bluuebunny/crossref_metadata_2025 huggingface dataset:
Isothiocyanates Potentiate Tazemetostat-Induced Apoptosis by Modulating the Expression of Apoptotic Genes, Members of Polycomb Repressive Complex 2, and Levels of Tri-Methylating Lysine 27 at Histone 3 in Human Malignant Melanoma Cells
Authors: Anestopoulos Ioannis , Paraskevaidis Ioannis , Kyriakou Sotiris , Giova Lambrini E. , Trafalis Dimitrios T. , Botaitis Sotiris , Franco Rodrigo , Pappa Aglaia , Panayiotidis Mihalis I.
Published: February 2024

In this study, we utilized an in vitro model consisting of human malignant melanoma as well as non-tumorigenic immortalized keratinocyte cells with the aim of characterizing the therapeutic effectiveness of the clinical epigenetic drug Tazemetostat alone or in combination with various isothiocyanates. In doing so, we assessed markers of cell viability, apoptotic induction, and expression levels of key proteins capable of mediating the therapeutic response. Our data indicated, for the first time, that Tazemetostat caused a significant decrease in viability levels of malignant melanoma cells in a dose- and time-dependent manner via the induction of apoptosis, while non-malignant keratinocytes were more resistant. Moreover, combinatorial treatment protocols caused a further decrease in cell viability, together with higher apoptotic rates. In addition, a significant reduction in the Polycomb Repressive Complex 2 (PRC2) members [e.g., Enhancer of Zeste Homologue 2 (EZH2), Embryonic Ectoderm Development (EED), and suppressor of zeste 12 (SUZ12)] and tri-methylating lysine 27 at Histone 3 (H3K27me3) protein expression levels was observed, at least partially, under specific combinatorial exposure conditions. Reactivation of major apoptotic gene targets was determined at much higher levels in combinatorial treatment protocols than Tazemetostat alone, known to be involved in the induction of intrinsic and extrinsic apoptosis. Overall, we developed an optimized experimental therapeutic platform aiming to ensure the therapeutic effectiveness of Tazemetostat in malignant melanoma while at the same time minimizing toxicity against neighboring non-tumorigenic keratinocyte cells.
Synergy between PEDF and Doxorubicin in Breast Cancer Cells: Effects on Metastatic and Metabolic Pathways
Authors: Abooshahab Raziyeh , Al-Salami Hani , Dass Crispin R.
Published: February 2024

Pigment epithelium-derived factor (PEDF), a serine protease inhibitor (Serpin) family member, shows promise in inhibiting tumour growth. In our study, we explored the effects of PEDF on the efficacy of the frontline chemotherapy agent doxorubicin (Dox) in BC cells. We found that Dox+PEDF treatment significantly reduced glucose uptake in MDA-MB-231 cells compared to the control (p = 0.0005), PEDF (p = 0.0137), and Dox (p = 0.0171) alone but paradoxically increased it in MCF-7 cells. Our findings further revealed that PEDF, Dox, and Dox+PEDF substantially hindered tumour cell migration from tumour spheroids, with Dox+PEDF showing the most significant impact (p < 0.0001). We also observed notable decreases in the expression of metastatic markers (uPAR, uPA, CXCR4, MT1-MMP, TNF-α) across all treatment groups (p < 0.0001) in both cell lines. When it comes to metabolic pathways, PEDF increased phosphorylated IRS-1 (p-IRS1) levels in MDA-MB-231 and MCF-7 (p < 0.0001), while Dox decreased it, and the combination led to an increase. In MDA-MB-231 cells, treatment with PEDF, Dox, and the combination led to a notable decrease in both phosphorylated AKT (p-AKT) and total AKT levels. In MCF-7, while PEDF, Dox, and their combination led to a reduction in p-AKT, total levels of AKT increased in the presence of Dox and Dox+PEDF. Combining PEDF with Dox enhances the targeting of metastatic and metabolic pathways in breast cancer cell lines. This synergy, marked by PEDF’s increasing roles in cancer control, may pave the way for more effective cancer treatments.
Pathophysiological Roles of Ion Channels in Epidermal Cells, Immune Cells, and Sensory Neurons in Psoriasis
Authors: Kim Hyungsup , Choi Mi Ran , Jeon Seong Ho , Jang Yongwoo , Yang Young Duk
Published: February 2024

Psoriasis is a chronic inflammatory skin disease characterized by the rapid abnormal growth of skin cells in the epidermis, driven by an overactive immune system. Consequently, a complex interplay among epidermal cells, immune cells, and sensory neurons contributes to the development and progression of psoriasis. In these cellular contexts, various ion channels, such as acetylcholine receptors, TRP channels, Ca2+ release-activated channels, chloride channels, and potassium channels, each serve specific functions to maintain the homeostasis of the skin. The dysregulation of ion channels plays a major role in the pathophysiology of psoriasis, affecting various aspects of epidermal cells, immune responses, and sensory neuron signaling. Impaired function of ion channels can lead to altered calcium signaling, inflammation, proliferation, and sensory signaling, all of which are central features of psoriasis. This overview summarizes the pathophysiological roles of ion channels in epidermal cells, immune cells, and sensory neurons during early and late psoriatic processes, thereby contributing to a deeper understanding of ion channel involvement in the interplay of psoriasis and making a crucial advance toward more precise and personalized approaches for psoriasis treatment.
Functional Studies of Deafness-Associated Pendrin and Prestin Variants
Authors: Takahashi Satoe , Kojima Takashi , Wasano Koichiro , Homma Kazuaki
Published: February 2024

