bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining Extracellular Vesicles Properties and miRNA Cargo Variability in Bovine Milk from Healthy Cows and Cows Undergoing Subclinical Mastitis
Authors: Saenz-de-Juano Maria dels Desemparats , Silvestrelli Giulia , Bauersachs Stefan , Ulbrich Susanne
Published: August 2021

Background: Subclinical mastitis, the inflammation of the mammary gland lacking clinical symptoms, is one of the most prevalent and costly diseases in dairy farming worldwide. Milk microRNAs (miRNAs) encapsulated in extracellular vesicles (EVs) have been proposed as potential biomarkers of different mammary gland conditions, including subclinical mastitis. However, little is known about the robustness of EVs analysis regarding sampling time-point or natural infections. To estimate the reliability of EVs measurements in raw bovine milk, we first evaluated changes in EVs size and concentration using Tunable Resistive Pulse Sensing (TRPS) during three consecutive days. Then, we analysed daily differences in miRNA cargo using small RNA-seq. Finally, we compared milk EVs differences from naturally infected udder quarters with their healthy adjacent quarters and quarters from uninfected udders.Results: We found that the milk EV miRNA cargo is very stable over the course of three days regardless of the health status of the quarter, and that infected quarters do not induce relevant changes in milk EVs of adjacent healthy quarters. Chronic subclinical mastitis induced changes in milk EV miRNA cargo, but neither in EVs size nor concentration. We observed that the changes in immunoregulatory miRNAs in quarters with chronic subclinical mastitis are cow-individual, however, the most upregulated miRNA was bta-miR-223-3p across all individuals.Conclusions: Our results showed that the miRNA profile and particle size characteristics remained constant throughout consecutive days, suggesting that miRNAs packed in EVs are physiological state-specific. In addition, since infected quarters are solely affected while adjacent healthy quarters remain unaffected. Finally, the cow-individual miRNA changes pointed towards infection-specific alterations.
Induction of Estrogen Receptor β-mediated Autophagy Sensitizes Breast Cancer Cells to TAD1822-7, a Novel Biphenyl Urea Taspine Derivative
Authors: Su Qi , Wu Qing , Chen Kun , Wang Jingjing , Sarwar Ammar , Zhang Yanmin
Published: August 2021

Female breast cancer has become the most commonly diagnosed cancer worldwide. As a tumor suppressor, estrogen receptor β (ERβ) is a potential target for breast cancer therapy. TAD1822-7 was evaluated for ERβ-mediated autophagy and cell death using cell proliferation assay, Annexin V/PI staining, immunofluorescence, western blotting and hypoxia cell models. TAD1822-7 upregulated ERβ causing cell death and induced mitochondrial dysfunction and autophagy companied with mitochondrial located ERβ. Enhanced levels of LC3-II and p62 indicated that TAD1822-7 blocked the late-stage autolysosome formation, leading to cell death. Mechanistically, TAD1822-7-induced cell death was mediated by PI3K/AKT signaling pathways. Moreover, TAD1822-7 modulated HIF functions and autophagy via the inhibition of HIF-1β in the context of hypoxia-induced autophagy. TAD1822-7 inhibited hypoxia-inducted autophagy and PI3K/AKT pathway. These findings provide new insight into the mechanism underlying the inhibitory effects of TAD1822-7 via ERβ-mediated pathways in breast cancer cells.
Evaluating Evapotranspiration By Using Data Mining Instead of The Physical Based Model In Remote Sensing
Authors: Neissi Lamya , Golabi Mona , Albaji Mohammad , Naseri Abd Ali
Published: August 2021

Precise calculations for plant water requirements and evapotranspiration is very crucial in determining the volume of water consumption for plant production. In order to estimate evapotranspiration in the extended area, different remote sensing algorithms required many climatological variables. Climatological variable measurements will cover small limited areas which can cause an error in extended areas. By using data mining and remote sensing, the evapotranspiration process can be modeled. In this research, the physical-based SEBAL evapotranspiration algorithm was modeled by M5 decision tree equations in GIS. Input variables of the M5 decision tree consisted of albedo, emissivity, and Normalized Difference Water Index (NDWI) which are represented as absorbed light, transformed light, and plant moisture, respectively. After extracting the best equations in the M5 decision tree model for 8 April 2019, these equations were modeled in GIS by using python scripts for 8 April 2019 and 3 April 2020. The calculated correlation coefficient (R2), Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE) for 8 April 2019 were 0.92, 0.54, and 0.42 and for 3 April 2020 were 0.95, 0.31, and 0.23, respectively. Also, sensitivity and uncertainty analysis were considered for more model evaluation. Those analysis revealed that evapotranspiration is sensitive to albedo more than the two other model inputs and the estimated evapotranspiration obtained by data mining is in acceptable range of certainty.
Shenzhuo Formula Treatment in Patients With Macroalbuminuria Secondary to Diabetic Kidney Disease: Protocol Update and Statistical Analysis Plan
Authors: Yu-Wei  , Zhang Ying , Li Yanbo , Yang Ze , Wang Xinmiao , Huang Yi-Shan , Zhao Lin-Hua , Tong Xiaolin
Published: August 2021

