore, cells modified with non-toxic plant polysaccharides such as β-mannan offer a modular chassis to produce and encapsulate sensitive cargo such as therapeutic proteins.

Graphic abstract
Clinical applications of the venous excess ultrasound (VExUS) score: conceptual review and case series
Authors: Rola Philippe , Miralles-Aguiar Francisco , Argaiz Eduardo , Beaubien-Souligny William , Haycock Korbin , Karimov Timur , Dinh Vi Am , Spiegel Rory 
Published: June 2021

AbstractThe importance of functional right ventricular failure and resultant splanchnic venous congestion has long been under-appreciated and is difficult to assess by traditional physical examination and standard diagnostic imaging. The recent development of the venous excess ultrasound score (VExUS) and growth of point-of-care ultrasound in the last decade has made for a potentially very useful clinical tool. We review the rationale for its use in several pathologies and illustrate with several clinical cases where VExUS was pivotal in clinical management.
Selective ablation of cochlear hair cells promotes engraftment of human embryonic stem cell-derived progenitors in the mouse organ of Corti
Authors: Takeda Hiroki , Dondzillo Anna , Randall Jessica A. , Gubbels Samuel P. 
Published: June 2021

Abstract
Background
Hearing loss affects 25% of the population at ages 60–69 years. Loss of the hair cells of the inner ear commonly underlies deafness and once lost this cell type cannot spontaneously regenerate in higher vertebrates. As a result, there is a need for the development of regenerative strategies to replace hair cells once lost. Stem cell-based therapies are one such strategy and offer promise for cell replacement in a variety of tissues. A number of investigators have previously demonstrated successful implantation, and certain level of regeneration of hair and supporting cells in both avian and mammalian models using rodent pluripotent stem cells. However, the ability of human stem cells to engraft and generate differentiated cell types in the inner ear is not well understood.

Methods
We differentiate human pluripotent stem cells to the pre-placodal stage in vitro then transplant them into the mouse cochlea after selective and complete lesioning of the endogenous population of hair cells.

Results
We demonstrate that hair cell ablation prior to transplantation leads to increased engraftment in the auditory sensory epithelium, the organ of Corti, as well as differentiation of transplanted cells into hair and supporting cell immunophenotypes.

Conclusion
We have demonstrated the feasibility of human stem cell engraftment into an ablated mouse organ of Corti.

Graphical abstract
Enhanced HSC-like cell generation from mouse pluripotent stem cells in a 3D induction system cocultured with stromal cells
Authors: Shan Wei , Yu Qin , Long Yan , Luo Qian , Li Honghu , Han Yingli , Xu Yulin , Fu Shan , Zeng Xiangjun , Wei Cong , Gao Yang , Li Xiaoqing , Li Xia , Zhang Lifei , Liu Lizhen , Chen Ming , Qian Pengxu , Huang He 
Published: June 2021

Abstract
Background
Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system.

Methods
In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. The in vivo hematopoietic reconstitution potential of c-kit+ cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system.

Results
The c-kit+ cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. We interestingly found that our 3D+OP9 system enriched a higher percentage of CD201+c-kit+cells that showed more similar HSC-like features such as transcriptome level and CFU formation ability than CD201-c-kit+cells, which have not been reported in the field of mouse PSCs hematopoietic differentiation. Moreover, CD201+ hematopoietic cells remained in a relatively slow cycling state, consistent with high expression levels of P57 and Ccng2. Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201+ hematopoietic cell induction from mouse PSCs.

Conclusions
Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application.
Adipose-derived stem cells therapy effectively attenuates PM2.5-induced lung injury
Authors: Gao Junling , Yuan Juntao , Liu Qun , Wang Yuanli , Wang Huiwen , Chen Yingjie , Ding Wenjun , Ji Guangju , Lu Zhongbing 
Published: June 2021

Abstract
Background
The adverse health effects of fine particulate matter (PM2.5) exposure are associated with marked inflammatory responses. Adipose-derived stem cells (ADSCs) have immunosuppressive effects, and ADSC transplantation could attenuate pulmonary fibrosis in different animal disease models. However, whether ADSCs affect PM2.5-induced lung injury has not been investigated.

