bluuebunny/crossref_metadata_2025 huggingface dataset:
Plastic Interactions with Pollutants and Consequences to Aquatic Ecosystems: What We Know and What We Do Not Know
Authors: Cássio Fernanda , Batista Daniela , Pradhan Arunava
Published: June 2022

Plastics are a group of synthetic materials made of organic polymers and some additives with special characteristics. Plastics have become part of our daily life due to their many applications and uses. However, inappropriately managed plastic waste has raised concern regarding their ecotoxicological and human health risks in the long term. Due to the non-biodegradable nature of plastics, their waste may take several thousands of years to partially degrade in natural environments. Plastic fragments/particles can be very minute in size and are mistaken easily for prey or food by aquatic organisms (e.g., invertebrates, fishes). The surface properties of plastic particles, including large surface area, functional groups, surface topography, point zero charge, influence the sorption of various contaminants, including heavy metals, oil spills, PAHs, PCBs and DDT. Despite the fact that the number of studies on the biological effects of plastic particles on biota and humans has been increasing in recent years, studies on mixtures of plastics and other chemical contaminants in the aquatic environment are still limited. This review aims to gather information about the main characteristics of plastic particles that allow different types of contaminants to adsorb on their surfaces, the consequences of this adsorption, and the interactions of plastic particles with aquatic biota. Additionally, some missing links and potential solutions are presented to boost more research on this topic and achieve a holistic view on the effects of micro- and nanoplastics to biological systems in aquatic environments. It is urgent to implement measures to deal with plastic pollution that include improving waste management, monitoring key plastic particles, their hotspots, and developing their assessment techniques, using alternative products, determining concentrations of micro- and nanoplastics and the contaminants in freshwater and marine food-species consumed by humans, applying clean-up and remediation strategies, and biodegradation strategies.
Djhsp60 Is Required for Planarian Regeneration and Homeostasis
Authors: Ma Kexue , Li Rui , Song Gege , Guo Fangying , Wu Meng , Lu Qiong , Li Xinwei , Chen Guangwen
Published: June 2022

HSP60, a well-known mitochondrial chaperone, is essential for mitochondrial homeostasis. HSP60 deficiency causes dysfunction of the mitochondria and is lethal to animal survival. Here, we used freshwater planarian as a model system to investigate and uncover the roles of HSP60 in tissue regeneration and homeostasis. HSP60 protein is present in all types of cells in planarians, but it is relatively rich in stem cells and head neural cells. Knockdown of HSP60 by RNAi causes head regression and the loss of regenerating abilities, which is related to decrease in mitotic cells and inhibition of stem cell-related genes. RNAi-HSP60 disrupts the structure of the mitochondria and inhibits the mitochondrial-related genes, which mainly occur in intestinal tissues. RNAi-HSP60 also damages the integrity of intestinal tissues and downregulates intestine-expressed genes. More interestingly, RNAi-HSP60 upregulates the expression of the cathepsin L-like gene, which may be the reason for head regression and necrotic-like cell death. Taking these points together, we propose a model illustrating the relationship between neoblasts and intestinal cells, and also highlight the essential role of the intestinal system in planarian regeneration and tissue homeostasis.
Overcoming the Limitations of Stem Cell-Derived Beta Cells
Authors: Karimova Mariana V. , Gvazava Inessa G. , Vorotelyak Ekaterina A.
Published: June 2022

Great advances in type 1 diabetes (T1D) and type 2 diabetes (T2D) treatment have been made to this day. However, modern diabetes therapy based on insulin injections and cadaveric islets transplantation has many disadvantages. That is why researchers are developing new methods to regenerate the pancreatic hormone-producing cells in vitro. The most promising approach is the generation of stem cell-derived beta cells that could provide an unlimited source of insulin-secreting cells. Recent studies provide methods to produce beta-like cell clusters that display glucose-stimulated insulin secretion—one of the key characteristics of the beta cell. However, in comparison with native beta cells, stem cell-derived beta cells do not undergo full functional maturation. In this paper we review the development and current state of various protocols, consider advantages, and propose ways to improve them. We examine molecular pathways, epigenetic modifications, intracellular components, and the microenvironment as a possible leverage to promote beta cell functional maturation. A possibility to create islet organoids from stem cell-derived components, as well as their encapsulation and further transplantation, is also examined. We try to combine modern research on beta cells and their crosstalk to create a holistic overview of developing insulin-secreting systems.
Clinical Implication of Preoperative Renal Function on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy
Authors: Kim Tae Heon , Sung Hyun Hwan , Oh Jong Jin , Kang Seok Ho , Seo Ho Kyung , Hong Bumsik , Ku Ja Hyeon , Jeong Byong Chang
Published: June 2022