BackgroundDiabetic kidney disease (DKD), as one of the significant complications of diabetes, has been the focus of attention. Our previous retrospective study indicated that Shenzhou Formula (SZF) might reduce the macroalbuminuria secondary to the DKD.Methods and designThis trial is a 24-week, randomized, multicentric, double-blinded, double-dummy clinical trial. 120 DKD patients (60 in each group) will be randomly divided randomized into two groups: SZF+ Irbesartan Simulator or Irbesartan + SZF Simulator. 24-h UP is the primary outcome measure is. The secondary outcome measures include Serum creatinine, estimated glomerular filtration rate, urinary albumin excretion rate, improvement in TCM symptoms, FBG, 2-h postprandial plasma glucose, HbA1C, Cholesterol, triglycerides, HDL, LDL, blood pressure, albumin to creatinine ratio, and the audit of diabetes-dependent quality of life 19 . Our recruitment began in May 2015, and we have enrolled 100 participants in this ongoing study, with a designed maximum sample size of 120. The interim results have been reviewed at N = 60 and continuing recruitment was recommended. This statistical analysis plan includes our approach to impute missing data, analysis primary, secondary outcomes, and safety endpoints.ConclusionThis SAP will standardize the clinical trial's statistical analysis, avoid outcome selective reporting bias and data-driven analysis. This trial will provide further clinical evidence for SZF treatment of macroalbuminuria secondary to DKD.Trial registrationChinese Clinical Trial Registry, ID: ChiCTR-ICR-15006311, registered on 26 May 2013. http://www.chictr.org.cn/showproj.aspx?proj=10862
Impact of COVID-19 on head and neck cancer advancement measured by the increasing numbers of acute dyspnea cases. What can be improved for the future?
Authors: Rosiak Oskar , Pietruszewska Wioletta , Burduk Paweł , Podlawska Paulina , Zakrzewski Bartosz , Barańska Magda , Kowalczyk Magdalena , Piątkowski Jakub , Solarz Paweł , Staszak Marta , Wierzbicka Małgorzata , Mikaszewski Bogusław
Published: August 2021

Background. The COVID-19 pandemic has altered all aspects of how the healthcare system is organized, and impacted patients with head and neck cancer (HNC), who delayed diagnosis and treatment. The result was the increased admission of patients with severe dyspnea and a need for tracheotomy due to extremely advanced HNC. The aim of this study was evaluate the characteristics of two multi-center cohorts of HNC patients admitted for dyspnea. Methods.. The therapeutic activity of four University Departments of Otolaryngology was studied over two time periods: September-February 2019/2020 and 2020/2021. Results. A group of 136 HNC patients who underwent tracheotomy in two time cohorts, pre-COVID-19 (N = 59) and COVID-19 (N = 77), were analyzed. The mean tracheotomy incidence proportion was 1.82% (SD: 1.12) for the pre-COVID-19 and 3.79% (SD: 2.76) for the COVID-19 period. A rise in emergency dyspnea was observed in the COVID-19 cohort. In the pre-COVID-19 period, 66% of patients presented with symptoms for more than a month in comparison to 78% of patients in COVID-19 times (p = 0.04). The number of tracheotomies performed under general anesthesia dropped in favor of local anesthesia during COVID-19 (64% vs. 56% respectively) due to extremely advanced HNC. In the COVID-19 cohort, most patients received a telemedicine consultation (N = 55, 71%) compared to the pre-COVID-19 period (N = 14, 24%). Conclusions. There should be a reorganization of the referral system, an adjustment of treatment capacity for an increased number of HNC patients, and a reserve for more extensive resection and reconstruction surgeries in ENT departments to not hamper future HNC treatment if there is another pandemic wave.
Age At Menarche, Age At Menopause, Reproductive Years and Risk of Fatal Stroke Occurrence Among Chinese Women: The Guangzhou Biobank Cohort Study
Authors: Hu Zhi-bing , Lu Ze-xiong , Zhu Feng
Published: August 2021

Background
The relationship between women’s reproductive characteristics and stroke events is unclear. We aimed to investigate age at menarche, age at menopause and number of reproductive years in relation to fatal stroke occurrence in the Guangzhou Biobank Cohort Study.
Methods
In total, 16504 postmenopausal women without stroke, heart disease or a cancer history at baseline were included and followed up for a median of 12.0 years. After review of available records, 222 stroke deaths were recorded. Cox proportional hazards regression was used to assess the associations between the risk of fatal stroke occurrence and age at menarche, age at menopause and number of reproductive years.
Results
In the whole cohort, compared with those aged 15 years at menarche, women aged 17 years at menarche had an increased risk for fatal stroke (adjusted hazard ratio [aHR] = 1.83, 95% confidence interval (CI) 1.10–3.05) and fatal haemorrhagic stroke (HR = 2.65, 95% CI 1.14–6.18), and women aged ≥ 18 years at menarche had an increased risk for fatal stroke (HR = 1.66, 95% CI 1.03–2.70) and fatal ischaemic stroke (HR = 2.01, 95% CI 1.01–3.99). Among postmenopausal women born before 1940, women aged < 43 years at menopause had an increased risk for fatal stroke (HR = 1.97, 95% CI 1.05–3.69) compared with those aged 51–52 years at menopause. Additionally, in the whole cohort, women with ≤ 28 reproductive years had an increased risk for fatal stroke (HR = 1.91, 95% CI 1.28–2.86) and fatal ischaemic stroke (HR = 2.26, 95% CI 1.26–4.05) compared with those with 32–34 reproductive years; postmenopausal women born before 1940 had a similar risk for fatal stroke and fatal ischaemic stroke.
Conclusions
Older age at menarche, younger age at menopause and fewer reproductive ages were related to an increased risk of fatal stroke in postmenopausal women.
Resistance Fracture of Minimally Prepared Endocrowns Made By Three Types of Restorative Materials: A 3D Finite Element Analysis
Authors: Meng Qingzhen , Zhang Yuejiao , Chi Danlu , Gong Qimei , Tong Zhongchun
Published: August 2021

