bluuebunny/crossref_metadata_2025 huggingface dataset:
A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation
Authors: Fernández-Aguilar Luis M. , Vico-Barranco Inmaculada , Arbulo-Echevarria Mikel M. , Aguado Enrique
Published: August 2023

Specific antigen recognition is one of the immune system’s features that allows it to mount intense yet controlled responses to an infinity of potential threats. T cells play a relevant role in the host defense and the clearance of pathogens by means of the specific recognition of peptide antigens presented by antigen-presenting cells (APCs), and, to do so, they are equipped with a clonally distributed antigen receptor called the T-cell receptor (TCR). Upon the specific engagement of the TCR, multiple intracellular signals are triggered, which lead to the activation, proliferation and differentiation of T lymphocytes into effector cells. In addition, this signaling cascade also operates during T-cell development, allowing for the generation of cells that can be helpful in the defense against threats, as well as preventing the generation of autoreactive cells. Early TCR signals include phosphorylation events in which the tyrosine kinases Lck and ZAP70 are involved. The sequential activation of these kinases leads to the phosphorylation of the transmembrane adaptor LAT, which constitutes a signaling hub for the generation of a signalosome, finally resulting in T-cell activation. These early signals play a relevant role in triggering the development, activation, proliferation and apoptosis of T cells, and the negative regulation of these signals is key to avoid aberrant processes that could generate inappropriate cellular responses and disease. In this review, we will examine and discuss the roles of the tyrosine kinases Lck and ZAP70 and the membrane adaptor LAT in these cellular processes.
Synthesis of Pore-Size-Tunable Porous Silica Particles and Their Effects on Dental Resin Composites
Authors: Chen Hongyan , Luo Jiaxin , Yang Jiawei , Zeng Chen , Jiang Xinquan
Published: August 2023

The filler/resin matrix interface interaction plays a vital role in the properties of dental resin composites (DRCs). Porous particles are promising fillers due to their potential in constructing micromechanical interlocking at filler/resin matrix interfaces, therefore improving the properties of the resulting DRCs, where the pore size is significantly important. However, how to control the pore size of porous particles via a simple synthesis method is still a challenge, and how their pore sizes affect the properties of resulting DRCs has not been studied. In this study, porous silica (DPS) with a dendritic structure and an adjustable pore size was synthesized by changing the amounts of catalyst in the initial microemulsion. These synthesized DPS particles were directly used as unimodal fillers and mixed with a resin matrix to formulate DRCs. The results showed that the DPS pore size affects the properties of DRCs, especially the mechanical property. Among various DPS particles with different pore sizes, DPS6 resulted in 19.5% and 31.4% improvement in flexural strength, and 24.4% and 30.7% enhancement in compression strength, respectively, compared to DPS1 and DPS9. These DPS particles could help to design novel dental restorative materials and have promising applications in biomedicine, catalysis, and adsorption.
Lipid Peroxidation and Antioxidant Protection
Authors: Valgimigli Luca
Published: August 2023

Lipid peroxidation (LP) is the most important type of oxidative-radical damage in biological systems, owing to its interplay with ferroptosis and to its role in secondary damage to other biomolecules, such as proteins. The chemistry of LP and its biological consequences are reviewed with focus on the kinetics of the various processes, which helps understand the mechanisms and efficacy of antioxidant strategies. The main types of antioxidants are discussed in terms of structure–activity rationalization, with focus on mechanism and kinetics, as well as on their potential role in modulating ferroptosis. Phenols, pyri(mi)dinols, antioxidants based on heavy chalcogens (Se and Te), diarylamines, ascorbate and others are addressed, along with the latest unconventional antioxidant strategies based on the double-sided role of the superoxide/hydroperoxyl radical system.
Application of Three Compounds Extracted from Cynodon dactylon against Streptococcus mutans Biofilm Formation to Prevent Oral Diseases
Authors: Habib Tasnia , Rahman Aminur , Nair Anroop B. , Islam S. M. Shahinul
Published: August 2023

Streptococcus mutans bacteria form a biofilm called plaque that causes oral diseases, including tooth decay. Therefore, inhibition of biofilm formation is essential to maintaining good oral health. The health and nutritional benefits of Cynodon dactylon are well documented, but very little is known about its use to treat against oral diseases. The aim of this study was to detect the adhesion strength of the S. mutans bacterial biofilm in 100 cases in the Rajshahi region and evaluate the inhibitory activity of different compound extracts of C. dactylon on the S. mutans bacterial biofilm by determining the composition of isolated compounds using phytochemical analysis. Nuclear magnetic resonance (NMR) spectroscopy confirmed that three specific compounds from C. dactylon were discovered in this study: 3,7,11,15 tetramethyl hexadec-2-4dien 1-o1, compound 3,7,11,15 tetramethylhexadec-2-en-1-o1 from phytol derivatives, and stigmasterol. Results indicated that the compound of 3,7,11,15-tetramethyl-hexadec-2-en-1-ol exhibited higher antibiofilm activities on S. mutans than those of the other compound extracts. A lower level of minimum inhibitory concentration was exposed by 3, 7, 11,15 tetramethyl hexadeca-2-en-1-o1 (T2) on S. mutans at 12.5 mL. In this case, the compound of 3,7,11,15 tetramethyl hexadec 2en-1-o1 was used, and patients showed a mean value and standard error reduced from 3.42 ± 0.21 to 0.33 ± 0.06 nm. The maximum inhibition was (80.10%) in the case of patient no. 17, with a value of p < 0.05 found for S. mutans to which 12.5 μL/mL ethyl acetate extract was applied. From these findings, it may be concluded that C. dactylon extracts can be incorporated into various oral preparations to prevent tooth decay.
Establishment of a Rat Model of Alcoholic Liver Fibrosis with Simulated Human Drinking Patterns and Low-Dose Chemical Stimulation
Authors: Lin Chien-Yu , Omoscharka Evanthia , Liu Yanli , Cheng Kun
Published: August 2023

