bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Organizational Culture Change on Organizational Performance of Kenya Wildlife Service Nairobi National Park
Authors: Okwata Phoebe Akoth , Wasike Susan , Andemariam Kifleyesus
Published: October 2022

Change is inevitable and is seen as a practice for organizations seeking to continuously provide quality services that meet stakeholder needs. Efficient and effective public service delivery has forced state corporations to adopt organizational culture change management to accommodate changes in the environment. However, government parastatals and state corporations such as Kenya Wildlife Service (KWS) often oppose transformation and change because they have uncertain outcomes and come with a lot of challenges. This study determined the effect of culture change on organizational performance at Kenya Wildlife Service Nairobi National Park. The study was guided by Geert Hofstede’s theory as the framework for cross-cultural communication, Edgar Schein’s model as the cultural inventions by a specific group, and the Denison dimension model theory. Using descriptive survey research design, on a target population of 100 employees drawn from various departments at Kenya Wildlife Service (KWS) Nairobi National Park, a structured questionnaire was used for data collection to effectively respond to the research problem. The study revealed that majority (35.9%) of the respondents were convinced that management ensures that old habits that are not effective are dropped and at the same time the management at KWS encourages employees to adapt to changes and be flexible, especially when the work environment is changing. Results revealed that KWS management ensures the organizational culture supports vision, goal and strategies. The respondents (40.5%) also agreed that managers encourage employees to adapt to changes and to care (35.9%) about fellow employees, customers, and stakeholders. The findings also revealed that 28.9% of the respondents agreed that managers are role models for employees in the organization and set standards for ethics. Correlation analyses show that culture affects performance directly and indirectly. The study concludes that organizational culture aligned with vision, goals, and company strategies guides employees towards a shared purpose and improves an organization’s capacity to perform excellently. We also conclude that KWS management encourages work ethics through consistency, and effective communication that improves work commitment that ultimately leads to better performance. The study recommends that there is need for more to be done on culture change as an approach to change management to improve performance. The mission, vision, and strategies are key to organizational performance and need to be reviewed from time to time to ensure that the organization lives its mission and moves towards its vision while applying its strategies. The study further recommends a replica of the same trial in other Kenya Wildlife Service branches in order to authenticate the findings and enable the generalization of the results.
Parameter Identification Method for a Periodic Time-Varying System Using a Block-Pulse Function
Authors: Wang Zhi , Wang Jun , Tian Jing , Liu Yu
Published: October 2022

For periodic time-varying systems, a method of parameter identification based on the block-pulse function is presented. Firstly, the state-space equation of the system was expanded using the block-pulse function, then the recursion formula of the parameter identification of a time-varying system was obtained, according to the irrespective and orthogonal characteristics of the block-pulse function. This study provides a wide range of applications by saving time in calculation with a highly accurate method. The parameter identification was carried out by including the numerical simulation model of a three-degree freedom system and the vibration experiment results of an asymmetrical rotor system. The state space wavelet method and EMD method were compared cross-sectionally with the proposed method; this shows that the proposed method is accurate and effective, which makes it valuable in numerous applications. It also has a certain application value for several related projects.
A Systematic Study of Estimating Potato N Concentrations Using UAV-Based Hyper- and Multi-Spectral Imagery
Authors: Zhou Jing , Wang Biwen , Fan Jiahao , Ma Yuchi , Wang Yi , Zhang Zhou
Published: October 2022

Potato growth depends largely on nitrogen (N) availability in the soil. However, the shallow-root crop coupled with its common cultivation in coarse-textured soils leads to its poor N use efficiency. Fast and accurate estimations of potato tissue N concentrations are urgently needed to assist the decision making in precision fertilization management. Remote sensing has been utilized to evaluate the potato N status by correlating spectral information with lab tests on leaf N concentrations. In this study, a systematic comparison was conducted to quantitatively evaluate the performance of hyperspectral and multispectral images in estimating the potato N status, providing a reference for the trade-off between sensor costs and performance. In the experiment, two potato varieties were planted under four fertilization rates with replicates. UAV images were acquired multiple times during the season with a narrow-band hyperspectral imager. Multispectral reflectance was simulated by merging the relevant narrow bands into broad bands to mimic commonly used multispectral cameras. The whole leaf total N concentration and petiole nitrate-N concentration were obtained from 160 potato leaf samples. A partial least square regression model was developed to estimate the two N status indicators using different groups of image features. The best estimation accuracies were given by reflectance of the full spectra with 2.2 nm narrow, with the coefficient of determination (R2) being 0.78 and root mean square error (RMSE) being 0.41 for the whole leaf total N concentration; while, for the petiole nitrate-N concentration, the 10 nm bands had the best performance (R2 = 0.87 and RMSE = 0.13). Generally, the model performance decreased with an increase of the spectral bandwidth. The hyperspectral full spectra largely outperformed all three multispectral cameras, but there was no significant difference among the three brands of multispectral cameras. The results also showed that spectral bands in the visible regions (400–700 nm) were the most highly correlated with potato N concentrations.
Ecosystem-Based Practices for Smallholders’ Adaptation to Climate Extremes: Evidence of Benefits and Knowledge Gaps in Latin America
Authors: Vignola Raffaele , Esquivel M. Jimena , Harvey Celia , Rapidel Bruno , Bautista-Solis Pavel , Alpizar Francisco , Donatti Camila , Avelino Jacques
Published: October 2022