Pendrin and prestin are evolutionary-conserved membrane proteins that are essential for normal hearing. Dysfunction of these proteins results in hearing loss in humans, and numerous deafness-associated pendrin and prestin variants have been identified in patients. However, the pathogenic impacts of many of these variants are ambiguous. Here, we report results from our ongoing efforts to experimentally characterize pendrin and prestin variants using in vitro functional assays. With previously established fluorometric anion transport assays, we determined that many of the pendrin variants identified on transmembrane (TM) 10, which contains the essential anion binding site, and on the neighboring TM9 within the core domain resulted in impaired anion transport activity. We also determined the range of functional impairment in three deafness-associated prestin variants by measuring nonlinear capacitance (NLC), a proxy for motor function. Using the results from our functional analyses, we also evaluated the performance of AlphaMissense (AM), a computational tool for predicting the pathogenicity of missense variants. AM prediction scores correlated well with our experimental results; however, some variants were misclassified, underscoring the necessity of experimentally assessing the effects of variants. Together, our experimental efforts provide invaluable information regarding the pathogenicity of deafness-associated pendrin and prestin variants.
Anti Gram-Positive Bacteria Activity of Synthetic Quaternary Ammonium Lipid and Its Precursor Phosphonium Salt
Authors: Bacchetti Francesca , Schito Anna Maria , Milanese Marco , Castellaro Sara , Alfei Silvana
Published: February 2024

Organic ammonium and phosphonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Particularly, quaternary ammonium lipids have demonstrated efficiency both as gene vectors and antibacterial agents. Here, aiming at finding new antibacterial devices belonging to both classes, we prepared a water-soluble quaternary ammonium lipid (6) and a phosphonium salt (1) by designing a synthetic path where 1 would be an intermediate to achieve 6. All synthesized compounds were characterized by Fourier-transform infrared spectroscopy and Nuclear Magnetic Resonance. Additionally, potentiometric titrations of NH3+ groups 1 and 6 were performed to further confirm their structure by determining their experimental molecular weight. The antibacterial activities of 1 and 6 were assessed first against a selection of multi-drug-resistant clinical isolates of both Gram-positive and Gram-negative species, observing remarkable antibacterial activity of both compounds against Gram-positive isolates of Enterococcus and Staphylococcus genus. Further investigations on a wider variety of strains of these species confirmed the remarkable antibacterial effects of 1 and 6 (MICs = 4–16 and 4–64 µg/mL, respectively), while 24 h-time-killing experiments carried out with 1 on different S. aureus isolates evidenced a bacteriostatic behavior. Moreover, both compounds 1 and 6, at the lower MIC concentration, did not show significant cytotoxic effects when exposed to HepG2 human hepatic cell lines, paving the way for their potential clinical application.
Matrix Metalloproteinases in the Periodontium—Vital in Tissue Turnover and Unfortunate in Periodontitis
Authors: Radzki Dominik , Negri Alessandro , Kusiak Aida , Obuchowski Michał
Published: February 2024

The extracellular matrix (ECM) is a complex non-cellular three-dimensional macromolecular network present within all tissues and organs, forming the foundation on which cells sit, and composed of proteins (such as collagen), glycosaminoglycans, proteoglycans, minerals, and water. The ECM provides a fundamental framework for the cellular constituents of tissue and biochemical support to surrounding cells. The ECM is a highly dynamic structure that is constantly being remodeled. Matrix metalloproteinases (MMPs) are among the most important proteolytic enzymes of the ECM and are capable of degrading all ECM molecules. MMPs play a relevant role in physiological as well as pathological processes; MMPs participate in embryogenesis, morphogenesis, wound healing, and tissue remodeling, and therefore, their impaired activity may result in several problems. MMP activity is also associated with chronic inflammation, tissue breakdown, fibrosis, and cancer invasion and metastasis. The periodontium is a unique anatomical site, composed of a variety of connective tissues, created by the ECM. During periodontitis, a chronic inflammation affecting the periodontium, increased presence and activity of MMPs is observed, resulting in irreversible losses of periodontal tissues. MMP expression and activity may be controlled in various ways, one of which is the inhibition of their activity by an endogenous group of tissue inhibitors of metalloproteinases (TIMPs), as well as reversion-inducing cysteine-rich protein with Kazal motifs (RECK).
Transcriptional Landscape of CUT-Class Homeobox Genes in Blastic Plasmacytoid Dendritic Cell Neoplasm
Authors: Nagel Stefan , Rand Ulfert , Pommerenke Claudia , Meyer Corinna
Published: February 2024