Although alcohol is a well-known causal factor associated with liver diseases, challenges remain in inducing liver fibrosis in experimental rodent models. These challenges include rodents’ natural aversion to high concentrations of alcohol, rapid alcohol metabolism, the need for a prolonged duration of alcohol administration, and technical difficulties. Therefore, it is crucial to establish an experimental model that can replicate the features of alcoholic liver fibrosis. The objective of this study was to develop a feasible rat model of alcoholic liver fibrosis that emulates human drinking patterns and combines low-dose chemicals within a relatively short time frame. We successfully developed an 8-week rat model of alcoholic liver fibrosis that mimics chronic and heavy drinking patterns. Rats were fed with a control liquid diet, an alcohol liquid diet, or alcohol liquid diet combined with multiple binges via oral gavage. To accelerate the progression of alcoholic liver fibrosis, we introduced low-dose carbon tetrachloride (CCl4) through intraperitoneal injection. This model allows researchers to efficiently evaluate potential therapeutics in preclinical studies of alcoholic liver fibrosis within a reasonable time frame.
Peroxisomal NAD(H) Homeostasis in the Yeast Debaryomyces hansenii Depends on Two Redox Shuttles and the NAD+ Carrier, Pmp47
Authors: Turkolmez Selva , Chornyi Serhii , Alhajouj Sondos , IJlst Lodewijk , Waterham Hans R. , Mitchell Phil J. , Hettema Ewald H. , van Roermund Carlo W. T.
Published: August 2023

Debaryomyces hansenii is considered an unconventional yeast with a strong biotechnological potential, which can produce and store high amounts of lipids. However, relatively little is known about its lipid metabolism, and genetic tools for this yeast have been limited. The aim of this study was to explore the fatty acid β-oxidation pathway in D. hansenii. To this end, we employed recently developed methods to generate multiple gene deletions and tag open reading frames with GFP in their chromosomal context in this yeast. We found that, similar as in other yeasts, the β-oxidation of fatty acids in D. hansenii was restricted to peroxisomes. We report a series of experiments in D. hansenii and the well-studied yeast Saccharomyces cerevisiae that show that the homeostasis of NAD+ in D. hansenii peroxisomes is dependent upon the peroxisomal membrane protein Pmp47 and two peroxisomal dehydrogenases, Mdh3 and Gpd1, which both export reducing equivalents produced during β-oxidation to the cytosol. Pmp47 is the first identified NAD+ carrier in yeast peroxisomes.
Regulation of Phosphoinositide Signaling by Scaffolds at Cytoplasmic Membranes
Authors: Wen Tianmu , Thapa Narendra , Cryns Vincent L. , Anderson Richard A.
Published: August 2023

Cytoplasmic phosphoinositides (PI) are critical regulators of the membrane–cytosol interface that control a myriad of cellular functions despite their low abundance among phospholipids. The metabolic cycle that generates different PI species is crucial to their regulatory role, controlling membrane dynamics, vesicular trafficking, signal transduction, and other key cellular events. The synthesis of phosphatidylinositol (3,4,5)-triphosphate (PI3,4,5P3) in the cytoplamic PI3K/Akt pathway is central to the life and death of a cell. This review will focus on the emerging evidence that scaffold proteins regulate the PI3K/Akt pathway in distinct membrane structures in response to diverse stimuli, challenging the belief that the plasma membrane is the predominant site for PI3k/Akt signaling. In addition, we will discuss how PIs regulate the recruitment of specific scaffolding complexes to membrane structures to coordinate vesicle formation, fusion, and reformation during autophagy as well as a novel lysosome repair pathway.
TRIM6: An Upregulated Biomarker with Prognostic Significance and Immune Correlations in Gliomas
Authors: Guo Jianrong , Feng Shoucheng , Liu Hong , Chen Zhuopeng , Ding Chao , Jin Yukai , Chen Xiaojiang , Ling Yudong , Zeng Yi , Long Hao , Qiu Haibo
Published: August 2023

This study investigates the expression and prognostic value of TRIM6 in gliomas, the most prevalent primary brain and spinal cord tumors. Our results show that TRIM6 is predominantly overexpressed in glioma tissues and is associated with reduced overall survival, disease-specific survival, and progression-free interval. Furthermore, TRIM6 expression is correlated with WHO grade and primary treatment outcomes. Functional analysis indicates that interactions between cytokines and their receptors play a critical role in the prognosis of glioma patients. A protein-protein interaction network reveals 10 hub genes closely linked to cytokine-cytokine receptor interaction. In vitro experiments demonstrate that silencing TRIM6 impairs the proliferation, invasion, and migration of glioma cells, while overexpressing TRIM6 enhances these abilities. Additionally, TRIM6 expression is positively associated with the abundance of innate immune cells and negatively associated with the abundance of adaptive immune cells. In summary, TRIM6 is significantly upregulated in gliomas and linked to poor prognosis, making it a potential diagnostic and prognostic biomarker. TRIM6 plays a crucial role in promoting cell viability, clonogenic potential, migration, and invasion in glioma cells. It may regulate glioma progression by modulating cytokine-cytokine receptor interaction, leading to an inflammatory response and an imbalance in immunomodulation, thereby representing a potential therapeutic target.
Information Flow between Parents and Offspring Is Essential for Successful Development
Authors: Holt William V. , Gadea Joaquin
Published: August 2023