Agricultural practices of smallholder farming systems of Latin America can play an important role in reducing their exposure to the risks associated with climate extremes. To date, however, there is no systematic analysis of scientific evidence for the extent to which these practices can provide the multiple benefits needed for smallholders to adapt to climate extremes. In this paper, we searched scientific databases to review scientific evidence of the benefit provided by twenty-six practices in crops commonly farmed by smallholders in the region and highly relevant for their food and nutrition security; namely, coffee, maize and beans. We reviewed scientific documents (n = 304) published in the period 1953–2021 to register evidence of the practices’ effects on fifty-five benefits. Our analysis of these documents found measurement records (n = 924) largely based on field experiments (85%). Our results show strong evidence of the multiple benefits that some ecosystem-based practices (e.g., tree-based practices for coffee and no tillage for maize) can provide to support the adaptation to climate extremes of smallholder farming systems and enhance a farm’s natural assets (e.g., biodiversity, water, soil). We also found that the majority of research on practices in the region focused more on the socioeconomic dimension (54%) rather than on the capacity of practices to improve the natural assets of a smallholder farmers or reduce the impact of climate extremes. Given these knowledge gaps, we discuss the importance of a renovated investment in research to address existing knowledge gaps. Our concluding suggestions for future research include the need for systematizing existing knowledge from different sources (e.g., peer-reviewed, gray literature, farmers, extension agencies, etc.), and to assess the extent to which these practices can provide multiple benefits for smallholder farming systems by improving their wellbeing, reducing their vulnerability to different hydroclimatic extremes while also contributing to ecosystem services provision at the landscape level.
Development of A Tool for Assessing the Reputation of Zoos: The Zoo Ethical Reputation Survey (ZERS)
Authors: Spiriti Maria Michela , Melchiori Francesco Maria , Dierkes Paul Wilhelm , Ferrante Linda , Bandoli Francesca , Biasetti Pierfrancesco , de Mori Barbara
Published: October 2022

Nowadays, most zoos have taken prominent and active positions in endangered species conservation and educating visitors about the value of biodiversity. However, to be effective and trusted in their mission, they must act ethically and have a good reputation. Yet, the drivers that can influence their reputation are still little investigated, and there are still few studies focused on assessing the reputation of these institutions. In the present work, we report the development of a tool, the Zoo Ethical Reputation Survey (ZERS), and its pilot application to assess the opinions of the visitors of two zoos, one in Italy and one in Germany, on drivers that may influence the ethical reputation of zoos. Preliminary results based on the answers of 274 respondents show that visitors’ opinions on zoos acting with ethical responsibility are correlated with emotional appeal and familiarity with these institutions. The application of ZERS can help zoos identify weaknesses in their reputation and develop new strategies to improve people’s attitudes towards them, bringing many benefits to the individual zoo and zoological institutions in general.
Are Marine Heatwaves Responsible for Mortalities of Farmed Mytilus galloprovincialis? A Pathophysiological Analysis of Marteilia Infected Mussels from Thermaikos Gulf, Greece
Authors: Lattos Athanasios , Papadopoulos Dimitrios K. , Feidantsis Konstantinos , Karagiannis Dimitrios , Giantsis Ioannis A. , Michaelidis Basile
Published: October 2022

Marine heatwaves (excessive seawater temperature increases) pose high risk to bivalves’ health and farming. The seawater temperature increase is responsible for various pathogen population expansions causing intense stress to marine organisms. Since the majority of knowledge so far derives from laboratory experiments, it is crucial to investigate stress responses in field conditions in order to understand the mechanisms leading to bivalves’ mortality events after exposure to temperature extremes. Thus, we evaluated the pathophysiological response of the Mediterranean mussel Mytilus galloprovincialis originating from mortality events enhanced by intense heatwaves in Thermaikos Gulf, north Greece, along with Marteilia refrigens infection. Mussels that have been exposed to high environmental stressors such as high temperature were examined for various molecular and biochemical markers, such as hsp70, bax, bcl-2, irak4 and traf6 gene expression, as well as the enzymatic activity of the hsp70, hsp90, bax, bcl-2, cleaved caspases, TNFa and ll-6 proteins. Furthermore, histopathology and molecular positivity to Marteilia sp. were addressed and correlated with the gene expression results. Our findings elucidate the molecular and biochemical pathways leading to mortality in farmed mussels in the context of Marteilia infection, which according to the results is multiplied by heatwaves causing a significant increase in pathophysiological markers.
Evaluation of Four Clinical Metrology Instruments for the Assessment of Osteoarthritis in Dogs
Authors: Alves João C. , Santos Ana , Jorge Patrícia , Lavrador Catarina , Carreira Luís Miguel
Published: October 2022

