bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging the Fragment Molecular Orbital Method to Explore the PLK1 Kinase Binding Site and Polo-Box Domain for Potent Small-Molecule Drug Design
Authors: Jin Haiyan , Kim Jongwan , Lee Onju , Kim Hyein , No Kyoung Tai
Published: October 2023

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as a promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become a focal point in contemporary research. The adenosine triphosphate (ATP)-binding site and the polo-box domain in PLK1 present crucial interaction sites for these inhibitors, aiming to disrupt the protein’s function. However, designing potent and selective small-molecule inhibitors can be challenging, requiring a deep understanding of protein–ligand interaction mechanisms at these binding sites. In this context, our study leverages the fragment molecular orbital (FMO) method to explore these site-specific interactions in depth. Using the FMO approach, we used the FMO method to elucidate the molecular mechanisms of small-molecule drugs binding to these sites to design PLK1 inhibitors that are both potent and selective. Our investigation further entailed a comparative analysis of various PLK1 inhibitors, each characterized by distinct structural attributes, helping us gain a better understanding of the relationship between molecular structure and biological activity. The FMO method was particularly effective in identifying key binding features and predicting binding modes for small-molecule ligands. Our research also highlighted specific “hot spot” residues that played a critical role in the selective and robust binding of PLK1. These findings provide valuable insights that can be used to design new and effective PLK1 inhibitors, which can have significant implications for developing anticancer therapeutics.
Novel Carboxylation Method for Polyetheretherketone (PEEK) Surface Modification Using Friedel–Crafts Acylation
Authors: Lyu Xinghui , Kanda Ryuhei , Tsuda Susumu , Hashimoto Yoshiya , Fujii Takamasa , Kashiwagi Kosuke
Published: October 2023

Recently, polyetheretherketone (PEEK) has shown promising dental applications. Surface treatment is essential for dental applications owing to its poor surface energy and wettability; however, no consensus on an effective treatment method has been achieved. In this study, we attempted to carboxylate PEEK sample surfaces via Friedel–Crafts acylation using succinic anhydride and AlBr3. The possibility of further chemical modifications using carboxyl groups was examined. The samples were subjected to dehydration–condensation reactions with 1H,1H-pentadecafluorooctylamine and N,N’-dicyclohexylcarbodiimide. Furthermore, the sample’s surface properties at each reaction stage were evaluated. An absorption band in the 3300–3500 cm−1 wavenumber region was observed. Additionally, peak suggestive of COOH was observed in the sample spectra. Secondary modification diminished the absorption band in 3300–3500 cm−1 and a clear F1s signal was observed. Thus, Friedel–Crafts acylation with succinic anhydride produced carboxyl groups on the PEEK sample surfaces. Further chemical modification of the carboxyl groups by dehydration-condensation reactions is also possible. Thus, a series of reactions can be employed to impart desired chemical structures to PEEK surfaces.
Cathelicidin Antimicrobial Peptide Acts as a Tumor Suppressor in Hepatocellular Carcinoma
Authors: Huang Lien-Hung , Rau Cheng-Shyuan , Liu Yueh-Wei , Lin Hui-Ping , Wu Yi-Chan , Tsai Chia-Wen , Chien Peng-Chen , Wu Chia-Jung , Huang Chun-Ying , Hsieh Ting-Min , Hsieh Ching-Hua
Published: October 2023

Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC against those in healthy people using isobaric tags for a relative or absolute quantitation (iTRAQ)-based quantitative proteomics analysis. The protein levels of von Willebrand factor (VWF), cathelicidin antimicrobial peptide (CAMP), and proteasome subunit beta type-2 (PSMB2) were altered in HCC. The increased levels of VWF and PSMB2 but decreased CAMP levels in the serum of patients with HCC were validated by enzyme-linked immunosorbent assays. The level of CAMP (the only cathelicidin found in humans) also decreased in the circulating exosomes and buffy coat of the HCC patients. The serum with reduced levels of CAMP protein in the HCC patients increased the cell proliferation of Huh-7 cells; this effect was reduced following the addition of CAMP protein. The depletion of CAMP proteins in the serum of healthy people enhances the cell proliferation of Huh-7 cells. In addition, supplementation with synthetic CAMP reduces cell proliferation in a dose-dependent manner and significantly delays G1-S transition in Huh-7 cells. This implies that CAMP may act as a tumor suppressor in HCC.
Expression of Matrix Metalloproteinases in the Circulating Immune Cells in Children with Helicobacter pylori Infection—Correlation with Clinical Factors
Authors: Helmin-Basa Anna , Kubiszewska Izabela , Wiese-Szadkowska Małgorzata , Strzyżewska Edyta , Skalska-Bugała Aleksandra , Balcerowska Sara , Rasmus Marta , Balcerczyk Daria , Pokrywczyńska Marta , Michałkiewicz Jacek , Krogulska Aneta , Główczewski Adam , Szaflarska-Popławska Anna
Published: October 2023

