bluuebunny/crossref_metadata_2025 huggingface dataset:
Process mediated by gold nanoparticles encapsulated in polymeric gels evidenced by EPR spectroscopy
Authors:   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania, MATEI Iulia , BEM Marioara ,   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania, LEONTIEŞ Anca Ruxandra ,   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania, RĂDUŢIU Cristina ,   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania, POPESCU Elena Irina ,   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania, MOCANU Sorin ,   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania, SAVONEA Florenţa ,   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania, BĂRĂŢOIU Rodica ,   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania, IONIŢĂ Gabriela ,   Roumanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, Bucharest, 060021, Roumania
Published: October 2021

Gold (Au0) nanoparticles (AuNPs) have been investigated for decades as selective catalysts for a series of reactions including alcohol oxidation, alkene hydrogenation and nucleophilic addition to C-C multiple bonds. In this study, the reduction/oxidation processes mediated by AuNPs embedded within a polymeric hydrogel have been tested. In particular, we monitored two processes: i) the reduction of 4-nitrophenol and ii) the reduction of a TEMPO moiety covalently linked to a fluorescent moiety, in the presence of AuNPs/hydrogel. The hybrid AuNPs/hydrogel material was obtained by reduction of a gold salt within the cross-linked poly(ethylene glycol)/β-cyclodextrin gel following a procedure previously reported. We found that this material is suitable for cyclic reduction of 4-nitrophenol as the material is not structurally modified after the reduction process. The electron paramagnetic resonance (EPR) signal of the TEMPO moiety decreases in the first instance, due to reduction by AuNPs, and slightly increases in time, proving the oxidizing property of AuNPs embedded in hydrogel.
Does Lack of EWSR1-ATF1 Fusion Exclude Diagnosis of Salivary Gland Clear Cell Carcinoma?
Authors: Sensu Sibel , Erdogan Nusret , Basak Kayhan , Qipa Egzona , Buyukdogan Murat
Published: October 2021

Introduction: Ewing sarcoma breakpoint region 1- activating transcription factor 1 (EWSR1-ATF1) fusion is mentioned as a diagnostic marker in favor of clear cell carcinoma in the differential diagnosis of clear cell neoplasms of salivary glands. However, in literature, its positivity is reported between 82% and 93%. In salivary glands, various benign and malignant primary tumors, as well as odontogenic neoplasms and metastatic cases, present with a varied number of clear cells. Clear cell carcinoma of the salivary gland is a rare entity with distinct histochemistry and immunohistochemistry features.Case Presentation: We present a clear cell carcinoma of the salivary gland showing cytoplasmic Periodic acid–Schiff (PAS) (+), mucin (-) staining, cytokeratin (CK), CK7, and P63 immunoreactivity without EWSR1-ATF1 fusion. Conclusions: We conclude that clinical, morphological, and immunohistochemical analyses should be the guide for diagnosis even though molecular analysis does not support it.
A Case Series of Spontaneous Chylothorax in Lymphoma
Authors: Widiastuti Widiastuti , Rakhmawati Eri , Nawawi Yusuf Syaeful , Rima Ana
Published: October 2021

Introduction: Chylothorax is a rare condition originating from lymphatic system damage as an accumulation of chyle in the pleural space. It can be classified into spontaneous or non-traumatic, traumatic, and idiopathic. A spontaneous chylothorax is primarily caused by neoplasm, such as lymphoma.Case Presentation: Herein, we report two cases of chylothorax presenting as massive pleural effusion in two patients of a 23-year-old male with nodular sclerosis type Hodgkin’s lymphoma and a 31-year-old female with metastatic lymphadenopathy of undifferentiated carcinoma from non-Hodgkin’s lymphoma.Conclusion: A spontaneous chylothorax is a rare condition that may lead to a life-threatening event when it is not properly and promptly treated.
Pengaruh Pemberian Ampas Hasil Fermentasi Buah Maja (Aegle marmelos) Terhadap Pertumbuhan Tanaman Bayam (Amaranthus sp.)
Authors: Mulyani Diyah Ayu Trisna , Laili Saimul , Lisminingsih Ratna Djuniwati
Published: October 2021