A thin endocrown restoration was often applied in endodontically treated teeth with vertical bite height loss or inadequate clinical crown length. A model of mandibular molars made by endocrown restoration with 1 mm thickness and 2 mm depth of pulp chamber was constructed and imported into FEA ANSYS v18.0 software. The three CAD/CAM materials, feldspathic (Mark2), lithium disilicate (EMAX) and lava ultimate (LU), were assigned, and the five load indenters were loaded on the full occlusal (FO), occlusal center (OC), central fossa (CF), buccal groove (BG) and mesiobuccal cusp (MC) of restoration in the model. The MinPS and MaxPS of the thin endocrown were significantly higher than those of tooth tissue in five types of loads except for the LU endocrown loaded in the FO group. The smaller the contact surface of the load was, the higher MaxPS and MinPS were. MaxPS and MinPS of the MC were the highest, followed by the BG and CF in the restoration. In the stress distribution of tooth tissue, MaxPS in the LU endocrown accumulated at the external edge of enamel and was significantly higher than MaxPS in Mark2 and EMAX endocrown concentrated on the chamber wall of dentin under OC, CF and BG loads. Within the limitations of this FEA study, the LU endocrown transferred more stress to tooth tissue than Mark2 and EMAX, and the maximum principal stress on endocrown restoration and tooth tissue at the mesiobuccal cusp load was higher than that at the central fossa and buccal groove load.
Fibrivirga Algicola Gen. Nov., Sp. Nov., An Algicidal Bacterium Isolated from a Freshwater River
Authors: Park Sanghwa , Cho JaYoung , Jung Dong-Hyun , Jang SeokWon , Eom JungHye , Nam SeungWon , Kwon DaeRyul , Ryu Jaewon , Kim Keugtae
Published: August 2021

An aerobic, gram-negative, pink-colored, non-motile, rod-shaped algicidal bacterium, designated JA-25T was isolated from the freshwater of the Geumgang River, Republic of Korea. It grew at 15–30°C, 6.0–9.0 pH, and in the presence of 0–1% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain JA-25T belongs to the Family ‘Spirosomaceae’ and is most closely related to Fibrella aestuarina BUZ 2T (93.6%). The strain JA-25T showed < 90% sequence similarity to other members of the Family ‘Spirosomaceae’. The average nucleotide identity(ANI), in silico DNA-DNA hybridization and the average amino acid identity(AAI) values based on the genomic sequences of JA-25T and F. aestuarina BUZ 2T were 74.4, 20.5 and 73.6 %, respectively. The genomic DNA G + C content was 52.5mol %. The major cellular fatty acids were Summed feature 3 (C16:1 ω6c/C16:1 ω7c), C16:1 ω5c, C16:0 (> 10%). The genomic DNA G + C content was 52.5 mol %. The major respiratory quinone was MK-7 and the polar lipids were phosphatidylethanolamine, two unidentified aminolipids, two phospholipids and five unidentified lipids. Considering the phylogenetic inference, phenotypic and chemotaxonomic data, strain JA-25T should be classified as a novel species of the novel genus Fibrivirga, with the proposed name Fibrivirga algicola sp. nov. The type strain is JA-25T (= KCCM 43334T = NBRC 114259T).
Stimulation of c-Kit+ Retinal Progenitor Cells by Stem Cell Factor Confers Protection Against Retinal Degeneration
Authors: Chen Xi , Li Shanshan , Liu Xiaoli , Zhao Jingjie , Yang Xiufen , You Ran , Wang Yanling
Published: August 2021

Background
c-Kit/CD117, expressed in a series of tissue-specific progenitor cells, plays an important role in tissue regeneration and tissue homeostasis. We previously demonstrated that organoid-derived c-Kit+ retinal progenitor cells can facilitate the restoration of degenerated retina. Meanwhile, we have identified a population of endogenous c-Kit+ cells in retinas of adult mouse. However, the exact role of these cells in retinal degeneration remains unclear.
Methods
Retinal degeneration was induced by intravitreal injection of N-methyl-D-aspartate (NMDA). Two days post NMDA challenge, intravitreal injection of stem cell factor (SCF) was performed. Distribution and abundance of c-Kit+ cells and other retinal cells were evaluated by immunochemistry. Retinal function of treated mice was tested via flash electroretinogram (fERG) and the light/dark transition test. Possible regulatory pathways were evaluated by RNA sequencing.
Results
NMDA challenge increased the total number of c-Kit+ cells in the retinal ganglion cell layer (GCL), while slightly deregulated the protein level of SCF, which is mainly expressed in Müller cells. Both fERG and light/dark transition tests showed that intravitreal injection of SCF effectively improve the visual function of NMDA-treated mice. Consistently, the activation of microglia in injured retina has also been inhibited after SCF treatment. Mechanistically, SCF administration not only prevent the loss of retinal ganglion cells (RGCs), but also maintained the function of RGCs as quantified by fERG. Further, we performed transcriptome sequencing analysis of the retinal cells isolated from SCF-treated mice and the parallel control. Gene Ontology analysis showed that SCF-induced transcriptome changes were closely correlated with eye development-related pathways. Crystallins and several protective factors such as Pitx3 were significantly upregulated by SCF treatment.
Conclusions
Our results revealed the role of c-Kit+ cells in the protection of RGCs in NMDA-treated mice, via inhibiting the loss of RGCs. Administration of SCF can act as a potent strategy for treating retinal degeneration-related diseases.
Vinasse: From A Residue To A High Added Value Biopolymer
Authors: Trapé Daiana , López Olivia V. , Villar Marcelo A.
Published: August 2021