Over the last several decades, the sciences of developmental biology and physiology have expanded and intertwined their scope enormously [...]
Towards Improved Human In Vitro Models for Cardiac Arrhythmia: Disease Mechanisms, Treatment, and Models of Atrial Fibrillation
Authors: Cofiño-Fabres Carla , Passier Robert , Schwach Verena
Published: August 2023

Heart rhythm disorders, arrhythmias, place a huge economic burden on society and have a large impact on the quality of life of a vast number of people. Arrhythmias can have genetic causes but primarily arise from heart tissue remodeling during aging or heart disease. As current therapies do not address the causes of arrhythmias but only manage the symptoms, it is of paramount importance to generate innovative test models and platforms for gaining knowledge about the underlying disease mechanisms which are compatible with drug screening. In this review, we outline the most important features of atrial fibrillation (AFib), the most common cardiac arrhythmia. We will discuss the epidemiology, risk factors, underlying causes, and present therapies of AFib, as well as the shortcomings and opportunities of current models for cardiac arrhythmia, including animal models, in silico and in vitro models utilizing human pluripotent stem cell (hPSC)-derived cardiomyocytes.
RUNX1-Regulated Signaling Pathways in Ovarian Cancer
Authors: Chen Yuanzhi , He Yingying , Liu Shubai
Published: August 2023

Ovarian cancer is the leading cause of gynecological death worldwide, and its poor prognosis and high mortality seriously affect the life of ovarian cancer patients. Runt-related transcription factor 1 (RUNX1) has been widely studied in hematological diseases and plays an important role in the occurrence and development of hematological diseases. In recent years, studies have reported the roles of RUNX1 in solid tumors, including the significantly increased expression of RUNX1 in ovarian cancer. In ovarian cancer, the dysregulation of the RUNX1 signaling pathway has been implicated in tumor progression, metastasis, and response to therapy. At the same time, the decreased expression of RUNX1 in ovarian cancer can significantly improve the sensitivity of clinical chemotherapy and provide theoretical support for the subsequent diagnosis and treatment target of ovarian cancer, providing prognosis and treatment options to patients with ovarian cancer. However, the role of RUNX1 in ovarian cancer remains unclear. Therefore, this article reviews the relationship between RUNX1 and the occurrence and development of ovarian cancer, as well as the closely regulated signaling pathways, to provide some inspiration and theoretical support for future research on RUNX1 in ovarian cancer and other diseases.
The Role of miRNA in Renal Fibrosis Leading to Chronic Kidney Disease
Authors: Gluba-Sagr Anna , Franczyk Beata , Rysz-Górzyńska Magdalena , Ławiński Janusz , Rysz Jacek
Published: August 2023

Chronic kidney disease (CKD) is an important health concern that is expected to be the fifth most widespread cause of death worldwide by 2040. The presence of chronic inflammation, oxidative stress, ischemia, etc., stimulates the development and progression of CKD. Tubulointerstitial fibrosis is a common pathomechanism of renal dysfunction, irrespective of the primary origin of renal injury. With time, fibrosis leads to end-stage renal disease (ESRD). Many studies have demonstrated that microRNAs (miRNAs, miRs) are involved in the onset and development of fibrosis and CKD. miRNAs are vital regulators of some pathophysiological processes; therefore, their utility as therapeutic agents in various diseases has been suggested. Several miRNAs were demonstrated to participate in the development and progression of kidney disease. Since renal fibrosis is an important problem in chronic kidney disease, many scientists have focused on the determination of miRNAs associated with kidney fibrosis. In this review, we present the role of several miRNAs in renal fibrosis and the potential pathways involved. However, as well as those mentioned above, other miRs have also been suggested to play a role in this process in CKD. The reports concerning the impact of some miRNAs on fibrosis are conflicting, probably because the expression and regulation of miRNAs occur in a tissue- and even cell-dependent manner. Moreover, different assessment modes and populations have been used. There is a need for large studies and clinical trials to confirm the role of miRs in a clinical setting. miRNAs have great potential; thus, their analysis may improve diagnostic and therapeutic strategies.
Distinct Cerebrospinal Fluid Lipid Signature in Patients with Subarachnoid Hemorrhage-Induced Hydrocephalus
Authors: Toft-Bertelsen Trine L. , Andreassen Søren Norge , Rostgaard Nina , Olsen Markus Harboe , Norager Nicolas H. , Capion Tenna , Juhler Marianne , MacAulay Nanna
Published: August 2023

Patients with subarachnoid hemorrhage (SAH) may develop posthemorrhagic hydrocephalus (PHH), which is treated with surgical cerebrospinal fluid (CSF) diversion. This diversion is associated with risk of infection and shunt failure. Biomarkers for PHH etiology, CSF dynamics disturbances, and potentially subsequent shunt dependency are therefore in demand. With the recent demonstration of lipid-mediated CSF hypersecretion contributing to PHH, exploration of the CSF lipid signature in relation to brain pathology is of interest. Despite being a relatively new addition to the omic’s landscape, lipidomics are increasingly recognized as a tool for biomarker identification, as they provide a comprehensive overview of lipid profiles in biological systems. We here employ an untargeted mass spectroscopy-based platform and reveal the complete lipid profile of cisternal CSF from healthy control subjects and demonstrate its bimodal fluctuation with age. Various classes of lipids, in addition to select individual lipids, were elevated in the ventricular CSF obtained from patients with SAH during placement of an external ventricular drain. The lipidomic signature of the CSF in the patients with SAH suggests dysregulation of the lipids in the CSF in this patient group. Our data thereby reveal possible biomarkers present in a brain pathology with a hemorrhagic event, some of which could be potential future biomarkers for hypersecretion contributing to ventriculomegaly and thus pharmacological targets for pathologies involving disturbed CSF dynamics.
Cytocompatibility and Osteoinductive Properties of Collagen-Fibronectin Hydrogel Impregnated with siRNA Targeting Glycogen Synthase Kinase 3β: In Vitro Study
Authors: Galitsyna Elena V. , Buianova Anastasiia A. , Kozhukhov Vadim I. , Domogatsky Sergey P. , Bukharova Tatiana B. , Goldshtein Dmitriy V.
Published: August 2023

