bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing Charge Carrier Mobility through Modifications of Terminal Groups of Y6: A Theoretical Study
Authors: Xiang Yunjie , Xu Chunlin , Zheng Shaohui
Published: May 2023

The applications of non-fullerene acceptor Y6 with a new type of A1-DA2D-A1 framework and its derivatives have increased the power conversion efficiency (PCE) of organic solar cells (OSCs) up to 19%. Researchers have made various modifications of the donor unit, central/terminal acceptor unit, and side alkyl chains of Y6 to study the influences on the photovoltaic properties of OSCs based on them. However, up to now, the effect of changes of terminal acceptor parts of Y6 on the photovoltaic properties is not very clear. In the present work, we have designed four new acceptors—Y6-NO2, Y6-IN, Y6-ERHD, and Y6-CAO—with different terminal groups, which possess diverse electron-withdrawing ability. Computed results show that with the enhanced electron-withdrawing ability of the terminal group, the fundamental gaps become lower; thus, the wavelengths of the main absorption peaks of UV-Vis spectra red-shifts and total oscillator strength increase. Simultaneously, the electron mobility of Y6-NO2, Y6-IN, and Y6-CAO is about six, four, and four times faster than that of Y6, respectively. Overall, Y6-NO2 could be a potential NFA because of its longer intramolecular charge-transfer distance, stronger dipole moment, higher averaged ESP, enhanced spectrum, and faster electron mobility. This work provides a guideline for the future research on modification of Y6.
The Crucial Roles of Pitx3 in Midbrain Dopaminergic Neuron Development and Parkinson’s Disease-Associated Neurodegeneration
Authors: Wang Xin , Chen Xi , Liu Guangdong , Cai Huaibin , Le Weidong
Published: May 2023

The degeneration of midbrain dopaminergic (mDA) neurons, particularly in the substantia nigra pars compacta (SNc), is one of the most prominent pathological hallmarks of Parkinson’s disease (PD). To uncover the pathogenic mechanisms of mDA neuronal death during PD may provide therapeutic targets to prevent mDA neuronal loss and slow down the disease’s progression. Paired-like homeodomain transcription factor 3 (Pitx3) is selectively expressed in the mDA neurons as early as embryonic day 11.5 and plays a critical role in mDA neuron terminal differentiation and subset specification. Moreover, Pitx3-deficient mice exhibit some canonical PD-related features, including the profound loss of SNc mDA neurons, a dramatic decrease in striatal dopamine (DA) levels, and motor abnormalities. However, the precise role of Pitx3 in progressive PD and how this gene contributes to mDA neuronal specification during early stages remains unclear. In this review, we updated the latest findings on Pitx3 by summarizing the crosstalk between Pitx3 and its associated transcription factors in mDA neuron development. We further explored the potential benefits of Pitx3 as a therapeutic target for PD in the future. To better understand the transcriptional network of Pitx3 in mDA neuron development may provide insights into Pitx3-related clinical drug-targeting research and therapeutic approaches.
Core–Shell Structured Silica-Coated Iron Nanowires Composites for Enhanced Electromagnetic Wave Absorption Properties
Authors: Yang Pingan , Ye Wenxian , Ruan Haibo , Li Rui , Shou Mengjie , Yin Yichen , Huang Xin , Zhang Yuxin , Luo Jiufei
Published: May 2023

In this study, we successfully prepared core–shell heterostructured nanocomposites (Fe NWs@SiO2), with ferromagnetic nanowires (Fe NWs) as the core and silica (SiO2) as the shell. The composites exhibited enhanced electromagnetic wave absorption and oxidation resistance and were synthesized using a simple liquid-phase hydrolysis reaction. We tested and analyzed the microwave absorption properties of Fe NWs@SiO2 composites with varied filling rates (mass fractions of 10 wt%, 30 wt%, and 50 wt% after mixing with paraffin). The results showed that the sample filled with 50 wt% had the best comprehensive performance. At the matching thickness of 7.25 mm, the minimum reflection loss (RLmin) could reach −54.88 dB at 13.52 GHz and the effective absorption bandwidth (EAB, RL < −10 dB) could reach 2.88 GHz in the range of 8.96–17.12 GHz. Enhanced microwave absorption performance of the core–shell structured Fe NWs@SiO2 composites could be attributed to the magnetic loss of the composite, the core–shell heterogeneous interface polarization effect, and the small-scale effect induced by the one-dimensional structure. Theoretically, this research provided Fe NWs@SiO2 composites with highly absorbent and antioxidant core–shell structures for future practical applications.
Detection of Early Endothelial Dysfunction by Optoacoustic Tomography
Authors: Höltke Carsten , Enders Leonie , Stölting Miriam , Geyer Christiane , Masthoff Max , Kuhlmann Michael T. , Wildgruber Moritz , Helfen Anne
Published: May 2023

