bluuebunny/crossref_metadata_2025 huggingface dataset:
The Anti-Cancer Activity of Pentamidine and Its Derivatives (WLC-4059) Is through Blocking the Interaction between S100A1 and RAGE V Domain
Authors: Parveen Nuzhat , Chiu Wei-Jung , Shen Li-Ching , Chou Ruey-Hwang , Sun Chung-Ming , Yu Chin
Published: January 2023

The S100A1 protein in humans is a calcium-binding protein. Upon Ca2+ binding to S100A1 EF-hand motifs, the conformation of S100A1 changes and promotes interactions with target proteins. RAGE consists of three domains: the cytoplasmic, transmembrane, and extracellular domains. The extracellular domain consists of C1, C2, and V domains. V domains are the primary receptors for the S100 protein. It was reported several years ago that S100A1 and RAGE V domains interact in a pathway involving S100A1-RAGE signaling, whereby S100A1 binds to the V domain, resulting in RAGE dimerization. The autophosphorylation of the cytoplasmic domain initiates a signaling cascade that regulates cell proliferation, cell growth, and tumor formation. In this study, we used pentamidine and a newly synthesized pentamidine analog (WLC-4059) to inhibit the S100A1-RAGE V interaction. 1H-15N HSQC NMR titration was carried out to characterize the interaction between mS100A1 (mutant S100A1, C86S) and pentamidine analogs. We found that pentamidine analogs interact with S100A1 via 1H-15N HSQC NMR spectroscopy. Based on the results, we utilized the HADDOCK program to generate structures of the mS100A1–WLC-4059 binary complex. Interestingly, the binary complex overlapped with the complex crystal structure of the mS100A1–RAGE-V domain, proving that WLC-4059 blocks interaction sites between S100A1 and RAGE-V. A WST-1 cell proliferation assay also supported these results. We conclude that pentamidine analogs could potentially enhance therapeutic approaches against cancers.
Expression of a Salt-Tolerant Pseudolysin in Yeast for Efficient Protein Hydrolysis under High-Salt Conditions
Authors: Liu Xiufang , Lu Qian , Xiao Han , Feng Yunzi , Su Guowan , Zhao Mouming , Huang Mingtao
Published: January 2023

Protease biocatalysis in a high-salt environment is very attractive for applications in the detergent industry, the production of diagnostic kits, and traditional food fermentation. However, high-salt conditions can reduce protease activity or even inactivate enzymes. Herein, in order to explore new protease sources, we expressed a salt-tolerant pseudolysin of Pseudomonas aeruginosa SWJSS3 isolated from deep-sea mud in Saccharomyces cerevisiae. After optimizing the concentration of ion cofactors in yeast peptone dextrose (YPD) medium, the proteolytic activity in the supernatant was 2.41 times more than that in the control group when supplemented with 5 mM CaCl2 and 0.4 mM ZnCl2. The extracellular proteolytic activity of pseudolysin reached 258.95 U/mL with optimized expression cassettes. In addition, the S. cerevisiae expression system increased the salt tolerance of pseudolysin to sodium chloride (NaCl)and sodium dodecyl sulfate (SDS) and the recombinant pseudolysin retained 15.19% activity when stored in 3 M NaCl for 7 days. The recombinant pseudolysin was able to efficiently degrade the β-conglycinin from low-denatured soy protein isolates and glycinin from high-denatured soy protein isolates under high temperatures (60 °C) and high-salt (3 M NaCl) conditions. Our study provides a salt-tolerant recombinant protease with promising applications in protein hydrolysis under high-salt conditions.
Identification of Bottle Gourd (Lagenaria siceraria) OVATE Family Genes and Functional Characterization of LsOVATE1
Authors: Feng Zishan , Wu Xiaohua , Wang Jian , Wu Xinyi , Wang Baogen , Lu Zhongfu , Ye Zihong , Li Guojing , Wang Ying
Published: January 2023

The OVATE gene family is a class of conserved transcription factors that play significant roles in plant growth, development, and abiotic stress, and also affect fruit shape in vegetable crops. Bottle gourd (Lagenaria siceraria), commonly known as calabash or gourd, is an annual climber belonging to the Cucurbitaceae family. Studies on bottle gourd OVATE genes are limited. In this study, we performed genome-wide identification of the OVATE gene family in bottle gourd, and identified a total of 20 OVATE family genes. The identified genes were unevenly distributed across 11 bottle gourd chromosomes. We also analyzed the gene homology, amino acid sequence conservation, and three-dimensional protein structure (via prediction) of the 20 OVATE family genes. We used RNA-seq data to perform expression analysis, which found 20 OVATE family genes to be differentially expressed based on spatial and temporal characteristics, suggesting that they have varying functions in the growth and development of bottle gourd. In situ hybridization and subcellular localization analysis showed that the expression characteristics of the LsOVATE1 gene, located on chromosome 7 homologous to OVATE, is a candidate gene for affecting the fruit shape of bottle gourd. In addition, RT-qPCR data from bottle gourd roots, stems, leaves, and flowers showed different spatial expression of the LsOVATE1 gene. The ectopic expression of LsOVATE1 in tomato generated a phenotype with a distinct fruit shape and development. Transgenic-positive plants that overexpressed LsOVATE1 had cone-shaped fruit, calyx hypertrophy, petal degeneration, and petal retention after flowering. Our results indicate that LsOVATE1 could serve important roles in bottle gourd development and fruit shape determination, and provide a basis for future research into the function of LsOVATE1.
The Yin and Yang of Mesenchymal Cells in the Corneal Stromal Fibrosis Response to Injury: The Cornea as a Model of Fibrosis in Other Organs
Authors: Wilson Steven E.
Published: January 2023