H. pylori gastritis is strongly associated with the upregulation of the expression of several matrix metalloproteinases (MMPs) in the gastric mucosa. However, the role of MMP-2 and MMP-9, and their inhibitors (tissue inhibitors of metalloproteinases -TIMPs) produced by immune cells in infected children have not been clearly defined. Moreover, the effects of H. pylori eradication therapy on MMPs and TIMPs production has not been evaluated. A total of 84 children were studied: 24—with newly diagnosed H. pylori gastritis, 25—after H. pylori eradication therapy (17 of them after successful therapy), 24—with H. pylori-negative gastritis, and 11—controls. Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 by ELISA; MMPs and TIMPs expression in lymphocytes; neutrophils and monocytes in peripheral blood by multiparameter flow cytometry; and mucosal mRNA expression levels of MMPs and TIMP-1 in gastric biopsies by RT-PCR were evaluated. Children with H. pylori-related gastritis showed the following: (1) increased MMP-2 and TIMP-2 plasma levels, (2) increased intracellular expression of MMP-2 in the circulating lymphocytes and neutrophils, (3) low frequencies of circulating TIMP-1+ and TIMP-2+ leukocytes, and (4) high expression of mRNA for MMP-9 along with low expression of mRNA for MMP-2 in the gastric mucosa. Unsuccessful H. pylori eradication was associated with the following: (1) high plasma levels of MMP-9 and TIMP-1, (2) increased pool of TIMP-1+ lymphocytes as well as high expression of MMP-9 in circulating lymphocytes, and (3) high expression of mRNA for MMP-9 in the gastric mucosa. Our data suggest that MMPs are important contributors to stomach remodelling in children with H. pylori-related gastritis. Unsuccessful H. pylori eradication is associated with increased MMP-9 in plasma, circulating lymphocytes, and gastric mucosa.
Overexpression of ZmSTOP1-A Enhances Aluminum Tolerance in Arabidopsis by Stimulating Organic Acid Secretion and Reactive Oxygen Species Scavenging
Authors: Liu Chan , Hu Xiaoqi , Zang Lei , Liu Xiaofeng , Wei Yuhui , Wang Xue , Jin Xinwu , Du Chengfeng , Yu Yan , He Wenzhu , Zhang Suzhi
Published: October 2023

Aluminum (Al) toxicity and low pH are major factors limiting plant growth in acidic soils. Sensitive to Proton Rhizotoxicity 1 (STOP1) transcription factors respond to these stresses by regulating the expression of multiple Al- or low pH-responsive genes. ZmSTOP1-A, a STOP1-like protein from maize (Zea mays), was localized to the nucleus and showed transactivation activity. ZmSTOP1-A was expressed moderately in both roots and shoots of maize seedlings, but was not induced by Al stress or low pH. Overexpression of ZmSTOP1-A in Arabidopsis Atstop1 mutant partially restored Al tolerance and improved low pH tolerance with respect to root growth. Regarding Al tolerance, ZmSTOP1-A/Atstop1 plants showed clear upregulation of organic acid transporter genes, leading to increased organic acid secretion and reduced Al accumulation in roots. In addition, the antioxidant enzyme activity in roots and shoots of ZmSTOP1-A/Atstop1 plants was significantly enhanced, ultimately alleviating Al toxicity via scavenging reactive oxygen species. Similarly, ZmSTOP1-A could directly activate ZmMATE1 expression in maize, positively correlated with the number of Al-responsive GGNVS cis-elements in the ZmMATE1 promoter. Our results reveal that ZmSTOP1-A is an important transcription factor conferring Al tolerance by enhancing organic acid secretion and reactive oxygen species scavenging in Arabidopsis.
Effects of Heat Stress on Plant-Nutrient Relations: An Update on Nutrient Uptake, Transport, and Assimilation
Authors: Mishra Sasmita , Spaccarotella Kim , Gido Jaclyn , Samanta Ishita , Chowdhary Gopal
Published: October 2023

As a consequence of global climate change, the frequency, severity, and duration of heat stress are increasing, impacting plant growth, development, and reproduction. While several studies have focused on the physiological and molecular aspects of heat stress, there is growing concern that crop quality, particularly nutritional content and phytochemicals important for human health, is also negatively impacted. This comprehensive review aims to provide profound insights into the multifaceted effects of heat stress on plant-nutrient relationships, with a particular emphasis on tissue nutrient concentration, the pivotal nutrient-uptake proteins unique to both macro- and micronutrients, and the effects on dietary phytochemicals. Finally, we propose a new approach to investigate the response of plants to heat stress by exploring the possible role of plant peroxisomes in the context of heat stress and nutrient mobilization. Understanding these complex mechanisms is crucial for developing strategies to improve plant nutrition and resilience during heat stress.
Long Non-Coding RNA Signatures in the Ileum and Colon of Crohn’s Disease Patients and Effect of Anti-TNF-α Treatment on Their Modulation
Authors: Baldan-Martin Montse , Rubín de Célix Cristina , Orejudo Macarena , Ortega Moreno Lorena , Fernández-Tomé Samuel , Soleto Irene , Ramirez Cristina , Arroyo Ricardo , Fernández Paloma , Santander Cecilio , Moreno-Monteagudo José Andrés , Casanova María José , Casals Fernando , Casabona Sergio , Becerro Irene , Lozano Juan J. , Aransay Ana M. , Chaparro María , Gisbert Javier P.
Published: October 2023