Homeobox genes encode developmental transcription factors regulating tissue-specific differentiation processes and drive cancerogenesis when deregulated. Dendritic cells (DCs) are myeloid immune cells occurring as two types, either conventional or plasmacytoid DCs. Recently, we showed that the expression of NKL-subclass homeobox gene VENTX is restricted to conventional DCs, regulating developmental genes. Here, we identified and investigated homeobox genes specifically expressed in plasmacytoid DCs (pDCs) and derived blastic plasmacytoid dendritic cell neoplasm (BPDCN). We analyzed gene expression data, performed RQ-PCR, protein analyses by Western blot and immuno-cytology, siRNA-mediated knockdown assays and subsequent RNA-sequencing and live-cell imaging. Screening of public gene expression data revealed restricted activity of the CUT-class homeobox gene CUX2 in pDCs. An extended analysis of this homeobox gene class in myelopoiesis showed that additional CUX2 activity was restricted to myeloid progenitors, while BPDCN patients aberrantly expressed ONECUT2, which remained silent in the complete myeloid compartment. ONECUT2 expressing BPDCN cell line CAL-1 served as a model to investigate its regulation and oncogenic activity. The ONECUT2 locus at 18q21 was duplicated and activated by IRF4, AUTS2 and TNF-signaling and repressed by BMP4-, TGFb- and IL13-signalling. Functional analyses of ONECUT2 revealed the inhibition of pDC differentiation and of CDKN1C and CASP1 expression, while SMAD3 and EPAS1 were activated. EPAS1 in turn enhanced survival under hypoxic conditions which thus may support dendritic tumor cells residing in hypoxic skin lesions. Collectively, we revealed physiological and aberrant activities of CUT-class homeobox genes in myelopoiesis including pDCs and in BPDCN, respectively. Our data may aid in the diagnosis of BPDCN patients and reveal novel therapeutic targets for this fatal malignancy.
Analysis of the Effect of an Open Hole on the Buckling of a Compressed Composite Plate
Authors: Wysmulski Pawel
Published: February 2024

This paper investigates the effect of an open hole on the stability of a compressed laminated composite plate. The study was carried out in two ways: using experimental tests and numerical analysis. As a result of the experiment, the buckling form and path of the plate were recorded. The form of buckling was determined using the ARAMIS non-contact measurement system. The critical load value was determined from the working path using the approximation method. The experimental results were verified by numerical analysis based on the finite element method. FEM investigations were carried out in terms of a linear eigenproblem analysis. This allowed the bifurcation load and the corresponding buckling form of the numerical model of the plate to be determined. Investigating the effect of the hole in the compressed plate at a critical state showed high agreement between the proposed test methods. No clear effect of the hole size on the buckling of the plate was observed. In contrast, a clear effect of the hole on the critical load value was determined. The maximum decrease in the critical load value was 14%. The same decrease was observed for the stiffness of the post-critical characteristics. It was shown that the [45|−45|90|0]s composite plate had more than three times lower strength compared to [0|−45|45|90]s and [0|90|0|90]s. The novelty of this article is the development of a research methodology based on new interdisciplinary research methods for describing the influence of the central hole on the stability of compressed composite plates. The ABAQUS system was used for the numerical analysis.
Investigation of Physical Characteristics and In Vitro Anti-Inflammatory Effects of Fucoidan from Padina arborescens: A Comprehensive Assessment against Lipopolysaccharide-Induced Inflammation
Authors: Lee Hyo-Geun , Liyanage N. , Yang Fengqi , Kim Young-Sang , Lee Seung-Hong , Ko Seok-Chun , Yang Hye-Won , Jeon You-Jin
Published: February 2024

A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from Padina arborescens (PAC) using celluclast-assisted extraction, purified, and evaluated for its anti-inflammatory potential in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structural analyses were performed using Fourier transform infrared (FTIR) and scanning electron microscopy. Among the purified fucoidans, fucoidan fraction 5 (F5) exhibited strong inhibitory activity against LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine generation through the regulation of iNOS/COX-2, MAPK, and NF-κB signaling in LPS-induced RAW 264.7 cells. Determination of the structural characteristics indicated that purified F5 exhibited characteristics similar to those of commercial fucoidan. In addition, further analyses suggested that F5 inhibits LPS-induced toxicity, cell death, and NO generation in zebrafish models. Taken together, these findings imply that P. arborescens fucoidans have exceptional anti-inflammatory action, both in vitro and in vivo, and that they may have prospective uses in the functional food sector.
Hollow Microcavity Electrode for Enhancing Light Extraction
Authors: Park Seonghyeon , Kang Byeongwoo , Lee Seungwon , Bi Jian Cheng , Park Jaewon , Hwang Young Hyun , Park Jun-Young , Hwang Ha , Park Young Wook , Ju Byeong-Kwon
Published: February 2024