This work aimed to study the feasibility to use vinasse for polyhydroxybutyrate (PHB) production by Bacillus megaterium. To optimize the culture medium, a Box Behnken design was employed considering carbon (C), nitrogen (N), and phosphorus (Ph) concentrations as independent variables and PHB productivity as the response variable. The productivity decreased when C or N were increased, probably due to the presence of phenolic compounds and the limitation of N for the production of PHB by Bacillus sp. bacteria. An additional experimental design to optimize the C/N ratio and growing conditions (fermentation time and temperature) was carried out. Fermentation time had a statistically significant effect on PHB productivity reaching 10.6 mg/L h. On the other hand, the variability in physicochemical properties of vinasse samples led to significant differences in PHB productivity. Lower productivity values were obtained when vinasse had DBO high values. Therefore, biopolymers production from vinasse is a feasible alternative to valorize this bioethanol by-product.
Ultra-High-Resolution CT Features of Pulmonary Nodules Correlate with Visceral Pleural Invasion in Early Stage Lung Adenocarcinoma
Authors: Li Lu , Li Huimin , Pan Jiangfeng , Chen Zhenwei , Chen Xiaorong , Shu Jiner , Pang Peipei
Published: August 2021

Backgroundvisceral pleural invasion (VPI) is an important prognostic factor in early stage lung adenocarcinoma, which can affect the TNM Classification of Tumors.PurposeTo investigate whether ultra-high-resolution computed tomography (U-HRCT) features can predict VPI of early stage pulmonary nodules contacting the interlobar pleura.Material and MethodsA total of 126 patients with lung adenocarcinoma (age, 24-77 years) confirmed by surgical pathology were retrospectively enrolled. All patients underwent U-HRCT scan and were divided into two groups according to pulmonary nodular type: pure (pGGN) and mixed (mGGN). Clinical features were recorded, and U-HRCT features were manually measured using PHILIPS EBW V4.5.5. Univariate and multivariate logistic regression were used to determine factors that can significantly predict VPI. ResultsU-HRCT and three-dimensional orthogonal post-processing method could better display the relationship between GGNs and interlobar fissures. Among all patients, fifteen patients (12%) had VPI. None of the patients with pGGN had VPI. In the mGGN group, the solid ratio (odds ratio [OR]=1.275, 95% CI 1.1-1.478; P=0.001) and solid diameter (OR=1.139, 95% CI 1.06-2.346; P=0.046) were independent risk factors for VPI in early stage lung adenocarcinoma. For VPI diagnosis, the area under the curve, sensitivity, and specificity of the solid ratio and solid diameter were 0.803, 80%, and 75% and 0.807, 80%, and 80.36%, respectively.ConclusionU-HRCT can display GGNs and interlobar fissures in detail. VPI was not detected in patients with pGGN. In patients with mGGNs, a solid diameter >6mm and solid ratio >38% can be independent predictors of VPI, which may be helpful in surgical decision-making.
Hypoxic Pretreatment Adipose-derived Stem Cell Exosomes Improve Cognition by Delivery Circ-Epc1 and Shifting Microglial M1/M2 Polarization in Alzheimer’s Disease Mice Model
Authors: Liu Haining , Jin Mingming , Ji Minxiu , Zhang Wei , Liu An , Wang Tao
Published: August 2021

Background: Alzheimer’s disease (AD) is the most major dementia in the globe. Increasing evidence informs that exosomes from hypoxic pretreatment adipose-derived stem cells (ADSCs) could therapeutically affect cognitive function in AD-associated pathophysiology. However, their role and regulatory mechanism remain largely unknown. Methods: High-throughput sequencing was used to identify differentially expressed exosomal circRNAs from ADSCs or hypoxia pretreated ADSCs. Luciferase reporter assays and RT-qPCR were used to investigate the relationships between circ-Epc1, miR-770-3p, and TREM2. APP/PS1 double transgenic AD model mice were then utilized to study therapeutic effect regarding circ-Epc1 in ADSCs exosomes. BV2 cells were used to understand the regulatory relationship between circ-Epc1, miR-770-3p, and TREM2 and how these interactions modulated phenotypic transformation and inflammatory cytokine expression in microglia. Results: The result show that exosomes from hypoxia pretreatment ADSCs had a greater therapeutic effect at improving cognitive function by decreasing neuronal damage in the hippocampus. High-throughput sequencing found that circ-Epc1 played an important role in hypoxia pretreated ADSC exosomes regarding their ability to improve cognitive function. Luciferase reporter assays showed that TREM2 and miR-770-3p were downstream targets of circ-Epc1. Overexpressing miR-770-3p or downregulating TREM2 reversed the effects of circ-Epc1 on M2 microglia under LPS treatment. In vivo experiments showed that circ-Epc1-containing ADSC exosomes increased the therapeutic effect of exosome at improving cognitive function by decreasing neuronal damage and shifting hippocampal microglia from M1 to M2 polarization. Conclusions: Taken together, the data found that hypoxic pretreatment ADSCs exosomes improve cognition by delivery circ-Epc1 and shifting microglial M1/M2 polarization in alzheimer’s disease mice model.
SEAM-ECM Jet Milling TC4 Titanium Alloy Using Gas-Liquid Mixed Medium
Authors: Zhang Shengsheng , Wang Lizhong , Zhou Jianping , Dai Xiangyu , Xu Yan , Qiu Weixing , Wang Shuaishuai , Hu Guoyu
Published: August 2021