In this study, we developed an osteoplastic material based on collagen–fibronectin hydrogel impregnated with siRNA molecules targeting glycogen synthase kinase 3β (GSK3β), which inhibits the osteogenic differentiation of mesenchymal stem cells. The hydrogel impregnated with polyplexes containing siRNA GSK3β and polyethylenimine has been shown to have no cytotoxic effect: there was no statistically significant change in the cell’s viability after 7 days of incubation in its presence compared to the control group. On days 2 and 7, an increase in the level of expression of markers of osteogenic differentiation was observed, which confirms the osteoinductive qualities of the material. It has been demonstrated that the hydrogel maintains cell adhesion. Our results obtained in vitro indicate cytocompatibility and osteoinductive properties of collagen–fibronectin hydrogel impregnated with siRNA GSK3β molecules.
Chronic Kidney Disease Has No Impact on Tear Film Substance P Concentration in Type 2 Diabetes
Authors: Asiedu Kofi , Alotaibi Sultan , Krishnan Arun V. , Kwai Natalie , Poynten Ann , Markoulli Maria , Dhanapalaratnam Roshan
Published: August 2023

Purpose: The study aimed to ascertain the potential effects of chronic kidney disease (CKD) on substance P concentration in the tear film of people with type 2 diabetes. Methods: Participants were classified into two groups: type 2 diabetes with concurrent chronic kidney disease (T2DM–CKD (n = 25)) and type 2 diabetes without chronic kidney disease (T2DM–no CKD (n = 25)). Ocular surface discomfort assessment, flush tear collection, in-vivo corneal confocal microscopy, and peripheral neuropathy assessment were conducted. Enzyme-linked immunosorbent assays were utilized to ascertain the levels of tear film substance P in collected flush tears. Correlation analysis, hierarchical multiple linear regression analysis, and t-tests or Mann–Whitney U tests were used in the analysis of data for two-group comparisons. Results: There was no substantial difference between the T2DM–CKD and T2DM–no CKD groups for tear film substance P concentration (4.4 (0.2–50.4) and 5.9 (0.2–47.2) ng/mL, respectively; p = 0.54). No difference was observed in tear film substance P concentration between the low-severity peripheral neuropathy and high-severity peripheral neuropathy groups (4.4 (0.2–50.4) and 3.3 (0.3–40.7) ng/mL, respectively; p = 0.80). Corneal nerve fiber length (9.8 ± 4.6 and 12.4 ± 3.8 mm/mm2, respectively; p = 0.04) and corneal nerve fiber density (14.7 ± 8.5 and 21.1 ± 7.0 no/mm2, respectively; p < 0.01) were reduced significantly in the T2DM–CKD group compared to the T2DM–no CKD group. There were significant differences in corneal nerve fiber density (21.0 ± 8.1 and 15.8 ± 7.7 no/mm2, respectively; p = 0.04) and corneal nerve fiber length (12.9 ± 4.2 and 9.7 ± 3.8 mm/mm2, respectively; p = 0.03) between the low- and high-severity peripheral neuropathy groups. Conclusion: In conclusion, no significant difference in tear film substance P concentration was observed between type 2 diabetes with and without CKD. Corneal nerve loss, however, was more significant in type 2 diabetes with chronic kidney disease compared to type 2 diabetes alone, indicating that corneal nerve morphological measures could serve greater utility as a tool to detect neuropathy and nephropathy-related corneal nerve changes.
Discriminative Identification of SARS-CoV-2 Variants Based on Mass-Spectrometry Analysis
Authors: Feldberg Liron , Zvi Anat , Yahalom-Ronen Yfat , Schuster Ofir
Published: August 2023

The spread of SARS-CoV-2 variants of concern (VOCs) is of great importance since genetic changes may increase transmissibility, disease severity and reduce vaccine effectiveness. Moreover, these changes may lead to failure of diagnostic measures. Therefore, variant-specific diagnostic methods are essential. To date, genetic sequencing is the gold-standard method to discriminate between variants. However, it is time-consuming (taking several days) and expensive. Therefore, the development of rapid diagnostic methods for SARS-CoV-2 in accordance with its genetic modification is of great importance. In this study we introduce a Mass Spectrometry (MS)-based methodology for the diagnosis of SARS-CoV-2 in propagated in cell-culture. This methodology enables the universal identification of SARS-CoV-2, as well as variant-specific discrimination. The universal identification of SARS-CoV-2 is based on conserved markers shared by all variants, while the identification of specific variants relies on variant-specific markers. Determining a specific set of peptides for a given variant consists of a multistep procedure, starting with an in-silico search for variant-specific tryptic peptides, followed by a tryptic digest of a cell-cultured SARS-CoV-2 variant, and identification of these markers by HR-LC-MS/MS analysis. As a proof of concept, this approach was demonstrated for four representative VOCs compared to the wild-type Wuhan reference strain. For each variant, at least two unique markers, derived mainly from the spike (S) and nucleocapsid (N) viral proteins, were identified. This methodology is specific, rapid, easy to perform and inexpensive. Therefore, it can be applied as a diagnostic tool for pathogenic variants.
Applying an Artificial Neuromolecular System to the Application of Robotic Arm Motion Control in Assisting the Rehabilitation of Stroke Patients—An Artificial World Approach
Authors: Chen Jong-Chen , Cheng Hao-Ming
Published: August 2023