Variations in vascular wall shear stress are often presumed to result in the formation of atherosclerotic lesions at specific arterial regions, where continuous laminar flow is disturbed. The influences of altered blood flow dynamics and oscillations on the integrity of endothelial cells and the endothelial layer have been extensively studied in vitro and in vivo. Under pathological conditions, the Arg-Gly-Asp (RGD) motif binding integrin αvβ3 has been identified as a relevant target, as it induces endothelial cell activation. Animal models for in vivo imaging of endothelial dysfunction (ED) mainly rely on genetically modified knockout models that develop endothelial damage and atherosclerotic plaques upon hypercholesterolemia (ApoE−/− and LDLR−/−), thereby depicting late-stage pathophysiology. The visualization of early ED, however, remains a challenge. Therefore, a carotid artery cuff model of low and oscillating shear stress was applied in CD-1 wild-type mice, which should be able to show the effects of altered shear stress on a healthy endothelium, thus revealing alterations in early ED. Multispectral optoacoustic tomography (MSOT) was assessed as a non-invasive and highly sensitive imaging technique for the detection of an intravenously injected RGD-mimetic fluorescent probe in a longitudinal (2–12 weeks) study after surgical cuff intervention of the right common carotid artery (RCCA). Images were analyzed concerning the signal distribution upstream and downstream of the implanted cuff, as well as on the contralateral side as a control. Subsequent histological analysis was applied to delineate the distribution of relevant factors within the carotid vessel walls. Analysis revealed a significantly enhanced fluorescent signal intensity in the RCCA upstream of the cuff compared to the contralateral healthy side and the downstream region at all time points post-surgery. The most obvious differences were recorded at 6 and 8 weeks after implantation. Immunohistochemistry revealed a high degree of αv-positivity in this region of the RCCA, but not in the left common carotid artery (LCCA) or downstream of the cuff. In addition, macrophages could be detected by CD68 immunohistochemistry in the RCCA, showing ongoing inflammatory processes. In conclusion, MSOT is capable of delineating alterations in endothelial cell integrity in vivo in the applied model of early ED, where an elevated expression of integrin αvβ3 was detected within vascular structures.
Potential Role of the mTORC1-PGC1α-PPARα Axis under Type-II Diabetes and Hypertension in the Human Heart
Authors: Hang Tianyu , Lumpuy-Castillo Jairo , Goikoetxea-Usandizaga Naroa , Azkargorta Mikel , Aldámiz Gonzalo , Martínez-Milla Juan , Forteza Alberto , Cortina José M. , Egido Jesús , Elortza Félix , Martínez-Chantar Malu , Tuñón José , Lorenzo Óscar
Published: May 2023