A novel combined machining approach combining short electric arc machining and electrochemical machining (SEAM-ECM) is proposed in this study. It aims to improve the surface integrity of TC4 titanium alloy by adding compressed air and electrolyte into the SEAM. This approach can change the material removal mechanism of the conventional SEAM and improve the gap flow field distribution and discharge state using the dual fluid properties of electrolyte and air mixed medium. The effects of gas addition on the state of the gap flow field and the electrical conductivity of the mixed medium are illustrated by flow field simulation. The effects of the presence or absence of air and the electrical conductivity of the solution on the machining performance are compared by experiments. The results show that the recast layer is weakened by using electrolyte and air mixed medium in SEAM-ECM compared to SEAM alone. The addition of high-speed air reduces defects such as melt drops, particles, holes. It performs with higher precision and finishes than ECM alone, the overall surface integrity has been significantly improved.
Known But Not Called by name: Recreational Fishers’ Ecological Knowledge of Freshwater Plants in Hungary
Authors: Löki Viktor , Nagy Jenő , Nagy András , Babai Dániel , Molnár Zsolt , Lukács Balázs András
Published: August 2021

Background: Documenting local ecological knowledge (LEK) has recently became a topic of considerable interest. LEK can contribute to various areas of ecology, including habitat management and conservation biology. It has been recently revealed that recreational fishers’ ecological knowledge (FEK) can also provide valuable information about different organisms and habitats, while recreational fishers’ ecological knowledge is understudied in many aspects and regions of the world. Methods: We aimed to record Hungarian recreational FEK on plant species related to freshwater habitats. Our research was conducted in three regularly fished water bodies in Hungary, namely Lake Velence, Keleti Main Canal, and Lake Látóképi, where a total of 72 interviews were conducted with recreational anglers. During interviews, 24 plant species occurring at freshwater habitats with common or sporadic distribution were shown to anglers as single species or in congeneric pairs. Miscellaneous plant related knowledge of anglers was also collected. Results: Anglers identified a total of 16 plant species. They used 45 botanical or folk names. An angler knew the name of 4.6 plants on average, and recognized 7.4 other species without naming it. According to our detailed analysis, anglers were able to name or at least recognise those plant species which are somehow related to fishing activities, are salient and/or common. Moreover, anglers at Lake Velence recognized less plant species, however, they also had less years of fishing experience compared to anglers of the other two locations. Conclusion: We found that recreational FEK exist even in the case of freshwater plants which are not the main focus of anglers. It is highly presumable that recreational fishers would be able to provide reliable ecologically related data for scientific research establishing future citizen science projects of nature conservation.
Intercellular Propagation and Aggregate Seeding of Mutant Ataxin-1
Authors: Huang Haoyang , Toker Nicholas , Burr Eliza , Okoro Jeff , Moog Maia , Hearing Casey , Lagalwar Sarita
Published: August 2021

Intercellular propagation of aggregated protein inclusions along actin-based tunneling nanotubes (TNTs) has been reported as a means of pathogenic spread in Alzheimer’s, Parkinson’s and Huntington’s Disease. Propagation of oligomeric-structured polyglutamine-expanded ataxin-1 (Atxn1[154Q]) has been reported in the cerebellum of a Spinocerebellar ataxia type 1 (SCA1) knock-in mouse to correlate with disease propagation. In this study, we investigated whether a physiologically-relevant polyglutamine-expanded ATXN1 protein (ATXN1[82Q]) could propagate intercellularly. Using a cerebellar-derived live cell model, we observed ATXN1 aggregates form in the nucleus, export out of the nucleus into the cytoplasm, and finally, propagate to neighboring cells along actin-based intercellular connections. Additionally, we observed the facilitation of aggregate-resistant proteins into aggregates given the presence of aggregation-prone proteins within a cell. Taken together, our results support a pathogenic role of intercellular propagation of polyglutamine-expanded ATXN1 inclusions.
The Potential Role of Naproxen in Promoting Rivastigmine Effect Against Aluminum Chloride-Induced Alzheimer-Like Model in Rats
Authors: Abdel-Aal Raafat A. , Hussein Ola A. , Elsaady Reham G. , Abdelzaher Lobna
Published: August 2021

Alzheimer’s disease (AD) is one of the leading causes of dependence and disability among the elderly worldwide. The traditional anti-Alzheimer medication, rivastigmine, one of the cholinesterase inhibitors (ChEIs), fails to achieve a definitive cure. Neuroinflammation plays a central role in AD pathogenesis. We tested the hypothesis that naproxen, a non-steroidal anti-inflammatory drug (NSAID), administration to the rivastigmine-treated aluminum chloride (AlCl3), Alzheimer's rat model, could provide an additive neuroprotective effect compared to rivastigmine alone. The studied groups were control (Cont), AlCl3 treated (Al), rivastigmine treated (RIVA), naproxen treated (Napro), and combined rivastigmine and naproxen treated (RIVA + Napro). Rats’ memory, spatial learning, and cognitive behavior were assessed followed by evaluation of hippocampal acetylcholinesterase (AChE) activity. Hippocampal and cerebellar histopathology were thoroughly examined. A marker of astroglial injury; glial fibrillary acidic protein (GFAP), the apoptosis maker; activated caspase-3 and the neuroepithelial stem cells marker; nestin expressions were immunohistochemically assayed. AD rats displayed significantly impaired memory and cognitive function, augmented hippocampal AChE activity, massive neurodegeneration associated with enhanced astrogliosis, apoptosis, and impaired neurogenesis. Rivastigmine, naproxen, and their combination decreased hippocampal AChE activity, mitigated behavioral and neuropathological changes in Al-intoxicated rats, possibly through downregulation of activated caspase-3 and upregulation of nestin. Except for the enhancement of neurogenesis and suppression of apoptosis, the combination therapy had no additional neuroprotective benefit over rivastigmine-only therapy. Naproxen's efficacy was demonstrated by its ability to act at the cellular level, enhance neurogenesis, and suppress apoptosis without having an additional mitigating impact in Al-induced cognitive impairment.
Bone marrow derived stem cells facilitate axonal regeneration in a rat model of 2, 5-hexanedione-induced neuropathy via miRNA-dependent and independent routes
Authors: Zuo Enjun , Hu Shuhai , Zhang Cong , Shi Xiaoxia , Yang Zhaofei , Li Shuangyue , Bai Qiufang , Gong Guanyu , Wang Ruoyu , Piao Fengyuan
Published: August 2021