Stroke patients cannot use their hands as freely as usual. However, recovery after a stroke is a long road for many patients. If artificial intelligence can assist human arm movement, it is believed that the possibility of stroke patients returning to normal hand movement can be significantly increased. In this study, the artificial neuromolecular system (ANM system) developed by our laboratory is used as the core motion control system to learn to control the mechanical arm, produce similar human rehabilitation actions, and assist patients in transiting between different activities. The strength of the ANM system lies in its ability to capture and process spatiotemporal information by exploiting the dynamic information processing inside neurons. Five experiments are conducted in this research: continuous learning, dimensionality reduction, moving problem domains, transfer learning, and fault tolerance. The results show that the ANM system can find out the arm movement trajectory when people perform different rehabilitation actions through the ability of continuous learning and reduce the activation of multiple muscle groups in stroke patients through the learning method of reducing dimensions. Finally, using the ANM system can reduce the learning time and performance required to switch between different actions through transfer learning.
Development of Electrochemical Sensor Using Iron (III) Phthalocyanine/Gold Nanoparticle/Graphene Hybrid Film for Highly Selective Determination of Nicotine in Human Salivary Samples
Authors: Kamalasekaran Kavitha , Magesh Vasanth , Atchudan Raji , Arya Sandeep , Sundramoorthy Ashok K.
Published: August 2023

Nicotine is the one of the major addictive substances; the overdose of nicotine (NIC) consumption causes increasing heart rate, blood pressure, stroke, lung cancer, and respiratory illnesses. In this study, we have developed a precise and sensitive electrochemical sensor for nicotine detection in saliva samples. It was built on a glassy carbon electrode (GCE) modified with graphene (Gr), iron (III) phthalocyanine-4,4′,4″,4′′′-tetrasulfonic acid (Fe(III)Pc), and gold nanoparticles (AuNPs/Fe(III)Pc/Gr/GCE). The AuNPs/Fe(III)Pc/Gr nanocomposite was prepared and characterized by using FE-SEM, EDX, and E-mapping techniques to confirm the composite formation as well as the even distribution of elements. Furthermore, the newly prepared AuNPs/Fe(III)Pc/Gr/GCE-nanocomposite-based sensor was used to detect the nicotine in phosphate-buffered solution (0.1 M PBS, pH 7.4). The AuNPs/Fe(III)Pc/Gr/GCE-based sensor offered a linear response against NIC from 0.5 to 27 µM with a limit of detection (LOD) of 17 nM using the amperometry (i–t curve) technique. This electrochemical sensor demonstrated astounding selectivity and sensitivity during NIC detection in the presence of common interfering molecules in 0.1 M PBS. Moreover, the effect of pH on NIC electro-oxidation was studied, which indicated that PBS with pH 7.4 was the best medium for NIC determination. Finally, the AuNPs/Fe(III)Pc/Gr/GCE sensor was used to accurately determine NIC concentration in human saliva samples, and the recovery percentages were also calculated.
Recent Progress in Biosensors Based on Biorecognition Molecules
Authors: Zhang Zhen
Published: August 2023

Biosensors are considered a popular technology to rapidly detect targets, and are generally composed of biorecognition molecules that specifically capture analytes and signal elements [...]
Microfluidic Bio-Sensors and Their Applications
Authors: Kant Krishna
Published: August 2023

Biosensors are a promising tool for a wide variety of target analyte detection and enable point-of-care diagnostics with reduced volume and space [...]
Recommendation Systems for the Metaverse
Authors: Wei Lingwen , Wang Xutian , Wang Ting , Duan Zhilan , Hong Yan , He Xiaoming , Huang Huawei
Published: August 2023

The metaverse, a virtual world closely intertwined with reality, represents the next-generation form of the Internet and encompasses advanced sociability and interaction. With the rapid growth of users and virtual products within this environment, the importance of recommendation systems becomes paramount. This article presents a comprehensive survey that examines the technologies influencing the development of recommendation systems tailored for the metaverse. Firstly, we identify the key trends and fundamental concepts associated with these systems. Secondly, we delve into the core supporting technologies and application scenarios within metaverse recommendation systems. Lastly, we provide insights into future research directions for this rapidly evolving field. Our survey reveals that while progress has been achieved, further investigation is necessary to optimize the technical layout and content of metaverse recommendation systems.
Life Cycle Sustainability Assessment of Healthcare Buildings: A Policy Framework
Authors: Ullah Zeeshan , Nasir Abdur Rehman , Alqahtani Fahad K. , Ullah Fahim , Thaheem Muhammad Jamaluddin , Maqsoom Ahsen
Published: August 2023