Luminous efficiency is a pivotal factor for assessing the performance of optoelectronic devices, wherein light loss caused by diverse factors is harvested and converted into the radiative mode. In this study, we demonstrate a nanoscale vacuum photonic crystal layer (nVPCL) for light extraction enhancement. A corrugated semi-transparent electrode incorporating a periodic hollow-structure array was designed through a simulation that utilizes finite-difference time-domain computational analysis. The corrugated profile, stemming from the periodic hollow structure, was fabricated using laser interference lithography, which allows the precise engineering of various geometrical parameters by controlling the process conditions. The semi-transparent electrode consisted of a 15 nm thick Ag film, which acted as the exit mirror and induced microcavity resonance. When applied to a conventional green organic light-emitting diode (OLED) structure, the optimized nVPCL-integrated device demonstrated a 21.5% enhancement in external quantum efficiency compared to the reference device. Further, the full width at half maximum exhibited a 27.5% reduction compared to that of the reference device, demonstrating improved color purity. This study presents a novel approach by applying a hybrid thin film electrode design to optoelectronic devices to enhance optical efficiency and color purity.
Insights on Determining Improved Conditions for Multipurpose Reagent Dosing to Increase Froth Flotation Efficiency: NaSH in Cu-Mo Selective Flotation Case Study
Authors: Fernandez Braulio , Montes-Atenas Gonzalo , Valenzuela Fernando , Yarmuch Juan Luis
Published: February 2024

The assessment of mineral surface hydrophobicity at the industrial scale is a challenge. In some industrial situations, such information is indirectly obtained from other proxy variables. A well-known example of this is observed in the Cu-Mo selective flotation operation, where sodium hydrosulphide is used to change the redox potential and, controlling this value, determine when Cu-sulphide floatability is inhibited. Preliminary experiments indicate that this reagent may also promote the formation of solid precipitates, reducing its impact on the redox potential. This study aims at designing a simple strategy at the laboratory scale to report and quantify NaSH losses due to parallel, irreversible, and/or fast reactions, such as precipitation. Experiments carried out using process water coming from a Cu-Mo selective flotation plant in Chile show that departing from different pH conditions and the addition of hydrosulphide ions effectively triggers the precipitation of specific metal ions, decreasing its availability to reduce the redox potential of the aqueous solution. For this specific case scenario and water quality, around 5% of the NaSH dosed precipitated. An SEM-EDX analysis of the produced solid phase shows that it is composed of mainly iron sulphide and hydroxide, along with other metal hydroxides. More importantly, it was found that dosing the reagent at the same concentration, but in the form of small increments, allows reaching the redox potential more efficiently, reducing to some extent the precipitate production and the unnecessary NaSH consumption in up to 30% of the NaSH dosed. Preliminary 1-D modelling of the process, based on mass transport coupled with reaction mechanisms, provided a first indication of the best dosing conditions for this reagent. The latter is expected to contribute to the development of better and improved reagent dosage technologies in froth flotation environments.
Elastic Properties of Alloyed Cementite M3X (M = Fe, Cr; X = C, B) Phases from First-Principle Calculations and CALPHAD Model
Authors: Huang Yongxing , Lin Yang , Wang Guangchi , Jiang Yehua , Chong Xiaoyu
Published: February 2024

Fe-Cr-C-B wear-resistant steels are widely used as wear-resistant alloys in harsh environments. The M3X (M = Fe, Cr; X = C, B) cementite-type material is a commonly used strengthening phase in these alloys. This study investigated the mechanical properties of cementite (Fe, Cr)3(C, B) using the first-principle density functional theory. We constructed crystal structures of (Fe, Cr)3(C, B) with different concentrations of Cr and B. The bulk modulus, shear modulus, Young’s modulus, Poisson’s ratio, and hardness of the material were calculated, and a comprehensive mechanical property database based on CALPHAD modeling of the full composition was established. The optimal concentrations of the (Fe, Cr)3(C, B) phase were systematically evaluated across its entire composition range. The material exhibited the highest hardness, shear modulus, and Young’s modulus at Cr and B concentrations in the range of 70–95 at% and 40 at%, respectively, rendering it difficult to compress and relatively poor in machinability. When the B content exceeded 90 at%, and the Cr content was zero, the shear modulus and hardness were low, resulting in poor resistance to deformation, reduced stiffness, and ease of plastic processing. This study provides an effective alloying strategy for balancing the brittleness and toughness of (Fe, Cr)3(C, B) phases.
Cancer-Related Mutations in the Sam Domains of EphA2 Receptor and Ship2 Lipid Phosphatase: A Computational Study
Authors: Vincenzi Marian , Mercurio Flavia Anna , Autiero Ida , Leone Marilisa
Published: February 2024

The lipid phosphatase Ship2 interacts with the EphA2 receptor by forming a heterotypic Sam (sterile alpha motif)–Sam complex. Ship2 works as a negative regulator of receptor endocytosis and consequent degradation, and anti-oncogenic effects in cancer cells should be induced by hindering its association with EphA2. Herein, a computational approach is presented to investigate the relationship between Ship2-Sam/EphA2-Sam interaction and cancer onset and further progression. A search was first conducted through the COSMIC (Catalogue of Somatic Mutations in Cancer) database to identify cancer-related missense mutations positioned inside or close to the EphA2–Sam and Ship2–Sam reciprocal binding interfaces. Next, potential differences in the chemical–physical properties of mutant and wild-type Sam domains were evaluated by bioinformatics tools based on analyses of primary sequences. Three-dimensional (3D) structural models of mutated EphA2–Sam and Ship2–Sam domains were built as well and deeply analysed with diverse computational instruments, including molecular dynamics, to classify potentially stabilizing and destabilizing mutations. In the end, the influence of mutations on the EphA2–Sam/Ship2–Sam interaction was studied through docking techniques. This in silico approach contributes to understanding, at the molecular level, the mutation/cancer relationship by predicting if amino acid substitutions could modulate EphA2 receptor endocytosis.
Efficient Escorting Strategy for Aggregation-Prone Notch EGF Repeats with Sparcl1
Authors: Kondo Yuji , Li Yuxin , Okajima Tetsuya
Published: February 2024