Osteoarthritis (OA) is the most commonly diagnosed joint disease in companion animals, and proper tools are necessary to assess patients and response to treatment. We aimed to perform the psychometric evaluation of several clinical metrology instruments (CMI), developed to evaluate pain and assess outcome. Fifty police working dogs with bilateral hip OA were assessed in a prospective, randomised, double-blinded study. Patients were evaluated using a stance analyser in six different moments divided over a 180-day period. Pedometer step count, weight-bearing symmetry index and deviation from normal weight-bearing were calculated and used for criterion validity. In each evaluation moment, a copy of the Hudson Visual Analogue Scale (HVAS), Canine Brief Pain Inventory (CBPI), Liverpool Osteoarthritis in Dogs (LOAD) and Canine Orthopaedic Index (COI) were completed by the dogs’ handlers. Correlations between CMIs were evaluated as construct validity. Further evaluation was performed with the Kaiser–Meyer–Olin measure of sampling adequacy, Eigenvalue and scree-plot analysis. Internal consistency was tested with Cronbach’s α. Significant weak correlation was found between all CMIs and stance analysis symmetry index measure and deviation, indicating criterion validity. Significant weak correlation was also found between pedometer count and LOAD plus COI. Cronbach’s α was 0.80 for HVAS, 0.98 for CBPI, 0.97 for LOAD and 0.98 for COI. Significant strong correlation was observed between CMIs, indicating construct validity. We present criterion and construct validity of these CMIs, which are able to capture various dimensions of OA. They can be used for the evaluation of osteoarthritis and response to treatment in dogs.
Heat Stress Increases Mammary Epithelial Cells and Reduces Viable Immune Cells in Milk of Dairy Cows
Authors: Lengi Andrea J. , Stewart Jacob W. , Makris Melissa , Rhoads Michelle L. , Corl Benjamin A.
Published: October 2022

Somatic cells normally found in milk are generally either immune cells such as lymphocytes, monocytes and granulocytes, or mammary epithelial cells. The number and composition of somatic cells in milk can be influenced by a variety of factors, including infection and temperature-humidity index. The objective of this study was to determine the specific effects of heat stress on the cellular composition of the somatic cell population in milk. We used flow cytometry to ascertain the concentration and viability of mammary epithelial cells, T cells, monocyte/macrophage, and granulocytes in milk from cows maintained under heat stressed conditions compared to thermoneutral conditions. We found a significant 10% increase in the natural log concentration of epithelial cells in the milk of heat stressed cows compared to thermoneutral cows (9.3 vs. 8.4 ln(cells/mL, p = 0.02)). We also found a 12% decrease in the log concentration of live CD45+ cells (p = 0.04), and a 17% decrease in the log concentration of live CD45+ granulocytes (p = 0.04). No changes were found in CD3+CD45+ cells or CD14+CD45+ cells, however, we noted an unusual population of CD14+CD45− cells that showed significant increases of 10% (p = 0.03) and 12% (p = 0.01) in the log concentration of total and dead cells, respectively, under heat stressed conditions. These results suggest that heat stress influences the relative populations and viability of some somatic cells populations in milk. Increased losses of secretory epithelial cells into milk could have implications for milk production, and fewer viable immune cells could negatively impact the immunocompetence of dairy cows under heat stress.
Influence of Different Base Materials on the Microstructure and Properties of Clad Rebar
Authors: Li Zhen , Tan Jianping , Qian Xuehai , Xiang Yong , Zeng Lei , Zhuang Zecheng
Published: October 2022

Clad rebars of four different base materials (20MnSiV, 35# steel, 45# steel, and 55# steel) were successfully produced by a vacuum hot rolling process. A metallographic optical microscope (OM), electron backscatter diffractometer (EBSD), electron probe micro-analyzer (EPMA), and salt spray corrosion chamber were used to investigate the clad contour, properties, and composite interface microstructure of all four rebars. The results demonstrated that the thickness of the clad layer in the 20MnSiV/316L rebar had a more uniform distribution than those in the 35#/316L rebar, 45#/316L rebar, and 55#/316L rebar because 20MnSiV was more similar to 316L stainless steel in terms of deformation tendency. As the carbon content in the base layer increased, the amount of chromium-rich carbides increased noticeably. These large amounts led to a deficiency of chromium in the rebar composite interface and reduced corrosion resistance. Furthermore, bonding performance tests revealed that the bonding strength of the rebar composite interface not only depended on the amount of chromium-rich carbides, but also on the grain size of the composite interface. The larger the grain size of the composite interface, the lower the bonding strength was.
Approximate Nonlocal Symmetries for a Perturbed Schrödinger Equation with a Weak Infinite Power-Law Memory
Authors: Lukashchuk Stanislav Yu.
Published: October 2022

A nonlocally perturbed linear Schrödinger equation with a small parameter was derived under the assumption of low-level fractionality by using one of the known general nonlocal wave equations with an infinite power-law memory. The problem of finding approximate symmetries for the equation is studied here. It has been shown that the perturbed Schrödinger equation inherits all symmetries of the classical linear equation. It has also been proven that approximate symmetries corresponding to Galilean transformations and projective transformations of the unperturbed equation are nonlocal. In addition, a special class of nonlinear, nonlocally perturbed Schrödinger equations that admits an approximate nonlocal extension of the Galilei group is derived. An example of constructing an approximately invariant solution for the linear equation using approximate scaling symmetry is presented.
A Review on the Technological Advances and Future Perspectives of Axon Guidance and Regeneration in Peripheral Nerve Repair
Authors: Tiwari Arjun Prasad , Lokai Taylor , Albin Bayne , Yang In Hong
Published: October 2022

Despite a significant advance in the pathophysiological understanding of peripheral nerve damage, the successful treatment of large nerve defects remains an unmet medical need. In this article, axon growth guidance for peripheral nerve regeneration was systematically reviewed and discussed mainly from the engineering perspective. In addition, the common approaches to surgery, bioengineering approaches to emerging technologies such as optogenetic stimulation and magnetic stimulation for functional recovery were discussed, along with their pros and cons. Additionally, clear future perspectives of axon guidance and nerve regeneration were addressed.
RTF-RCNN: An Architecture for Real-Time Tomato Plant Leaf Diseases Detection in Video Streaming Using Faster-RCNN
Authors: Alruwaili Madallah , Siddiqi Muhammad Hameed , Khan Asfandyar , Azad Mohammad , Khan Abdullah , Alanazi Saad
Published: October 2022