Type-2 diabetes (T2DM) and arterial hypertension (HTN) are major risk factors for heart failure. Importantly, these pathologies could induce synergetic alterations in the heart, and the discovery of key common molecular signaling may suggest new targets for therapy. Intraoperative cardiac biopsies were obtained from patients with coronary heart disease and preserved systolic function, with or without HTN and/or T2DM, who underwent coronary artery bypass grafting (CABG). Control (n = 5), HTN (n = 7), and HTN + T2DM (n = 7) samples were analysed by proteomics and bioinformatics. Additionally, cultured rat cardiomyocytes were used for the analysis (protein level and activation, mRNA expression, and bioenergetic performance) of key molecular mediators under stimulation of main components of HTN and T2DM (high glucose and/or fatty acids and angiotensin-II). As results, in cardiac biopsies, we found significant alterations of 677 proteins and after filtering for non-cardiac factors, 529 and 41 were changed in HTN-T2DM and in HTN subjects, respectively, against the control. Interestingly, 81% of proteins in HTN-T2DM were distinct from HTN, while 95% from HTN were common with HTN-T2DM. In addition, 78 factors were differentially expressed in HTN-T2DM against HTN, predominantly downregulated proteins of mitochondrial respiration and lipid oxidation. Bioinformatic analyses suggested the implication of mTOR signaling and reduction of AMPK and PPARα activation, and regulation of PGC1α, fatty acid oxidation, and oxidative phosphorylation. In cultured cardiomyocytes, an excess of the palmitate activated mTORC1 complex and subsequent attenuation of PGC1α-PPARα transcription of β-oxidation and mitochondrial electron chain factors affect mitochondrial/glycolytic ATP synthesis. Silencing of PGC1α further reduced total ATP and both mitochondrial and glycolytic ATP. Thus, the coexistence of HTN and T2DM induced higher alterations in cardiac proteins than HTN. HTN-T2DM subjects exhibited a marked downregulation of mitochondrial respiration and lipid metabolism and the mTORC1-PGC1α-PPARα axis might account as a target for therapeutical strategies.
Effects and Mechanisms of Kaempferol in the Management of Cancers through Modulation of Inflammation and Signal Transduction Pathways
Authors: Almatroudi Ahmad , Allemailem Khaled S. , Alwanian Wanian M. , Alharbi Basmah F. , Alrumaihi Faris , Khan Amjad Ali , Almatroodi Saleh A. , Rahmani Arshad Husain
Published: May 2023

Cancer is the principal cause of death and its incidence is increasing continuously worldwide. Various treatment approaches are in practice to treat cancer, but these treatment strategies may be associated with severe side effects and also produce drug resistance. However, natural compounds have established their role in cancer management with minimal side effects. In this vista, kaempferol, a natural polyphenol, mainly found in vegetables and fruits, has been revealed to have many health-promoting effects. Besides its health-promoting potential, its anti-cancer potential has also been described in in vivo as well as in in vitro studies. The anti-cancer potential of kaempferol has been proven through modulation of cell signaling pathways in addition to the induction of apoptosis and cell cycle arrest in cancer cells. It leads to the activation of tumor suppressor genes, inhibition of angiogenesis, PI3K/AKT pathways, STAT3, transcription factor AP-1, Nrf2 and other cell signaling molecules. Poor bioavailability of this compound is one of the major limitations for its proper and effective disease management actions. Recently, some novel nanoparticle-based formulations have been used to overcome these limitations. The aim of this review is to provide a clear picture regarding the mechanism of action of kaempferol in different cancers through the modulation of cell signaling molecules. Besides this, strategies to improve the efficacy and synergistic effects of this compound have also been described. However, more studies are needed based on clinical trials to fully explore the therapeutic role of this compound, especially in cancer treatment.
Characterisation of miRNA Expression in Dental Pulp Cells during Epigenetically-Driven Reparative Processes
Authors: Kearney Michaela , Cooper Paul R. , Smith Anthony J. , Duncan Henry F.
Published: May 2023

Within regenerative endodontics, exciting opportunities exist for the development of next-generation targeted biomaterials that harness epigenetic machinery, including microRNAs (miRNAs), histone acetylation, and DNA methylation, which are used to control pulpitis and to stimulate repair. Although histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) induce mineralisation in dental pulp cell (DPC) populations, their interaction with miRNAs during DPC mineralisation is not known. Here, small RNA sequencing and bioinformatic analysis were used to establish a miRNA expression profile for mineralising DPCs in culture. Additionally, the effects of a HDACi, suberoylanilide hydroxamic acid (SAHA), and a DNMTi, 5-aza-2′-deoxycytidine (5-AZA-CdR), on miRNA expression, as well as DPC mineralisation and proliferation, were analysed. Both inhibitors increased mineralisation. However, they reduced cell growth. Epigenetically-enhanced mineralisation was accompanied by widespread changes in miRNA expression. Bioinformatic analysis identified many differentially expressed mature miRNAs that were suggested to have roles in mineralisation and stem cell differentiation, including regulation of the Wnt and MAPK pathways. Selected candidate miRNAs were demonstrated by qRT-PCR to be differentially regulated at various time points in mineralising DPC cultures treated with SAHA or 5-AZA-CdR. These data validated the RNA sequencing analysis and highlighted an increased and dynamic interaction between miRNA and epigenetic modifiers during the DPC reparative processes.
Overexpression of microRNA-21-5p and microRNA-221-5p in Monocytes Increases the Risk of Developing Coronary Artery Disease
Authors: Torres-Paz Yazmín Estela , Gamboa Ricardo , Fuentevilla-Álvarez Giovanny , Soto María Elena , González-Moyotl Nadia , Martínez-Alvarado Rocío , Torres-Tamayo Margarita , Ramírez-Marroquín Edgar Samuel , Vásquez-Jiménez Xicoténcatl , Sainz-Escarrega Víctor , Huesca-Gómez Claudia
Published: May 2023