Biological therapies only benefit one-third of patients with Crohn’s disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome.
Spectral Physics of Stable Cu(III) Produced by Oxidative Addition of an Alkyl Halide
Authors: Cao En , Sun Mengtao
Published: October 2023

In this paper, we theoretically investigated spectral physics on Cu(III) complexes formed by the oxidative addition of α-haloacetonitrile to ionic and neutral Cu(I) complexes, stimulated by recent experimental reports. Firstly, the electronic structures of reactants of α-haloacetonitrile and neutral Cu(I) and two kinds of products of Cu(III) complexes are visualized with the density of state (DOS) and orbital energy levels of HOMO and LUMO. The visually manifested static and dynamic polarizability as well as the first hyperpolarizability are employed to reveal the vibrational modes of the normal and resonance Raman spectra of two Cu(III) complexes. The nuclear magnetic resonance (NMR) spectra are not only used to identify the reactants and products but also to distinguish between two Cu(III) complexes. The charge difference density (CDD) reveals intramolecular charge transfer in electronic transitions in optical absorption spectra. The CDDs in fluorescence visually reveal electron–hole recombination. Our results promote a deeper understanding of the physical mechanism of stable Cu(III) produced by the oxidative addition of an alkyl halide.
miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer
Authors: Giordano Cinzia , Accattatis Felice Maria , Gelsomino Luca , Del Console Piercarlo , Győrffy Balázs , Giuliano Mario , Veneziani Bianca Maria , Arpino Grazia , De Angelis Carmine , De Placido Pietro , Pietroluongo Erica , Zinno Francesco , Bonofiglio Daniela , Andò Sebastiano , Barone Ines , Catalano Stefania
Published: October 2023

Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.
Novel Targets Regulating the Role of Endothelial Cells and Angiogenesis after Infarction: A RNA Sequencing Analysis
Authors: Ortega María , Molina-García Tamara , Gavara Jose , de Dios Elena , Pérez-Solé Nerea , Marcos-Garcés Victor , Chorro Francisco J. , Rios-Navarro Cesar , Ruiz-Sauri Amparo , Bodi Vicente
Published: October 2023

Endothelial cells (ECs) are a key target for cardioprotection due to their role in preserving cardiac microvasculature and homeostasis after myocardial infarction (MI). Our goal is to identify the genes involved in post-MI EC proliferation, EC apoptosis, and angiogenesis regulation via RNA-sequencing transcriptomic datasets. Using eight studies from the Gene Expression Omnibus, RNA-sequencing data from 92 mice submitted to different times of coronary ischemia or sham were chosen. Functional enrichment analysis was performed based on gene ontology biological processes (BPs). Apoptosis-related BPs are activated up to day 3 after ischemia onset, whereas endothelial proliferation occurs from day 3 onwards, including an overrepresentation of up to 37 genes. Endothelial apoptosis post-MI is triggered via both the extrinsic and intrinsic signaling pathways, as reflected by the overrepresentation of 13 and 2 specific genes, respectively. BPs implicated in new vessel formation are upregulated soon after ischemia onset, whilst the mechanisms aiming at angiogenesis repression can be detected at day 3. Overall, 51 pro-angiogenic and 29 anti-angiogenic factors displayed altered transcriptomic expression post-MI. This is the first study using RNA sequencing datasets to evaluate the genes participating in post-MI endothelium physiology and angiogenesis regulation. These novel data could lay the groundwork to advance understanding of the implication of ECs after MI.
Alkylbenzoic and Alkyloxybenzoic Acid Blending for Expanding the Liquid Crystalline State and Improving Its Rheology
Authors: Yadykova Anastasiya Y. , Konstantinov Ivan I. , Vlasova Anna V. , Varfolomeeva Lydia A. , Ilyin Sergey O.
Published: October 2023