Epidermal growth factor (EGF) repeats are present in various proteins and form well-defined structures with three disulfide bonds. One representative protein is the Notch receptor. Each EGF repeat contains unique atypical O-linked glycans, such as O-linked N-acetylglucosamine (O-GlcNAc). To generate a monoclonal antibody against the O-GlcNAc moiety in mouse Notch1, we expressed the recombinant C-terminal His6-tagged Notch1 EGF14-15 protein in HEK293T cells to prepare the immunogen. Most of the proteins were not secreted and showed higher molecular weight ladders in the cell lysate, suggesting protein aggregation. To overcome this issue, we fused Sparcl1 as an extracellular escorting tag to the N-terminus of Notch1 EGF14-15. The fusion protein was efficiently secreted extracellularly without protein aggregates in the lysates. Following PreScission protease treatment, Notch1 EGF14-15 was efficiently released from the escorting tag. Notch1 EGF14-15 prepared using this method was indeed O-GlcNAcylated. The optimal length of the escorting tag was determined by generating deletion mutants to improve the extracellular secretion of EGF14-15. Hence, a large amount of EGF14-15 was successfully prepared from the culture supernatant of HEK293T cells, which were otherwise prone to aggregation.
Production and Immunogenicity Assessment of LTp50: An Escherichia coli-Made Chimeric Antigen Targeting S1- and S2-Epitopes from the SARS-CoV-2/BA.5 Spike Protein
Authors: Wong-Arce Alejandra , Gonzalez-Ortega Omar , Romero-Maldonado Andrea , Miranda-López Arleth , García-Soto Mariano , Farfán-Castro Susan , Betancourt-Mendiola Lourdes , Teeravechyan Samaporn , Srisutthisamphan Kanjana , Comas-García Mauricio , Solís Andrade Karla I. , Rosales-Mendoza Sergio
Published: February 2024

Subunit vaccines stand as a leading approach to expanding the current portfolio of vaccines to fight against COVID-19, seeking not only to lower costs but to achieve long-term immunity against variants of concern and have the main attributes that could overcome the limitations of the current vaccines. Herein a chimeric protein targeting S1 and S2 epitopes, called LTp50, was designed as a convenient approach to induce humoral responses against SARS-CoV-2. LTp50 was produced in recombinant Escherichia coli using a conventional pET vector, recovering the expected antigen in the insoluble fraction. LTp50 was purified by chromatography (purity > 90%). The solubilization and refolding stages helped to obtain a stable protein amenable for vaccine formulation. LTp50 was adsorbed onto alum, resulting in a stable formulation whose immunogenic properties were assessed in BALB/c mice. Significant humoral responses against the S protein (BA.5 variant) were detected in mice subjected to three subcutaneous doses (10 µg) of the LTp50/alum formulation. This study opens the path for the vaccine formulation optimization using additional adjuvants to advance in the development of a highly effective anti-COVID-19 vaccine directed against the antigenic regions of the S protein, which are less prone to mutations.
Use of Medicinal Plants in the Process of Wound Healing: A Literature Review
Authors: Cedillo-Cortezano Mayra , Martinez-Cuevas Luis Ruben , López Jesús A. Márquez , Barrera López Ingrid L. , Escutia-Perez Samantha , Petricevich Vera L.
Published: February 2024

The literature on the use of medicinal plants in wound healing was comprehensively searched to obtain and assess the data. The data were procured via clinical studies that utilized medicinal plants and their compounds in vitro and in vivo for wound healing. This review collected data from electronic databases, including Google Scholar, PubMed, Science Direct, Web of Science, SciFinder, Thesis, and Scopus, using the search terms “natural products”, “wound healing”, and “natural compounds”, along with the keywords “plants”, “extracts”, and “phytochemicals”. Results from the last decade reveal a total of 62 families and 109 genera of medicinal plants, and their compounds have been studied experimentally both in vivo and in vitro and clinically found to effectively promote healing. This activity is related to the presence of secondary metabolites such as flavonoids, alkaloids, saponins, tannins, terpenoids, and phenolic compounds, which act at different stages through different mechanisms to exert anti-inflammatory, antimicrobial, and antioxidant effects, confirming that the use of medicinal plants could be an adequate alternative to current conventional practices for treating wounds.
Advancing Precision Medicine: A Review of Innovative In Silico Approaches for Drug Development, Clinical Pharmacology and Personalized Healthcare
Authors: Marques Lara , Costa Bárbara , Pereira Mariana , Silva Abigail , Santos Joana , Saldanha Leonor , Silva Isabel , Magalhães Paulo , Schmidt Stephan , Vale Nuno
Published: February 2024