The healthcare industry significantly impacts the environment due to its high usage of energy and natural resources and the associated waste generation. This study applied a cradle-to-grave Life Cycle Sustainability Assessment (LCSA) approach to assess the environmental and social life cycles of public hospitals. One hundred twenty-four public hospitals were selected for the current study; their sustainability performance was compared with those certified by Leadership in Energy and Environmental Design (LEED). The comparison revealed several factors contributing to the poor sustainability performance of public hospitals. These include inadequate management, substandard planning, political interference, insufficient staffing and funding, high energy consumption, high expenses, inconsistent healthcare policies, and conventional building designs. System thinking was leveraged, and a causal loop diagram (CLD) was developed to visualize the interdependency of the identified indicators of LCSA. Based on the findings of the study, a policy framework is proposed to guide the development of sustainable healthcare buildings. The framework includes using eco-friendly materials and techniques in construction, harnessing solar energy, improving hospital management practices, promoting public awareness about sustainability, conserving energy and water, and adopting sustainable waste management and transportation. Additionally, it emphasizes addressing social issues such as improving indoor air quality, thermal comfort, lighting, acoustics, patient safety, and security and ensuring that healthcare services are accessible and affordable. This study contributes to the literature on sustainable healthcare buildings by providing a practical policy framework for achieving sustainability in the healthcare sector.
Dynamic Optical Coherence Tomography of Blood Vessels in Cutaneous Melanoma—Correlation with Histology, Immunohistochemistry and Dermoscopy
Authors: Schuh Sandra , Sattler Elke , Rubeck Anna , Schiele Stefan , De Carvalho Nathalie , Themstrup Lotte , Ulrich Martina , Jemec Gregor , Holmes Jon , Pellacani Giovanni , Welzel Julia
Published: August 2023

Dermoscopy adds important information to the assessment of cutaneous melanoma, but the risk of progression is predicted by histologic parameters and therefore requires surgery and histopathologic preparation. Neo-vascularization is crucial for tumor progression and worsens prognosis. The aim of this study was the in vivo evaluation of blood vessel patterns in melanoma with dynamic optical coherence tomography (D-OCT) and the correlation with dermoscopic and histologic malignancy parameters for the risk assessment of melanoma. In D-OCT vessel patterns, shape, distribution and presence/type of branching of 49 melanomas were evaluated in vivo at three depths and correlated with the same patterns in dermoscopy and with histologic parameters after excision. In D-OCT, blood vessel density and atypical shapes (coils and serpiginous vessels) increased with higher tumor stage. The histologic parameters ulceration and Hmb45- and Ki67-positivity increased, whereas regression, inflammation and PD-L1-positivity decreased with risk. CD31, VEGF and Podoplanin correlated with D-OCT vasculature findings. B-RAF mutation status had no influence. Due to pigment overlay and the summation effect, the vessel evaluation in dermoscopy and D-OCT did not correlate well. In summary, atypical vessel patterns in melanoma correlate with histologic parameters for risk for metastases. Tumor vasculature can be noninvasively assessed using D-OCT before surgery.
Association of Hepatobiliary Phase of Gadoxetic-Acid-Enhanced MRI Imaging with Immune Microenvironment and Response to Atezolizumab Plus Bevacizumab Treatment
Authors: Tamura Yosuke , Ono Atsushi , Nakahara Hikaru , Hayes Clair Nelson , Fujii Yasutoshi , Zhang Peiyi , Yamauchi Masami , Uchikawa Shinsuke , Teraoka Yuji , Uchida Takuro , Fujino Hatsue , Nakahara Takashi , Murakami Eisuke , Tsuge Masataka , Serikawa Masahiro , Miki Daiki , Kawaoka Tomokazu , Okamoto Wataru , Imamura Michio , Nakamura Yuko , Awai Kazuo , Kobayashi Tsuyoshi , Ohdan Hideki , Fujita Masashi , Nakagawa Hidewaki , Chayama Kazuaki , Aikata Hiroshi , Oka Shiro
Published: August 2023

It has been reported that high intensity in the hepatobiliary (HB) phase of Gd-EOB-DTPA-enhanced MRI (EOB-MRI) is associated with an immune-cold microenvironment in HCC. The aim of this study is to reveal whether non-high-intensity HCCs are homogeneous with respect to the immune microenvironment and to investigate the predictive ability of EOB-MRI for the response to atezolizumab + bevacizumab therapy (Atezo/Bev). The association between differences in stepwise signal intensity of HB phase and molecular subtypes and somatic mutations associated with the immune microenvironment was investigated in 65 HCC patients (cohort 1). The association between EOB-MRI and the therapeutic effect of Atezo/Bev was evaluated in the Atezo/Bev cohort (60 patients in cohort 2). The proportion of HCCs having CTNNB1 mutations and classified as Chiang CTNNB1 and Hoshida S3 was high in the high-intensity HB-phase group. Infiltration of tumor-associated macrophages (TAM) and regulatory T-lymphocytes (Treg) was characteristic of the high-intensity and low-intensity groups, respectively. Although EOB-MRI could not predict the response to Atezo/Bev treatment, our results demonstrate that EOB-MRI could serve as a surrogate marker predicting the immune microenvironment. This suggests that Atezo/Bev treatment can be selected regardless of signal intensity in the EOB-MRI HB phase.
Cystic Fibrosis and Cancer: Unraveling the Complex Role of CFTR Gene in Cancer Susceptibility
Authors: Parisi Giuseppe Fabio , Papale Maria , Pecora Giulia , Rotolo Novella , Manti Sara , Russo Giovanna , Leonardi Salvatore
Published: August 2023