Mesenchymal cells (keratocytes, corneal fibroblasts, and myofibroblasts), as well as mesenchymal progenitor bone marrow-derived fibrocytes, are the major cellular contributors to stromal fibrosis after injury to the cornea. Corneal fibroblasts, in addition to being major progenitors to myofibroblasts, also have anti-fibrotic functions in (1) the production of non-basement membrane collagen type IV that binds activated transforming growth factor (TGF) beta-1 and TGF beta-2 to downregulate TGF beta effects on cells in the injured stroma, (2) the production of chemokines that modulate the entry of bone marrow-derived cells into the stroma, (3) the production of hepatocyte growth factor and keratinocyte growth factor to regulate corneal epithelial healing, (4) the cooperation with the epithelium or corneal endothelium in the regeneration of the epithelial basement membrane and Descemet’s membrane, and other functions. Fibrocytes also serve as major progenitors to myofibroblasts in the corneal stroma. Thus, mesenchymal cells and mesenchymal cell progenitors serve Yin and Yang functions to inhibit and promote tissue fibrosis depending on the overall regulatory milieu within the injured stroma.
Efavirenz: History, Development and Future
Authors: Costa Bárbara , Vale Nuno
Published: January 2023

Efavirenz (Sustiva®) is a first-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat human immunodeficiency virus (HIV) type 1 infection or to prevent the spread of HIV. In 1998, the FDA authorized efavirenz for the treatment of HIV-1 infection. Patients formerly required three 200 mg efavirenz capsules daily, which was rapidly updated to a 600 mg tablet that only required one tablet per day. However, when given 600 mg once daily, plasma efavirenz concentrations were linked not only to poor HIV suppression but also to toxicity. Clinical data suggested that the standard dose of efavirenz could be reduced without compromising its effectiveness, resulting in a reduction in side effects and making the drug more affordable. Therefore, ENCORE1 was performed to compare the efficiency and safeness of a reduced dose of efavirenz (400 mg) with the standard dose (600 mg) plus two NRTI in antiretroviral-naïve HIV-infected individuals. Nowadays, due to the emergence of integrase strand transfer inhibitors (INSTIs), some consider that it is time to stop using efavirenz as a first-line treatment on a global scale, in the parts of the world where that is possible. Efavirenz has been a primary first-line antiviral drug for more than 15 years. However, at this moment, the best use for efavirenz could be for pre-exposure prophylaxis (PrEP) and repurposing in medicine.
Assessment of Fibrinogen-like 2 (FGL2) in Human Chronic Kidney Disease through Transcriptomics Data Analysis
Authors: Denicolò Sara , Nair Viji , Leierer Johannes , Rudnicki Michael , Kretzler Matthias , Mayer Gert , Ju Wenjun , Perco Paul
Published: January 2023

Fibrinogen-like 2 (FGL2) was recently found to be associated with fibrosis in a mouse model of kidney damage and was proposed as a potential therapeutic target in chronic kidney disease (CKD). We assessed the association of renal FGL2 mRNA expression with the disease outcome in two independent CKD cohorts (NEPTUNE and Innsbruck CKD cohort) using Kaplan Meier survival analysis. The regulation of FGL2 in kidney biopsies of CKD patients as compared to healthy controls was further assessed in 13 human CKD transcriptomics datasets. The FGL2 protein expression in human renal tissue sections was determined via immunohistochemistry. The regulators of FGL2 mRNA expression in renal tissue were identified in the co-expression and upstream regulator analysis of FGL2-positive renal cells via the use of single-cell RNA sequencing data from the kidney precision medicine project (KPMP). Higher renal FGL2 mRNA expression was positively associated with kidney fibrosis and negatively associated with eGFR. Renal FGL2 mRNA expression was upregulated in CKD as compared with healthy controls and associated with CKD progression in the Innsbruck CKD cohort (p-value = 0.0036) and NEPTUNE cohort (p-value = 0.0048). The highest abundance of FGL2 protein in renal tissue was detected in the thick ascending limb of the loop of Henle and macula densa, proximal tubular cells, as well as in glomerular endothelial cells. The upstream regulator analysis identified TNF, IL1B, IFNG, NFKB1, and SP1 as factors potentially inducing FGL2-co-expressed genes, whereas factors counterbalancing FGL2-co-expressed genes included GLI1, HNF1B, or PPARGC1A. In conclusion, renal FGL2 mRNA expression is elevated in human CKD, and higher FGL2 levels are associated with fibrosis and worse outcomes.
Construction of Bi-Enzyme Self-Assembly Clusters Based on SpyCatcher/SpyTag for the Efficient Biosynthesis of (R)-Ethyl 2-hydroxy-4-phenylbutyrate
Authors: Wang Jinmei , Lu Yuan , Cheng Pengpeng , Zhang Chuyue , Tang Lan , Du Lihua , Li Jinghua , Ou Zhimin
Published: January 2023