This study aims to evaluate the impact of preoperative renal function on oncological outcomes in patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). We performed a retrospective analysis of patients who underwent RNU between 2000 and 2012 at six academic centers. The patients were stratified into two groups based on preoperative renal function: eGFR < 60 mL/min/1.73 m2 (chronic kidney disease; CKD) and eGFR ≥ 60 mL/min/1.73 m2 (non-CKD). We investigated oncological outcomes, including overall survival, cancer-specific survival, and progression-free survival dichotomized by preoperative renal function. Multivariable Cox proportional hazards regression was used to determine if preoperative CKD was associated with oncological outcomes. In total, 1733 patients were eligible for the present study (CKD = 707 and non-CKD = 1026). Significant differences were noted in the clinical and pathologic features among the two groups, including age, sex, tumor localization, pathological T stage, tumor grade, and number of patients who received adjuvant chemotherapy. The estimated five-year overall survival (79.4 vs. 67.5%, log-rank p < 0.001), cancer-specific survival (83.5 vs. 73.6%, log-rank p < 0.001), and progression-free survival (74.6 vs. 61.5%, log-rank p < 0.001) were significantly different between the two groups, longer in the non-CKD group. Upon multivariable analysis, preoperative CKD status was associated with increased risk of overall mortality, cancer-specific mortality, and progression (p = 0.010, p = 0.016, and p = 0.008, respectively). UTUC patients with preoperative CKD had a higher risk of poor overall survival, cancer-specific survival, and progression-free survival after RNU than those without CKD.
Exploring the Binding Capacity of Mycelium and Wood-Based Composites for Use in Construction
Authors: Saez Dana , Grizmann Denis , Trautz Martin , Werner Anett
Published: June 2022

Existing research on mycelium-based materials recognizes the binding capacity of fungal hyphae. Fungal hyphae digest and bond to the surface of the substrate, form entangled networks, and enhance the mechanical strength of mycelium-based composites. This investigation was driven by the results of an ongoing project, where we attempt to provide basic concepts for a broad application of a mycelium and chipped wood composite for building components. Simultaneously, we further explore the binding capacity of mycelium and chipped wood composites with a series of experiments involving different mechanical interlocking patterns. Although the matrix material was analyzed on a micro-scale, the samples were developed on a meso-scale to enhance the bonding surface. The meso-scale allows exploring the potential of the bio-based material for use in novel construction systems. The outcome of this study provides a better understanding of the material and geometrical features of mycelium-based building elements.
Ensem-HAR: An Ensemble Deep Learning Model for Smartphone Sensor-Based Human Activity Recognition for Measurement of Elderly Health Monitoring
Authors: Bhattacharya Debarshi , Sharma Deepak , Kim Wonjoon , Ijaz Muhammad Fazal , Singh Pawan Kumar
Published: June 2022

Biomedical images contain a huge number of sensor measurements that can provide disease characteristics. Computer-assisted analysis of such parameters aids in the early detection of disease, and as a result aids medical professionals in quickly selecting appropriate medications. Human Activity Recognition, abbreviated as ‘HAR’, is the prediction of common human measurements, which consist of movements such as walking, running, drinking, cooking, etc. It is extremely advantageous for services in the sphere of medical care, such as fitness trackers, senior care, and archiving patient information for future use. The two types of data that can be fed to the HAR system as input are, first, video sequences or images of human activities, and second, time-series data of physical movements during different activities recorded through sensors such as accelerometers, gyroscopes, etc., that are present in smart gadgets. In this paper, we have decided to work with time-series kind of data as the input. Here, we propose an ensemble of four deep learning-based classification models, namely, ‘CNN-net’, ‘CNNLSTM-net’, ‘ConvLSTM-net’, and ‘StackedLSTM-net’, which is termed as ‘Ensem-HAR’. Each of the classification models used in the ensemble is based on a typical 1D Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) network; however, they differ in terms of their architectural variations. Prediction through the proposed Ensem-HAR is carried out by stacking predictions from each of the four mentioned classification models, then training a Blender or Meta-learner on the stacked prediction, which provides the final prediction on test data. Our proposed model was evaluated over three benchmark datasets, WISDM, PAMAP2, and UCI-HAR; the proposed Ensem-HAR model for biomedical measurement achieved 98.70%, 97.45%, and 95.05% accuracy, respectively, on the mentioned datasets. The results from the experiments reveal that the suggested model performs better than the other multiple generated measurements to which it was compared.
Intelligent Biosignal Processing in Wearable and Implantable Sensors
Authors: Costin Hariton-Nicolae , Sanei Saeid
Published: June 2022

Wearable technology including sensors, sensor networks, and the associated devices have opened up space in a variety of applications [...]
Laser-Induced Graphene-Based Wearable Epidermal Ion-Selective Sensors for Noninvasive Multiplexed Sweat Analysis
Authors: Liao Jianjun , Zhang Xiangya , Sun Zihan , Chen Hande , Fu Jian , Si Hewei , Ge Chengjun , Lin Shiwei
Published: June 2022

Wearable sweat sensors are a rapidly rising research area owing to their convenience for personal healthcare and disease diagnosis in a real-time and noninvasive manner. However, the fast and scalable fabrication of flexible electrodes remains a major challenge. Here, we develop a wearable epidermal sensor for multiplexed sweat analysis based on the laser-induced graphene (LIG) technique. This simple and mask-free technique allows the direct manufacturing of graphene electrode patterns on commercial polyimide foils. The resulting LIG devices can simultaneously monitor the pH, Na+, and K+ levels in sweat with the sensitivities of 51.5 mV/decade (pH), 45.4 mV/decade (Na+), and 43.3 mV/decade (K+), respectively. Good reproducibility, stability, and selectivity are also observed. On-body testing of the LIG-based sensor integrated with a flexible printed circuit board during stationary cycling demonstrates its capability for real-time sweat analysis. The concentrations of ions can be remotely and wirelessly transmitted to a custom-developed smartphone application during the period in which the sensor user performs physical activities. Owing to the unique advantages of LIG technique, including facile fabrication, mass production, and versatile, more physiological signals (glucose, uric acid, tyrosine, etc.) could be easily expanded into the LIG-based wearable sensors to reflect the health status or clinical needs of individuals.
FECC-Net: A Novel Feature Enhancement and Context Capture Network Based on Brain MRI Images for Lesion Segmentation
Authors: Huang Zhaohong , Zhang Xiangchen , Song Yehua , Cai Guorong
Published: June 2022