In today’s era, vegetables are considered a very important part of many foods. Even though every individual can harvest their vegetables in the home kitchen garden, in vegetable crops, Tomatoes are the most popular and can be used normally in every kind of food item. Tomato plants get affected by various diseases during their growing season, like many other crops. Normally, in tomato plants, 40–60% may be damaged due to leaf diseases in the field if the cultivators do not focus on control measures. In tomato production, these diseases can bring a great loss. Therefore, a proper mechanism is needed for the detection of these problems. Different techniques were proposed by researchers for detecting these plant diseases and these mechanisms are vector machines, artificial neural networks, and Convolutional Neural Network (CNN) models. In earlier times, a technique was used for detecting diseases called the benchmark feature extraction technique. In this area of study for detecting tomato plant diseases, another model was proposed, which was known as the real-time faster region convolutional neural network (RTF-RCNN) model, using both images and real-time video streaming. For the RTF-RCNN, we used different parameters like precision, accuracy, and recall while comparing them with the Alex net and CNN models. Hence the final result shows that the accuracy of the proposed RTF-RCNN is 97.42%, which is higher than the rate of the Alex net and CNN models, which were respectively 96.32% and 92.21%.
Applications of Immunomagnetic Reduction Technology as a Biosensor in Therapeutic Evaluation of Chinese Herbal Medicine in Tauopathy Alleviation of an AD Drosophila Model
Authors: Su Ming-Tsan , Lu Chen-Wen , Wu Wen-Jhen , Jheng Yong-Sin , Yang Shieh-Yueh , Chuang Wu-Chang , Lee Ming-Chung , Wu Chung-Hsin
Published: October 2022

Alzheimer’s disease (AD) is the most common form of dementia. The most convincing biomarkers in the blood for AD are currently β-amyloid (Aβ) and Tau protein because amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with AD. The development of assay technologies in diagnosing early-stage AD is very important. The study of human AD subjects is hindered by ethical and technical limitations. Thus, many studies have therefore turned to AD animal models, such as Drosophila melanogaster, to explore AD pathology. However, AD biomarkers such as Aβ and p-Tau protein in Drosophilamelanogaster occur at extremely low levels and are difficult to detect precisely. In this study, we applied the immunomagnetic reduction (IMR) technology of nanoparticles for the detection of p-Tau expressions in hTauR406W flies, an AD Drosophila model. Furthermore, we used IMR technology as a biosensor in the therapeutic evaluation of Chinese herbal medicines in hTauR406W flies with Tau-induced toxicity. To uncover the pathogenic pathway and identify therapeutic interventions of Chinese herbal medicines in Tau-induced toxicity, we modeled tauopathy in the notum of hTauR406W flies. Our IMR data showed that the selected Chinese herbal medicines can significantly reduce p-Tau expressions in hTauR406W flies. Using evidence of notal bristle quantification and Western blotting analysis, we confirmed the validity of the IMR data. Thus, we suggest that IMR can serve as a new tool for measuring tauopathy and therapeutic evaluation of Chinese herbal medicine in an AD Drosophila model.
Autophagy in Hematological Malignancies
Authors: García Ruiz Olga , Sánchez-Maldonado José Manuel , López-Nevot Miguel Ángel , García Paloma , Macauda Angelica , Hernández-Mohedo Francisca , González-Sierra Pedro Antonio , Martínez-Bueno Manuel , Pérez Eva , Reyes-Zurita Fernando Jesús , Campa Daniele , Canzian Federico , Jurado Manuel , Rodríguez-Sevilla Juan José , Sainz Juan
Published: October 2022

Autophagy is a highly conserved metabolic pathway via which unwanted intracellular materials, such as unfolded proteins or damaged organelles, are digested. It is activated in response to conditions of oxidative stress or starvation, and is essential for the maintenance of cellular homeostasis and other vital functions, such as differentiation, cell death, and the cell cycle. Therefore, autophagy plays an important role in the initiation and progression of tumors, including hematological malignancies, where damaged autophagy during hematopoiesis can cause malignant transformation and increase cell proliferation. Over the last decade, the importance of autophagy in response to standard pharmacological treatment of hematological tumors has been observed, revealing completely opposite roles depending on the tumor type and stage. Thus, autophagy can promote tumor survival by attenuating the cellular damage caused by drugs and/or stabilizing oncogenic proteins, but can also have an antitumoral effect due to autophagic cell death. Therefore, autophagy-based strategies must depend on the context to create specific and safe combination therapies that could contribute to improved clinical outcomes. In this review, we describe the process of autophagy and its role on hematopoiesis, and we highlight recent research investigating its role as a potential therapeutic target in hematological malignancies. The findings suggest that genetic variants within autophagy-related genes modulate the risk of developing hemopathies, as well as patient survival.
Identification of EGFR-Related LINC00460/mir-338-3p/MCM4 Regulatory Axis as Diagnostic and Prognostic Biomarker of Lung Adenocarcinoma Based on Comprehensive Bioinformatics Analysis and Experimental Validation
Authors: Jia Mingxi , Feng Shanshan , Cao Fengxi , Deng Jing , Li Wen , Zhou Wangyan , Liu Xiang , Bai Weidong
Published: October 2022