Cascade reactions catalyzed by multi-enzyme systems are important in science and industry and can be used to synthesize drugs and nutrients. In this study, two types of macromolecules of bi-enzyme self-assembly clusters (BESCs) consisting of carbonyl reductase (CpCR) and glucose dehydrogenase (GDH) were examined. Stereoselective CpCR and GDH were successfully fused with SpyCatcher and SpyTag, respectively, to obtain four enzyme modules, namely: SpyCatcher-CpCR, SpyCatcher-GDH, SpyTag-CpCR, and SpyTag-GDH, which were covalently coupled in vitro to form two types of hydrogel-like BESCs: CpCR-SpyCatcher-SpyTag-GDH and GDH-SpyCatcher-SpyTag-CpCR. CpCR-SpyCatcher-SpyTag-GDH showed a better activity and efficiently converted ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl(R)2-hydroxy-4-phenylbutanoate ((R)-HPBE), while regenerating NADPH. At 30 °C and pH 7, the conversion rate of OPBE with CpCR-SpyCatcher-SpyTag-GDH as a catalyst reached 99.9%, with the ee% of (R)-HPBE reaching above 99.9%. This conversion rate was 2.4 times higher than that obtained with the free bi-enzyme. The pH tolerance and temperature stability of the BESCs were also improved compared with those of the free enzymes. In conclusion, bi-enzyme assemblies were docked using SpyCatcher/SpyTag to produce BESCs with a special structure and excellent catalytic activity, improving the catalytic efficiency of the enzyme.
Ploidy Status of Ovarian Cancer Cell Lines and Their Association with Gene Expression Profiles
Authors: Du Ming , Zhang Shuo , Liu Xiaoxia , Xu Congjian , Zhang Xiaoyan
Published: January 2023

As a cancer type potentially dominated by copy number variations, ovarian cancer shows hyperploid karyotypes and large-scale chromosome alterations, which might be promising biomarkers correlated with tumor metastasis and chemoresistance. Experimental studies have provided more information about the roles of aneuploids and polyploids in ovarian cancer. However, ploidy evaluation of ovarian cancer cell lines is still limited, even in some ploidy-related research. Herein, the ploidy landscape of 51 ovarian cancer cell lines from the Cancer Cell Line Encyclopedia (CCLE) were analyzed, and the ploidy statuses of 13 human ovarian cancer cell lines and 2 murine cell lines were evaluated using G-banding and flow cytometry. Most human ovarian cancer cell lines were aneuploid, with modal numbers of 52–86 and numerical complexity ranging from 5 to 12. A2780, COV434 and TOV21G were screened as diploid cell lines, with a modal number of 46, a low aneuploid score and a near-diploid ploidy value. Two murine cell lines, both OV2944-HM1 and ID-8, were near-tetraploid. Integrated information on karyotypes, aneuploid score and ploidy value supplied references for a nondiploid model construction and a parallel analysis of diploid versus aneuploid. Moreover, the gene expression profiles were compared between diploid and aneuploid cell lines. The functions of differentially expressed genes were mainly enriched in terms of protein function regulation, TGF-β signaling and cell adhesion molecules. Genes downregulated in the aneuploid group were mainly related to metabolism and protein function regulation, and genes upregulated in the aneuploid group were mainly involved in immune regulation. Differentially expressed genes were randomly distributed on all chromosomes, while chromosome 1 alteration might contribute to immune-related alterations in aneuploid cell lines. Chromosome 19 alteration might be potentially significant for aneuploid ovarian cancer cell lines and patients, which needs further verification in ploidy research.
PI3K–AKT-Targeting Breast Cancer Treatments: Natural Products and Synthetic Compounds
Authors: Yuan Yeqin , Long Huizhi , Zhou Ziwei , Fu Yuting , Jiang Binyuan
Published: January 2023

Breast cancer is the most commonly diagnosed cancer in women. The high incidence of breast cancer, which is continuing to rise, makes treatment a significant challenge. The PI3K–AKT pathway and its downstream targets influence various cellular processes. In recent years, mounting evidence has shown that natural products and synthetic drugs targeting PI3K–AKT signaling have the potential to treat breast cancer. In this review, we discuss the role of the PI3K–AKT signaling pathway in the occurrence and development of breast cancer and highlight PI3K–AKT-targeting natural products and drugs in clinical trials for the treatment of breast cancer.
Three-Dimensional FEA Analysis of the Stress Distribution on Titanium and Graphene Frameworks Supported by 3 or 6-Implant Models
Authors: Desai Shrikar R. , Koulgikar Kiran Deepak , Alqhtani Nasser Raqe , Alqahtani Ali Robaian , Alqahtani Abdullah Saad , Alenazi Adel , Heboyan Artak , Fernandes Gustavo V. O. , Mustafa Mohammed
Published: January 2023