Method
C57BL/6 mice were exposed to PM2.5 every other day via intratracheal instillation for 4 weeks. After that, the mice received tail vein injections of ADSCs every 2 weeks.

Results
ADSC transplantation significantly attenuated systemic and pulmonary inflammation, cardiac dysfunction, fibrosis, and cell death in PM2.5-exposed mice. RNA-sequencing results and bioinformatic analysis suggested that the downregulated differentially expressed genes (DEGs) were mainly enriched in inflammatory and immune pathways. Moreover, ADSC transplantation attenuated PM2.5-induced cell apoptosis and pyroptosis in the lungs and hearts.

Conclusion
ADSCs protect against PM2.5-induced adverse health effects through attenuating pulmonary inflammation and cell death. Our findings suggest that ADSC transplantation may be a potential therapeutic approach for severe air pollution-associated diseases.
Embryoid research calls for reassessment of legal regulations
Authors: Hengstschläger Markus , Rosner Margit 
Published: June 2021

AbstractIt is known that in countries, in which basic research on human embryos is in fact prohibited by law, working with imported human embryonic stem cells (hESCs) can still be permitted. As long as hESCs are not capable of development into a complete human being, it might be the case that they do not fulfill all criteria of the local definition of an embryo. Recent research demonstrates that hESCs can be developed into entities, called embryoids, which increasingly could come closer to actual human embryos in future. By discussing the Austrian situation, we want to highlight that current embryoid research could affect the prevailing opinion on the legal status of work with hESCs and therefore calls for reassessment of the regulations in all countries with comparable definitions of the embryo.
Almost absolute weighted summability with index k and matrix transformations
Authors: Sarıgöl M. A. , Mursaleen M. 
Published: June 2021

AbstractIn this paper we generalize the space $\hat{\ell }_{k}$

ℓ
ˆ

k

of absolutely almost convergent series (J. Math. Anal. Appl. 161:50–56, 1991) via weighted mean transformations. We study some inclusion relations and their topological properties. Further we characterize certain matrix transformations.
Three-dimensional niche partitioning between two colonially nesting ardeid species in central China
Authors: Ye Yuanxing , Hu Canshi , Jiang Yiting , Davison Geoffrey W. H. , Ding Changqing 
Published: June 2021

Abstract
Background
Interspecific competition is known to be strongest between those species that are both closely related and sympatric. Egrets are colonially nesting wetland birds that often overlap and can therefore be expected to compete in roosting and nesting habitat as well as in diet. According to the niche partitioning hypothesis, it is to be expected that these similar species would show differentiation in at least one of the main niche dimensions to reduce competition. We tested niche partitioning between the colonially nesting Little Egret (Egretta garzetta) and Cattle Egret (Bubulcus ibis) in temporal, spatial and trophic dimensions.

Methods
Field study was conducted in three mixed egret colonies in Yangxian County, southwest Shaanxi Province, central China. For each nest colony we recorded its spatial location, the height of nesting trees and of nests, the height of roosting trees and of roosting individuals within the trees. We determined the first egg-laying and first hatching dates of the two species. Craw dissection of storm-killed egret nestlings was used to measure the diet. Six transects were surveyed to study foraging habitat selection.

Results
We found that hatching time of Little Egrets peaked earlier (by about 1 month) than that of Cattle Egrets. Cattle Egrets nested and roosted higher than Little Egrets. The foraging habitats used by Little Egrets were dominated by river banks (73.49%), followed by paddy fields (13.25%) and reservoirs (10.84%), whereas Cattle Egret foraging sites were characterized by grasslands (44.44%), paddy fields (33.33%) and river banks (22.22%). Little Egrets consumed more fishes (65.66%) and Odonata larvae (13.69%) than Cattle Egrets, while Cattle Egrets were found feeding mainly on Coleoptera (29.69%) and Orthoptera (23.29%). Little Egrets preyed on larger mean biomasses of food items than Cattle Egrets.