In recent years, the increasing incidence of morbidity of brain stroke has made fast and accurate segmentation of lesion areas from brain MRI images important. With the development of deep learning, segmentation methods based on the computer have become a solution to assist clinicians in early diagnosis and treatment planning. Nevertheless, the variety of lesion sizes in brain MRI images and the roughness of the boundary of the lesion pose challenges to the accuracy of the segmentation algorithm. Current mainstream medical segmentation models are not able to solve these challenges due to their insufficient use of image features and context information. This paper proposes a novel feature enhancement and context capture network (FECC-Net), which is mainly composed of an atrous spatial pyramid pooling (ASPP) module and an enhanced encoder. In particular, the ASPP model uses parallel convolution operations with different sampling rates to enrich multi-scale features and fully capture image context information in order to process lesions of different sizes. The enhanced encoder obtains deep semantic features and shallow boundary features in the feature extraction process to achieve image feature enhancement, which is helpful for restoration of the lesion boundaries. We divide the pathological image into three levels according to the number of pixels in the real mask area and evaluate FECC-Net on an open dataset called Anatomical Tracings of Lesions After Stroke (ATLAS). The experimental results show that our FECC-Net outperforms mainstream methods, such as DoubleU-Net and TransUNet. Especially in small target tasks, FECC-Net is 4.09% ahead of DoubleU-Net on the main indicator DSC. Therefore, FECC-Net is encouraging and can be relied upon for brain MRI image applications.
Deep Brain Stimulation in Early-Stage Parkinson’s Disease: Patient Experience after 11 Years
Authors: Stoehr Kaitlyn , Pazira Kian , Bonnet Kemberlee , Schlundt David , Charles David , Hacker Mallory
Published: June 2022

The deep brain stimulation (DBS) in early-stage Parkinson’s disease (PD) pilot trial began more than a decade ago and remains the only investigation of DBS in mildly symptomatic patients. Patients completed therapeutic washouts biannually for two years, outpatient assessments through five years, and a longitudinal washout assessment after 11 years. Here, the patient experience of participating in the early DBS pilot trial is described. Semi-structured interviews were audio-recorded and transcribed. Transcripts were coded, analyzed using an iterative inductive-deductive approach, and used to develop a conceptual framework. Ten participants (n = 6 early optimal drug therapy (ODT), n = 4 early DBS + ODT) were interviewed. Motivations for participation included benefit to future PD patients and potential personal benefit, while hesitations included risk of surgical complications. While early ODT patients who received standard-of-care DBS described significant changes in their functional capacities after surgery, early DBS patients described a maintenance of quality of life that made PD less impactful over an extended period. Patients expressed high satisfaction with trial participation and early DBS. This study suggests that the PD experience with early DBS may notably differ from standard-of-care DBS. The FDA has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016).
An Arabic Sedentary Behaviors Questionnaire (ASBQ): Development, Content Validation, and Pre-Testing Findings
Authors: Al-Hazzaa Hazzaa M. , Alothman Shaima A. , Albawardi Nada M. , Alghannam Abdullah F. , Almasud Alaa A.
Published: June 2022

Background: Sedentary behaviors (SB) are very prevalent nowadays. Prolonged sitting associates with chronic disease risks and increased mortality even while controlling for physical activity. Objective measurement of SB is costly, requires technical expertise, and is challenging in terms of time and management. Currently, there is no validated self-reported instrument in the Arabic language that assesses SB among individuals and relates sedentary time to social, environmental, and health outcomes. The aim of this research was to develop a multi-item Arabic SB questionnaire (ASBQ). Methods: The ASBQ was developed through an extensive literature review and discussion by the research team (n = 5), then went through content validation (n = 10 experts) and pre-testing using cognitive interviewing procedures (n = 51 respondents, mean (SD) age was 38.3 (18.2) years, and with 49% females). Results: The ASBQ included 13 questions comprising a wide range of sedentary activities. The Arabic SB instrument showed excellent content validity for assessing sedentary time in adolescents and adults with a very high item-level and scale-level content validity index. A kappa statistic, a measure of interrater reliability, was 0.95. The pre-testing showed that the instrument was highly rated by a diverse sample of Saudi adolescents and adults. Conclusion: The ASBQ received excellent acceptance by a panel of experts with promising pre-test results. Further testing of psychometric properties, including test-retest reliability and criterion validity is required.
A Technical Proposal for the Implementation of Transfer of Development Rights (TDR) on Preserved Historic Buildings in Turkey
Authors: Konbul Yunus , Yanalak Mustafa
Published: June 2022