Titanium is the main component of dental implants. It is also routinely used as a framework material for implant-supported full-arch prostheses due to its low density, biocompatibility, and other mechanical properties. Remarkable mechanical properties such as lesser mass density and higher young’s modulus of graphene have gained popularity among scientists, improving the properties of biomedical implants. Thus, our study aimed to compare the outcome through the von Mises stresses generated on All-on-6 and All-on-3 implant models, as well as on the framework, and evaluate the effect of stress patterns on the crestal bone around implants in the mandible. FEA (Finite Element Analysis) study was carried out using edentulous mandible models. Four 3D FEA models with 3 and 6 implants were used (Model 1: Titanium bar-supported 6 straight implants; Model 2: Graphene bar-supported 6 straight implants; Model 3: Titanium bar-supported 3 implants with 30 degrees-tilted; Model 4: Graphene bar-supported 3 implants with 30 degrees-tilted) in order to simulate endosseous implant designs. The implant measuring 4.2 mm in diameter and 11.5 mm in length were used. The most distal implants in the 3-implant models were placed with angulation of 30 degrees; in 6 implants, they were vertically placed. All the models were analyzed for vertical and oblique axis with a single force magnitude of 100 N. In all four implant models and under loading conditions, the peak stress points were always on the neck of the most distal implant. von Mises stresses were within the normal stress range. In a conventional six-straight implant model supported by a titanium framework, the cortical stress in the region of implants was 25.27 MPa, whereas, in the graphene framework, it was 12.18 MPa. Under vertical load, there was a significant difference in the cortical stress around the tilted implants (30 degrees) in the 3-implant system of titanium and graphene frameworks, respectively, 70.31 MPa and 21.27 MPa. The graphene framework demonstrated better results than the titanium framework for the conventional six-implant system under vertical load, achieving stress of 30.09 MPa and 76.60 MPa, respectively. In the case of the 3-implant system, a significant difference in the bar stress was observed between graphene and titanium, respectively, 256.32 MPa and 180.1 MPa of bar stress. Within the limitation of this study, the peri-implant stresses were decreased using graphene framework models. Hence, it was possible to conclude that the best load-bearing capacity results were found in the graphene framework group compared to the titanium framework for All-on-6 and All-on-3 implant models, even though both materials are reliable options used as framework materials in implant-supported full-arch prostheses.
Electrochemical Immunosensor Using Electroactive Carbon Nanohorns for Signal Amplification for the Rapid Detection of Carcinoembryonic Antigen
Authors: Domínguez-Aragón Angélica , Zaragoza-Contreras Erasto Armando , Figueroa-Miranda Gabriela , Offenhäusser Andreas , Mayer Dirk
Published: January 2023

In this work, a novel sandwich-type electrochemical immunosensor was developed for the quantitative detection of the carcinoembryonic antigen, an important tumor marker in clinical tests. The capture antibodies were immobilized on the surface of a gold disk electrode, while detection antibodies were attached to redox-tagged single-walled carbon nanohorns/thionine/AuNPs. Both types of antibody immobilization were carried out through Au-S bonds using the novel photochemical immobilization technique that ensures control over the orientation of the antibodies. The electroactive SWCNH/Thi/AuNPs nanocomposite worked as a signal tag to carry out both the detection of carcinoembryonic antigen and the amplification of the detection signal. The current response was monitored by differential pulse voltammetry. A clear dependence of the thionine redox peak was observed as a function of the carcinoembryonic antigen concentration. A linear detection range from 0.001–200 ng/mL and a low detection limit of 0.1385 pg/mL were obtained for this immunoassay. The results showed that carbon nanohorns represent a promising matrix for signal amplification in sandwich-type electrochemical immune assays working as a conductive and binding matrix with easy and versatile modification routes to antibody and redox tag immobilization, which possesses great potential for clinical diagnostics of CEA and other biomarkers.
Applications of Optical Fiber in Label-Free Biosensors and Bioimaging: A Review
Authors: Li Baocheng , Zhang Ruochong , Bi Renzhe , Olivo Malini
Published: January 2023

Biosensing and bioimaging are essential in understanding biological and pathological processes in a living system, for example, in detecting and understanding certain diseases. Optical fiber has made remarkable contributions to the biosensing and bioimaging areas due to its unique advantages of compact size, immunity to electromagnetic interference, biocompatibility, fast response, etc. This review paper will present an overview of seven common types of optical fiber biosensors and optical fiber-based ultrasound detection in photoacoustic imaging (PAI) and the applications of these technologies in biosensing and bioimaging areas. Of course, there are many types of optical fiber biosensors. Still, this paper will review the most common ones: optical fiber grating, surface plasmon resonance, Sagnac interferometer, Mach–Zehnder interferometer, Michelson interferometer, Fabry–Perot Interferometer, lossy mode resonance, and surface-enhanced Raman scattering. Furthermore, different optical fiber techniques for detecting ultrasound in PAI are summarized. Finally, the main challenges and future development direction are briefly discussed.
Full-Cut Manufacture of Skin-Interfaced Microfluidic Patch with Copper Electrode for In Situ Admittance Sensing of Sweat Rate
Authors: Wei Lei , He Yuxin , Lv Zihan , Guo Daoyou , Cheng Lin , Wu Huaping , Liu Aiping
Published: January 2023

Sweat-rate measurement has received more and more attention, especially for specific groups, such as athletes, soldiers and manual workers, due to their excessive sweat loss under prolonged intense heat stress, which increases the risk of dehydration and electrolyte imbalance. The highly effective manufacture of a sweat-sensing device is essential to its wide range of applications in perspiration-related physiological information detection. In this work, we propose a simple and cost-effective strategy for the manufacture of a microfluidic sweat-rate-sensing patch via laser cutting and transfer printing technology. A copper foil tape is used as the electrode for in situ admittance based sweat-rate-sensing. The detection circuits and measurement conditions are optimized to prevent the negative effect of an electrochemical reaction between a copper electrode and sweat for precise admittance measurement. In vitro and on-body experiments demonstrate that the copper electrode is applicable for admittance-based sweat sensing and is capable of achieving equivalent sensing accuracy as a gold electrode and that the proposed sensor structure can perform consecutive and accurate sweat-rate-sensing and facilitates a significant increase in manufacturing efficiency.
A Novel Microfluidic-Based OMC-PEDOT-PSS Composite Electrochemical Sensor for Continuous Dopamine Monitoring
Authors: Nuh Sofwan , Numnuam Apon , Thavarungkul Panote , Phairatana Tonghathai
Published: January 2023