Background

Peripheral polyneuropathies are clinically difficult situations and can be caused by exposure to occupational hazardous materials, such as N-hexane, which is still being used in developing countries. Autologous transplantation with bone marrow-mesenchymal stem cells (BMSCs) could be a promising therapeutical approach but its effect on toxic chemical-induced neuropathy remains undetermined. The present study sought to understand whether BMSCs could improve axon regeneration in Hexane-caused polyneuropathies and attempted to understand the associated molecular mechanisms.
Methods

A rat model of 2,5-hexanedine (HD)-induced polyneuropathy was established by intraperitoneally injection of 400 mg/kg/day HD, 5 times/week for 5 weeks. After the development of characteristic phenotypes, rats were given a single bolus tail-vein injection of BMSCs (5×107 cells/kg) and followed-up for 5 weeks. Sciatic nerves of HD/HD + BMSCs treated rats, as a representative tissue for peripheral nerve, were analyzed using electron microscopy, immunohistochemistry, western blotting and RNA sequencing. To further dissect the underlying mechanism, cultured DRG neurons +/- Schwann cells were challenged with HD/BMSC-derived conditional medium (BMSC-CM), in the presence or absence of NGF/Akt/mTOR inhibitors, recombinant NGF, miRNA mimics or miRNA inhibitors and further tested for changes in cellular and molecular levels.
Results

BMSCs engrafting significantly improved motor function recovery. Accelerated axon regeneration in sciatic nerves was evidenced by transmission electron microscopy, GAP43 western blotting and MBP/SMI312 immunostaining. Increased NGF expression and signaling activation was evidenced in response to BMSC/BMSC-CM treatment. In cultured cells, BMSC-CM’s effect was abolished by anti-NGF antibody or TrkA inhibitor K252a but reinforced by recombinant NGF. The activation of PI3K-Akt-mTOR-CREB signaling was observed and Akt and mTOR inhibitors were shown to attenuate BMSCS-promoted axon regeneration. While NGF was shown to be secreted by BMSCs in culture medium, miRNA array suggested certain miRNAs might also participate to regulate NGF expression. Three let-7 family miRNAs, including let-7a-5p, let-7d-5p and let-7e-5p, and 69 other miRNAs were found to be differentially expressed in HD and HD/BMSC groups. The regulatory effect of let-7e-5p on NGF expression was examined using miRNA mimics and inhibitors.
Conclusions

Together, our study demonstrated that BMSC transplantation significantly improve axon regeneration in hexane-induced polyneuropathy by activating NGF-PI3K-Akt-mTOR-CREB signaling via two independent mechanisms.
Social complexity, life-history and lineage influence the molecular basis of caste in a major transition in evolution
Authors: Wyatt Christopher , Bentley Michael , Taylor Daisy , Favreau Emeline , Brock Ryan , Taylor Benjamin , Bell Emily , Leadbeater Ellouise , Sumner Seirian
Published: August 2021

Major evolutionary transitions describe how biological complexity arises; e.g. in the evolution of complex multicellular bodies, and superorganismal insect societies. Such transitions involve the evolution of division of labour, e.g. as queen and worker castes in insect societies. A key mechanistic hypothesis for the evolution of division of labour is that a shared set of genes co-opted from a common solitary ancestral ground plan - a so-called genetic toolkit for sociality - regulate insect castes across different levels of social complexity. The vespid wasps represent an excellent system in which to test this. Here, using conventional and machine learning analyses of brain transcriptome data from nine species of vespid wasps, we find evidence of a shared genetic toolkit across species representing different levels of social complexity, with a large suite of genes classifying castes correctly across species. However, we also found evidence of additional fine-scale differences in predictive gene sets, functional enrichment and rates of gene evolution that were related to level of social complexity, but also life-history traits (e.g. mode of colony founding). Thus, there appear to be shifts in the gene networks regulating social behaviour and rates of gene evolution that are influenced by innovations in both social complexity and life-history. These results suggest that the concept of a shared genetic toolkit for sociality may be too simplistic to fully describe the process of the major transition to sociality, even within a single lineage. Diversity in lineage, social complexity and life-history traits must be taken into account in the quest to uncover the molecular bases of the major transition to sociality.
Identification of Genes Associated with Human-Canine Communication in Canine Evolution.
Authors: Tonoike Akiko , Otaki Ken-ichi , Terauchi Go , Ogawa Misato , Katayama Maki , Sakata Hikari , Miyasako Fumina , Mogi Kazutaka , Kikusui Takefumi , Nagasawa Miho
Published: August 2021