Background: Lung adenocarcinoma (LUAD) is one of the most aggressive and lethal tumor types and requires effective diagnostic and therapeutic targets. Though the epidermal growth factor receptor (EGFR) is an important target for LUAD therapy, acquired resistance is still inevitable. In recent years, the regulation of the EGFR by competing endogenous RNAs (ceRNAs) has been extensively studied and significant progress has been made. Therefore, we aim to find new targets for the diagnosis and treatment of LUAD by analyzing the EGFR-related ceRNA network in LUAD and expect to address the problem of EGFR resistance. Methods: We identified differentially expressed lncRNAs, miRNAs and mRNAs closely associated with the EGFR by analyzing transcriptome data from LUAD samples. Comprehensive bioinformatics analysis strongly suggests that the LINC00460—mir-338-3p—MCM4 ceRNA network plays an important role in the diagnosis and prognosis of LUAD. The effects of different patterns of the LINC00460/MCM4 axis on the overall survival of patients with LUAD were analyzed by a polygene regulation model. We also verified the expression of these genes in LUAD cell lines and tumor tissues by RT-PCR and immunohistochemistry. The functional enrichment analysis and targeted drug prediction of the MCM4 gene were performed. Results: Survival analysis indicated that high expressions of LINC00460 and MCM4 predict a shorter survival period for patients. Univariate and multivariate regression analyses demonstrated that higher expressions of LINC00460 and MCM4 were significantly associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. A multi-gene regulation model analysis revealed that the LINC00460 (downregulation)—mir-338-3p (upregulation)—MCM4 (downregulation) pattern significantly improved the overall survival of LUAD patients (p = 0.0093). RT-PCR and immunohistochemical experiments confirmed our analytical results. In addition, the functional enrichment analysis indicated that MCM4-related genes were mainly enriched in the cell cycle and cell division. A functional association network analysis showed that MCM4 was closely related to the EGFR. Finally, the possible targeted drugs of MCM4 were queried through the drug database platform, hoping to solve its drug resistance problem by targeting EGFR-related genes. Conclusions: In summary, the LINC00460/MCM4 axis can be used as a potential new perspective for targeting EGFR genes in precision medicine and is expected to serve as a diagnostic, prognostic and drug target for LUAD.
Efficient Synthesis with Green Chemistry Approach of Novel Pharmacophores of Imidazole-Based Hybrids for Tumor Treatment: Mechanistic Insights from In Situ to In Silico
Authors: Khan Majid , Shah Syed Raza , Khan Faizullah , Halim Sobia Ahsan , Rahman Shaikh Mizanoor , Khalid Mohammad , Khan Ajmal , Al-Harrasi Ahmed
Published: October 2022

Imidazole-based pyrimidine hybrids are considered a remarkable class of compounds in pharmaceutical chemistry. Here, we report the anticancer bioactivities of eleven imidazole-based pyrimidine hybrids (1–11) that specifically target cytosolic carbonic anhydrase (CAs) isoenzymes, including human CA-II and human CA-IX (hCA-II, and hCA-IX). A highly eco-friendly aqueous approach was used for the formation of a carbon–carbon bond by reacting aromatic nitro group substitution of nitroimidazoles with carbon nucleophiles. The in vitro results indicate that this new class of compounds (1–11) includes significant inhibitors of hCA IX with IC50 values in the range of 9.6 ± 0.2–32.2 ± 1.0 µM, while hCA II showed IC50 values in range of 11.6 ± 0.2–31.1 ± 1.3 µM. Compound 2 (IC50 = 12.3 ± 0.1 µM) showed selective inhibition for hCA-II while 7, 8, and 10 (IC50 = 9.6–32.2 µM) were selective for hCA-IX. The mechanism of action was investigated through in vitro kinetics studies that revealed that compounds 7, 3, 11, 10, 4, and 9 for CA-IX and 1, 2, and 11 for CA-II are competitive inhibitors with dissociation constant (Ki) in the range of 7.32–17.02 µM. Furthermore, the in situ cytotoxicity of these compounds was investigated in the human breast cancer cell line MDA-MB-231 and compared with the normal human breast cell line, MCF-10A. Compound 5 showed excellent anticancer/cytotoxic activity in MDA-MB-231 with no toxicity to the normal breast cells. In addition, in silico molecular docking was employed to predict the binding mechanism of active compounds with their targets. This in silico observation aligned with our experimental results. Our findings signify that imidazole-based hybrids could be a useful choice to design anticancer agents for breast and lung tumors, or antiglaucoma compounds, by specific inhibition of carbonic anhydrases.
Long-Term IGF1 Stimulation Leads to Cellular Senescence via Functional Interaction with the Thioredoxin-Interacting Protein, TXNIP
Authors: Nagaraj Karthik , Sarfstein Rive , Laron Zvi , Werner Haim
Published: October 2022