Fast and precise analysis techniques using small sample volumes are required for next-generation clinical monitoring at the patient’s bedside, so as to provide the clinician with relevant chemical data in real-time. The integration of an electrochemical sensor into a microfluidic chip allows for the achievement of real-time chemical monitoring due to the low consumption of analytes, short analysis time, low cost, and compact size. In this work, dopamine, used as a model, is an important neurotransmitter responsible for controlling various vital life functions. The aim is to develop a novel serpentine microfluidic-based electrochemical sensor, using a screen-printed electrode for continuous dopamine detection. The developed sensor employed the composite of ordered mesoporous carbon (OMC) and poly (3,4 ethylenedioxythiophene)-poly (styrene sulfonate) (PEDOT-PSS). The performance of a microfluidic, integrated with the sensor, was amperometrically evaluated using a computer-controlled microfluidic platform. The microfluidic-based dopamine sensor exhibited a sensitivity of 20.2 ± 0.6 μA μmol L−1, and a detection limit (LOD) of 21.6 ± 0.002 nmol L−1, with high selectivity. This microfluidic-based electrochemical sensor was successfully employed to determine dopamine continuously, which could overcome the problem of sensor fouling with more than 90% stability for over 24 h. This novel microfluidic sensor platform provides a powerful tool for the development of a continuous dopamine detection system for human clinical application.
A Microfluidic Cell Co-Culture Chip for the Monitoring of Interactions between Macrophages and Fibroblasts
Authors: Li Pengcheng , Cui Feiyun , Chen Heying , Yang Yao , Li Gang , Mao Hongju , Lyu Xiaoyan
Published: January 2023

Macrophages and fibroblasts are two types of important cells in wound healing. The development of novel platforms for studying the interrelationship between these two cells is crucial for the exploration of wound-healing mechanisms and drug development. In this study, a microfluidic chip composed of two layers was designed for the co-culturing of these two cells. An air valve was employed to isolate fibroblasts to simulate the wound-healing microenvironment. The confluence rate of fibroblasts in the co-culture system with different macrophages was explored to reflect the role of different macrophages in wound healing. It was demonstrated that M2-type macrophages could promote the activation and migration of fibroblasts and it can be inferred that they could promote the wound-healing process. The proposed microfluidic co-culture system was designed for non-contact cell–cell interactions, which has potential significance for the study of cell–cell interactions in biological processes such as wound healing, tumor microenvironment, and embryonic development.
Selective Antibody-Free Sensing Membranes for Picogram Tetracycline Detection
Authors: Ben Halima Hamdi , Baraket Abdoullatif , Vinas Clara , Zine Nadia , Bausells Joan , Jaffrezic-Renault Nicole , Teixidor Francesc , Errachid Abdelhamid
Published: January 2023

As an antibody-free sensing membrane for the detection of the antibiotic tetracycline (TC), a liquid PVC membrane doped with the ion-pair tetracycline/θ-shaped anion [3,3′-Co(1,2-C2B9H11)2]− ([o-COSAN]−) was formulated and deposited on a SWCNT modified gold microelectrode. The chosen transduction technique was electrochemical impedance spectroscopy (EIS). The PVC membrane was composed of: the tetracycline/[o-COSAN]− ion-pair, a plasticizer. A detection limit of 0.3 pg/L was obtained with this membrane, using bis(2-ethylhexyl) sebacate as a plasticizer. The sensitivity of detection of tetracycline was five times higher than that of oxytetracycline and of terramycin, and 22 times higher than that of demeclocycline. A shelf-life of the prepared sensor was more than six months and was used for detection in spiked honey samples. These results open the way to having continuous monitoring sensors with a high detection capacity, are easy to clean, avoid the use of antibodies, and produce a direct measurement.
A Review of Commercial and Non-Commercial Wearables Devices for Monitoring Motor Impairments Caused by Neurodegenerative Diseases
Authors: Prieto-Avalos Guillermo , Sánchez-Morales Laura Nely , Alor-Hernández Giner , Sánchez-Cervantes José Luis
Published: January 2023

Neurodegenerative diseases (NDDs) are among the 10 causes of death worldwide. The effects of NDDs, including irreversible motor impairments, have an impact not only on patients themselves but also on their families and social environments. One strategy to mitigate the pain of NDDs is to early identify and remotely monitor related motor impairments using wearable devices. Technological progress has contributed to reducing the hardware complexity of mobile devices while simultaneously improving their efficiency in terms of data collection and processing and energy consumption. However, perhaps the greatest challenges of current mobile devices are to successfully manage the security and privacy of patient medical data and maintain reasonable costs with respect to the traditional patient consultation scheme. In this work, we conclude: (1) Falls are most monitored for Parkinson’s disease, while tremors predominate in epilepsy and Alzheimer’s disease. These findings will provide guidance for wearable device manufacturers to strengthen areas of opportunity that need to be addressed, and (2) Of the total universe of commercial wearables devices that are available on the market, only a few have FDA approval, which means that there is a large number of devices that do not safeguard the integrity of the users who use them.
Paper-Based Colorimetric Detection of miRNA-21 Using Pre-Activated Nylon Membrane and Peroxidase-Mimetic Activity of Cysteamine-Capped Gold Nanoparticles
Authors: Aamri Maliana El , Mohammadi Hasna , Amine Aziz
Published: January 2023