The dog (Canis familiaris) was the first domesticated animal and hundreds of breeds exist today. During domestication, dogs experienced strong selection for temperament, behaviour, and cognitive ability. However, the genetic basis of these abilities is not well-understood. We focused on ancient dog breeds to investigate breed-related differences in social cognitive abilities. In a problem-solving task, ancient breeds showed a lower tendency to look back at humans than other European breeds. In a two-way object choice task, they showed no differences in correct response rate or ability to read human communicative gestures. We examined gene polymorphisms in oxytocin, oxytocin receptor, melanocortin 2 receptor, and a Williams–Beuren syndrome-related gene (WBSCR17), as candidate genes of dog domestication. The single-nucleotide polymorphisms on melanocortin 2 receptor were related to both tasks, while other polymorphisms were associated with the unsolvable task. This indicates that glucocorticoid functions are involved in the cognitive skills acquired during dog domestication.
Plastidial Wax Ester Biosynthesis As A Tool To Synthesize Shorter And More Saturated Wax Esters
Authors: Vollheyde Katharina , Hornung Ellen , Herrfurth Cornelia , Ischebeck Till , Feussner Ivo
Published: August 2021

Background: Wax esters (WE) are neutral lipids that consist of a fatty alcohol esterified to a fatty acid. WE are valuable feedstocks in industry for producing lubricants, coatings and cosmetics. They can be produced chemically from fossil fuel or plant derived triacylglycerol. As fossil fuel resources are finite, the synthesis of WE in transgenic plants may serve as an alternative source. As chain length and desaturation degree of the alcohol and acyl moieties determine the physicochemical properties of WE and their field of application, a tightly controlled tailor-made WE synthesis in plants is aimed for. Here, we report the generation of ten combinations of WE producing transgenes expressed in Arabidopsis thaliana. In order to study their suitability for WE production in planta, we analyzed WE amount and synthesized WE species in the transgenic plants.Results: The transgenes consisted of different combinations of a fatty acyl-CoA/ACP reductase (FAR) and two wax synthases/acyl-CoA:diacylglycerol O-acyltransferases (WSD) namely WSD2 and WSD5 from the bacterium Marinobacter aquaeoleoi. We generated constructs with and without plastidial transit peptides to access diverse alcohol and acyl substrate pools within A. thaliana. We observed WE formation with plastid and cytosol-localized FAR and WSD in seeds. A comparative WE analysis revealed the production of shorter and more saturated WE by plastid-localized WE biosynthesis compared to cytosolic WE synthesis.Conclusions: A shift of WE formation into seed plastids is a suitable approach for tailor-made WE production and can be used to synthesize WE mainly derived from mid and long chain saturated and monounsaturated substrates.
Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmissibility
Authors: Lin Yun , Yang Bingyi , Cobey Sarah , Lau Eric , Adam Dillon , Wong Jessica , Bond Helen , Cheung Justin K. , Ho Faith , Gao Huizhi , Ali Sheikh Taslim , Leung Nancy , Tsang Tim , Wu Peng , Leung Gabriel , Cowling Benjamin
Published: August 2021

Many locations around the world have used real-time estimates of the time-varying effective reproductive number (\({R}_{t}\)) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of \({R}_{t}\) are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the incubation period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by cycle threshold values) and estimates of \({R}_{t}\) based on case counts. We demonstrate that cycle threshold values could be used to improve real-time \({R}_{t}\) estimation, enabling more timely tracking of epidemic dynamics.
Rational Medicine Prescription and Adherence to Prescription Format: A Description of Practices in the Private Sector in Addis Ababa, Ethiopia
Authors: Mekuria Getahun Asmamaw , Ejigu Nahu , Tewihubo Dinksew , Ayenew Wondim
Published: August 2021

Background: In Ethiopia, despite the private health sector's role in healthcare delivery is growing, studies on private health sector prescribing practices are uncommon. The main aim of this study was to evaluate the private health sector's rational prescribing practices and adherence to prescription format, using some of the World Health Organization (WHO) core drug use indicators in Addis Ababa, Ethiopia. Method: A retrospective cross sectional study design was used to collect quantitative data from prescriptions prescribed and dispensed by private health sectors in the Lemi-kura sub-city, Addis Ababa. The study was conducted from June to July, 2021. The WHO criteria were used to evaluate prescribing and prescription completeness indicators. Prescriptions, kept for the last 1-year that prescribed between January 1, 2020 to January 1, 2021 by private drug outlets, were analyzed. A combination of simple random sampling and systematic sampling procedures were employed. All the statistical calculations were performed using SPSS® V 20.0 software. Result: Off total of 1,200 prescriptions, 2,192 drugs were prescribed and the average number of drugs per prescription was 1.83 (Standard Deviation (SD)=0.9). Generic names, antibiotics, injections, and issued from national essential medicines list accounted for 77.4%, 63.8%, 11.5%, and 80.6% of all prescriptions, respectively. The patients' full names, ages, and sexes were mentioned in 99%, 95.3%, and 96.3% of prescriptions, respectively. The patient's card number (54.3%) and weight (2.3%) were not adhered to properly. The drug name, strength, dose, frequency, duration, and how to use, ranges from 85 to 99% of the prescriptions. Dosage forms (35.5%) and diagnoses (31.7%) were less likely to be completed. Only 36.6% and 25.8% of prescriptions, respectively, contained names and qualifications of prescribers. Obtaining prescription papers with the full name (9%), qualification (1.3%), and signature (26.8%) of the dispenser, and date of dispensing (0.7%), is extremely difficult. Interestingly, no dispenser filled out all of this information on a single prescription. Conclusion: The study's findings indicated rational prescribing and prescription completeness indicators were all considerably deviate from WHO standards and hence unsuitable. To promote rational medication use, health practitioners in the private sector should be given regulatory interventions, ongoing monitoring from relevant bodies, and regular training on good prescribing and dispensing practices.
Metabolic engineering strategies to produce medium-chain oleochemicals via acyl-ACP:CoA transacylase activity
Authors: Yan Qiang , Cordell William , Jindra Michael , Courtney Dylan , Kuckuk Madeline , Chen Xuanqi , Pfleger Brian
Published: August 2021