The growth hormone (GH)–insulin-like growth factor-1 (IGF1) signaling pathway plays a major role in orchestrating cellular interactions, metabolism, growth and aging. Studies from worms to mice showed that downregulated activity of the GH/IGF1 pathway could be beneficial for the extension of lifespan. Laron syndrome (LS) is an inherited autosomal recessive disorder caused by molecular defects of the GH receptor (GHR) gene, leading to congenital IGF1 deficiency. Life-long exposure to minute endogenous IGF1 levels in LS is associated with low stature as well as other endocrine and metabolic deficits. Epidemiological surveys reported that patients with LS have a reduced risk of developing cancer. Studies conducted on LS-derived lymphoblastoid cells led to the identification of a novel link between IGF1 and thioredoxin-interacting protein (TXNIP), a multifunctional mitochondrial protein. TXNIP is highly expressed in LS patients and plays a critical role in cellular redox regulation by thioredoxin. Given that IGF1 affects the levels of TXNIP under various stress conditions, including high glucose and oxidative stress, we hypothesized that the IGF1–TXNIP axis plays an essential role in helping maintain a physiological balance in cellular homeostasis. In this study, we show that TXNIP is vital for the cell fate choice when cells are challenged by various stress signals. Furthermore, prolonged IGF1 treatment leads to the establishment of a premature senescence phenotype characterized by a unique senescence network signature. Combined IGF1/TXNIP-induced premature senescence can be associated with a typical secretory inflammatory phenotype that is mediated by STAT3/IL-1A signaling. Finally, these mechanistic insights might help with the understanding of basic aspects of IGF1-related pathologies in the clinical setting.
Metabolic Advantage of 25(OH)D3 versus 1,25(OH)2D3 Supplementation in Infantile Nephropathic Cystinosis-Associated Adipose Tissue Browning and Muscle Wasting
Authors: Zhou Ping , Cheung Wai W. , Gonzalez Alex , Vaddi Venya , Oliveira Eduardo A. , Mak Robert H.
Published: October 2022

Manifestations of infantile nephropathic cystinosis (INC) often include cachexia and deficiency of circulating vitamin D metabolites. We examined the impact of 25(OH)D3 versus 1,25(OH)2D3 repletion in Ctns null mice, a mouse model of INC. Six weeks of intraperitoneal administration of 25(OH)D3 (75 μg/kg/day) or 1,25(OH)2D3 (60 ng/kg/day) resulted in Ctns−/− mice corrected low circulating 25(OH)D3 or 1,25(OH)2D3 concentrations. While 25(OH)D3 administration in Ctns−/− mice normalized several metabolic parameters characteristic of cachexia as well as muscle function in vivo, 1,25(OH)2D3 did not. Administration of 25(OH)D3 in Ctns−/− mice increased muscle fiber size and decreased fat infiltration of skeletal muscle, which was accompanied by a reduction of abnormal muscle signaling pathways. 1,25(OH)2D3 administration was not as effective. In conclusion, 25(OH)D3 supplementation exerts metabolic advantages over 1,25(OH)2D3 supplementation by amelioration of muscle atrophy and fat browning in Ctns−/− mice.
Microstructural Characteristics of 3Y-TZP Ceramics and Their Effects on the Flexural Strength
Authors: Alves Manuel Fellipe Rodrigues Pais , de Campos Leonardo Queiroz Bueno , Simba Bruno Galvão , da Silva Cosme Roberto Moreira , Strecker Kurt , dos Santos Claudinei
Published: October 2022

This work evaluates the effects of grain growth and tetragonality of the t-ZrO2 phase on the mechanical properties of 3Y-TZP ceramics. Samples were sintered at 1475 °C for 2 h, and at 1600 °C for 2, 12, or 24 h. After sintering, the tetragonal ZrO2 polytypes t and t′ were observed under all sintering conditions, while a residual content of monoclinic ZrO2 was detected in samples sintered at 1600 °C for 24 h. The average grain size was found to vary from 0.65 ± 0.10 to 2.20 ± 0.35 μm. Moreover, zirconia ceramics sintered at 1475 °C for 2 h exhibit higher flexural strength (1210 ± 85 MPa), while samples sintered at 1600 °C for 24 h exhibit the lowest flexural strength (910 ± 90 MPa). These results were related to the progressive formation of Y3+-rich grains (t′-ZrO2) due to the grain boundary segregation-induced phase (GBSIPT) mechanism. Due to the high stabilizer concentration in the solid solution, these grains present lower tetragonality, being highly stable at room temperature. Consequently, the observed strength reduction of samples sintered at 1600 °C for 24 h is related to the presence of the t′-ZrO2 phase, which is less prompt to the phase transformation toughening process, limiting shielding zones’ effectiveness at the crack tip.
Ru-Doped PtTe2 Monolayer as a Promising Exhaled Breath Sensor for Early Diagnosis of Lung Cancer: A First-Principles Study
Authors: Wan Qianqian , Chen Xiaoqi , Xiao Song
Published: October 2022