Thermotropic mesogens typically exist as liquid crystals (LCs) in a narrow region of high temperatures, making lowering their melting point with the temperature expansion of the mesophase state an urgent task. Para-substituted benzoic acids can form LCs through noncovalent dimerization into homodimers via hydrogen bonds, whose strength and, consequently, the temperature region of the mesophase state can be potentially altered by creating asymmetric heterodimers from different acids. This work investigates equimolar blends of p-n-alkylbenzoic (kBA, where k is the number of carbon atoms in the alkyl radical) and p-n-alkyloxybenzoic (kOBA) acids by calorimetry and viscometry to establish their phase transitions and regions of mesophase existence. Non-symmetric dimerization of acids leads to the extension of the nematic state region towards low temperatures and the appearance of new monotropic and enantiotropic phase transitions in several cases. Moreover, the crystal–nematic and nematic–isotropic phase changes have a two-step character for some acid blends, suggesting the formation of symmetric and asymmetric associates from heterodimers. The mixing of 6BA and 8OBA most strongly extends the region of the nematic state towards low temperatures (from 95–114 °C and 108–147 °C for initial homodimers, respectively, to 57–133 °C for the resulting heterodimer), whereas the combination of 4OBA and 5OBA gives the most extended high-temperature nematic phase (up to 156 °C) and that of 6BA and 9OBA (or 12OBA) provides the existence of a smectic phase at the lowest temperatures (down to 51 °C).
Comparative Transcriptome Analysis between Resistant and Susceptible Pakchoi Cultivars in Response to Downy Mildew
Authors: Chen Yaosong , Miao Liming , Li Xiaofeng , Liu Yiwen , Xi Dandan , Zhang Dingyu , Gao Lu , Zhu Yuying , Dai Shaojun , Zhu Hongfang
Published: October 2023

Downy mildew caused by the obligate parasite Hyaloperonospora brassicae is a devastating disease for Brassica species. Infection of Hyaloperonospora brassicae often leads to yellow spots on leaves, which significantly impacts quality and yield of pakchoi. In the present study, we conducted a comparative transcriptome between the resistant and susceptible pakchoi cultivars in response to Hyaloperonospora brassicae infection. A total of 1073 disease-resistance-related differentially expressed genes were identified using a Venn diagram. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these genes were mainly involved in plant−pathogen interaction, plant hormone signal transduction, and other photosynthesis-related metabolic processes. Analysis of the phytohormone content revealed that salicylic acid increased significantly in the resistant material after inoculation with Hyaloperonospora brassicae, whereas the contents of jasmonic acid, abscisic acid, and 1-aminocyclopropane-1-carboxylic acid decreased. Exogenous salicylic acid treatment also significantly upregulated Hyaloperonospora brassicae-induced genes, which further confirmed a crucial role of salicylic acid during pakchoi defense against Hyaloperonospora brassicae. Based on these findings, we suggest that the salicylic-acid-mediated signal transduction contributes to the resistance of pakchoi to downy mildew, and PAL1, ICS1, NPR1, PR1, PR5, WRKY70, WRKY33, CML43, CNGC9, and CDPK15 were involved in this responsive process. Our findings evidently contribute to revealing the molecular mechanism of pakchoi defense against Hyaloperonospora brassicae.
Newly Synthesized CoFe2−xDyxO4 (x = 0; 0.1; 0.2; 0.4) Nanoparticles Reveal Promising Anticancer Activity against Melanoma (A375) and Breast Cancer (MCF-7) Cells
Authors: Rotunjanu Slaviţa , Racoviceanu Roxana , Mioc Alexandra , Milan Andreea , Negrea-Ghiulai Roxana , Mioc Marius , Marangoci Narcisa Laura , Şoica Codruţa
Published: October 2023

The current study focuses on the synthesis via combustion of dysprosium-doped cobalt ferrites that were subsequently physicochemically analyzed in terms of morphological and magnetic properties. Three types of doped nanoparticles were prepared containing different Dy substitutions and coated with HPGCD for higher dispersion properties and biocompatibility, and were later submitted to biological tests in order to reveal their potential anticancer utility. Experimental data obtained through FTIR, XRD, SEM and TEM confirmed the inclusion of Dy3+ ions in the nanoparticles’ structure. The size of the newly formed nanoparticles ranged between 20 and 50 nm revealing an inverse proportional relationship with the Dy content. Magnetic studies conducted by VSM indicated a decrease in remanent and saturation mass magnetization, respectively, in Dy-doped nanoparticles in a direct proportionality with the Dy content; the decrease was further amplified by cyclodextrin complexation. Biological assessment in the presence/absence of red light revealed a significant cytotoxic activity in melanoma (A375) and breast (MCF-7) cancer cells, while healthy keratinocytes (HaCaT) remained generally unaffected, thus revealing adequate selectivity. The investigation of the underlying cytotoxic molecular mechanism revealed an apoptotic process as indicated by nuclear fragmentation and shrinkage, as well as by Western blot analysis of caspase 9, p53 and cyclin D1 proteins. The anticancer activity for all doped Co ferrites varied was in a direct correlation to their Dy content but without being affected by the red light irradiation.
A High-K+ Affinity Transporter (HKT) from Actinidia valvata Is Involved in Salt Tolerance in Kiwifruit
Authors: Gu Shichao , Han Shiming , Abid Muhammad , Bai Danfeng , Lin Miaomiao , Sun Leiming , Qi Xiujuan , Zhong Yunpeng , Fang Jinbao
Published: October 2023