MicroRNAs (miRs) regulate gene expression at the post-transcriptional level and are found to be present in monocytes. This study aimed to investigate miR-221-5p, miR-21-5p, and miR-155-5p, their expression in monocytes, and their role in coronary arterial disease (CAD). The study population comprised 110 subjects, and RT-qPCR was used to examine the miR-221-5p, miR-21-5p, and miR-155-5p expressions in monocytes. Results: the miR-21-5p (p = 0.001) and miR-221-5p (p < 0.001) expression levels were significantly higher in the CAD group, and the miR-155-5p (p = 0.021) expression levels were significantly lower in the CAD group; only miR-21-5p and miR-221-5p upregulation was found to be associated with an increased CAD risk. The results show significant increases in miR-21-5p in the unmedicated CAD group with the metformin patients vs. the healthy control group (p = 0.001) and vs. the medicated CAD group with metformin (p = 0.022). The same was true for miR-221-5p in the CAD patients unmedicated with metformin vs. the healthy control group (p < 0.001). Our results from Mexican CAD patients show that the overexpression in monocytes of miR-21-5p and miR-221-5p increases the risk of the development of CAD. In addition, in the CAD group, the metformin downregulated the expression of miR-21-5p and miR-221-5p. Also, the expression of endothelial nitric oxide synthase (NOS3) decreased significantly in our patients with CAD, regardless of whether they were medicated. Therefore, our findings allow for the proposal of new therapeutic strategies for the diagnosis and prognosis of CAD and the evaluation of treatment efficacy.
NOTCH1 Gene as a Novel Cause of Thoracic Aortic Aneurysm in Patients with Tricuspid Aortic Valve: Two Cases Reported
Authors: Torres-Juan Laura , Rico Yolanda , Fortuny Elena , Pons Jaume , Ramos Rafael , Santos-Simarro Fernando , Asensio Víctor , Martinez Iciar , Heine-Suñer Damian
Published: May 2023

Thoracic aortic aneurysms (TAA) consist of abnormal dilation or the widening of a portion of the ascending aorta, due to weakness or destructuring of the walls of the vessel and are potentially lethal. The congenital bicuspid aortic valve (BAV) is considered a risk factor for the development of TAA because asymmetric blood flow through the bicuspid aortic valve detrimentally influences the wall of the ascending aorta. NOTCH1 mutations have been associated with non-syndromic TAAs as a consequence of BAV, but little is known regarding its haploinsufficiency and its relationship with connective tissue abnormalities. We report two cases in which there is clear evidence that alterations in the NOTCH1 gene are the cause of TAA in the absence of BAV. On the one hand, we describe a 117 Kb deletion that includes a large part of the NOTCH1 gene and no other coding genes, suggesting that haploinsufficiency can be considered a pathogenic mechanism for this gene associated with TAA. In addition, we describe two brothers who carry two variants, one in the NOTCH1 gene and another in the MIB1 gene, corroborating the involvement of different genes of the Notch pathway in aortic pathology.
Effect of Triazole Fungicides Titul Duo and Vintage on the Development of Pea (Pisum sativum L.) Symbiotic Nodules
Authors: Gorshkov Artemii P. , Kusakin Pyotr G. , Borisov Yaroslav G. , Tsyganova Anna V. , Tsyganov Viktor E.
Published: May 2023

Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). The use of fungicides can negatively affect the legume-Rhizobium symbiosis. In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. The data obtained indicate the need for further research on the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use.
Schiff Bases Functionalized with T-Butyl Groups as Adequate Ligands to Extended Assembly of Cu(II) Helicates
Authors: Fernández-Fariña Sandra , Velo-Heleno Isabel , Martínez-Calvo Miguel , Maneiro Marcelino , Pedrido Rosa , González-Noya Ana M.
Published: May 2023