Using the first-principles theory, the geometric and electronic properties of the Ru-doped PtTe2 (Ru-PtTe2) monolayer, and its sensing performance for three VOCs biomarkers, namely, 2-propenal (C3H4O), acetone (C3H6O) and isoprene (C5H8), were analyzed, to expound its potential for exhaled breath analysis and diagnosis of lung cancer. It was found that the Ru-substitution on the surface of the pristine PtTe2 surface with a Te atom is energy-favorable, with the formation energy of −1.22 eV. Upon adsorption of the three VOC gas species, chemisorption was identified with the adsorption energies of −1.72, −1.12 and −1.80 eV for C3H4O, C3H6O and C5H8, respectively. The Ru-doping results in a strong magnetic property for the PtTe2 monolayer, whereas the gas adsorption eliminates this magnetic behavior. The electronic properties reveal the sensing mechanism of the Ru-PtTe2 monolayer for gas detection, and the bandgap change indicates its admirable positive sensing response for the three gas species. Therefore, we conclude that the Ru-PtTe2 monolayer is a promising sensing material to realize the diagnosis of lung cancer through exhaled gas detection, with a remarkable decrease in its electrical conductivity. This work paves the way for further exploration of the PtTe2-based gas sensor for early diagnosis of lung cancer, and we hope that more sensing materials can be investigated using the PtTe2 monolayer.
Gas Sensitivity of IBSD Deposited TiO2 Thin Films
Authors: Almaev Aleksei V. , Yakovlev Nikita N. , Kushnarev Bogdan O. , Kopyev Viktor V. , Novikov Vadim A. , Zinoviev Mikhail M. , Yudin Nikolay N. , Podzivalov Sergey N. , Erzakova Nadezhda N. , Chikiryaka Andrei V. , Shcheglov Mikhail P. , Baalbaki Houssain , Olshukov Alexey S.
Published: October 2022

TiO2 films of 130 nm and 463 nm in thickness were deposited by ion beam sputter deposition (IBSD), followed by annealing at temperatures of 800 °C and 1000 °C. The effect of H2, CO, CO2, NO2, NO, CH4 and O2 on the electrically conductive properties of annealed TiO2 thin films in the operating temperature range of 200–750 °C were studied. The prospects of IBSD deposited TiO2 thin films in the development of high operating temperature and high stability O2 sensors were investigated. TiO2 films with a thickness of 130 nm and annealed at 800 °C demonstrated the highest response to O2, of 7.5 arb.un. when exposed to 40 vol. %. An increase in the annealing temperature of up to 1000 °C at the same film thickness made it possible to reduce the response and recovery by 2 times, due to changes in the microstructure of the film surface. The films demonstrated high sensitivity to H2 and nitrogen oxides at an operating temperature of 600 °C. The possibility of controlling the responses to different gases by varying the conditions of their annealing and thicknesses was shown. A feasible mechanism for the sensory effect in the IBSD TiO2 thin films was proposed and discussed.
Flow of Maxwell Fluid with Heat Transfer through Porous Medium with Thermophoresis Particle Deposition and Soret–Dufour Effects: Numerical Solution
Authors: AL Nuwairan Muneerah , Hafeez Abdul , Khalid Asma , Souayeh Basma , Alfadhli Norah , Alnaghmosh Aminh
Published: October 2022

In this paper, we study the magnetohydrodynamics of Darcy flow in a non-Newtonian liquid. The influence of thermophoresis on particle deposition is examined in the Darcy flow of a Maxwell nanofluid. In our model, the temperature distribution is generated by the Fourier law of heat conduction with nonlinear thermal radiation and heat sink/source. We also examine the Soret–Dufour effects in the mass concentration equations. The Brownian and thermophoretic diffusions are assumed to be generated by nanoparticle dispersion in the fluid. The similarity method is used to transform the partial differential equations into nonlinear ordinary differential equations. The transformed flow equations were solved numerically using the BVP Midrich scheme. The results of the computation are displayed graphically and in tabular form. The results obtained show that increasing the Deborah number leads to a decline in radial and angular motion and a decrease in the magnitude of axial flow. As expected, the strength of the heat source and the values of the thermal radiation parameters determine the temperature of the liquid. We also found that as the Soret number rises (or the Dufour number falls), so does the mass transfer rate.
Unfolded Lipase at Interfaces Studied via Interfacial Dilational Rheology: The Impact of Urea
Authors: Dowlati Saeid , Javadi Aliyar , Miller Reinhard , Eckert Kerstin , Kraume Matthias
Published: October 2022

Unfolding can interrupt the activity of enzymes. Lipase, the enzyme responsible for triglyceride catalysis, can be deactivated by unfolding, which can significantly affect the yield of enzymatic processes in biochemical engineering. Different agents can induce lipase unfolding, among which we study the impact of urea as a strong denaturant. Unfolding weakens the rigidity and stability of globular proteins, thereby changing the viscoelastic properties of the protein adsorbed layers. These changes can be detected and quantified using interfacial dilational rheology. The urea-induced unfolding of lipase destructs its globular structure, making it more flexible. The interfacial tension and viscoelastic moduli of lipase adsorbed layers reduce upon the addition of urea in the range of studied concentrations. The results agree with the theory that, upon unfolding, a distal region of the loop and tail domain forms adjacent to the proximal region of the interface. The exchange of matter between these regions reduces the viscoelasticity of the unfolded lipase adsorbed layers. Additionally, unfolding reduces the rigidity and brittleness of the lipase adsorbed layers: the aged adsorbed layer of native lipase can break upon high-amplitude perturbations of the interfacial area, unlike the case for urea-induced unfolded lipase.
Development of Enzyme-Based Cosmeceuticals: Studies on the Proteolytic Activity of Arthrospira platensis and Its Efficient Incorporation in a Hydrogel Formulation
Authors: Ioannou Elisavet , Labrou Nikolaos E.
Published: October 2022