Maja is a plant belonging to the Rutaceae family which originates from the tropics. Green spinach (Amaranthus sp.) belongs to the Amaranthaceae family. Spinach is one of the vegetables consumed by people. The purpose of this study was to determine the effect of giving dreg from fermented maja fruit (Aegle marmelos) on the growth of spinach (Amaranthus sp. L) and the dose of dreg from fermented maja fruit (Aegle marmelos) which has the most influence on the growth of pulled spinach (Amaranthus sp. L). By using this research methodology using experimental Completely Randomized Design (CRD). There were 5 treatment combinations with 4 replications so that there were 20 experimental samples, with a treatment combination of 15gr, 30gr, 45gr and 60g. With research procedures the process of sampling maja fruit, seeding, planting, harvesting. Data analysis with analysis of variance (ANOVA), there is a real difference followed by LSD test 5%. For plant height, the average yield was 38.59 cm, the number of leaves was 14.5, root length 33.5 cm, wet weight 19.5 grams, and dry weight 9.35 grams. Provision of fermented dreg has a significant effect on the growth of spinach at a dose of 60 grams / plant. Keywords: Spinach, Maja Fruit Fermentation, Spinach Plant Growth ABSTRAKMaja adalah tanaman yang tergolong dalam family Rutaceae yang berasal dari daerah tropis. Tanaman bayam hijau (Amaranthus sp.) termasuk family Amaranthaceae. Bayam adalah salah satu sayuran yang dikonsumsi masyarakatTujuan penelitian ini adalah untuk mengetahui pengaruh pemberian ampas hasil fermentasi buah maja (Aegle marmelos) terhadap pertumbuhan tanaman bayam cabut (Amaranthus sp. L) dan dosis ampas hasil fermentasi buah maja (Aegle marmelos) yang paling berpengaruh terhadap pertumbuhan tanaman bayam cabut (Amaranthus sp. L). Dengan menggunakan metode penelitian ini menggunakan eksperimental Rancangan Acak Lengkap (RAL). Terdapat 5 kombinasi perlakuan 4 ulangan sehingga terdapat 20 sampel percobaan, dengan kombinasi perlakuan 15gr, 30gr, 45gr dan 60 gr. Dengan prosedur penelitian proses pengambilan sampel buah maja, penyemaian benih, penanaman, panen. Analisis data dengan Analisis of Varian (ANOVA), jika ada perbedaan nyata dilanjut dengan uji BNT 5%. Untuk tinggi tanaman mendapatkan hasil rata-rata 38,59 cm, jumlah daun 14,5 helai, panjang akar 33,5 cm, berat basah 19,5 gram, dan berat kering 9,35gram. Pemberian ampas hasil fermetasi memberikan pengaruh yang nyata terhadap  pertumbuhan tanaman bayam dengan dosis 60 gram/ tanaman. Kata kunci : Bayam, Fermentasi Buah Maja, Pertumbuhan Tanaman Bayam
ROLE OF REGIONAL DEVELOPMENT INSTITUTIONS IN CREATION OF PETROLEUM AND GAS CHEMICAL CLUSTERS OF THE ANGARO-YENISEI MACROREGION
Authors: Plyaskina Nina I. , Kharitonova Viktoriya N.
Published: October 2021

The article presents an analysis of the capabilities of the Yenisei Siberia Corporation and regional development institutions of the Irkutsk region in organizing systematic state support for innovative projects for the formation of the East Siberian petrochemical cluster. The directions of correction of its specialization were discussed in connection with the expected growth in demand of Arctic and northern projects of the mining sector for low-tonnage chemistry products and long-term factors of stabilization of demand for large-tonnage supplies of Russian polymers in the APR markets. On the basis of a comparative analysis of the competences and powers of regional development institutions, the organizational advantages of the Yenisei Siberia Corporation were revealed: The presence of strategic partners and the possibility of creating technological and investment platforms at the federal level. To assess the effectiveness of innovative directions for the development of the East Siberian oil and gas chemical cluster, it is proposed to use the author's model toolkit for the formation of a megaproject of the East Siberian oil and gas complex (VSOGK).
Current Opportunities and Challenges in Biopolymer Thin Film Analysis—Determination of Film Thickness
Authors: Spirk Stefan , Palasingh Chonnipa , Nypelö Tiina
Published: October 2021

Polymer thin films with thickness below 100 nm are a fascinating class of 2D materials with commercial and research applications in many branches ranging from coatings to photoresists and insulating materials, to mention just a few uses. Biopolymers have extended the scope of polymer thin films with unique materials such as cellulose, cellulose nanocrystals, cellulose nanofibrils with tunable water uptake, crystallinity and optical properties. The key information needed in thin biopolymer film use and research is film thickness. It is often challenging to determine precisely and hence several techniques and their combinations are used. Additional challenges with hydrophilic biopolymers such as cellulose are the presence of humidity and the soft and often heterogenous structure of the films. This minireview summarizes currently used methods and techniques for biopolymer thin film thickness analysis and outlines challenges for accurate and reproducible characterization. Cellulose is chosen as the representative biopolymer.
Reverse Time Migration Based on the Pseudo-Space-Domain First-Order Velocity-Stress Acoustic Wave Equation
Authors: Zhang Xiaobo , Wang Xiutian , Liu Baohua , Song Peng , Tan Jun , Xie Chuang
Published: October 2021

Reverse time migration (RTM) is an ideal seismic imaging method for complex structures. However, in conventional RTM based on rectangular mesh discretization, the medium interfaces are usually distorted. Besides, reflected waves generated by the two-way wave equation can cause artifacts during imaging. To overcome these problems, a high-order finite-difference (FD) scheme and stability condition for the pseudo-space-domain first-order velocity-stress acoustic wave equation were derived, and based on the staggered-grid FD scheme, the RTM of the pseudo-space-domain acoustic wave equation was implemented. Model experiments showed that the proposed RTM of the pseudo-space-domain acoustic wave equation could systematically avoid the interface distortion problem when the velocity interfaces were considered to compute the pseudo-space-domain intervals. Moreover, this method could effectively suppress the false scattering of dipping interfaces and reflections during wavefield extrapolation, thereby reducing migration artifacts on the profile and significantly improving the quality of migration imaging.
Investigating the Factors That are Associated With Teachers’ Intentions to Utilize Research in Remote Areas of Greece
Authors: Trikoilis Dionysios , Papanastasiou Elena C.
Published: October 2021