Irregular expression of MicroRNA-21 (miRNA-21) is considered as a promising biomarker for early cancer diagnosis. In this paper, a new genosensor based on paper and nanozyme activity of cysteamine-capped gold nanoparticles (Cys/AuNPs) was developed to detect picomolar concentrations of miRNA-21. Such nanozyme catalyzes the colorimetric reaction of hydrogen peroxide (H2O2) and 3,3′,5,5′ tetramethylbenzidine (TMB), to produce a blue color measurable by a smartphone. Due to their positive charge, Cys/AuNPs were attached to the negative phosphate groups of the DNA strand backbone via electrostatic interactions, leading to the quantitative determination of miRNA-21 concentration by the peroxidase-like activity of Cys/AuNPs. Furthermore, a paper-based assay was carried out on nylon disk devices to allow fast immobilization of DNAprobe. After performing the paper-based assay, a good linear range was observed between 1 pM and 1 nM (Y = 0.080 [MiRNA-21]/pM + 13.846, R2 = 0.993) with a detection limit of 0.5 pM. The developed method was effective, selective, and sensitive for the miRNA-21 detection. The application of the proposed method for miRNA-21 detection was examined in a human serum sample, and a recovery rate of 90.0–97.6% was obtained showing the acceptable accuracy of the developed approach.
Strain Sensor-Inserted Microchannel for Gas Viscosity Measurement
Authors: Shiba Kota , Liu Linbo , Li Guangming
Published: January 2023

Quantifying the viscosity of a gas is of great importance in determining its properties and can even be used to identify what the gas is. While many techniques exist for measuring the viscosities of gases, it is still challenging to probe gases with a simple, robust setup that will be useful for practical applications. We introduce a facile approach to estimating gas viscosity using a strain gauge inserted in a straight microchannel with a height smaller than that of the gauge. Using a constrained geometry for the strain gauge, in which part of the gauge deforms the channel to generate initial gauge strain that can be transduced into pressure, the pressure change induced via fluid flow was measured. The change was found to linearly correlate with fluid viscosity, allowing estimation of the viscosities of gases with a simple device.
Impact of Cranioplasty on Rehabilitation Course of Patients with Traumatic or Hemorrhagic Brain Injury
Authors: Mele Chiara , Bassetto Anna , Boetto Valentina , Nardone Antonio , Pingue Valeria
Published: January 2023

Background: Some authors have hypothesized that cranioplasty after decompressive craniectomy (DC) could positively influence functional recovery through several mechanisms. However, only a few studies with small sample sizes have investigated the effects of cranioplasty on functional recovery. Our study aims at evaluating the role of post-DC cranioplasty in influencing the functional recovery in a large cohort of patients with different etiologies of acquired brain injury (ABI). Methods: This retrospective study consecutively enrolled 253 patients with ABI, consisting of 108 adults who underwent post-DC cranioplasty and 145 adults who did not. All the subjects underwent a 6-month individual rehabilitation program. Demographic data, etiology, classification and anatomical site of brain injury, neurological and functional assessment at baseline and on discharge, and number of deaths during hospitalization were recorded. Results: In our cohort, 145 patients (57.3%) and 108 patients (42.7%) had, respectively, a hemorrhagic stroke (HS) and a traumatic brain injury (TBI). Only in the patients with TBI cranioplasty emerged as an independent predictor of better functional outcome in terms of the Functional Independence Measure (FIM) total score at discharge (β = 0.217, p = 0.001) and of the FIM variation during rehabilitation (ΔFIM) (β = 0.315, p = 0.001). Conversely, in the case of HS, no associations were found between post-DC cranioplasty and functional recovery. Conclusions: Post-DC cranioplasty was associated with better functional recovery six months after TBI but not in the patients with HS. Although the pathophysiological mechanisms underlying HS are different from those of TBI and possibly play a role in the different outcomes between the two groups, further studies are needed to investigate the mechanisms underlying the observed differences.
Association between Beta Oscillations from Subthalamic Nucleus and Quantitative Susceptibility Mapping in Deep Gray Matter Structures in Parkinson’s Disease
Authors: Lin Mangui , Cai Guoen , Li YongJie , Sun Yifang , Song Yang , Cai Guofa , Jiang Rifeng
Published: January 2023

This study aimed to investigate the association between beta oscillations and brain iron deposition. Beta oscillations were filtered from the microelectrode recordings of local field potentials (LFP) in the subthalamic nucleus (STN), and the ratio of the power spectral density of beta oscillations (PSDXb) to that of the LFP signals was calculated. Iron deposition in the deep gray matter (DGM) structures was indirectly assessed using quantitative susceptibility mapping (QSM). The Unified Parkinson’s Disease Rating Scale (UPDRS), part III, was used to assess the severity of symptoms. Spearman correlation coefficients were applied to assess the associations of PSDXb with QSM values in the DGM structures and the severity of symptoms. PSDXb showed a significant positive correlation with the average QSM values in DGM structures, including caudate and substantia nigra (SN) (p = 0.008 and 0.044). Similarly, the PSDXb showed significant negative correlations with the severity of symptoms, including axial symptoms and the gait in the medicine-off state (p = 0.006 for both). The abnormal iron metabolism in the SN and striatum pathways may be one of the underlying mechanisms for the occurrence of abnormal beta oscillations in the STN, and beta oscillations may serve as important pathophysiological biomarkers of PD.
Neuropsychological Alterations of Prolactinomas’ Cognitive Flexibility in Task Switching
Authors: Cao Chenglong , Wen Wen , Chen Aobo , Wang Shuochen , Xu Guozheng , Niu Chaoshi , Song Jian
Published: January 2023