The study of the inherent factors that influence the isolation of one type of metallosupramolecular architecture over another is one of the main objectives in the field of Metallosupramolecular Chemistry. In this work, we report two new neutral copper(II) helicates, [Cu2(L1)2]·4CH3CN and [Cu2(L2)2]·CH3CN, obtained by means of an electrochemical methodology and derived from two Schiff-based strands functionalized with ortho and para-t-butyl groups on the aromatic surface. These small modifications let us explore the relationship between the ligand design and the structure of the extended metallosupramolecular architecture. The magnetic properties of the Cu(II) helicates were explored by Electron Paramagnetic Resonance (EPR) spectroscopy and Direct Current (DC) magnetic susceptibility measurements.
Boosting the Antibacterial Activity of Azithromycin on Multidrug-Resistant Escherichia coli by Efflux Pump Inhibition Coupled with Outer Membrane Permeabilization Induced by Phenylalanine-Arginine β-Naphthylamide
Authors: Al-Marzooq Farah , Ghazawi Akela , Daoud Lana , Tariq Saeed
Published: May 2023

The global spread of multidrug-resistant (MDR) bacteria increases the demand for the discovery of new antibiotics and adjuvants. Phenylalanine-arginine β-naphthylamide (PAβN) is an inhibitor of efflux pumps in Gram-negative bacteria, such as the AcrAB-TolC complex in Escherichia coli. We aimed to explore the synergistic effect and mechanism of action of PAβN combined with azithromycin (AZT) on a group of MDR E. coli strains. Antibiotic susceptibility was tested for 56 strains, which were screened for macrolide resistance genes. Then, 29 strains were tested for synergy using the checkerboard assay. PAβN significantly enhanced AZT activity in a dose-dependent manner in strains expressing the mphA gene and encoding macrolide phosphotransferase, but not in strains carrying the ermB gene and encoding macrolide methylase. Early bacterial killing (6 h) was observed in a colistin-resistant strain with the mcr-1 gene, leading to lipid remodeling, which caused outer membrane (OM) permeability defects. Clear OM damage was revealed by transmission electron microscopy in bacteria exposed to high doses of PAβN. Increased OM permeability was also proven by fluorometric assays, confirming the action of PAβN on OM. PAβN maintained its activity as an efflux pump inhibitor at low doses without permeabilizing OM. A non-significant increase in acrA, acrB, and tolC expression in response to prolonged exposure to PAβN was noted in cells treated with PAβN alone or with AZT, as a reflection of bacterial attempts to counteract pump inhibition. Thus, PAβN was found to be effective in potentiating the antibacterial activity of AZT on E. coli through dose-dependent action. This warrants further investigations of its effect combined with other antibiotics on multiple Gram-negative bacterial species. Synergetic combinations will help in the battle against MDR pathogens, adding new tools to the arsenal of existing medications.
Relationship between the Reduced Expression of Zinc Finger Protein 668 in Bladder Cancer and Its Invasiveness
Authors: Okuno Yumiko , Hattori-Kato Mami , Tanaka Hiroki , Tonooka Akiko , Takeuchi Takumi
Published: May 2023

The zinc finger protein 668 (ZNF668) gene encodes a Kruppel C2H2-type zinc-finger protein with 16 C2H2-type zinc fingers. The ZNF668 gene functions as a tumor suppressor gene in breast cancer. We histologically analyzed ZNF668 protein expression in bladder cancer and examined mutations of the ZNF668 gene in 68 cases of bladder cancer. In bladder cancer, the ZNF668 protein was expressed in the nuclei of cancer cells. In bladder cancer with submucosal and muscular infiltration, the expression of ZNF668 protein was significantly lower than that without submucosal and muscular infiltration. Eight heterozygous somatic mutations were detected in exon3 in five cases, and five of the mutations resulted in amino acid sequence mutations. Mutations resulting in amino acid sequence alterations also resulted in lower ZNF668 protein expression in bladder cancer cell nuclei, but no significant association with bladder cancer infiltration was detected. Decreased ZNF668 expression in bladder cancer was associated with submucosal and muscle invasion of cancer cells. Somatic mutations resulting in amino acid mutations in ZNF668 were found in 7.3% of the bladder cancer cases.
Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical Plasma
Authors: Nitsch Andreas , Qarqash Sara , Römer Sarah , Schoon Janosch , Ekkernkamp Axel , Niethard Maya , Reichert Johannes C. , Wassilew Georgi I. , Tzvetkov Mladen V. , Haralambiev Lyubomir
Published: May 2023