The landscape of medical treatments is undergoing a transformative shift. Precision medicine has ushered in a revolutionary era in healthcare by individualizing diagnostics and treatments according to each patient’s uniquely evolving health status. This groundbreaking method of tailoring disease prevention and treatment considers individual variations in genes, environments, and lifestyles. The goal of precision medicine is to target the “five rights”: the right patient, the right drug, the right time, the right dose, and the right route. In this pursuit, in silico techniques have emerged as an anchor, driving precision medicine forward and making this a realistic and promising avenue for personalized therapies. With the advancements in high-throughput DNA sequencing technologies, genomic data, including genetic variants and their interactions with each other and the environment, can be incorporated into clinical decision-making. Pharmacometrics, gathering pharmacokinetic (PK) and pharmacodynamic (PD) data, and mathematical models further contribute to drug optimization, drug behavior prediction, and drug–drug interaction identification. Digital health, wearables, and computational tools offer continuous monitoring and real-time data collection, enabling treatment adjustments. Furthermore, the incorporation of extensive datasets in computational tools, such as electronic health records (EHRs) and omics data, is also another pathway to acquire meaningful information in this field. Although they are fairly new, machine learning (ML) algorithms and artificial intelligence (AI) techniques are also resources researchers use to analyze big data and develop predictive models. This review explores the interplay of these multiple in silico approaches in advancing precision medicine and fostering individual healthcare. Despite intrinsic challenges, such as ethical considerations, data protection, and the need for more comprehensive research, this marks a new era of patient-centered healthcare. Innovative in silico techniques hold the potential to reshape the future of medicine for generations to come.
Oromucosal Administration of Oxytocin: The Development of ‘Oxipops’
Authors: Xu Dan , Lan Chunmei , Kou Juan , Yao Shuxia , Zhao Weihua , Kendrick Keith M.
Published: February 2024

The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research over the last few decades due, most notably, to its reported involvement in promoting social cognition and motivation, reducing anxiety, and relieving pain. It is also increasingly being considered as an important therapeutic intervention in a variety of disorders with social dysfunction as a symptom. While, in recent years, studies in humans have administered oxytocin primarily via an intranasal route, since it may partly enter the brain directly this way via the olfactory and trigeminal nerves, there is increasing evidence that many of its functional effects can be peripherally mediated via increasing its concentration in the blood. This has opened up an oromucosal administration route as an alternative, which is beneficial since the oral consumption of peptides is problematic due to their rapid breakdown in the acidic environment of the gastrointestinal system. In this review we will discuss both the methodologies we have developed for administering oxytocin via lingual application and medicated lollipops, ‘oxipops’, in terms of increasing blood concentrations and the bioavailability of the peptide, and also their validation in terms of functional effects on the brain and behavior. While areas under the curve are significantly greater in terms of plasma oxytocin concentrations following intranasally relative to oromucosally administered oxytocin, with the estimated absolute bioavailability of the latter being around 4.4% compared with 11.1% for intranasal administration, the time to peak concentrations (around 30 min) and functional effects on the brain and behavior are broadly similar. We will also discuss potential therapeutic advantages of the oromucosal administration of oxytocin in different clinical contexts and its wider application for other peptides which are increasingly being developed for therapeutic use.
Polyolefin-Based Smart Self-Healing Composite Coatings Modified with Calcium Carbonate and Sodium Alginate
Authors: Nawaz Muddasir , Shakoor Rana Abdul , Al-Qahtani Noora , Bhadra Jolly , Al-Thani Noora Jabor , Kahraman Ramazan
Published: February 2024

Corrosion-related damage incurs significant capital costs in many industries. In this study, an anti-corrosive pigment was synthesized by modifying calcium carbonate with sodium alginate (SA), and smart self-healing coatings were synthesized by reinforcing the anti-corrosive pigments into a polyolefin matrix. Structural changes during the synthesis of the anti-corrosive pigment were examined using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Moreover, thermal gravimetric analysis confirmed the loading of the corrosion inhibitor, and electrochemical impedance spectroscopic analysis revealed a stable impedance value, confirming the improved corrosion resistance of the modified polyolefin coatings. The incorporation of the anticorrosive pigment into a polyolefin matrix resulted in improved pore resistance properties and capacitive behavior, indicating a good barrier property of the modified coatings. The formation of a protective film on the steel substrate reflected the adsorption of the corrosion inhibitor (SA) on the steel substrate, which further contributed to enhancing the corrosion resistance of the modified coatings. Moreover, the formation of the protective film was also analyzed by profilometry and elemental mapping analysis.
The Effect of Carbon-Based Nanofillers on Cryogenic Temperature Mechanical Properties of CFRPs
Authors: Zotti Aldobenedetto , Zuppolini Simona , Borriello Anna , Vinti Valeria , Trinchillo Luigi , Zarrelli Mauro
Published: February 2024