Ion transport is crucial for salt tolerance in plants. Under salt stress, the high-affinity K+ transporter (HKT) family is mainly responsible for the long-distance transport of salt ions which help to reduce the deleterious effects of high concentrations of ions accumulated within plants. Kiwifruit is well known for its susceptibility to salt stress. Therefore, a current study was designed to decipher the molecular regulatory role of kiwifruit HKT members in the face of salt stress. The transcriptome data from Actinidia valvata revealed that salt stress significantly induced the expression of AvHKT1. A multiple sequence alignment analysis indicated that the AvHKT1 protein contains three conserved amino acid sites for the HKT family. According to subcellular localization analysis, the protein was primarily present in the cell membrane and nucleus. Additionally, we tested the AvHKT1 overexpression in ‘Hongyang’ kiwifruit, and the results showed that the transgenic lines exhibited less leaf damage and improved plant growth compared to the control plants. The transgenic lines displayed significantly higher SPAD and Fv/Fm values than the control plants. The MDA contents of transgenic lines were also lower than that of the control plants. Furthermore, the transgenic lines accumulated lower Na+ and K+ contents, proving this protein involvement in the transport of Na+ and K+ and classification as a type II HKT transporter. Further research showed that the peroxidase (POD) activity in the transgenic lines was significantly higher, indicating that the salt-induced overexpression of AvHKT1 also scavenged POD. The promoter of AvHKT1 contained phytohormone and abiotic stress-responsive cis-elements. In a nutshell, AvHKT1 improved kiwifruit tolerance to salinity by facilitating ion transport under salt stress conditions.
TOR Complex 1: Orchestrating Nutrient Signaling and Cell Cycle Progression
Authors: Foltman Magdalena , Sanchez-Diaz Alberto
Published: October 2023

The highly conserved TOR signaling pathway is crucial for coordinating cellular growth with the cell cycle machinery in eukaryotes. One of the two TOR complexes in budding yeast, TORC1, integrates environmental cues and promotes cell growth. While cells grow, they need to copy their chromosomes, segregate them in mitosis, divide all their components during cytokinesis, and finally physically separate mother and daughter cells to start a new cell cycle apart from each other. To maintain cell size homeostasis and chromosome stability, it is crucial that mechanisms that control growth are connected and coordinated with the cell cycle. Successive periods of high and low TORC1 activity would participate in the adequate cell cycle progression. Here, we review the known molecular mechanisms through which TORC1 regulates the cell cycle in the budding yeast Saccharomyces cerevisiae that have been extensively used as a model organism to understand the role of its mammalian ortholog, mTORC1.
From Static to Dynamic: Smart Materials Pioneering Additive Manufacturing in Regenerative Medicine
Authors: Kantaros Antreas , Ganetsos Theodore
Published: October 2023

The emerging field of regenerative medicine holds immense promise for addressing complex tissue and organ regeneration challenges. Central to its advancement is the evolution of additive manufacturing techniques, which have transcended static constructs to embrace dynamic, biomimetic solutions. This manuscript explores the pivotal role of smart materials in this transformative journey, where materials are endowed with dynamic responsiveness to biological cues and environmental changes. By delving into the innovative integration of smart materials, such as shape memory polymers and stimulus-responsive hydrogels, into additive manufacturing processes, this research illuminates the potential to engineer tissue constructs with unparalleled biomimicry. From dynamically adapting scaffolds that mimic the mechanical behavior of native tissues to drug delivery systems that respond to physiological cues, the convergence of smart materials and additive manufacturing heralds a new era in regenerative medicine. This manuscript presents an insightful overview of recent advancements, challenges, and future prospects, underscoring the pivotal role of smart materials as pioneers in shaping the dynamic landscape of regenerative medicine and heralding a future where tissue engineering is propelled beyond static constructs towards biomimetic, responsive, and regenerative solutions.
Critical Velocity, Maximal Lactate Steady State, and Muscle MCT1 and MCT4 after Exhaustive Running in Mice
Authors: Orsi Juan B. , Araujo Lara S. , Scariot Pedro P. M. , Polisel Emanuel E. C. , Cardoso Luisa O. , Gobatto Claudio A. , Manchado-Gobatto Fúlvia B.
Published: October 2023