Buildings that have cultural and historical significance are very important elements of our living spaces and they must be protected by public authorities. However, the preservation of these buildings prevents their landowners from using their development rights and causes economic losses. If those losses are not compensated, it results in social injustice. Leaving this problem unsolved makes historic buildings a target for arson, facilitates the destruction of unregistered (unlisted) historic buildings for redevelopment with a higher density. The traditional methods, namely expropriation and property exchange, generally fail to compensate those development losses. However, the method of transfer of development rights (TDR) can be a good option for this task in Turkey as well. Although there have been some important legislative actions, an “implementing regulation” could not be enacted so far. In this study, we attempt to develop a step-by-step methodology for the implementation of a TDR program from the perspective of land management. The methodology introduced in this paper is also tested for its validity by interviewing 18 professionals from related sectors and all the interviewees agreed on them with minor suggestions. The results derived from this study could benefit not only property owners, but also overall preservation efforts in the country.
Evaluating the Annual Effect of the Sky View Factor on the Indoor Thermal Environment of Residential Buildings by Envi-met
Authors: Zheng Bohong , Li Jiayu
Published: June 2022

The effect of the sky view factor (SVF) on outdoor thermal comfort has been extensively explored, while its impact on the indoor thermal environment is ignored. This research combined Envi-met and kriging models to explore the annual effect of the sky view factor on the indoor thermal environment. Different from previous studies, this study explored the effect of the sky view factor on indoor temperature rather than outdoor temperature, and from the perspective of a full year instead of a typical summer day. The analytical results reveal that an increase in the sky view factor raised the indoor air temperature every month. Although a low sky view factor was beneficial to the insulation of the built environment at night, it was proven that in Chenzhou city, the indoor air temperature was still higher in a built area with a high sky view factor than with a low sky view factor. In addition, the sky view factor was shown to have a nonlinear relationship with indoor thermal comfort throughout the year. When the sky view factor increased from 0.05 to 0.45, the indoor temperature increased by around 10 °C at 16:00 and increased by about 4 °C throughout the night for each month, and from the view of the annual cycle, the cooling demand duration increased by 1611.6 h (18.4%), and the heating demand duration decreased by 1192.3 h (13.61%).
Effect of External Tendon Profile on Improving Structural Performance of RC Beams
Authors: Mohamed Gouda A. , Eisa Ahmed S. , Purcz Pavol , Ručinský Rastislav , El-Feky Mohamed H.
Published: June 2022

The objective of the research is to improve the structural behavior of reinforced concrete (RC) T–beams by applying various techniques of external pre-stressing tendons, thus enhancing the load-carrying capacities and raising the resistance to applied forces. Seven identical RC T–beams were subjected to four-point loading to study the influence of the deviator number, tension mechanism, and tendon profile on flexural behavior. Of these, one beam was an original specimen without any tendons. The other six beams were strengthened with external tendons: two identical specimens with straight–line tendons but with a different number of inner deviators; two identical specimens with V–shaped tendons but with a different tension direction; and finally, two identical specimens with U–shaped tendons but with a different tension direction. The results and discussion were achieved using finite element (FE) software, ANSYS WORKBENCH. The results from all specimens were listed and analyzed for the failure mechanism, load-carrying capacity, deflection, and ductility. According to the FE results, external tendons greatly enhance the load-carrying and stiffness of RC beams. In addition, strengthening beams with external pre-stressing techniques can delay the early cracking load, yield load, and ultimate load by approximately 250%, 570%, and 30%, respectively, when compared to an unstrengthened beam. Moreover, the straight-line tendon with inner deviators was obtained to be the most effective technique for simple beams.
Midline Skull Base Meningiomas: Transcranial and Endonasal Perspectives
Authors: Mastantuoni Ciro , Cavallo Luigi Maria , Esposito Felice , d’Avella Elena , de Divitiis Oreste , Somma Teresa , Bocchino Andrea , Fabozzi Gianluca Lorenzo , Cappabianca Paolo , Solari Domenico
Published: June 2022

Skull base meningiomas have always represented a challenge for neurosurgeons. Despite their histological nature, they may be associated with unfavorable outcomes due to their deep-seated location and the surrounding neurovascular structures. The state of the art of skull base meningiomas accounts for both transcranial, or high, and endonasal, or low, routes. A comprehensive review of the pertinent literature was performed to address the surgical strategies and outcomes of skull base meningioma patients treated through a transcranial approach, an endoscopic endonasal approach (EEA), or both. Three databases (PubMed, Ovid Medline, and Ovid Embase) have been searched. The review of the literature provided 328 papers reporting the surgical, oncological, and clinical results of different approaches for the treatment of skull base meningiomas. The most suitable surgical corridors for olfactory groove, tuberculum sellae, clival and petroclival and cavernous sinus meningiomas have been analyzed. The EEA was proven to be associated with a lower extent of resection rates and better clinical outcomes compared with transcranial corridors, offering the possibility of achieving the so-called maximal safe resection.
The Extracellular Matrix Stiffening: A Trigger of Prostate Cancer Progression and Castration Resistance?
Authors: Luthold Carole , Hallal Tarek , Labbé David P. , Bordeleau François
Published: June 2022