Cystic fibrosis (CF) is a genetic disorder affecting multiple organs, primarily the lungs and digestive system. Over the years, advancements in medical care and treatments have significantly increased the life expectancy of individuals with CF. However, with this improved longevity, concerns about the potential risk of developing certain types of cancers have arisen. This narrative review aims to explore the relationship between CF, increased life expectancy, and the associated risk for cancers. We discuss the potential mechanisms underlying this risk, including chronic inflammation, immune system dysregulation, and genetic factors. Additionally, we review studies that have examined the incidence and types of cancers seen in CF patients, with a focus on gastrointestinal, breast, and respiratory malignancies. We also explore the impact of CFTR modulator therapies on cancer risk. In the gastrointestinal tract, CF patients have an elevated risk of developing colorectal cancer, pancreatic cancer, and possibly esophageal cancer. The underlying mechanisms contributing to these increased risks are not fully understood, but chronic inflammation, altered gut microbiota, and genetic factors are believed to play a role. Regular surveillance and colonoscopies are recommended for early detection and management of colorectal cancer in CF patients. Understanding the factors contributing to cancer development in CF patients is crucial for implementing appropriate surveillance strategies and improving long-term outcomes. Further research is needed to elucidate the molecular mechanisms involved and develop targeted interventions to mitigate cancer risk in individuals with CF.
N-Doped TiO2-Nb2O5 Sol–Gel Catalysts: Synthesis, Characterization, Adsorption Capacity, Photocatalytic and Antioxidant Activity
Authors: Fuziki Maria E. K. , Ribas Laura S. , Abreu Eduardo , Fernandes Luciano , dos Santos Onélia A. A. , Brackmann Rodrigo , de Tuesta Jose L. D. , Tusset Angelo M. , Lenzi Giane G.
Published: August 2023

TiO2-based semiconductors are formidable photocatalysts for redox reaction applications. Although N-doped TiO2-Nb2O5 catalysts have already been explored in the literature, studies on their antioxidant activity are scarce, and systematic investigations on the effects of synthesis parameters over a wide range of %Nb and NH4OH concentrations are limited. In addition, the relationship between optimal pH and %Nb has not yet been adequately explored. In the present work, the sol–gel synthesis of N-doped TiO2-Nb2O5 catalysts was optimized using a design of experiments approach focused on photocatalysis, adsorption, and antioxidant applications. The samples were characterized by TGA, SEM/EDS, XRD, PZC tests, photoacoustic spectroscopy, and N2-adsorption/desorption experiments. The salicylic acid (SA) degradation tests and DPPH radical scavenging assays demonstrated the superior photocatalytic activity (up to 72.9% SA degradation in 30 min, pH 5) and antioxidant capacity (IC50 = 88.9 μg mL−1) of pure TiO2 compared to the N-doped TiO2-Nb2O5 catalysts. The photocatalytic activity, however, proved to be intensely dependent on the pH and %Nb interaction, and at pH 3, the 25Nb-1N-400 catalyst promoted more significant SA degradation (59.9%) compared to pure TiO2 (42.8%). In the methylene blue (MB) adsorption tests, the catalysts N-doped TiO2-Nb2O5 showed removals at least seven times greater than TiO2 catalysts without Nb.
Marine PET Hydrolase (PET2): Assessment of Terephthalate- and Indole-Based Polyester Depolymerization
Authors: Wagner-Egea Paula , Aristizábal-Lanza Lucía , Tullberg Cecilia , Wang Ping , Bernfur Katja , Grey Carl , Zhang Baozhong , Linares-Pastén Javier A.
Published: August 2023

Enzymatic polyethylene terephthalate (PET) recycling processes are gaining interest for their low environmental impact, use of mild conditions, and specificity. Furthermore, PET hydrolase enzymes are continuously being discovered and engineered. In this work, we studied a PET hydrolase (PET2), initially characterized as an alkaline thermostable lipase. PET2 was produced in a fusion form with a 6-histidine tag in the N-terminal. The PET2 activity on aromatic terephthalate and new indole-based polyesters was evaluated using polymers in powder form. Compared with IsPETase, an enzyme derived from Ideonella sakaiensis, PET2 showed a lower PET depolymerization yield. However, interestingly, PET2 produced significantly higher polybutylene terephthalate (PBT) and polyhexylene terephthalate (PHT) depolymerization yields. A clear preference was found for aromatic indole-derived polyesters over non-aromatic ones. No activity was detected on Akestra™, an amorphous copolyester with spiroacetal structures. Docking studies suggest that a narrower and more hydrophobic active site reduces its activity on PET but favors its interaction with PBT and PHT. Understanding the enzyme preferences of polymers will contribute to their effective use to depolymerize different types of polyesters.
Reference Gene U2 Enables Direct Comparison between Relative Gene Expression Levels of Vascular Smooth Muscle Cells in Tissue and Culture Using Real-Time Quantitative PCR
Authors: Rager Christine , Klöpper Tobias , Pfeil Uwe , Tasch Sabine , Whittaker Michael Raymond , Exintaris Betty , Mietens Andrea , Middendorff Ralf
Published: August 2023