Teachers around the world, serving in remote areas experience professional isolation (Bouck, 2004). In addition to being geographically isolated, challenges to remote teaching include a lack of professional support (Ralph, 2002) and experience of social isolation. Yet, the utilization of educational research has the potential to alleviate this issue. Therefore, this study examines the interplay between the factors that can possibly explain the teacher’s intentions to use research for professional development purposes in remote schools in Greece. Based on the results of the Structural Equation Model that was examined, research attitudes had the strongest direct relationship to intending to use research for professional development purposes, although research skills also played a major role (directly, and indirectly) in this relationship.
Patient-Identified Problems and Influences Associated With Diagnostic Delay of Acromegaly: A Nationwide Cross-Sectional Study
Authors: Wang Kailu , Guo Xiaopeng , Yu Siyue , Gao Lu , Wang Zihao , Zhu Huijuan , Xing Bing , Zhang Shuyang , Dong Dong
Published: October 2021

Background

Insidious-onset acromegaly may easily be overlooked by non-specialists of acromegaly and cause diagnostic delay. This study aims to examine the association between diagnostic delay and advice from doctors before any confirmed diagnosis and subsequent comorbidities, and elicit patient-perceived reasons for misdiagnoses.

Methods

An online nationwide cross-sectional study was conducted through China Acromegaly Patient Association. Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) levels at diagnosis and cancerous, endocrine-metabolic, musculoskeletal, cardiovascular, respiratory, and psychiatric comorbidities were reported by patients. The association between diagnostic delay and pre-diagnostic advice from doctors as well as subsequent comorbidities after diagnosis were examined.

Results

In total, 447 valid responses were collected. Overall, 58.8% patients experienced misdiagnoses, and 22.6% had diagnostic delay. Before arriving at any diagnosis, patients without treatment (adjusted odds ratio [AOR]: 3.66, 95% confidence interval [CI]: 1.30-10.33) or receiving treatment to symptoms only (AOR: 7.05, 95%CI: 4.09-12.17) had greater chance of being misdiagnosed, and hence had diagnostic delay. Patients believed insufficient specialists, limited awareness of acromegaly of non-specialists and poor doctor-patient communications were major reasons of misdiagnosis. Diagnostic delay were associated with higher GH level at diagnosis and endocrine-metabolic, musculoskeletal and cardiovascular comorbidities (all P<0.05).

Conclusions

Suboptimal pre-diagnostic advice for patients, reflecting limited awareness of acromegaly among non-specialists, may delay the diagnosis and increase comorbidities. Feedbacks on the patients’ final diagnosis from specialists to non-specialists should be considered, and doctor-patient communication and clinical decision-making process should be improved. Comorbidities should be screened and monitored particularly for patients with diagnostic delay.
Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Renin-Angiotensin-Aldosterone System
Authors: Puglisi Soraya , Rossini Alessandro , Poli Roberta , Dughera Francesca , Pia Anna , Terzolo Massimo , Reimondo Giuseppe
Published: October 2021

Sodium-glucose cotransporters inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP1-RA) are glucose-lowering drugs that are proved to reduce the cardiovascular (CV) risk in type 2 diabetes mellitus (T2DM). In this process, the renin-angiotensin-aldosterone system (RAAS) is assumed to play a role. The inhibition of SGLT2 improves hyperglycemia hampering urinary reabsorption of glucose and inducing glycosuria. This “hybrid” diuretic effect, which couples natriuresis with osmotic diuresis, potentially leads to systemic RAAS activation. However, the association between SGLT2-i and systemic RAAS activation is not straightforward. Available data indicate that SGLT2-i cause plasma renin activity (PRA) increase in the early phase of treatment, while PRA and aldosterone levels remain unchanged in chronic treated patients. Furthermore, emerging studies provide evidence that SGLT2-i might have an interfering effect on aldosterone/renin ratio (ARR) in patients with T2DM, due to their diuretic and sympathoinhibition effects. The cardio- and reno-protective effects of GLP-1-RA are at least in part related to the interaction with RAAS. In particular, GLP1-RA counteract the action of angiotensin II (ANG II) inhibiting its synthesis, increasing the inactivation of its circulating form and contrasting its action on target tissue like glomerular endothelial cells and cardiomyocytes. Furthermore, GLP1-RA stimulate natriuresis inhibiting Na+/H+ exchanger NHE-3, which is conversely activated by ANG II. Moreover, GLP1 infusion acutely reduces circulating aldosterone, but this effect does not seem to be chronically maintained in patients treated with GLP1-RA. In conclusion, both SGLT2-i and GLP1-RA seem to have several effects on RAAS, though additional studies are needed to clarify this relationship.
Practice Patterns and Learning Curve in Transoral Endoscopic Thyroidectomy Vestibular Approach With Neuromonitoring
Authors: Kuo Ting-Chun , Duh Quan-Yang , Wang Yi-Chia , Lai Chieh-Wen , Chen Kuen-Yuan , Lin Ming-Tsan , Wu Ming-Hsun
Published: October 2021

Objectives

Intraoperative neuromonitoring has not been routinely applied in early experience with the transoral endoscopic thyroidectomy vestibular approach (TOETVA). Because the preparation and surgical interventions are much different from conventional thyroidectomies, most endocrine surgeons willing to adapt to TOETVA lack access to information regarding the practice pattern and proficiency in the learning curve. We aimed to investigate the outcomes and to define the learning curve for TOETVA in this study.

Methods

A retrospective analysis was used on patients who underwent TOETVA at our hospital between December 2016 and July 2019. The cumulative sum graphic model was used to implement the learning curve as a surrogate for procedural proficiency.