Although the critical velocity (CV) protocol has been used to determine the aerobic capacity in rodents, there is a lack of studies that compare CV with maximal lactate steady state intensity (iMLSS) in mice. As a consequence, their physiological and molecular responses after exercise until exhaustion at CV intensity remain unclear. Thus, we aimed to compare and correlate CV with iMLSS in running mice, following different mathematical models for CV estimation. We also evaluated their physiological responses and muscle MCT1 and MCT4 after running until exhaustion at CV. Thirty C57BL/6J mice were divided into two groups (exercised-E and control-C). Group E was submitted to a CV protocol (4 days), using linear (lin1 and lin2) and hyperbolic (hyp) mathematical models to determine the distance, velocity, and time to exhaustion (tlim) of each predictive CV trial, followed by an MLSS protocol. After a running effort until exhaustion at CV intensity, the mice were immediately euthanized, while group C was euthanized at rest. No differences were observed between iMLSS (21.1 ± 1.1 m.min−1) and CV estimated by lin1 (21.0 ± 0.9 m.min−1, p = 0.415), lin2 (21.3 ± 0.9 m.min−1, p = 0.209), and hyp (20.6 ± 0.9 m.min−1, p = 0.914). According to the results, CV was significantly correlated with iMLSS. After running until exhaustion at CV (tlim = 28.4 ± 8,29 min), group E showed lower concentrations of hepatic and gluteal glycogen than group C, but no difference in the content of MCT1 (p = 0.933) and MCT4 (p = 0.123) in soleus muscle. Significant correlations were not found between MCT1 and MCT4 and tlim at CV intensity. Our results reinforce that CV is a valid and non-invasive protocol to estimate the maximal aerobic capacity in mice and that the content of MCT1 and MCT4 was not decisive in determining the tlim at CV, at least when measured immediately after the running effort.
Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts
Authors: Song Hee-Jin , Kim Ji-Eun , Jin You-Jeong , Roh Yu-Jeong , Seol Ayun , Kim Tae-Ryeol , Park Ki-Ho , Park Eun-Seo , An Beum-Soo , Yang Seung-Yun , Seo Sungbaek , Jo Seong-Min , Jung Young-Suk , Hwang Dae-Youn
Published: October 2023

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.
Silencing the CsSnRK2.11 Gene Decreases Drought Tolerance of Cucumis sativus L.
Authors: Wang Peng , Wan Zilong , Luo Shilei , Wei Haotai , Zhao Jianuo , Wang Guoshuai , Yu Jihua , Zhang Guobin
Published: October 2023

Drought stress restricts vegetable growth, and abscisic acid plays an important role in its regulation. Sucrose non-fermenting1-related protein kinase 2 (SnRK2) is a key enzyme in regulating ABA signal transduction in plants, and it plays a significant role in response to multiple abiotic stresses. Our previous experiments demonstrated that the SnRK2.11 gene exhibits a significant response to drought stress in cucumbers. To further investigate the function of SnRK2.11 under drought stress, we used VIGS (virus-induced gene silencing) technology to silence this gene and conducted RNA-seq analysis. The SnRK2.11-silencing plants displayed increased sensitivity to drought stress, which led to stunted growth and increased wilting speed. Moreover, various physiological parameters related to photosynthesis, chlorophyll fluorescence, leaf water content, chlorophyll content, and antioxidant enzyme activity were significantly reduced. The intercellular CO2 concentration, non-photochemical burst coefficient, and malondialdehyde and proline content were significantly increased. RNA-seq analysis identified 534 differentially expressed genes (DEGs): 311 were upregulated and 223 were downregulated. GO functional annotation analysis indicated that these DEGs were significantly enriched for molecular functions related to host cells, enzyme activity, and stress responses. KEGG pathway enrichment analysis further revealed that these DEGs were significantly enriched in phytohormone signalling, MAPK signalling, and carotenoid biosynthesis pathways, all of which were associated with abscisic acid. This study used VIGS technology and transcriptome data to investigate the role of CsSnRK2.11 under drought stress, offering valuable insights into the mechanism of the SnRK2 gene in enhancing drought resistance in cucumbers.
Contribution of the LAC Genes in Fruit Quality Attributes of the Fruit-Bearing Plants: A Comprehensive Review
Authors: Khan Muhammad Khalil Ullah , Zhang Xiaojie , Ma Zitan , Huang Mingxia , Yang Ce , Wang Xiaoming , Liu Mengjun , Peng Jianying
Published: October 2023

Laccase genes produce laccase enzymes that play a crucial role in the production of lignin and oxidation reactions within plants. Lignin is a complex polymer that provides structure and toughness to the cell walls of numerous fruit plants. The LAC genes that encode laccase enzymes play vital roles in plant physiology, including the synthesis of pigments like PA that contribute to the colors of fruits, and in defending against pathogens and environmental stresses. They are crucial for fruit development, ripening, structural maintenance in plants, and adaptation to various environmental factors. As such, these genes and enzymes are essential for plant growth and development, as well as for various biotechnological applications in environmental remediation and industrial processes. This review article emphasizes the significance of genes encoding laccase enzymes during fruit growth, specifically pertaining to the strengthening of the endocarp through lignification. This process is crucial for ensuring fruit defense and optimizing seed scattering. The information gathered in this article will aid breeders in producing future fruit-bearing plants that are resistant to disease, cost-effective, and nutrient-rich.
Anxiety Modulation by Cannabinoids—The Role of Stress Responses and Coping
Authors: Haller József
Published: October 2023