Despite advancements made in diagnosis and treatment, prostate cancer remains the second most diagnosed cancer among men worldwide in 2020, and the first in North America and Europe. Patients with localized disease usually respond well to first-line treatments, however, up to 30% develop castration-resistant prostate cancer (CRPC), which is often metastatic, making this stage of the disease incurable and ultimately fatal. Over the last years, interest has grown into the extracellular matrix (ECM) stiffening as an important mediator of diseases, including cancers. While this process is increasingly well-characterized in breast cancer, a similar in-depth look at ECM stiffening remains lacking for prostate cancer. In this review, we scrutinize the current state of literature regarding ECM stiffening in prostate cancer and its potential association with disease progression and castration resistance.
Clinical Study of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers
Authors: Garland Linda L. , Guillen-Rodriguez José , Hsu Chiu-Hsieh , Davis Lisa E. , Szabo Eva , Husted Christopher R. , Liu Hanqiao , LeClerc Ashley , Alekseyev Yuriy O. , Liu Gang , Bauman Julie E. , Spira Avrum E. , Beane Jennifer , Wojtowicz Malgorzata , Chow H.-H. Sherry
Published: June 2022

The chemopreventive effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on lung cancer risk is supported by epidemiologic and preclinical studies. Zileuton, a 5-lipoxygenase inhibitor, has additive activity with NSAIDs against tobacco carcinogenesis in preclinical models. We hypothesized that cyclooxygenase plus 5-lipoxygenase inhibition would be more effective than a placebo in modulating the nasal epithelium gene signatures of tobacco exposure and lung cancer. We conducted a randomized, double-blinded study of low-dose aspirin plus zileuton vs. double placebo in current smokers to compare the modulating effects on nasal gene expression and arachidonic acid metabolism. In total, 63 participants took aspirin 81 mg daily plus zileuton (Zyflo CR) 600 mg BID or the placebo for 12 weeks. Nasal brushes from the baseline, end-of-intervention, and one-week post intervention were profiled via microarray. Aspirin plus zilueton had minimal effects on the modulation of the nasal or bronchial gene expression signatures of smoking, lung cancer, and COPD but favorably modulated a bronchial gene expression signature of squamous dysplasia. Aspirin plus zileuton suppressed urinary leukotriene but not prostaglandin E2, suggesting shunting through the cyclooxygenase pathway when combined with 5-lipoxygenase inhibition. Continued investigation of leukotriene inhibitors is needed to confirm these findings, understand the long-term effects on the airway epithelium, and identify the safest, optimally dosed agents.
Preparation and Performance of the Lipid Hydrodeoxygenation of a Nickel-Induced Graphene/HZSM-5 Catalyst
Authors: Luo Wen , Zeng Qiongyao , Al-Haimi Akram Ali Nasser Mansoor , Li Ming , Yang Lingmei , Sun Zhigang , Xing Shiyou , Fu Junying , Lv Pengmei
Published: June 2022

Graphene-encapsulated nickel nanoclusters are a feasible strategy to inhibit the nickel deactivation of nickel-based catalysts. In this work, graphene-encapsulated catalysts (Ni@C/HZSM-5) were prepared by a compression forming process, using pseudo-boehmite, Al2O3, and ZrO2 as binders. The pseudo-boehmite was gradually transformed from amorphous to crystalline alumina at high temperatures, which destroyed the nucleation of Ni@C. In contrast, the crystal-stabilized zirconia was more favorable for the nucleation of Ni@C. The extensive dispersion of alumina on the surface of HZSM-5 covers the acid sites of HZSM-5. In contrast, when zirconia was used as the binder, the binder existed in the form of the direct aggregation of ~100 nm zirconia spheres; this distribution form reduced better the damage of the binder to the acid site of the catalyst. Furthermore, the particle size of Ni crystals in the graphene-encapsulated catalysts decreased significantly (mostly <11 nm), and no evident agglomeration of nickel particles appeared. It was found that the stabilization of the metal interface delayed, to an extent, the accumulation rate of carbon deposits and, thus, postponed the deactivation of the acid sites. After 8 h of continuous reaction, the conversion of the traditional catalyst Ni/Z5+Zr dropped significantly to 60%. In contrast, the conversion of Ni@C catalysts prepared with ZrO2 remained above 90%. The regeneration test shows that air roasting could effectively remove carbon deposits and restore the catalyst activity.
Detailed Kinetic Modeling of CO2-Based Fischer–Tropsch Synthesis
Authors: Brübach Lucas , Hodonj Daniel , Biffar Linus , Pfeifer Peter
Published: June 2022

The direct hydrogenation of CO2 to long-chain hydrocarbons, so called CO2-based Fischer–Tropsch synthesis (FTS), is a viable future production route for various hydrocarbons used in the chemical industry or fuel applications. The detailed modeling of the reactant consumption and product distribution is very important for further process improvements but has gained only limited attention so far. We adapted proven modeling approaches from the traditional FTS and developed a detailed kinetic model for the CO2-FTS based on experiments with an Fe based catalyst in a lab-scale tubular reactor. The model is based on a direct CO2 dissociation mechanism for the reverse water gas shift and the alkyl mechanism with an H-assisted CO dissociation step for the FTS. The model is able to predict the reactant consumption, as well as the hydrocarbon distribution, reliably within the experimental range studied (10 bar, 280–320 °C, 900–120,000 mLN h−1 g−1 and H2/CO2 molar inlet ratios of 2–4) and demonstrates the applicability of traditional FTS models for the CO2-based synthesis. Peculiarities of the fractions of individual hydrocarbon classes (1-alkenes, n-alkanes, and iso-alkenes) are accounted for with chain-length-dependent kinetic parameters for branching and dissociative desorption. However, the reliable modeling of class fractions for high carbon number products (>C12) remains a challenge not only from a modeling perspective but also from product collection and analysis.
CeO2-ZrO2 Solid Solution Catalyzed and Moderate Acidic–Basic Sites Dominated Cycloaddition of CO2 with Epoxides: Halogen-Free Synthesis of Cyclic Carbonates
Authors: Gao Jie , Yue Chengguang , Wang Hao , Li Jiaxin , Yao He , Wang Mei-Yan , Ma Xinbin
Published: June 2022