Results

The 119 patients had a mean age of 44.65 years and a mean body mass index of 22.49 k/m2, including 107 women, 20 thyroiditis, and 106 hemithyroidectomy. The learning curve revealed two phases, an initial (35 cases) and a mature (84 cases) phase, for surgeons based on operation time (144.2 vs. 114.2 min, p = 0.0001). There were more bilateral thyroidectomies (15.5% vs. 0, p = 0.0100), larger indicated nodules (6.06 cm3vs. 3.32 cm3, p = 0.0468), or larger thyroids to resect (16.38 cm3vs. 8.75 cm3, p = 0.0001) in the mature phase. Procedure-related complications decreased significantly in the mature phase in comparison to the initial phase (3.57% vs. 31.43%, p = 0.0001).

Conclusions

The learning curve of TOETVA with neuromonitoring is 35 cases. With the accumulation of proficiency, the indications will expand. Step-by-step improvements from the experience of each case can reduce procedure-related complications.
Improved Random Forest Method for Ultra-short-term Prediction of the Output Power of a Photovoltaic Cluster
Authors: Yang Mao , Zhao Meng , Liu Dingze , Ma Miaomiao , Su Xin
Published: October 2021

Current models for the prediction of the output power of photovoltaic (PV) clusters suffer from low prediction accuracy and are prone to overfitting. To address these problems, we propose an improved random forest (RF)-based method for ultra-short-term prediction of PV cluster output power. The total output power data for the PV clusters are used as the training dataset and fed into the RF model to obtain preliminary predictions. The error and accuracy of the preliminary predictions for individual sampling points concerning the actual values of the PV cluster output power are assessed. Each of the daily time series of preliminary predictions is divided into two phases according to whether the output power is increasing (morning) or decreasing (afternoon). The final ultra-short-term predictions of the PV cluster output power are obtained by correcting the two phases of preliminary predictions through trend correction and peak correction, respectively. The results show that, compared with the unimproved model, the accuracy of the stochastic forest model is 1.48% higher than that of the modified random forest model., which proves the effectiveness and practicability of the proposed method.
Surviving the Urban Jungle: Anthropogenic Threats, Wildlife-Conflicts, and Management Recommendations for African Crowned Eagles
Authors: McPherson Shane C. , Sumasgutner Petra , Hoffman Ben H. , Padbury Bruce D. L. , Brown Mark , Caine Tammy P. , Downs Colleen T.
Published: October 2021

Larger carnivores often trigger human-wildlife conflicts that arise from perceived threats to humans and domestic animals’ safety, which generate the need for management and removal strategies. These issues become especially challenging when humans and wildlife coexist close to one another, for example, in urban landscapes. African Crowned Eagles (Stephanoaetus coronatus) are powerful forest raptors that breed within the metropolitan green-space system of Durban and Pietermaritzburg, South Africa. Negative human-wildlife interactions can occur because eagles occasionally predate on pets, such as cats (Felis catus) and small dogs (Canis lupus familiaris), and provisioning domestic stock to nest sites has previously been quantified. Here, wildlife management becomes critical, usually aimed at reducing or eliminating causes of economic or social harm, but have to be balanced against conservation goals regarding threatened species. In this study, we (i) identified causes of harm or loss of Crowned Eagles because of injuries (n = 53 incidents; 31 mortalities); and (ii) describe interactions with negative perceptions to human livelihoods, particularly concerning predation on pets and livestock. Anthropogenic causes of mortality were more likely to be reported than remote natural deaths, which provides important opportunities for mitigation measures. Most avoidable are electrocution on utility poles, persecution via gunshot wounds and poisoning (targeted or secondary), while collisions with anthropogenic structures, such as glass panes, vehicles and fence wires, are more challenging to mitigate. Out of 44 verified Crowned Eagle vs. pets and livestock conflicts, we documented 19 dog attacks (2012–2020), with detrimental impacts on social perception and acceptance of urban eagles. Pet and livestock conflicts were primarily associated with juveniles and immature eagles (83%). Of these, 19% occurred during September alone, which marks the end of the post-fledging dependency period; 70% occurred outside the breeding season. We provide management recommendations regarding various categories of Crowned Eagle human-wildlife interactions. For example, activities such as rehabilitation and falconry can coordinate to achieve a high standard of public support and conservation outcomes for Crowned Eagles. Finally, we discuss using different management intervention strategies, including rehabilitation, falconry, re-wildling processes, and lethal control of specific “problem” individuals toward achieving the goal of sustainable, healthy Crowned Eagle populations that coexist with humans in urban landscapes.
Multi-Sensor Data Fusion for Accurate Traffic Speed and Travel Time Reconstruction
Authors: Kessler Lisa , Rempe Felix , Bogenberger Klaus
Published: October 2021

This paper studies the joint reconstruction of traffic speeds and travel times by fusing sparse sensor data. Raw speed data from inductive loop detectors and floating cars as well as travel time measurements are combined using different fusion techniques. A novel fusion approach is developed, which extends existing speed reconstruction methods to integrate low-resolution travel time data. Several state-of-the-art methods and the novel approach are evaluated on their performance in reconstructing traffic speeds and travel times using various combinations of sensor data. Algorithms and sensor setups are evaluated with real loop detector, floating car and Bluetooth data collected during severe congestion on German freeway A9. Two main aspects are examined: 1) which algorithm provides the most accurate result depending on the used data and 2) which type of sensor and which combination of sensors yields highest estimation accuracy. Results show that, overall, the novel approach applied to a combination of floating-car data and loop data provides the best speed and travel time accuracy. Furthermore, a fusion of sources improves the reconstruction quality in many, but not all cases. In particular, Bluetooth data only provide a benefit for reconstruction purposes if integrated subtly.
Identifying New COVID-19 Receptor Neuropilin-1 in Severe Alzheimer’s Disease Patients Group Brain Using Genome-Wide Association Study Approach
Authors: Lim Key-Hwan , Yang Sumin , Kim Sung-Hyun , Joo Jae-Yeol
Published: October 2021