Endocannabinoids were implicated in a variety of pathological conditions including anxiety and are considered promising new targets for anxiolytic drug development. The optimism concerning the potentials of this system for anxiolysis is probably justified. However, the complexity of the mechanisms affected by endocannabinoids, and discrepant findings obtained with various experimental approaches makes the interpretation of research results difficult. Here, we review the anxiety-related effects of the three main interventions used to study the endocannabinoid system: pharmacological agents active at endocannabinoid-binding sites present on both the cell membrane and in the cytoplasm, genetic manipulations targeting cannabinoid receptors, and function-enhancers represented by inhibitors of endocannabinoid degradation and transport. Binding-site ligands provide inconsistent findings probably because they activate a multitude of mechanisms concomitantly. More robust findings were obtained with genetic manipulations and particularly with function enhancers, which heighten ongoing endocannabinoid activation rather than affecting all mechanisms indiscriminately. The enhancement of ongoing activity appears to ameliorate stress-induced anxiety without consistent effects on anxiety in general. Limited evidence suggests that this effect is achieved by promoting active coping styles in critical situations. These findings suggest that the functional enhancement of endocannabinoid signaling is a promising drug development target for stress-related anxiety disorders.
NBSTRN Tools to Advance Newborn Screening Research and Support Newborn Screening Stakeholders
Authors: Chan Kee , Hu Zhanzhi , Bush Lynn W. , Cope Heidi , Holm Ingrid A. , Kingsmore Stephen F. , Wilhelm Kevin , Scharfe Curt , Brower Amy
Published: October 2023

Rapid advances in the screening, diagnosis, and treatment of genetic disorders have increased the number of conditions that can be detected through universal newborn screening (NBS). However, the addition of conditions to the Recommended Uniform Screening Panel (RUSP) and the implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here, we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders worldwide. The NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs, including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases, have utilized NBSTRN’s tools and, in turn, contributed research data to further expand and refine these resources. Additionally, we discuss ongoing tool development to facilitate the expansion of genetic disease screening in increasingly diverse populations. In conclusion, NBSTRN’s tools and resources provide a trusted platform to enable NBS stakeholders to advance NBS research and improve clinical care for patients and their families.
Microstructural and Mechanical Characterization of the Dissimilar AA7075 and AA2024 Aluminum Alloys Reinforced with Different Carbide Particles Welded by Friction Stir Welding
Authors: Moustafa Essam B. , Sharaf Mazen , Alsoruji Ghazi , Mosleh Ahmed O. , Mohamed S. S. , Hussein Hossameldin
Published: October 2023

In the present study, AA7075 and AA2024 aluminum alloys were reinforced with ZrC, and the particles of WC were joined using the friction stir welding (FSW) method. The microstructural and mechanical properties of the welds were investigated using SEM, EDS, and tensile tests. The FSW process resulted in high-quality welds with fine grain structure; the stirred zone has 666% smaller grain size than AA7075 and AA2024 aluminum alloys. The tensile test showed strong and ductile welds. The fracture test showed ductile and less brittle composite joints of AA2024 and AA7075 alloys reinforced with WC and ZrC. The processing parameters in the FSW process significantly affect tensile strength (UTS); therefore, the improvement of UTS with tool speed is much greater than with welding speed. Increasing the tool speed from 400 to 560 rpm increased UTS by 7.1%, and from 560 to 700 rpm by 5.4%. The tensile test results showed that the welds exhibited considerable strength and ductility. Fracture analysis showed that the composite joints made of different AA2024 and AA7075 alloys and reinforced with WC and ZrC were ductile and less brittle. This study showed that FSW can efficiently fuse different aluminum alloys reinforced with ceramic particles.
Domain-Aware Few-Shot Learning for Optical Coherence Tomography Noise Reduction
Authors: Pereg Deborah
Published: October 2023

Speckle noise has long been an extensively studied problem in medical imaging. In recent years, there have been significant advances in leveraging deep learning methods for noise reduction. Nevertheless, adaptation of supervised learning models to unseen domains remains a challenging problem. Specifically, deep neural networks (DNNs) trained for computational imaging tasks are vulnerable to changes in the acquisition system’s physical parameters, such as: sampling space, resolution, and contrast. Even within the same acquisition system, performance degrades across datasets of different biological tissues. In this work, we propose a few-shot supervised learning framework for optical coherence tomography (OCT) noise reduction, that offers high-speed training (of the order of seconds) and requires only a single image, or part of an image, and a corresponding speckle-suppressed ground truth, for training. Furthermore, we formulate the domain shift problem for OCT diverse imaging systems and prove that the output resolution of a despeckling trained model is determined by the source domain resolution. We also provide possible remedies. We propose different practical implementations of our approach, verify and compare their applicability, robustness, and computational efficiency. Our results demonstrate the potential to improve sample complexity, generalization, and time efficiency, for coherent and non-coherent noise reduction via supervised learning models, that can also be leveraged for other real-time computer vision applications.
Critical Thinking, Intelligence, and Unsubstantiated Beliefs: An Integrative Review
Authors: Bensley D. Alan
Published: October 2023