For the production of cyclic carbonates from the cycloaddition of CO2 with epoxides, halogen pollution and product purity are two of the most common problems due to the usage of homogeneous halogen-containing catalysts such as ammonium salt and alkali metal halide. Hence, the development of a novel, halogen-free and efficient catalyst for the synthesis of high-purity cyclic carbonates is significant. Here, a series of acid–base bifunctional Ce1-xZrxO2 nanorods were successfully prepared. The Ce1-xZrxO2 nanorods could catalyze the cycloaddition of CO2 with epoxides efficiently without any halogen addition. Especially for the Ce0.7Zr0.3O2 catalyst, a conversion of 96% with 100% 1,2-butylene carbonate selectivity was achieved. The excellent catalytic performance of Ce1-xZrxO2 nanorods is attributed to the formation of the CeO2-ZrO2 solid solution, which contributes to abundant moderate acidic–basic active sites on the catalyst surface. It is the synergistic effect of moderate acidic–basic sites that dominates the conversion of CO2 with epoxides, which will supply important references for the synthesis of efficient metal oxide catalyst for the cycloaddition of CO2 with epoxides.
Ice Control during Cryopreservation of Heart Valves and Maintenance of Post-Warming Cell Viability
Authors: Brockbank Kelvin G. M. , Bischof John C. , Chen Zhenzhen , Greene Elizabeth D. , Gao Zhe , Campbell Lia H.
Published: June 2022

Heart valve cryopreservation was employed as a model for the development of complex tissue preservation methods based upon vitrification and nanowarming. Porcine heart valves were loaded with cryoprotectant formulations step wise and vitrified in 1–30 mL cryoprotectant formulations ± Fe nanoparticles ± 0.6 M disaccharides, cooled to −100 °C, and stored at −135 °C. Nanowarming was performed in a single ~100 s step by inductive heating within a magnetic field. Controls consisted of fresh and convection-warmed vitrified heart valves without nanoparticles. After washing, cell viability was assessed by metabolic assay. The nanowarmed leaflets were well preserved, with a viability similar to untreated fresh leaflets over several days post warming. The convection-warmed leaflet viability was not significantly different than that of the nanowarmed leaflets immediately after rewarming; however, a significantly higher nanowarmed leaflet viability (p < 0.05) was observed over time in vitro. In contrast, the associated artery and fibrous cardiac muscle were at best 75% viable, and viability decreased over time in vitro. Supplementation of lower concentration cryoprotectant formulations with disaccharides promoted viability. Thicker tissues benefited from longer-duration cryoprotectant loading steps. The best outcomes included a post-warming incubation step with α-tocopherol and an apoptosis inhibitor, Q-VD-OPH. This work demonstrates progress in the control of ice formation and cytotoxicity hurdles for the preservation of complex tissues.
Pathological Complete Response to Neoadjuvant Chemoimmunotherapy for Early Triple-Negative Breast Cancer: An Updated Meta-Analysis
Authors: Rizzo Alessandro , Cusmai Antonio , Massafra Raffaella , Bove Samantha , Comes Maria Colomba , Fanizzi Annarita , Rinaldi Lucia , Acquafredda Silvana , Gadaleta-Caldarola Gennaro , Oreste Donato , Zito Alfredo , Giotta Francesco , Lorusso Vito , Palmiotti Gennaro
Published: June 2022

Immune checkpoint inhibitors (ICIs) have made a breakthrough in the systemic treatment for metastatic triple-negative breast cancer (TNBC) patients. However, results of phase II and III clinical trials assessing ICIs plus chemotherapy as neoadjuvant treatment were controversial and conflicting. We performed a meta-analysis aimed at assessing the Odds Ratio (OR) of the pathological complete response (pCR) rate in trials assessing neoadjuvant chemoimmunotherapy in TNBC. According to our results, the use of neoadjuvant chemoimmunotherapy was associated with higher pCR (OR 1.95; 95% Confidence Intervals, 1.27–2.99). In addition, we highlighted that this benefit was observed regardless of PD-L1 status since the analysis reported a statistically significant and clinically meaningful benefit in both PD-L1 positive and PD-L1 negative patients. These findings further support the exploration of the role of ICIs plus chemotherapy in early-stage TNBC, given the potentially meaningful clinical impact of these agents. Further studies aimed at more deeply investigating this emerging topic in breast cancer immunotherapy are warranted.
Evaluating the Impact of gRNA SNPs in CasRx Activity for Reducing Viral RNA in HCoV-OC43
Authors: Mayes Cathryn Michelle , Santarpia Joshua
Published: June 2022