Recent preclinical studies show that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, we hypothesize that NRP1 may be upregulated in Alzheimer’s disease (AD) patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist as angiotensin converting enzyme 2 (ACE2). We used an AD mouse model that mimics AD and performed high-throughput total RNA-seq with brain tissue and whole blood. For quantification of NRP1 in AD, brain tissues and blood were subjected to Western blotting and real-time quantitative PCR (RT-qPCR) analysis. In silico analysis for NRP1 expression in AD patients has been performed on human hippocampus data sets. Many cases of severe symptoms of COVID-19 are concentrated in an elderly group with complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that the Nrp1 gene was commonly overexpressed in the AD model. Similar to ACE2, the NRP1 protein is also strongly expressed in AD brain tissues. Interestingly, in silico analysis revealed that the level of expression for NRP1 was distinct at age and AD progression. Given that NRP1 is highly expressed in AD, it is important to understand and predict that NRP1 may be a risk factor for SARS-CoV-2 infection in AD patients. This supports the development of potential therapeutic drugs to reduce SARS-CoV-2 transmission.
Genome-Wide Analysis of Major Facilitator Superfamily and Its Expression in Response of Poplar to Fusarium oxysporum
Authors: Diao Jian , Li Shuxuan , Ma Ling , Zhang Ping , Bai Jianyang , Wang Jiaqi , Ma Xiaoqian , Ma Wei
Published: October 2021

The major facilitator superfamily (MFS) is one of the largest known membrane transporter families. MFSs are involved in many essential functions, but studies on the MFS family in poplar have not yet been reported. Here, we identified 41 MFS genes from Populus trichocarpa (PtrMFSs). We built a phylogenetic tree, which clearly divided members of PtrMFS into six groups with specific gene structures and protein motifs/domains. The promoter regions contain various cis-acting elements involved in stress and hormone responsiveness. Genes derived from segmental duplication events are unevenly distributed in 17 poplar chromosomes. Collinearity analysis showed that PtrMFS genes are conserved and homologous to corresponding genes from four other species. Transcriptome data indicated that 40 poplar MFS genes were differentially expressed when treated with Fusarium oxysporum. Co-expression networks and gene function annotations of MFS genes showed that MFS genes tightly co-regulated and closely related in function of transmembrane transport. Taken together, we systematically analyzed structure and function of genes and proteins in the PtrMFS family. Evidence indicated that poplar MFS genes play key roles in plant development and response to a biological stressor.
A Bovine Enteric Mycobacterium Infection Model to Analyze Parenteral Vaccine-Induced Mucosal Immunity and Accelerate Vaccine Discovery
Authors: Facciuolo Antonio , Lee Amy H. , Trimble Michael J. , Rawlyk Neil , Townsend Hugh G. G. , Bains Manjeet , Arsic Natasa , Mutharia Lucy M. , Potter Andrew , Gerdts Volker , Napper Scott , Hancock Robert E. W. , Griebel Philip J.
Published: October 2021

Mycobacterial diseases of cattle are responsible for considerable production losses worldwide. In addition to their importance in animals, these infections offer a nuanced approach to understanding persistent mycobacterial infection in native host species. Mycobacteriumavium ssp. paratuberculosis (MAP) is an enteric pathogen that establishes a persistent, asymptomatic infection in the small intestine. Difficulty in reproducing infection in surrogate animal models and limited understanding of mucosal immune responses that control enteric infection in the natural host have been major barriers to MAP vaccine development. We previously developed a reproducible challenge model to establish a consistent MAP infection using surgically isolated intestinal segments prepared in neonatal calves. In the current study, we evaluated whether intestinal segments could be used to screen parenteral vaccines that alter mucosal immune responses to MAP infection. Using Silirum® – a commercial MAP bacterin – we demonstrate that intestinal segments provide a platform for assessing vaccine efficacy within a relatively rapid period of 28 days post-infection. Significant differences between vaccinates and non-vaccinates could be detected using quantitative metrics including bacterial burden in intestinal tissue, MAP shedding into the intestinal lumen, and vaccine-induced mucosal immune responses. Comparing vaccine-induced responses in mucosal leukocytes isolated from the site of enteric infection versus blood leukocytes revealed substantial inconsistences between these immune compartments. Moreover, parenteral vaccination with Silirum did not induce equal levels of protection throughout the small intestine. Significant control of MAP infection was observed in the continuous but not the discrete Peyer’s patches. Analysis of these regional mucosal immune responses revealed novel correlates of immune protection associated with reduced infection that included an increased frequency of CD335+ innate lymphoid cells, and increased expression of IL21 and IL27. Thus, intestinal segments provide a novel model to accelerate vaccine screening and discovery by testing vaccines directly in the natural host and provides a unique opportunity to interrogate mucosal immune responses to mycobacterial infections.
Premature Senescence and Telomere Shortening Induced by Oxidative Stress From Oxalate, Calcium Oxalate Monohydrate, and Urine From Patients With Calcium Oxalate Nephrolithiasis
Authors: Chuenwisad Kamonchanok , More-krong Pimkanya , Tubsaeng Praween , Chotechuang Nattida , Srisa-Art Monpichar , Storer Robin James , Boonla Chanchai
Published: October 2021