Although Ewing’s sarcoma (ES) is a rare, but very aggressive tumor disease affecting the musculoskeletal system, especially in children, it is very aggressive and difficult to treat. Although medical advances and the establishment of chemotherapy represent a turning point in the treatment of ES, resistance to chemotherapy, and its side effects, continue to be problems. New treatment methods such as the application of cold physical plasma (CPP) are considered potential supporting tools since CPP is an exogenous source of reactive oxygen and nitrogen species, which have similar mechanisms of action in the tumor cells as chemotherapy. This study aims to investigate the synergistic effects of CPP and commonly used cytostatic chemotherapeutics on ES cells. The chemotherapy drugs doxorubicin and vincristine, the most commonly used in the treatment of ES, were applied to two different ES cell lines (RD-ES and A673) and their IC20 and IC50 were determined. In addition, individual chemotherapeutics in combination with CPP were applied to the ES cells and the effects on cell growth, cell viability, and apoptosis processes were examined. A single CPP treatment resulted in the dose-dependent growth inhibition of ES cells. The combination of different cytostatics and CPP led to significant growth inhibition, a reduction in cell viability, and higher rates of apoptosis compared to cells not additionally exposed to CPP. The combination of CPP treatment and the application of cytostatic drugs to ES cells showed promising results, significantly enhancing the cytotoxic effects of chemotherapeutic agents. These preclinical in vitro data indicate that the use of CPP can enhance the efficacy of common cytostatic chemotherapeutics, and thus support the translation of CPP as an anti-tumor therapy in clinical routine.
Identification of Endometrial Cancer-Specific microRNA Biomarkers in Endometrial Fluid
Authors: Yang Jianing , Barkley Joel E. , Bhattarai Bikash , Firouzi Kameron , Monk Bradley J. , Coonrod Dean V. , Zenhausern Frederic
Published: May 2023

Abnormal uterine bleeding is a common benign gynecological complaint and is also the most common symptom of endometrial cancer (EC). Although many microRNAs have been reported in endometrial carcinoma, most of them were identified from tumor tissues obtained at surgery or from cell lines cultured in laboratories. The objective of this study was to develop a method to detect EC-specific microRNA biomarkers from liquid biopsy samples to improve the early diagnosis of EC in women. Endometrial fluid samples were collected during patient-scheduled in-office visits or in the operating room prior to surgery using the same technique performed for saline infusion sonohysterography (SIS). The total RNA was extracted from the endometrial fluid specimens, followed by quantification, reverse transcription, and real-time PCR arrays. The study was conducted in two phases: exploratory phase I and validation phase II. In total, endometrial fluid samples from 82 patients were collected and processed, with 60 matched non-cancer versus endometrial carcinoma patients used in phase I and 22 in phase II. The 14 microRNA biomarkers, out of 84 miRNA candidates, with the greatest variation in expression from phase I, were selected to enter phase II validation and statistical analysis. Among them, three microRNAs had a consistent and substantial fold-change in upregulation (miR-429, miR-183-5p, and miR-146a-5p). Furthermore, four miRNAs (miR-378c, miR-4705, miR-1321, and miR-362-3p) were uniquely detected. This research elucidated the feasibility of the collection, quantification, and detection of miRNA from endometrial fluid with a minimally invasive procedure performed during a patient in-office visit. The screening of a larger set of clinical samples was necessary to validate these early detection biomarkers for endometrial cancer.
Mesenchymal Stem Cells Pretreated with Collagen Promote Skin Wound-Healing
Authors: Kou Zheng , Li Balun , Aierken Aili , Tan Ning , Li Chenchen , Han Miao , Jing Yuanxiang , Li Na , Zhang Shiqiang , Peng Sha , Zhao Xianjun , Hua Jinlian
Published: May 2023