Viruses within a given family often share common essential genes that are highly conserved due to their critical role for the virus’s replication and survival. In this work, we developed a proof-of-concept for a pan-coronavirus CRISPR effector system by designing CRISPR targets that are cross-reactive among essential genes of different human coronaviruses (HCoV). We designed CRISPR targets for both the RNA-dependent RNA polymerase (RdRp) gene as well as the nucleocapsid (N) gene in coronaviruses. Using sequencing alignment, we determined the most highly conserved regions of these genes to design guide RNA (gRNA) sequences. In regions that were not completely homologous among HCoV species, we introduced mismatches into the gRNA sequence and tested the efficacy of CasRx, a Cas13d type CRISPR effector, using reverse transcription quantitative polymerase chain reaction (RT-qPCR) in HCoV-OC43. We evaluated the effect that mismatches in gRNA sequences has on the cleavage activity of CasRx and found that this CRISPR effector can tolerate up to three mismatches while still maintaining its nuclease activity in HCoV-OC43 viral RNA. This work highlights the need to evaluate off-target effects of CasRx with gRNAs containing up to three mismatches in order to design safe and effective CRISPR experiments.
Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer’s Disease
Authors: Espinoza Sandra , Grunenwald Felipe , Gomez Wileidy , García Felipe , Abarzúa-Catalan Lorena , Oyarce-Pezoa Sebastián , Hernandez Maria Fernanda , Cortés Bastián I. , Uhrig Markus , Ponce Daniela P. , Durán-Aniotz Claudia , Hetz Claudio , SanMartín Carol D. , Cornejo Victor H. , Ezquer Fernando , Parra Valentina , Behrens Maria Isabel , Manque Patricio A. , Rojas-Rivera Diego , Vidal René L. , Woehlbier Ute , Nassif Melissa
Published: June 2022

Alzheimer’s disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon’s role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid β burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid β burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid β secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid β homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid β secretion, defining a new way to target AD and other similar diseases therapeutically.
New Phenylglycinamide Derivatives with Hybrid Structure as Candidates for New Broad-Spectrum Anticonvulsants
Authors: Jakubiec Marcin , Abram Michał , Zagaja Mirosław , Andres-Mach Marta , Szewczyk Aleksandra , Latacz Gniewomir , Szulczyk Bartłomiej , Socała Katarzyna , Nieoczym Dorota , Wlaź Piotr , Metcalf Cameron S. , Wilcox Karen , Kamiński Rafał M. , Kamiński Krzysztof
Published: June 2022

In the present study, a focused combinatorial chemistry approach was applied to merge structural fragments of well-known TRPV1 antagonists with a potent anticonvulsant lead compound, KA-104, that was previously discovered by our group. Consequently, a series of 22 original compounds has been designed, synthesized, and characterized in the in vivo and in vitro assays. The obtained compounds showed robust in vivo antiseizure activity in the maximal electroshock (MES) test and in the 6 Hz seizure model (using both 32 and 44 mA current intensities). The most potent compounds 53 and 60 displayed the following pharmacological profile: ED50 = 89.7 mg/kg (MES), ED50 = 29.9 mg/kg (6 Hz, 32 mA), ED50 = 68.0 mg/kg (6 Hz, 44 mA), and ED50 = 73.6 mg/kg (MES), ED50 = 24.6 mg/kg (6 Hz, 32 mA), and ED50 = 56.3 mg/kg (6 Hz, 44 mA), respectively. Additionally, 53 and 60 were effective in the ivPTZ seizure threshold and had no influence on the grip strength and body temperature in mice. The in vitro binding and functional assays indicated a multimodal mechanism of action for 53 and 60. These molecules, beyond TRPV1 antagonism, inhibited calcium currents and fast sodium currents in patch-clamp assays. Further studies proved beneficial in vitro ADME-Tox properties for 53 and 60 (i.e., high metabolic stability, weak influence on CYPs, no neurotoxicity, etc.). Overall, 53 and 60 seem to be interesting candidates for future preclinical development in epilepsy and pain indications due to their interaction with the TRPV1 channel.
hLMSC Secretome Affects Macrophage Activity Differentially Depending on Lung-Mimetic Environments
Authors: Falcones Bryan , Söderlund Zackarias , Ibáñez-Fonseca Arturo , Almendros Isaac , Otero Jordi , Farré Ramon , Rolandsson Enes Sara , Elowsson Rendin Linda , Westergren-Thorsson Gunilla
Published: June 2022

Mesenchymal stromal cell (MSC)-based therapies for inflammatory diseases rely mainly on the paracrine ability to modulate the activity of macrophages. Despite recent advances, there is scarce information regarding changes of the secretome content attributed to physiomimetic cultures and, especially, how secretome content influence on macrophage activity for therapy. hLMSCs from human donors were cultured on devices developed in house that enabled lung-mimetic strain. hLMSC secretome was analyzed for typical cytokines, chemokines and growth factors. RNA was analyzed for the gene expression of CTGF and CYR61. Human monocytes were differentiated to macrophages and assessed for their phagocytic capacity and for M1/M2 subtypes by the analysis of typical cell surface markers in the presence of hLMSC secretome. CTGF and CYR61 displayed a marked reduction when cultured in lung-derived hydrogels (L-Hydrogels). The secretome showed that lung-derived scaffolds had a distinct secretion while there was a large overlap between L-Hydrogel and the conventionally (2D) cultured samples. Additionally, secretome from L-Scaffold showed an HGF increase, while IL-6 and TNF-α decreased in lung-mimetic environments. Similarly, phagocytosis decreased in a lung-mimetic environment. L-Scaffold showed a decrease of M1 population while stretch upregulated M2b subpopulations. In summary, mechanical features of the lung ECM and stretch orchestrate anti-inflammatory and immunosuppressive outcomes of hLMSCs.
Prostaglandin 2α Promotes Autophagy and Mitochondrial Energy Production in Fish Hepatocytes
Authors: Tian Jingjing , Du Yihui , Yu Ermeng , Lei Caixia , Xia Yun , Jiang Peng , Li Hongyan , Zhang Kai , Li Zhifei , Gong Wangbao , Xie Jun , Wang Guangjun
Published: June 2022