Prolactinomas have been reported to impair cognition in broad aspects. However, few studies investigated the influence of prolactinomas on cognitive flexibility never mentioning the underlying neural and electrophysiological mechanism. We recorded scalp electroencephalography (EEG) in a colour-shape switching task. Patients with prolactinomas showed longer reaction time in switch trials and larger switch costs relative to healthy controls (HCs). Compared to HCs who showed stronger frontal theta activity in switch trials, the generally weak frontal theta activity in patients implied that they could not afford the executive control to configure task sets. Meanwhile, machine-learning based classification revealed that patients manifested non-selective brain patterns in response to different task types (colour vs. shape task) and different task states (switch vs. repeat state), which collectively suggested the cognitive dysfunction in preparation for a changing environment. Compared to HCs who showed stronger frontoparietal synchronization in switch trials, this enhanced frontoparietal connectivity was disrupted among patients with severe prolactinomas. This finding implicated greater hyperprolactinemia was linked to a larger decrease in cognitive performance. Taken together, the present study highlighted frontal theta power, and frontoparietal connectivity at theta band as the electrophysiological markers of the impaired cognitive flexibility and task control in patients with prolactinomas.
Intermediate-Length GGC Repeat Expansion in NOTCH2NLC Was Identified in Chinese Patients with Amyotrophic Lateral Sclerosis
Authors: Wan Mengxia , He Ji , Huo Junyan , Sun Can , Fu Yu , Fan Dongsheng
Published: January 2023

GGC repeat expansions in the 5’ untranslated region (5’UTR) of the Notch Homolog 2 N-terminal-like C gene (NOTCH2NLC) have been reported to be the genetic cause of neuronal intranuclear inclusion disease (NIID). However, whether they exist in other neurodegenerative disorders remains unclear. To determine whether there is a medium-length amplification of NOTCH2NLC in patients with amyotrophic lateral sclerosis (ALS), we screened 476 ALS patients and 210 healthy controls for the presence of a GGC repeat expansion in NOTCH2NLC by using repeat-primed polymerase chain reaction (RP-PCR) and fragment analysis. The repeat number in ALS patients was 16.11 ± 5.7 (range 7–46), whereas the repeat number in control subjects was 16.19 ± 3.79 (range 10–29). An intermediate-length GGC repeat expansion was observed in two ALS patients (numbers of repeats: 45, 46; normal repeat number ≤ 40) but not in the control group. The results suggested that the intermediate NOTCH2NLC GGC repeat expansion was associated with Chinese ALS patients, and further functional studies for intermediate-length variation are required to identify the mechanism.
Altered Fractional Amplitude of Low-Frequency Fluctuation in Anxious Parkinson’s Disease
Authors: Zhang Peiyao , Gao Yunpeng , Hu Yingying , Luo Yuan , Wang Lu , Wang Kang , Tian Hong , Jin Miao
Published: January 2023

Objective: Anxiety symptoms are persistent in Parkinson’s disease (PD), but the underlying neural substrates are still unclear. In the current study, we aimed to explore the underlying neural mechanisms in PD patients with anxiety symptoms. Methods: 42 PD-A patients, 41 PD patients without anxiety symptoms (PD-NA), and 40 healthy controls (HCs) were recruited in the present study. All the subjects performed 3.0T fMRI scans. The fractional amplitude of low-frequency fluctuation (fALFF) analysis was used to investigate the alterations in neural activity among the three groups. A Pearson correlation analysis was performed between the altered fALFF value of the PD-A group and anxiety scores. Results: Compared with HCs, PD-A patients had higher fALFF values in the left cerebellum, cerebellum posterior lobe, bilateral temporal cortex, and brainstem and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, and left inferior parietal lobule. Moreover, between the two PD groups, PD-A patients showed higher fALFF values in the right precuneus and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, left inferior parietal lobule, and left occipital lobe. Furthermore, Pearson’s correlation analysis demonstrated that the right precuneus and left caudate were correlated with the Hamilton Anxiety Rating Scale scores. Conclusion: Our study found that anxiety symptoms in PD patients may be related to alterations of neurological activities in multiple brain regions. Furthermore, these may be critical radiological biomarkers for PD-A patients. Therefore, these findings can improve our understanding of the pathophysiological mechanisms underlying PD-A.
10 Minutes Frontal 40 Hz tACS—Effects on Working Memory Tested by Luck-Vogel Task
Authors: Kvašňák Eugen , Magyarová Eva , Domankuš Miroslav , Tesař Michael , Kymplová Jaroslava , Fetissov Vitaly , Abubaker Mohammed , Al Qasem Wiam
Published: January 2023

Working memory is a cognitive process that involves short-term active maintenance, flexible updating, and processing of goal- or task-relevant information. All frequency bands are involved in working memory. The activities of the theta and gamma frequency bands in the frontoparietal network are highly involved in working memory processes; theta oscillations play a role in the temporal organization of working memory items, and gamma oscillations influence the maintenance of information in working memory. Transcranial alternating current stimulation (tACS) results in frequency-specific modulation of endogenous oscillations and has shown promising results in cognitive neuroscience. The electrophysiological and behavioral changes induced by the modulation of endogenous gamma frequency in the prefrontal cortex using tACS have not been extensively studied in the context of working memory. Therefore, we aimed to investigate the effects of frontal gamma-tACS on working memory outcomes. We hypothesized that a 10-min gamma tACS administered over the frontal cortex would significantly improve working memory outcomes. Young healthy participants performed Luck–Vogel cognitive behavioral tasks with simultaneous pre- and post-intervention EEG recording (Sham versus 40 Hz tACS). Data from forty-one participants: sham (15 participants) and tACS (26 participants), were used for the statistical and behavioral analysis. The relative changes in behavioral outcomes and EEG due to the intervention were analyzed. The results show that tACS caused an increase in the power spectral density in the high beta and low gamma EEG bands and a decrease in left-right coherence. On the other hand, tACS had no significant effect on success rates and response times. Conclusion: 10 min of frontal 40 Hz tACS was not sufficient to produce detectable behavioral effects on working memory, whereas electrophysiological changes were evident. The limitations of the current stimulation protocol and future directions are discussed in detail in the following sections.
A Discussion about the Rod Position in the Splitting Tensile Tests on Hollow Concrete Blocks
Authors: Chávez-Gómez Jorge H. , Álvarez-Pérez José , Mesa-Lavista Milena , Fajardo-San-Miguel G. , Cavazos-de-Lira Diego , González-Alcorta Ricardo
Published: January 2023