Oxidative stress, a well-known cause of stress-induced premature senescence (SIPS), is increased in patients with calcium oxalate (CaOx) kidney stones (KS). Oxalate and calcium oxalate monohydrate (COM) induce oxidative stress in renal tubular cells, but to our knowledge, their effect on SIPS has not yet been examined. Here, we examined whether oxalate, COM, or urine from patients with CaOx KS could induce SIPS and telomere shortening in human kidney (HK)-2 cells, a proximal tubular renal cell line. Urine from age- and sex-matched individuals without stones was used as a control. In sublethal amounts, H2O2, oxalate, COM, and urine from those with KS evoked oxidative stress in HK-2 cells, indicated by increased protein carbonyl content and decreased total antioxidant capacity, but urine from those without stones did not. The proportion of senescent HK-2 cells, as indicated by SA-βgal staining, increased after treatment with H2O2, oxalate, COM, and urine from those with KS. Expression of p16 was higher in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS than it was in cells treated with urine from those without stones and untreated controls. p16 was upregulated in the SA-βgal positive cells. Relative telomere length was shorter in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS than that in cells treated with urine from those without stones and untreated controls. Transcript expression of shelterin components (TRF1, TRF2 and POT1) was decreased in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS, in which case the expression was highest. Urine from those without KS did not significantly alter TRF1, TRF2, and POT1 mRNA expression in HK-2 cells relative to untreated controls. In conclusion, oxalate, COM, and urine from patients with CaOx KS induced SIPS and telomere shortening in renal tubular cells. SIPS induced by a lithogenic milieu may result from upregulation of p16 and downregulation of shelterin components, specifically POT1, and might contribute, at least in part, to the development of CaOx KS.
A Comprehensive Analysis of the Colonic Flora Diversity, Short Chain Fatty Acid Metabolism, Transcripts, and Biochemical Indexes in Heat-Stressed Pigs
Authors: Hu Canying , Niu Xueting , Chen Shengwei , Wen Jiaying , Bao Minglong , Mohyuddin Sahar Ghulam , Yong Yanhong , Liu Xiaoxi , Wu Lianyun , Yu Zhichao , Ma Xinbin , Ju Xianghong
Published: October 2021

Heat stressed pigs show typical characteristics of inflammatory bowel disease (IBD). However, little is known about the pathogenesis of heat stress (HS)-induced IBD in pigs. In this study, we determined the effects of HS on colon morphology, intestinal microbiota diversity, transcriptome genes (transcripts), and short chain fatty acids (SCFAs) metabolism in pigs. In addition, the correlation among these parameters was analyzed by weighted gene co-expression network analysis. Results showed that the liver and kidney functions related to blood biochemical indexes were partially changed in pigs under HS. Furthermore, the levels of diamine oxidase and D-lactic acid were significantly increased, whereas the levels of secretory immunoglobulin A were decreased. The integrity of colonic tissue was damaged under HS, as bleeding, lymphatic infiltration, and villi injury were observed. The concentrations of SCFAs in the colon, such as acetic acid and butyric acid, were decreased significantly. In addition, the composition of colon microbiota, such as decrease in Lactobacillus johnsonii, Lactobacillus reuteri and increase in Clostridium sensu stricto 1 of day 7 and 14 while under HS. These changes were associated with changes in the concentration of SCFAs and biochemical indexes above mentioned. Differentially expressed genes were enriched in the nucleotide-binding oligomerization domain-like receptor signaling pathway, Th17 cell differentiation, and IBD pathway, which were also associated with the changes in SCFAs. Thus, the structure, diversity of intestinal microorganisms, and changes in the levels of SCFAs in colon of heat stressed pigs changed significantly, contributing to the activation of immune response and inflammatory signal pathways and causing abnormal physiological and biochemical indexes and intestinal mucosal damage. These results highlight the interconnections between intestinal microbiota, SCFAs, and immune response and their role in the pathogenesis of stress induced IBD therapy.
A Dynamic Transcriptome Map of Different Tissue Microenvironment Cells Identified During Gastric Cancer Development Using Single-Cell RNA Sequencing
Authors: Yin Honghao , Guo Rui , Zhang Huanyu , Liu Songyi , Gong Yuehua , Yuan Yuan
Published: October 2021

Gastric cancer (GC) development trends have identified multiple processes ranging from inflammation to carcinogenesis, however, key pathogenic mechanisms remain unclear. Tissue microenvironment (TME) cells are critical for the progression of malignant tumors. Here, we generated a dynamic transcriptome map of various TME cells during multi-disease stages using single-cell sequencing analysis. We observed a set of key transition markers related to TME cell carcinogenic evolution, and delineated landmark dynamic carcinogenic trajectories of these cells. Of these, macrophages, fibroblasts, and endothelial cells exerted considerable effects toward epithelial cells, suggesting these cells may be key TME factors promoting GC occurrence and development. Our results suggest a phenotypic convergence of different TME cell types toward tumor formation processes in GC. We believe our data would pave the way for early GC detection, diagnosis, and treatment therapies.
Milking the Cow: Cattle-Derived Chimeric Ultralong CDR-H3 Antibodies and Their Engineered CDR-H3-Only Knobbody Counterparts Targeting Epidermal Growth Factor Receptor Elicit Potent NK Cell-Mediated Cytotoxicity
Authors: Pekar Lukas , Klewinghaus Daniel , Arras Paul , Carrara Stefania C. , Harwardt Julia , Krah Simon , Yanakieva Desislava , Toleikis Lars , Smider Vaughn V. , Kolmar Harald , Zielonka Stefan
Published: October 2021