The existing treatment modalities for skin injuries mainly include dressings, negative-pressure wound treatment, autologous skin grafting, and high-pressure wound treatment. All of these therapies have limitations such as high time cost, the inability to remove inactivated tissue in a timely manner, surgical debridement, and oxygen toxicity. Mesenchymal stem cells have a unique self-renewal ability and wide differentiation potential, and they are one of the most promising stem cell types in cell therapy and have great application prospects in the field of regenerative medicine. Collagen exerts structural roles by promoting the molecular structure, shape, and mechanical properties of cells, and adding it to cell cultures can also promote cell proliferation and shorten the cell doubling time. The effects of collagen on MSCs were examined using Giemsa staining, EdU staining, and growth curves. Mice were subjected to allogeneic experiments and autologous experiments to reduce individual differences; all animals were separated into four groups. Neonatal skin sections were detected by HE staining, Masson staining, immunohistochemical staining, and immunofluorescence staining. We found that the MSCs pretreated with collagen accelerated the healing of skin wounds in mice and canines by promoting epidermal layer repair, collagen deposition, hair follicle angiogenesis, and an inflammatory response. Collagen promotes the secretion of the chemokines and growth factors associated with skin healing by MSCs, which positively influences skin healing. This study supports the treatment of skin injuries with MSCs cultured in medium with collagen added.
Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA
Authors: Zheng Yi , Dong Xian , Wang Xinyu , Wang Jie , Chen Shuo , He Yang , An Jingang , He Linhai , Zhang Yi
Published: May 2023

Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were partially impaired in the IL-1RA-deficient exosome group. Our results indicated that MSC(AT)s-Exo might prevent the onset of MRONJ via an IL-1RA-mediated anti-inflammatory effect in the gingiva wound and improve the migration and collagen synthesis abilities of HGFs.
Sevoflurane Exposure in Neonates Perturbs the Expression Patterns of Specific Genes That May Underly the Observed Learning and Memory Deficits
Authors: Jimenez-Tellez Nerea , Pehar Marcus , Visser Frank , Casas-Ortiz Alberto , Rice Tiffany , Syed Naweed I.
Published: May 2023

Exposure to commonly used anesthetics leads to neurotoxic effects in animal models—ranging from cell death to learning and memory deficits. These neurotoxic effects invoke a variety of molecular pathways, exerting either immediate or long-term effects at the cellular and behavioural levels. However, little is known about the gene expression changes following early neonatal exposure to these anesthetic agents. We report here on the effects of sevoflurane, a commonly used inhalational anesthetic, on learning and memory and identify a key set of genes that may likely be involved in the observed behavioural deficits. Specifically, we demonstrate that sevoflurane exposure in postnatal day 7 (P7) rat pups results in subtle, but distinct, memory deficits in the adult animals that have not been reported previously. Interestingly, when given intraperitoneally, pre-treatment with dexmedetomidine (DEX) could only prevent sevoflurane-induced anxiety in open field testing. To identify genes that may have been altered in the neonatal rats after sevoflurane and DEX exposure, specifically those impacting cellular viability, learning, and memory, we conducted an extensive Nanostring study examining over 770 genes. We found differential changes in the gene expression levels after exposure to both agents. A number of the perturbed genes found in this study have previously been implicated in synaptic transmission, plasticity, neurogenesis, apoptosis, myelination, and learning and memory. Our data thus demonstrate that subtle, albeit long-term, changes observed in an adult animal’s learning and memory after neonatal anesthetic exposure may likely involve perturbation of specific gene expression patterns.
Discovery of AI-2 Quorum Sensing Inhibitors Targeting the LsrK/HPr Protein–Protein Interaction Site by Molecular Dynamics Simulation, Virtual Screening, and Bioassay Evaluation
Authors: Xu Yijie , Zeng Chunlan , Wen Huiqi , Shi Qianqian , Zhao Xu , Meng Qingbin , Li Xingzhou , Xiao Junhai
Published: May 2023

Quorum sensing (QS) is a cell-to-cell communication mechanism that regulates bacterial pathogenicity, biofilm formation, and antibiotic sensitivity. Among the identified quorum sensing, AI-2 QS exists in both Gram-negative and Gram-positive bacteria and is responsible for interspecies communication. Recent studies have highlighted the connection between the phosphotransferase system (PTS) and AI-2 QS, with this link being associated with protein-protein interaction (PPI) between HPr and LsrK. Here, we first discovered several AI-2 QSIs targeting the LsrK/HPr PPI site through molecular dynamics (MD) simulation, virtual screening, and bioassay evaluation. Of the 62 compounds purchased, eight compounds demonstrated significant inhibition in LsrK-based assays and AI-2 QS interference assays. Surface plasmon resonance (SPR) analysis confirmed that the hit compound 4171-0375 specifically bound to the LsrK-N protein (HPr binding domain, KD = 2.51 × 10−5 M), and therefore the LsrK/HPr PPI site. The structure-activity relationships (SARs) emphasized the importance of hydrophobic interactions with the hydrophobic pocket and hydrogen bonds or salt bridges with key residues of LsrK for LsrK/HPr PPI inhibitors. These new AI-2 QSIs, especially 4171-0375, exhibited novel structures, significant LsrK inhibition, and were suitable for structural modification to search for more effective AI-2 QSIs.
Behavior Characteristics and Thermal Energy Absorption Mechanism of Physical Blowing Agents in Polyurethane Foaming Process
Authors: Wang Haozhen , Liu Yingshu , Lin Lin
Published: May 2023