Different loading conditions cause different tensile stress patterns in masonry structures. Several studies related to masonry behavior use indirect tensile tests to obtain that value, where the splitting test from ASTM-C-1006 is usually employed. In this paper, an experimental analysis of the tensile strength of hollow concrete blocks is reported. Different locations of the rod from the ASTM-C-1006 splitting test were analyzed. The tensile strength was evaluated in four different ways, placing the rod: (1) in the transversal direction over the gross area, (2) in the transversal direction over the net area, (3) in the longitudinal direction, and (4) 200 mm from the central region of the block in the longitudinal direction. The obtained results were compared with the tensile strength values measured from the direct tensile test in the longitudinal direction. In addition, an axial compressive test was performed to characterize the blocks, and a discussion about the tensile/compression ratio is shown. The experimental results from the splitting tests show that for each configuration setup, the tensile stress is different. The main result was that the splitting test over the net area with the rod positioned in the longitudinal direction can overestimate the tensile strength by more than 21% of the one over the gross area.
Mechanical Property and Dimensional Stability of Chopped Basalt Fiber-Reinforced Recycled Concrete and Modeling with Fuzzy Inference System
Authors: Jiao Chu-Jie , Zhang Xiu-Cheng , Chen Wei-Zhi , Chen Xue-Fei
Published: January 2023

The rising amount of construction and demolition wastes (C & DWs) is triggering serious environmental and social problems globally. This study conducted an experimental investigation of basalt fiber (BF)-reinforced concrete with recycled aggregates (RAs) sourced from C & DWs. The flexural strength, the flexural to compressive strength ratio, and the drying shrinkage are set as indicators for the evaluation of the coupling effect of BF and RA in concrete. Results show that BF generated a significant effect on the flexural strength until the BF dosage was no higher than 1%. The excessive mixing amount of BF, though it still contributed to a positive effect on elevating the flexural strength, was of a reduced utility. Regarding the flexural to compressive strength ratio (denoted as ratio), BF and RA jointly produced a positive synergistic effect. In addition, the BF was verified as competent in curbing the adverse effect of RA incorporation upon the drying shrinkage. Relative to the benchmark concrete which contains 100% RA and no BF, 1% BF contributed to a 31.6% reduction in the drying shrinkage. The results prove that BF reinforcement is a feasible and promising approach to curb the drawbacks of RA concrete.
Optimizing Building Orientation and Roof Angle of a Typhoon-Resilient Single-Family House Using Genetic Algorithm and Computational Fluid Dynamics
Authors: Mata Jun L. , Orejudos Jerson N. , Opon Joel G. , Guirnaldo Sherwin A.
Published: January 2023

In the event of a typhoon, the majority of houses suffer from large amounts of damage because they were not built with typhoon resilience in mind. For instance, the Philippines is one of the world’s most vulnerable countries to typhoons. Often, roof structures are ripped off during typhoons with average or more vigorous wind gustiness, and houses are easily ruined. This situation led us to search for the appropriate building orientation and roof angle of single-family residential houses through simulations using MATLAB’s genetic algorithm (GA) and SolidWorks’ computational fluid dynamics (CFD). The GA provides the set of design points, while CFD generates a fitness score for each design point. The goal of the optimization is to determine the orientation and roof angle while minimizing the drag force along the direction of a constant wind speed (315 km/h). The lower and upper bounds for house orientation are 0∘ and 90∘, respectively; the roof angle is between 3∘ and 60∘. After 100 generations, the GA converged to values equal to an 80∘ orientation and 11∘ roof angle. The final results provide a good standpoint for future experiments on physical structures.
In Vitro Diffuse Large B-Cell Lymphoma Cell Line Models as Tools to Investigate Novel Immunotherapeutic Strategies
Authors: Kubacz Matylda , Kusowska Aleksandra , Winiarska Magdalena , Bobrowicz Małgorzata
Published: January 2023

Despite the high incidence of diffuse large B-cell lymphoma (DLBCL), its management constitutes an ongoing challenge. The most common DLBCL variants include activated B-cell (ABC) and germinal center B-cell-like (GCB) subtypes including DLBCL with MYC and BCL2/BCL6 rearrangements which vary among each other with sensitivity to standard rituximab (RTX)-based chemoimmunotherapy regimens and lead to distinct clinical outcomes. However, as first line therapies lead to resistance/relapse (r/r) in about half of treated patients, there is an unmet clinical need to identify novel therapeutic strategies tailored for these patients. In particular, immunotherapy constitutes an attractive option largely explored in preclinical and clinical studies. Patient-derived cell lines that model primary tumor are indispensable tools that facilitate preclinical research. The current review provides an overview of available DLBCL cell line models and their utility in designing novel immunotherapeutic strategies.