In the present work, the effects of carbon-based nanofillers (0.5 wt%), i.e., graphene nanoplatelets (GNPs), carbon nanofibers (CNFs), and carbon nanotubes (CNTs), on the cryogenic temperature (77 K) mechanical properties of carbon fiber reinforced polymers (CFRPs) were investigated. The study utilized an ex situ conditioning method for cryogenic tests. The nanofillers were mixed with the epoxy matrix by a solvent-free fluidized bed mixing technique (FBM), while unidirectional carbon fibers were impregnated with the resulting nanocomposites to manufacture CFRP samples. Optical microscopy was employed to analyze the dispersion of the carbon-based fillers within the matrix, revealing a homogeneous distribution in nanocomposites containing GNPs and CNFs. Fracture toughness tests confirmed the homogeneity of the GNP-loaded systems, showing an improvement in the stress intensity factor (KC) by 13.2% and 14.7% compared to the unmodified matrix at RT (25 °C) and 77 K, respectively; moreover, flexural tests demonstrated a general increase in flexural strength with the presence of carbon-based nanofillers at both temperature levels (RT and 77 K). Additionally, interlaminar shear strength (ILSS) tests were performed and analyzed using the same ex situ conditioning method.
Development and Characterization of Bio-Based Formaldehyde Free Sucrose-Based Adhesive for Fabrication of Plywood
Authors: Liu Longjiang , Jia Yongbo , Zheng Lulu , Luo Rui , Essawy Hisham , Huang Heming , Wang Yaming , Deng Shuduan , Zhang Jun
Published: February 2024

In order to solve the problem of excessive consumption of petrochemical resources and the harm of free formaldehyde release to human health, biomass raw materials, such as sucrose (S) and ammonium dihydrogen phosphate (ADP) can be chemically condensed in a simple route under acidic conditions to produce a formaldehyde free wood adhesive (S-ADP), characterized by good storage stability and water resistance, and higher wet shear strength with respect to petroleum based phenolic resin adhesive. The dry and boiling shear strength of the plywood based on S-ADP adhesive are as high as 1.05 MPa and 1.19 MPa, respectively. Moreover, is Modulus of Elasticity (MOE) is as high as 4910 MPa. Interestingly, the plywood based on the developed S-ADP adhesive exhibited good flame retardancy. After burning for 90 s, its shape remains unchanged. Meanwhile, it can be concluded from thermomechanical analysis (TMA) and thermogravimetric analysis (TGA) that the S-ADP acquired excellent modulus of elasticity (MOE) and good thermal stability. It is thus thought promisingly that the use of S-ADP adhesive as a substitute for PF resin adhesive seems feasible in the near future.
Application of Deep Learning Algorithm in Optimization Control of Electrostatic Precipitator in Coal-Fired Power Plants
Authors: Zhu Jianjun , Feng Chao , Zhao Zhongyang , Yang Haoming , Liu Yujie
Published: February 2024

The new energy structure needs to balance energy security and dual carbon goals, which has brought major challenges to coal-fired power plants. The pollution reduction and carbon emissions reduction in coal-fired power plants will be a key task in the future. In this paper, an optimization technique for the operation of an electrostatic precipitator is proposed. Firstly, the voltage-current model is constructed based on the modified dust charging mechanism; the modified parameters are trained through the gradient descent method. Then, the outlet dust concentration prediction model is constructed by coupling the mechanism model with the data model; the data model adopts the long short-term memory network and the attention mechanism. Finally, the particle swarm optimization algorithm is used to achieve the optimal energy consumption while ensuring stable outlet dust concentration. By training with historical data collected on site, accurate predictions of the secondary current and outlet dust concentration of the electrostatic precipitator have been achieved. The mean absolute percentage error of the voltage-current characteristic model is 1.43%, and the relative root mean-squared error is 2%. The mean absolute percentage error of the outlet dust concentration prediction model on the testing set is 5.2%, and the relative root mean-squared error is 6.9%. The optimization experiment is carried out in a 330 MW coal-fired power plant. The results show that the fluctuation of the outlet dust concentration is more stable, and the energy saving is about 43% after optimization; according to the annual operation of 300 days, the annual average carbon reduction is approximately 2621.34 tons. This method is effective and can be applied widely.
Deep Learning-Based Target Point Localization for UAV Inspection of Point Cloud Transmission Towers
Authors: Li Xuhui , Li Yongrong , Chen Yiming , Zhang Geng , Liu Zhengjun
Published: February 2024

UAV transmission tower inspection is the use of UAV technology for regular inspection and troubleshooting of towers on transmission lines, which helps to improve the safety and reliability of transmission lines and ensures the stability of the power supply. From the traditional manual tower boarding to the current way of manually selecting target camera shooting points from 3D point clouds to plan the inspection path of the UAV, operational efficiency has drastically improved. However, indoor planning work is still labor-consuming and expensive. In this paper, a deep learning-based point cloud transmission tower segmentation (PCTTS) model combined with the corresponding target point localization algorithm is proposed for automatic segmentation of transmission tower point cloud data and automatically localizing the key inspection component as the target point for UAV inspection. First, we utilize octree sampling with unit ball normalization to simplify the data and ensure translation invariance before putting the data into the model. In the feature extraction stage, we encode the point set information and combine Euclidean distance and cosine similarity features to ensure rotational invariance. On this basis, we adopt multi-scale feature extraction, construct a local coordinate system, and introduce the offset-attention mechanism to enhance model performance further. Then, after the feature propagation module, gradual up-sampling is used to obtain the features of each point to complete the point cloud segmentation. Finally, combining the segmentation results with the target point localization algorithm completes the automatic extraction of UAV inspection target points. The method has been applied to six kinds of transmission tower point cloud data of part segmentation results and three kinds of transmission tower point cloud data of instance segmentation results. The experimental results show that the model achieves mIOU of 94.1% on the self-built part segmentation dataset and 86.9% on the self-built instance segmentation dataset, and the segmentation accuracy outperforms that of the methods for point cloud segmentation, such as PointNet++, DGCNN, Point Transformer, and PointMLP. Meanwhile, the experimental results of UAV inspection target point localization also verify the method’s effectiveness in this paper.
Recent Developments of Fluorescence Sensors Constructed from Pillar[n]arene-Based Supramolecular Architectures Containing Metal Coordination Sites
Authors: Li Xu , Jin Yan , Zhu Nansong , Yin Jinghua , Jin Long Yi
Published: February 2024