In nearly every lab, real-time quantitative polymerase chain reaction (qPCR) is used to quantify gene expression. However, a comparison of different samples requires the careful selection of suitable reference genes (RGs), sometimes referred to as housekeeping genes. In the case of vascular smooth muscle cells (vSMCs), it is important to know under which conditions gene expression in isolated and cultured vSMCs can be compared with vSMCs in a healthy blood vessel. We isolated the vSMC-containing layer of the rat aorta (tunica media) and used one (longitudinal) half for direct RNA extraction, while the other half served to isolate and culture vSMCs prior to RNA extraction. First, the expression of the routinely used RGs beta-actin (Actb) and Glyceraldehyde-3-phosphate dehydrogenase (Gapdh) is investigated in intact media and corresponding cultured vSMCs. Significant differences in their Ct values show that these RGs could not be used for such direct comparisons; therefore, we select 15 different RGs. Only the gene expression of the small ribonuclear protein (snRNP) U2 shows no significant differences between the absolute Ct values of cultured vSMCs and the intact media; moreover, no differences were found between male and female rats in our experimental setup. In conclusion, U2 was shown to be an appropriate (sex-independent) RG to compare relative expression levels of vSMCs in culture to those vSMCs within their physiological tissue environment.
Myeloid-CITED2 Deficiency Exacerbates Diet-Induced Obesity and Pro-Inflammatory Macrophage Response
Authors: Zafar Atif , Ng Hang Pong , Chan E. Ricky , Dunwoodie Sally L. , Mahabeleshwar Ganapati H.
Published: August 2023

Macrophages are the principal component of the innate immune system that are found in all tissues and play an essential role in development, homeostasis, tissue repair, and immunity. Clinical and experimental studies have shown that transcriptionally dynamic pro-inflammatory macrophages are involved in the pathogenesis of diet-induced obesity and insulin resistance. However, cell-intrinsic mechanisms must exist that bridle uncontrolled pro-inflammatory macrophage activation in metabolic organs and disease pathogenesis. In this study, we show that CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) is an essential negative regulator of pro-inflammatory macrophage activation and inflammatory disease pathogenesis. Our in vivo studies show that myeloid-CITED2 deficiency significantly elevates high-fat diet (HFD)-induced expansion of adipose tissue volume, obesity, glucose intolerance, and insulin resistance. Moreover, myeloid-CITED2 deficiency also substantially augments HFD-induced adipose tissue inflammation and adverse remodeling of adipocytes. Our integrated transcriptomics and gene set enrichment analyses show that CITED2 deficiency curtails BCL6 signaling and broadly elevates BCL6-repressive gene target expression in macrophages. Using complementary gain- and loss-of-function studies, we found that CITED2 deficiency attenuates, and CITED2 overexpression elevates, inducible BCL6 expression in macrophages. At the molecular level, our analyses show that CITED2 promotes BCL6 expression by restraining STAT5 activation in macrophages. Interestingly, siRNA-mediated knockdown of STAT5 fully reversed elevated pro-inflammatory gene target expression in CITED2-deficient macrophages. Overall, our findings highlight that CITED2 restrains inflammation by promoting BCL6 expression in macrophages, and limits diet-induced obesity and insulin resistance.
Chemical and Process Inherent Safety Analysis of Large-Scale Suspension Poly(Vinyl Chloride) Production
Authors: González-Delgado Ángel Darío , Aguilar-Vásquez Eduardo , Ramos-Olmos Miguel
Published: August 2023

In this work, a safety assessment was carried out for the suspension polymerization method, known for the lack of studies about its sustainable performance and long history of chemical accidents. Therefore, a safety analysis was conducted using the inherent safety methodology to assess and determine the inherent risks of the poly(vinyl chloride) (PVC) suspension production process using computer-aided process engineering (CAPE). The indicators were calculated using data from safety databases and the specialized literature, considering downstream stages like vinyl chloride monomer (VCM) recovery, PVC purification and PVC drying. The obtained indicators revealed that the process has a negative performance regarding inherent safety, with a total inherent safety index of 30. The chemical inherent safety index had a value of 19, with the main chemical risk of the process being presented by the vinyl chloride monomer (with a value of 11), along with the risk of the exothermic reactions. The process safety index had a value of 15, highlighting the inventory as the primary concern of the process (with a value of 5), followed by the presence of unsafe equipment such as furnaces, burners, and dryers. The safety structure index had a score of 3, categorizing the process as probably risky, with the reaction and purification stages being more susceptible to accidents. Lastly, it is recommended to reduce the size of the process inventory and to substitute out unsafe process units.
Psychosis Caused by a Somatic Condition: How to Make the Diagnosis? A Systematic Literature Review
Authors: Dissaux Nolwenn , Neyme Pierre , Kim-Dufor Deok-Hee , Lavenne-Collot Nathalie , Marsh Jonathan J. , Berrouiguet Sofian , Walter Michel , Lemey Christophe
Published: August 2023

Background: First episode of psychosis (FEP) is a clinical condition that usually occurs during adolescence or early adulthood and is often a sign of a future psychiatric disease. However, these symptoms are not specific, and psychosis can be caused by a physical disease in at least 5% of cases. Timely detection of these diseases, the first signs of which may appear in childhood, is of particular importance, as a curable treatment exists in most cases. However, there is no consensus in academic societies to offer recommendations for a comprehensive medical assessment to eliminate somatic causes. Methods: We conducted a systematic literature search using a two-fold research strategy to: (1) identify physical diseases that can be differentially diagnosed for psychosis; and (2) determine the paraclinical exams allowing us to exclude these pathologies. Results: We identified 85 articles describing the autoimmune, metabolic, neurologic, infectious, and genetic differential diagnoses of psychosis. Clinical presentations are described, and a complete list of laboratory and imaging features required to identify and confirm these diseases is provided. Conclusion: This systematic review shows that most differential diagnoses of psychosis should be considered in the case of a FEP and could be identified by providing a systematic checkup with a laboratory test that includes ammonemia, antinuclear and anti-NMDA antibodies, and HIV testing; brain magnetic resonance imaging and lumbar puncture should be considered according to the clinical presentation. Genetic research could be of interest to patients presenting with physical or developmental symptoms associated with psychiatric manifestations.