In this work, we have generated epidermal growth factor receptor (EGFR)-specific cattle-derived ultralong CDR-H3 antibodies by combining cattle immunization with yeast surface display. After immunization, ultralong CDR-H3 regions were specifically amplified and grafted onto an IGHV1-7 scaffold by homologous recombination to facilitate Fab display. Antigen-specific clones were readily obtained by fluorescence-activated cell sorting (FACS) and reformatted as chimeric antibodies. Binning experiments revealed epitope targeting of domains I, II, and IV of EGFR with none of the generated binders competing with Cetuximab, Matuzumab, or EGF for binding to EGFR. Cattle-derived chimeric antibodies were potent in inducing antibody-dependent cell-mediated cytotoxicity (ADCC) against EGFR-overexpressing tumor cells with potencies (EC50 killing) in the picomolar range. Moreover, most of the antibodies were able to significantly inhibit EGFR-mediated downstream signaling. Furthermore, we demonstrate that a minor fraction of CDR-H3 knobs derived from generated antibodies was capable of independently functioning as a paratope facilitating EGFR binding when grafted onto the Fc part of human IgG1. Besides slightly to moderately diminished capacities, these engineered Knobbodies largely retained main properties of their parental antibodies such as cellular binding and triggering of ADCC. Hence, Knobbodies might emerge as promising tools for biotechnological applications upon further optimization.
Comprehensive Analyses Identify APOBEC3A as a Genomic Instability-Associated Immune Prognostic Biomarker in Ovarian Cancer
Authors: Xu Fangfang , Liu Tingwei , Zhou Zhuonan , Zou Chang , Xu Shaohua
Published: October 2021

Ovarian cancer (OC) is one of the most malignant tumors whose mortality rate ranks first in gynecological tumors. Although immunotherapy sheds new light on clinical treatments, the low response still restricts its clinical use because of the unique characteristics of OC such as immunosuppressive microenvironment and unstable genomes. Further exploration on determining an efficient biomarker to predict the immunotherapy response of OC patients is of vital importance. In this study, integrative analyses were performed systematically using transcriptome profiles and somatic mutation data from The Cancer Genome Atlas (TCGA) based on the immune microenvironment and genomic instability of OC patients. Firstly, intersection analysis was conducted to identify immune-related differentially expressed genes (DEGs) and genomic instability-related DEGs. Secondly, Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3A (APOBEC3A) was recognized as a protective factor for OC, which was also verified through basic experiments such as quantitative reverse transcription PCR (RT-qPCR), immunohistochemistry (IHC), Cell Counting Kit-8 (CCK-8), and transwell assays. Thirdly, the correlation analyses of APOBEC3A expression with tumor-infiltrating immune cells (TICs), inhibitory checkpoint molecules (ICPs), Immunophenoscores (IPS), and response to anti-PD-L1 immunotherapy were further applied along with single-sample GSEA (ssGSEA), demonstrating APOBEC3A as a promising biomarker to forecast the immunotherapy response of OC patients. Last, the relationship between APOBEC3A expression with tumor mutation burden (TMB), DNA damage response (DDR) genes, and m6A-related regulators was also analyzed along with the experimental verification of immunofluorescence (IF) and RT-qPCR, comprehensively confirming the intimate association of APOBEC3A with genomic instability in OC. In conclusion, APOBEC3A was identified as a protective signature and a promising prognostic biomarker for forecasting the survival and immunotherapy effect of OC patients, which might accelerate the clinical application and improve immunotherapy effect.
Role of TLR4 in Neutrophil Dynamics and Functions: Contribution to Stroke Pathophysiology
Authors: Durán-Laforet Violeta , Peña-Martínez Carolina , García-Culebras Alicia , Cuartero María Isabel , Lo Eng H. , Moro María Ángeles , Lizasoain Ignacio
Published: October 2021

Background and Purpose

The immune response subsequent to an ischemic stroke is a crucial factor in its physiopathology and outcome. It is known that TLR4 is implicated in brain damage and inflammation after stroke and that TLR4 absence induces neutrophil reprogramming toward a protective phenotype in brain ischemia, but the mechanisms remain unknown. We therefore asked how the lack of TLR4 modifies neutrophil function and their contribution to the inflammatory process.

Methods

In order to assess the role of the neutrophilic TLR4 after stroke, mice that do not express TLR4 in myeloid cells (TLR4loxP/Lyz-cre) and its respective controls (TLR4loxP/loxP) were used. Focal cerebral ischemia was induced by occlusion of the middle cerebral artery and infarct size was measured by MRI. A combination of flow cytometry and confocal microscopy was used to assess different neutrophil characteristics (circadian fluctuation, cell surface markers, cell complexity) and functions (apoptosis, microglia engulfment, phagocytosis, NETosis, oxidative burst) in both genotypes.