Fatty liver, characterized by excessive lipid droplet (LD) accumulation in hepatocytes, is a common physiological condition in humans and aquaculture species. Lipid mobilization is an important strategy for modulating the number and size of cellular LDs. Cyclooxygenase (COX)-mediated arachidonic acid derivatives are known to improve lipid catabolism in fish; however, the specific derivatives remain unknown. In the present study, we showed that serum starvation induced LD degradation via autophagy, lipolysis, and mitochondrial energy production in zebrafish hepatocytes, accompanied by activation of the COX pathway. The cellular concentration of PGF2α, but not other prostaglandins, was significantly increased. Administration of a COX inhibitor or interference with PGF2α synthase abolished serum deprivation-induced LD suppression, LD–lysosome colocalization, and expression of autophagic genes. Additionally, exogenous PGF2α suppressed the accumulation of LDs, promoted the accumulation of lysosomes with LD and the autophagy marker protein LC3A/B, and augmented the expression of autophagic genes. Moreover, PGF2α enhanced mitochondrial accumulation and ATP production, and increased the transcript levels of β-oxidation- and mitochondrial respiratory chain-related genes. Collectively, these findings demonstrate that the COX pathway is implicated in lipid degradation induced by energy deprivation, and that PGF2α is a key molecule triggering autophagy, lipolysis, and mitochondrial development in zebrafish hepatocytes.
Uncovering Functional Contributions of PMAT (Slc29a4) to Monoamine Clearance Using Pharmacobehavioral Tools
Authors: Beaver Jasmin N. , Weber Brady L. , Ford Matthew T. , Anello Anna E. , Kassis Sarah K. , Gilman T. Lee
Published: June 2022

Plasma membrane monoamine transporter (PMAT, Slc29a4) transports monoamine neurotransmitters, including dopamine and serotonin, faster than more studied monoamine transporters, e.g., dopamine transporter (DAT), or serotonin transporter (SERT), but with ~400–600-fold less affinity. A considerable challenge in understanding PMAT’s monoamine clearance contributions is that no current drugs selectively inhibit PMAT. To advance knowledge about PMAT’s monoamine uptake role, and to circumvent this present challenge, we investigated how drugs that selectively block DAT/SERT influence behavioral readouts in PMAT wildtype, heterozygote, and knockout mice of both sexes. Drugs typically used as antidepressants (escitalopram, bupropion) were administered acutely for readouts in tail suspension and locomotor tests. Drugs with psychostimulant properties (cocaine, D-amphetamine) were administered repeatedly to assess initial locomotor responses plus psychostimulant-induced locomotor sensitization. Though we hypothesized that PMAT-deficient mice would exhibit augmented responses to antidepressant and psychostimulant drugs due to constitutively attenuated monoamine uptake, we instead observed sex-selective responses to antidepressant drugs in opposing directions, and subtle sex-specific reductions in psychostimulant-induced locomotor sensitization. These results suggest that PMAT functions differently across sexes, and support hypotheses that PMAT’s monoamine clearance contribution emerges when frontline transporters (e.g., DAT, SERT) are absent, saturated, and/or blocked. Thus, known human polymorphisms that reduce PMAT function could be worth investigating as contributors to varied antidepressant and psychostimulant responses.
Analysis of the Expression and Subcellular Distribution of eEF1A1 and eEF1A2 mRNAs during Neurodevelopment
Authors: Wefers Zoe , Alecki Celia , Huang Ryan , Jacob-Tomas Suleima , Vera Maria
Published: June 2022

Neurodevelopment is accompanied by a precise change in the expression of the translation elongation factor 1A variants from eEF1A1 to eEF1A2. These are paralogue genes that encode 92% identical proteins in mammals. The switch in the expression of eEF1A variants has been well studied in mouse motor neurons, which solely express eEF1A2 by four weeks of postnatal development. However, changes in the subcellular localization of eEF1A variants during neurodevelopment have not been studied in detail in other neuronal types because antibodies lack perfect specificity, and immunofluorescence has a low sensitivity. In hippocampal neurons, eEF1A is related to synaptic plasticity and memory consolidation, and decreased eEF1A expression is observed in the hippocampus of Alzheimer’s patients. However, the specific variant involved in these functions is unknown. To distinguish eEF1A1 from eEF1A2 expression, we have designed single-molecule fluorescence in-situ hybridization probes to detect either eEF1A1 or eEF1A2 mRNAs in cultured primary hippocampal neurons and brain tissues. We have developed a computational framework, ARLIN (analysis of RNA localization in neurons), to analyze and compare the subcellular distribution of eEF1A1 and eEF1A2 mRNAs at specific developmental stages and in mature neurons. We found that eEF1A1 and eEF1A2 mRNAs differ in expression and subcellular localization over neurodevelopment, and eEF1A1 mRNAs localize in dendrites and synapses during dendritogenesis and synaptogenesis. Interestingly, mature hippocampal neurons coexpress both variant mRNAs, and eEF1A1 remains the predominant variant in dendrites.