Conclusions
Our results confirm the niche partitioning hypothesis as a mechanism for coexistence among ecologically similar species. In two coexisting egret species, niche partitioning is multidimensional, such that the two coexistent species occupy differing ecological space based on all three temporal, spatial and trophic niche dimensions.
Functional recovery in post-stroke patients on hemodialysis during the convalescent phase: a comparison with those not undergoing hemodialysis
Authors: Ishida Takeki , Kono Kenichi , Nishida Yuusuke , Yoshida Masahiro 
Published: June 2021

Abstract
Background
Low physical fitness is often found in patients undergoing hemodialysis. It may be possible that the recovery of impaired motor function with rehabilitative training might be affected when the patient is on hemodialysis. So far, however, no researcher has clinically investigated this issue in post-stroke patients. The purpose of this study is to clarify the difference of functional recovery during the convalescent phase between post-stroke patients with and without hemodialysis.

Methods
A cohort of 82 post-stroke hemiparetic patients who were admitted to our rehabilitation hospital, were subjected. On the day of admission and discharge, some clinical parameters including Functional Independence Measure (FIM) and Functional Ambulation Category (FAC) were evaluated for each patient. The changes during the hospitalization and the values at the discharge in these parameters were statistically compared between the patients with and without hemodialysis.

Results
The FIM motor score at the discharge was significantly lower in hemodialysis patients than non-hemodialysis patients (64.7 ± 21.2 points in hemodialysis patients and 81.8 ± 28.0 points in non-hemodialysis patients, p < 0.05). In addition, the frequency of FAC at the discharge of ≥ 3 was significantly lower in hemodialysis patients than non-hemodialysis patients (40.0% in hemodialysis patients and 72.2% in non-hemodialysis patients, p < 0.05).

Conclusion
In patients undergoing hemodialysis seem to experience a worse functional recovery during the convalescent phase compared to those not undergoing hemodialysis. We might have to modify the rehabilitative program during the convalescent phase after stroke if the patient was on hemodialysis.
The multiplicity of halal standards: a case study of application to slaughterhouses
Authors: Abdallah Ali , Rahem Mohammed Abdel , Pasqualone Antonella 
Published: June 2021

AbstractFood products suitable for Muslim consumers should behalalcertified, particularly when their origins or production processes are doubtful. However, there is a multiplicity ofhalalstandards. This situation may generate confusion, particularly for producers in Western countries who would like to certify their products in order to export them to Islamic countries. This study analyzed the reasons underlying the multiplicity of standards and reviewed the attempts of harmonization over time. Then, the case study of application to slaughterhouses was considered, by comparing four differenthalalstandards (namely GSO 993:2015, OIC/SMIIC 1:2019, HAS 23103:2012, and MS 1500:2019) representative of different geographic areas. Animal stunning was critically examined, comparing tradition with modernity. The study evidenced that the basic requirements related to slaughtering are common to all thehalalstandards considered, but several differences occur in more specific details. Only a close collaboration between the authorities of all the countries involved in issuinghalalcertifications will lead to a homogeneous regulatory framework with unified certification and accreditation procedures, increasingly required in a globalized market.
Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases
Authors: Meldolesi Jacopo 
Published: June 2021

AbstractLast century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.
Checkpoint Kinase 1 (Chk1) inhibition fails to activate the Stimulator of Interferon Genes (STING) innate immune signalling in a human coculture cancer system
Authors: Brooks Teresa , Wayne Joanne , Massey Andrew J. 
Published: June 2021