Results

As previously demonstrated, mice with TLR4 lacking-neutrophils had smaller infarct volumes than control mice. Our results show that the absence of TLR4 keeps neutrophils in a steady youth status that is dysregulated, at least in part, after an ischemic insult, preventing neutrophils from their normal circadian fluctuation. TLR4-lacking neutrophils showed a higher phagocytic activity in the basal state, they were preferentially engulfed by the microglia after stroke, and they produced less radical oxygen species (ROS) in the first stage of the inflammatory process.

Conclusions

TLR4 is specifically involved in neutrophil dynamics under physiological conditions as well as in stroke-induced tissue damage. This research contributes to the idea that TLR4, especially when targeted in specific cell types, is a potential target for neuroprotective strategies.
Growth Factors and Their Roles in Multiple Sclerosis Risk
Authors: Lu Hui , Wu Peng-Fei , Ma Deng-Lei , Zhang Wan , Sun Meichen
Published: October 2021

Background

Previous studies have suggested essential roles of growth factors on the risk of Multiple Sclerosis (MS), but it remains undefined whether the effects are causal.

Objective

We applied Mendelian randomization (MR) approaches to disentangle the causal relationship between genetically predicted circulating levels of growth factors and the risk of MS.

Methods

Genetic instrumental variables for fibroblast growth factor (FGF) 23, growth differentiation factor 15 (GDF15), insulin growth factor 1 (IGF1), insulin-like growth factor binding proteins 3 (IGFBP3) and vascular endothelial growth factor (VEGF) were obtained from up-to-date genome-wide association studies (GWAS). Summary-level statistics of MS were obtained from the International Multiple Sclerosis Genetics Consortium, incorporating 14,802 subjects with MS and 26,703 healthy controls of European ancestry. Inverse-variance weighted (IVW) MR was used as the primary method and multiple sensitivity analyses were employed in this study.

Results

Genetically predicted circulating levels of FGF23 were associated with risk of MS. The odds ratio (OR) of IVW was 0.63 (95% confidence interval [CI], 0.49–0.82; p < 0.001) per one standard deviation increase in circulating FGF23 levels. Weighted median estimators also suggested FGF23 associated with lower MS risk (OR = 0.67; 95% CI, 0.51-0.87; p = 0.003). While MR-Egger approach provided no evidence of horizontal pleiotropy (intercept = -0.003, p = 0.95). Results of IVW methods provided no evidence for causal roles of GDF1, IGF1, IGFBP3 and VEGF on MS risks, and additional sensitivity analyses confirmed the robustness of these null findings.

Conclusion

Our results implied a causal relationship between FGF23 and the risk of MS. Further studies are warranted to confirm FGF23 as a genetically valid target for MS.
Thymic B Cells as a New Player in the Type 1 Diabetes Response
Authors: Greaves Richard B. , Chen Dawei , Green E. Allison
Published: October 2021

Type 1 diabetes (T1d) results from a sustained autoreactive T and B cell response towards insulin-producing β cells in the islets of Langerhans. The autoreactive nature of the condition has led to many investigations addressing the genetic or cellular changes in primary lymphoid tissues that impairs central tolerance- a key process in the deletion of autoreactive T and B cells during their development. For T cells, these studies have largely focused on medullary thymic epithelial cells (mTECs) critical for the effective negative selection of autoreactive T cells in the thymus. Recently, a new cellular player that impacts positively or negatively on the deletion of autoreactive T cells during their development has come to light, thymic B cells. Normally a small population within the thymus of mouse and man, thymic B cells expand in T1d as well as other autoimmune conditions, reside in thymic ectopic germinal centres and secrete autoantibodies that bind selective mTECs precipitating mTEC death. In this review we will discuss the ontogeny, characteristics and functionality of thymic B cells in healthy and autoimmune settings. Furthermore, we explore howin silicoapproaches may help decipher the complex cellular interplay of thymic B cells with other cells within the thymic microenvironment leading to new avenues for therapeutic intervention.
Identification of the Plasmid-Mediated Colistin Resistance Gene mcr-1 in Escherichia coli Isolates From Migratory Birds in Guangdong, China
Authors: Zhang Yan , Kuang Xu , Liu Juan , Sun Ruan-Yang , Li Xing-Ping , Sun Jian , Liao Xiao-Ping , Liu Ya-Hong , Yu Yang
Published: October 2021

We determined the prevalence and transmission characteristics of mcr-1-positive Escherichia coli (MCRPEC) isolates from migratory birds Anser indicus in Guangdong, China. We identified 22 MCRPEC from 303 A. indicus fecal samples (7.3%) in Guangzhou, Zhaoqing, and Futian. The mcr-1 gene coexisted with 24 other types of antibiotic resistance genes (ARG), and 11 ARGs were highly prevalent at levels >50%. The MCRPEC displayed a diversity of sequence types (ST), and 19 distinct STs were identified with ST10, ST1146, and ST1147 as the most prevalent. In addition, these MCRPEC from birds were closely related phylogenetically to those from other sources in China. Whole-genome sequencing analysis demonstrated that mcr-1 was located on IncX4 (n=9, 40.9%), IncI2 (n=5, 22.7%) and IncP (n=1, 4.5%) plasmids and the latter shared an identical plasmid backbone with other sources. These results highlight the significance of migratory birds in the transmission of antibiotic resistance and provide powerful evidence that migratory birds are potential transmitters of antibiotic resistance.