A review of the research shows that critical thinking is a more inclusive construct than intelligence, going beyond what general cognitive ability can account for. For instance, critical thinking can more completely account for many everyday outcomes, such as how thinkers reject false conspiracy theories, paranormal and pseudoscientific claims, psychological misconceptions, and other unsubstantiated claims. Deficiencies in the components of critical thinking (in specific reasoning skills, dispositions, and relevant knowledge) contribute to unsubstantiated belief endorsement in ways that go beyond what standardized intelligence tests test. Specifically, people who endorse unsubstantiated claims less tend to show better critical thinking skills, possess more relevant knowledge, and are more disposed to think critically. They tend to be more scientifically skeptical and possess a more rational–analytic cognitive style, while those who accept unsubstantiated claims more tend to be more cynical and adopt a more intuitive–experiential cognitive style. These findings suggest that for a fuller understanding of unsubstantiated beliefs, researchers and instructors should also assess specific reasoning skills, relevant knowledge, and dispositions which go beyond what intelligence tests test.
Song Notes and Patterns of the Mediterranean Fin Whale (Balaenoptera physalus) in the Ionian Sea
Authors: Sciacca Virginia , Morello Giuseppe , Beranzoli Laura , Embriaco Davide , Filiciotto Francesco , Marinaro Giuditta , Riccobene Giorgio Maria , Simeone Francesco , Viola Salvatore
Published: October 2023

The Mediterranean fin whale emits two types of 20-Hz calls, known as “classic” and “backbeat”, that can be produced in irregular series or in patterned sequences called songs. The analysis of songs is recognized as a meaningful approach to study baleen whales and can be used to investigate populations’ identities. Mediterranean fin whale songs have been studied previously, but only in the western Mediterranean Sea. This work describes the structure of the songs recorded in the Ionian Sea. The inter-note intervals and the alternation of 20-Hz note types were considered to assess the occurrence of recurring patterns. Differences between patterned songs and irregular sequences were also investigated. Acoustic data were sampled continuously for about 10 months by the cabled observatory NEMO-SN1, deployed at 2100 m depth, 25 km offshore Catania; 28 call sequences were isolated and 10 of these were classified as either patterned songs or irregular sequences. Significant differences were observed in the spectral features of classic notes between songs and irregulars; four-note patterns were found repeatedly over different months, indicating a regular structure in detected songs. This work establishes a reference to interpret Mediterranean fin whale songs, and to assess the acoustic behavior of the population.
A Deep-Sea Broadband Sound Source Depth Estimation Method Based on the Interference Structure of the Compensated Beam Output
Authors: Liang Yan , Chen Yu , Meng Zhou , Zhou Xin , Zhang Yichi
Published: October 2023

This paper proposes an underwater broadband target depth estimation method based on the multipath arrival structure in medium and short-range deep-sea environments. The proposed approach involves separating the multipath rays arriving at the vertical line array using the matched filtering technique. The combined beamforming is then applied to the vector hydrophone vertical array (VHVA) to obtain more accurate elevation angle estimates. The components of the interference sound field at different distances are judged, and the signal received by the array is compensated using suitable estimated angles. Finally, the multipath time delay difference is extracted from the pulse peaks of the compensated signal, and the target depth is estimated by establishing the relationship among the multipath time delay difference, the elevation angle and depth. Simulations and experiments demonstrate the effectiveness of this method in reducing the depth estimation bias and avoiding the misjudgment of surface or submerged targets.
The SAVEMEDCOASTS-2 webGIS: The Online Platform for Relative Sea Level Rise and Storm Surge Scenarios up to 2100 for the Mediterranean Coasts
Authors: Falciano Antonio , Anzidei Marco , Greco Michele , Trivigno Maria Lucia , Vecchio Antonio , Georgiadis Charalampos , Patias Petros , Crosetto Michele , Navarro Josè , Serpelloni Enrico , Tolomei Cristiano , Martino Giovanni , Mancino Giuseppe , Arbia Francesco , Bignami Christian , Doumaz Fawzi
Published: October 2023

Here we show the SAVEMEDCOASTS-2 web-based geographic information system (webGIS) that supports land planners and decision makers in considering the ongoing impacts of Relative Sea Level Rise (RSLR) when formulating and prioritizing climate-resilient adaptive pathways for the Mediterranean coasts. The webGIS was developed within the framework of the SAVEMEDCOASTS and SAVEMEDCOASTS-2 projects, funded by the European Union, which respond to the need to protect people and assets from natural disasters along the Mediterranean coasts that are vulnerable to the combined effects of Sea Level Rise (SLR) and Vertical Land Movements (VLM). The geospatial data include available or new high-resolution Digital Terrain Models (DTM), bathymetric data, rates of VLM, and multi-temporal coastal flooding scenarios for 2030, 2050, and 2100 with respect to 2021, as a consequence of RSLR. The scenarios are derived from the 5th Assessment Report (AR5) provided by the Intergovernmental Panel on Climate Change (IPCC) and encompass different Representative Concentration Pathways (RCP2.6 and RCP8.5) for climate projections. The webGIS reports RSLR scenarios that incorporate the temporary contribution of both the highest astronomical tides (HAT) and storm surges (SS), which intensify risks to the coastal infrastructure, local community, and environment.