AbstractUtilising Checkpoint Kinase 1 (Chk1) inhibitors to increase cytoplasmic DNA may be a potential strategy to increase the sensitivity of tumours to immune checkpoint modulators. The appearance of DNA in the cytoplasm can drive Cyclic GMP-AMP Synthase-2′,3′-Cyclic Guanosine Monophosphate–Adenosine Monophosphate-Stimulator of Interferon Genes (cGAS-cGAMP-STING) inflammatory, anti-tumour T-cell activity via a type I interferon (IFN) and nuclear factor-κB response. In the THP1-Dual reporter cell line, the STING agonist cGAMP activated both reporters, and increased phosphorylation of the innate immune pathway signallers Tank Binding Kinase 1 (TBK1) and Interferon Regulatory Factor (IRF) 3. Inhibition of Chk1 increased TBK1 but not IRF3 phosphorylation and did not induce IRF or NF-κB reporter activation. cGAMP induced a Type I IFN response in THP1 cells whereas inhibition of Chk1 did not. HT29 or HCC1937 cell treatment with a Chk1 inhibitor increased cytoplasmic dsDNA in treated HCC1937 but not HT29 cells and increased IRF reporter activation in cocultured THP1-Dual cells. HT29 cells pre-treated with gemcitabine or camptothecin had elevated cytoplasmic dsDNA and IRF reporter activation in cocultured THP1-Dual cells. Camptothecin or gemcitabine plus a Chk1 inhibitor increased cytoplasmic dsDNA but Chk1 inhibition suppressed IRF reporter activation in cocultured THP1 cells. In THP1-Dual cells treated with cGAMP, Chk1 inhibition suppressed the activation of the IRF reporter compared to cGAMP alone. These results suggest that, in some cellular models, there is little evidence to support the combination of Chk1 inhibitors with immune checkpoint modulators and, in some combination regimes, may even prove deleterious.
Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies
Authors: Sarafoglou Kyriakie , Barnes Chris N , Huang Michael , Imel Erik A , Madu Ivy-Joan , Merke Deborah P , Moriarty David , Nakhle Samer , Newfield Ron S , Vogiatzi Maria G , Auchus Richard J 
Published: June 2021

Abstract

Context
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction.

Objective
Assess tildacerfont safety and efficacy.

Design and Setting
Two Phase 2 open-label studies.

Patients
Adults with 21OHD.

Intervention
Oral tildacerfont 200 to 1000 mg once daily (QD) (n = 10) or 100 to 200 mg twice daily (n = 9 and 7) for 2 weeks (Study 1), and 400 mg QD (n = 11) for 12 weeks (Study 2).

Main Outcome Measure
Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4 ≤ 2× upper limit of normal (ULN) or A4 &gt; 2× ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments.

Results
In Study 1, evaluable participants with baseline A4 &gt; 2× ULN (n = 11; 19-67 years, 55% female) had reductions from baseline in ACTH (−59.4% to −28.4%), 17-OHP (−38.3% to 0.3%), and A4 (−24.2% to −18.1%), with no clear dose response. In Study 2, participants with baseline A4 &gt; 2× ULN (n = 5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 ≤ 2× ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%).

Conclusions
For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal.
Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome
Authors: Yang Yue-Lian , Zhou Wei-Wei , Wu Shan , Tang Wen-Li , Wang Zong-Wei , Zhou Zu-Yi , Li Ze-Wen , Huang Qing-Fa , He Yan , Zhou Hong-Wei 
Published: June 2021

Abstract

Context
The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear.

Objective
To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS.

Setting and design
The intestinal flora of treatment-naïve PCOS patients and hormonally healthy controls was analyzed. Phenotype analysis, intestinal flora analysis, and global metabolomic profiling of caecal contents were performed on a letrozole-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing was performed on the PCOS mouse model after a 35-day CDCA treatment. Mice receiving fecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks.

Results
Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism.

Conclusions
Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.