Microbial lipid metabolism is an attractive route for producing aliphatic chemicals, commonly referred to as oleochemicals. The predominant metabolic engineering strategy centers on heterologous thioesterases capable of producing fatty acids of desired size. To convert acids to desired oleochemicals (e.g. fatty alcohols, ketones), metabolic engineers modify cells to block beta-oxidation, reactivate fatty acids as coenzyme-A thioesters, and redirect flux towards termination enzymes with broad substrate utilization ability. These genetic modifications narrow the substrate pool available for the termination enzyme but cost one ATP per reactivation - an expense that could be saved if the acyl-chain was directly transferred from ACP- to CoA-thioester. In this work, we demonstrate an alternative acyl-transferase strategy for producing medium-chain oleochemicals. Through bioprospecting, mutagenesis, and metabolic engineering, we developed strains of Escherichia coli capable of producing over 1 g/L of medium-chain free fatty acids, fatty alcohols, and methyl ketones using the transacylase strategy.
Interleukin 13 Affects the Recovery Processes in a Mouse Model of Hemorrhagic Stroke with Bilateral Tibial Fracture
Authors: Yan Ya'nan , Gao Cheng , Chen Guang , Chen Xueshi , Wu Yanglin , Xu Heng , Cheng Zhiqi , Luo Chengliang , Zhang Mingyang , Wang Tao , Lin Jun , Chen Xiping , Tao Luyang
Published: August 2021

As one form of stroke, intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease, which has high morbidity and mortality, and lacks of effective medical treatment. An increased infiltration of inflammatory cytokines coupled with pyroptotic cell death is involved in the pathophysiological process of ICH. However, little is known about whether concomitant fracture patients have the same progression of inflammation and pyroptosis. Hence, we respectively established mouse ICH model and ICH with bilateral tibial fracture model (MI) to explore the potential cross-talk between the above two injuries. We found that MI obviously reversed the expressions of pyroptosis-associated proteins, which were remarkably up-regulated at the acute phase after ICH. Similar results were observed in neuronal expressions via double immunostaining. Furthermore, brain edema was also significantly alleviated in mice who suffered MI, when compared with ICH alone. To better clarify the potent mechanisms mediated this cross-talk, recombinant mouse interleukin-13 (IL-13) was used to investigate its effect on pyroptosis in the mouse MI model, in which lower level of IL-13 was observed. Remarkably, IL-13 administration re-awakened cell death, which was mirrored by the re-upregulation of pyroptosis-associated proteins and PI positive cell counts. The results of hemorrhage volume and behavioral tests further confirmed its critical role in regulating the neurological functions. Besides, IL-13-treated MI group showed poor outcomes of fracture healing. To sum up, our research indicates that controlling the IL-13 content in acute phase would be a promising target in influencing the outcomes of brain injury and fracture, and meanwhile, provides new evidence in repairing compound injuries in clinics.
Physiological and Dual Transcriptional Analysis of Microalga Graesiella Emersonii–Amoeboaphelidium Protococcarum Pathosystem Uncovers Conserved Defense Response and Robust Pathogenicity
Authors: Ding Yi , Wang Zhongjie , Wang Yali , Geng Yahong , Wen Xiaobin , Li Yeguang
Published: August 2021

Background: The oleaginous microalga Graesiella emersonii, a potential industrial strain for lipid production, is frequently infected by the endoparasite Amoeboaphelidium protococcarum. It is essential to investigate the microalgae–endoparasite interaction to prevent and control microalgal diseases. However, the underlying mechanisms of microalgal host-pathogen interactions remain largely unknown. In this study, we applied physiological and simultaneous dual transcriptomic analysis to characterize the G. emersonii–A. protococcarum interaction for the first time. Results: Three infection stages were determined according to infection rate and physiological features. Dual RNA-seq results showed that the genes expression of G. emersonii and A. protococcarum were strongly dynamically regulated during the infection. For microalgal hosts, the expression of defense genes involved in the pattern recognition receptors, large heat shock proteins, and reactive oxygen scavenging enzymes (glutathione, ferritin, and catalase) were significantly upregulated during infection. However, some genes encoding resistance proteins (R proteins) with a leucine-rich repeat domain exhibited no significant changes during infection. Furthermore, ubiquitin-mediated proteolysis and endocytosis were strongly affected by A. protococcarum infection. For endoparasite A. protococcarum, genes for carbohydrate-active enzymes, pathogen-host interactions, and putative effectors were significantly upregulated during infection. Furthermore, the genes in cluster II were significantly enriched in pathways associated with the modulation of vacuole transport, including endocytosis, phagosome, ubiquitin-mediated proteolysis, and SNARE interactions in vesicular transport pathways.Conclusions: Our data provide a new promising basis for complete understanding of the algal host defense strategies and parasite pathogenicity. This is beneficial for the screening of resistant microalgal strains and developing control strategies for microalgal diseases.