Microalgae are a valuable source of enzymes and active ingredients due to their biochemical variability, health-beneficial properties, lower production cost and viability on an industrial scale. In addition, the growing demand for sustainable products constitutes microalgae as a viable resource for the development of a range of innovative products. In the present work, the proteolytic activity of Arthrospira platensis lysate was assessed and characterized using kinetics analysis and zymography employing different substrates, pH values and divalent ions. The results suggest the presence of two main proteolytic enzymes in the lysate. In addition, a rapid and easy purification protocol of the proteolytic activity, under mild conditions, was developed using a polyethyleneglycol (PEG)/phosphate aqueous two-phase system (ATPS). The proteolytic activity of A. platensis lysate was used to develop a hydrogel formulation as an enzyme-based cosmeceutical, with potential application as a topical exfoliating agent. The incorporation of the A. platensis extract in the developed hydrogel formulation significantly improved its operational stability over time, which is a significant advantage in enzyme-based product development.
Complications and Risk Factors in En Bloc Resection of Spinal Tumors: A Retrospective Analysis on 298 Patients Treated in a Single Institution
Authors: Bandiera Stefano , Noli Luigi Emanuele , Griffoni Cristiana , Tosini Giovanni , Carretta Elisa , Pasini Stefano , Pesce Eleonora , Ruinato Alfio Damiano , Barbanti Brodano Giovanni , Tedesco Giuseppe , Girolami Marco , Terzi Silvia , Ghermandi Riccardo , Evangelisti Gisberto , Pipola Valerio , Gasbarrini Alessandro
Published: October 2022

En bloc resection consists in the surgical removal of a vertebral tumor in a single piece with a sufficient margin, to improve survival and reduce recurrence rate. This procedure is technically demanding and correlates with a high complication rate. The purpose of this study is to investigate the risk factors for complications in en bloc resection and evaluate if benefits overcome the risks in term of overall survival. We retrospectively analyzed prospectively collected data of patients treated with en bloc resection between 1980 and 2021. Complications were classified according to SAVES-V2. Overall Survival was estimated using Kaplan-Meier method. A total of 149 patients out of 298 (50%) suffered from at least one complication. Moreover, 220 adverse events were collected (67 intraoperative, 82 early post-operative, 71 late post-operative), 54% of these were classified as grade 3 (in a severity scale from 1 to 6). Ten years overall survival was 67% (95% CI 59–74). The occurrence of relapses was associated to an increased risk of mortality with OR 3.4 (95% CI 2.1–5.5), while complications did not affect the overall survival. Despite a high complication rate, en bloc resection allows for a better control of disease and should be performed in selected patients by specialized surgeons.
Effects of Different Forest Gap Ages on Soil Physical Properties and Stoichiometric Characteristics in Cryptomeria japonica plantations (L.f.) D.Don, 1839
Authors: Xiao Tingqi , Wang Chen , Yuan Xi , Tao Lingjian , Li Peng , Deng Wenping , Liu Yuanqiu
Published: October 2022

In this study, the evergreen plant Cryptomeria japonica (L.f.) D.Don, 1839 forest gap in the subtropical region of China were taken as the research object. The effects of different forest gap ages (<10 years, 10–20 years, >20 years) on soil physical properties and stoichiometric characteristics were analyzed in Lushan Mountain, China. With the increase of forest gap ages, the physical properties of soil surface layer in forest gap were improved, and the water holding capacity of soil was enhanced. The capillary porosity and total porosity of soil increased significantly, and the soil bulk density of 10–20 cm soil layer decreased. The increase of forest gap recovery years is beneficial to the increase of large particle size soil aggregates, and the increase of large particle size aggregates has a good effect on improving soil structure. The contents of carbon (C), nitrogen (N), and phosphorus (P) in soil showed an overall increasing trend with the increase of forest gap age and were significantly higher than those of Cryptomeria japonica pure forest (p < 0.05). The nutrient content of forest gap in 10–20 years was the highest, and the nutrient content of 0–10 cm soil layer was generally higher than that of 0–20 cm soil layer. The C:P and N:P in the soil showed an overall decreasing trend, while C:N was significantly smaller than other age gaps in 10–20 years. The results showed that soil physical properties and stoichiometric characteristics were improved with the increase of forest gap ages.
Numerical Investigation of a Class of Nonlinear Time-Dependent Delay PDEs Based on Gaussian Process Regression
Authors: Gu Wei , Zhang Wenbo , Han Yaling
Published: October 2022

Probabilistic machine learning and data-driven methods gradually show their high efficiency in solving the forward and inverse problems of partial differential equations (PDEs). This paper will focus on investigating the forward problem of solving time-dependent nonlinear delay PDEs with multi-delays based on multi-prior numerical Gaussian processes (MP-NGPs), which are constructed by us to solve complex PDEs that may involve fractional operators, multi-delays and different types of boundary conditions. We also quantify the uncertainty of the prediction solution by the posterior distribution of the predicted solution. The core of MP-NGPs is to discretize time firstly, then a Gaussian process regression based on multi-priors is considered at each time step to obtain the solution of the next time step, and this procedure is repeated until the last time step. Different types of boundary conditions are studied in this paper, which include Dirichlet, Neumann and mixed boundary conditions. Several numerical tests are provided to show that the methods considered in this paper work well in solving nonlinear time-dependent PDEs with delay, where delay partial differential equations, delay partial integro-differential equations and delay fractional partial differential equations are considered. Furthermore, in order to improve the accuracy of the algorithm, we construct Runge–Kutta methods under the frame of multi-prior numerical Gaussian processes. The results of the numerical experiments prove that the prediction accuracy of the algorithm is obviously improved when the Runge–Kutta methods are employed.