The field of fluorescence sensing, leveraging various supramolecular self-assembled architectures constructed from macrocyclic pillar[n]arenes, has seen significant advancement in recent decades. This review comprehensively discusses, for the first time, the recent innovations in the synthesis and self-assembly of pillar[n]arene-based supramolecular architectures (PSAs) containing metal coordination sites, along with their practical applications and prospects in fluorescence sensing. Integrating hydrophobic and electron-rich cavities of pillar[n]arenes into these supramolecular structures endows the entire system with self-assembly behavior and stimulus responsiveness. Employing the host–guest interaction strategy and complementary coordination forces, PSAs exhibiting both intelligent and controllable properties are successfully constructed. This provides a broad horizon for advancing fluorescence sensors capable of detecting environmental pollutants. This review aims to establish a solid foundation for the future development of fluorescence sensing applications utilizing PSAs. Additionally, current challenges and future perspectives in this field are discussed.
Passive Infrared Sensor-Based Occupancy Monitoring in Smart Buildings: A Review of Methodologies and Machine Learning Approaches
Authors: Shokrollahi Azad , Persson Jan A. , Malekian Reza , Sarkheyli-Hägele Arezoo , Karlsson Fredrik
Published: February 2024

Buildings are rapidly becoming more digitized, largely due to developments in the internet of things (IoT). This provides both opportunities and challenges. One of the central challenges in the process of digitizing buildings is the ability to monitor these buildings’ status effectively. This monitoring is essential for services that rely on information about the presence and activities of individuals within different areas of these buildings. Occupancy information (including people counting, occupancy detection, location tracking, and activity detection) plays a vital role in the management of smart buildings. In this article, we primarily focus on the use of passive infrared (PIR) sensors for gathering occupancy information. PIR sensors are among the most widely used sensors for this purpose due to their consideration of privacy concerns, cost-effectiveness, and low processing complexity compared to other sensors. Despite numerous literature reviews in the field of occupancy information, there is currently no literature review dedicated to occupancy information derived specifically from PIR sensors. Therefore, this review analyzes articles that specifically explore the application of PIR sensors for obtaining occupancy information. It provides a comprehensive literature review of PIR sensor technology from 2015 to 2023, focusing on applications in people counting, activity detection, and localization (tracking and location). It consolidates findings from articles that have explored and enhanced the capabilities of PIR sensors in these interconnected domains. This review thoroughly examines the application of various techniques, machine learning algorithms, and configurations for PIR sensors in indoor building environments, emphasizing not only the data processing aspects but also their advantages, limitations, and efficacy in producing accurate occupancy information. These developments are crucial for improving building management systems in terms of energy efficiency, security, and user comfort, among other operational aspects. The article seeks to offer a thorough analysis of the present state and potential future advancements of PIR sensor technology in efficiently monitoring and understanding occupancy information by classifying and analyzing improvements in these domains.
Spatial Downscaling of ERA5 Reanalysis Air Temperature Data Based on Stacking Ensemble Learning
Authors: Zhang Yuna , Li Jing , Liu Deren
Published: February 2024

High-resolution air temperature distribution data are of crucial significance for studying climate change and agriculture in the Yellow River Basin. Obtaining accurate and high-resolution air temperature data has been a persistent challenge in research. This study selected the Yellow River Basin as its research area and assessed multiple variables, including the land surface temperature (LST), Normalized Difference Vegetation Index (NDVI), Digital Elevation Model (DEM), slope, aspect, longitude, and latitude. We constructed three downscaling models, namely, ET, XGBoost, and LightGBM, and applied a stacking ensemble learning algorithm to integrate these three models. Through this approach, ERA5-Land reanalysis air temperature data were successfully downscaled from a spatial resolution of 0.1° to 1 km, and the downscaled results were validated using observed data from meteorological stations. The results indicate that the stacking ensemble model significantly outperforms the three independent machine learning models. The integrated model, combined with the selected set of multiple variables, provides a feasible approach for downsizing ERA5 air temperature data. The stacking ensemble model not only effectively enhances the spatial resolution of ERA5 reanalysis air temperature data but also improves downscaled results to a certain extent. The downscaled air temperature data exhibit richer spatial texture information, better revealing spatial variations in air temperature within the same land class. This research outcome provides robust technical support for obtaining high-resolution air temperature data in meteorologically sparse or topographically complex regions, contributing significantly to climate, ecosystem, and sustainable development research.