Polyurethane rigid foam is a widely used insulation material, and the behavior characteristics and heat absorption performance of the blowing agent used in the foaming process are key factors that affect the molding performance of this material. In this work, the behavior characteristics and heat absorption of the polyurethane physical blowing agent in the foaming process were studied; this is something which has not been comprehensively studied before. This study investigated the behavior characteristics of polyurethane physical blowing agents in the same formulation system, including the efficiency, dissolution, and loss rates of the physical blowing agents during the polyurethane foaming process. The research findings indicate that both the physical blowing agent mass efficiency rate and mass dissolution rate are influenced by the vaporization and condensation process of physical blowing agent. For the same type of physical blowing agent, the amount of heat absorbed per unit mass decreases gradually as the quantity of physical blowing agent increases. The relationship between the two shows a pattern of initial rapid decrease followed by a slower decrease. Under the same physical blowing agent content, the higher the heat absorbed per unit mass of physical blowing agent, the lower the internal temperature of the foam when the foam stops expanding. The heat absorbed per unit mass of the physical blowing agents is a key factor affecting the internal temperature of the foam when it stops expanding. From the perspective of heat control of the polyurethane reaction system, the effects of physical blowing agents on the foam quality were ranked in order from good to poor as follows: HFC-245fa, HFC-365mfc, HFCO-1233zd(E), HFO-1336mzzZ, and HCFC-141b.
A Probabilistic Model of Human Activity Recognition with Loose Clothing
Authors: Shen Tianchen , Di Giulio Irene , Howard Matthew
Published: May 2023

Human activity recognition has become an attractive research area with the development of on-body wearable sensing technology. Textiles-based sensors have recently been used for activity recognition. With the latest electronic textile technology, sensors can be incorporated into garments so that users can enjoy long-term human motion recording worn comfortably. However, recent empirical findings suggest, surprisingly, that clothing-attached sensors can actually achieve higher activity recognition accuracy than rigid-attached sensors, particularly when predicting from short time windows. This work presents a probabilistic model that explains improved responsiveness and accuracy with fabric sensing from the increased statistical distance between movements recorded. The accuracy of the comfortable fabric-attached sensor can be increased by 67% more than rigid-attached sensors when the window size is 0.5s. Simulated and real human motion capture experiments with several participants confirm the model’s predictions, demonstrating that this counterintuitive effect is accurately captured.
An Anisotropic Velocity Model for Microseismic Events Localization in Tunnels
Authors: Shen Tong , Wang Songren , Jiang Xuan , Peng Guili , Tuo Xianguo
Published: May 2023

The velocity model is one of the main factors affecting the accuracy of microseismic event localization. This paper addresses the issue of the low accuracy of microseismic event localization in tunnels and, combined with active-source technology, proposes a “source–station” velocity model. The velocity model assumes that the velocity from the source to each station is different, and it can greatly improve the accuracy of the time-difference-of-arrival algorithm. At the same time, for the case of multiple active sources, the MLKNN algorithm was selected as the velocity model selection method through comparative testing. The results of numerical simulation and laboratory tests in the tunnel showed that the average location accuracy of the “source–station” velocity model was improved compared with that of the isotropic velocity and sectional velocity models, with numerical simulation experiments improving accuracy by 79.82% and 57.05% (from 13.28 m and 6.24 m to 2.68 m), and laboratory tests in the tunnel improving accuracy by 89.26% and 76.33% (from 6.61 m and 3.00 m to 0.71 m). The results of the experiments showed that the method proposed in this paper can effectively improve the location accuracy of microseismic events in tunnels.
TransNet: Transformer-Based Point Cloud Sampling Network
Authors: Lee Hookyung , Jeon Jaeseung , Hong Seokjin , Kim Jeesu , Yoo Jinwoo
Published: May 2023

As interest in point cloud processing has gradually increased in the industry, point cloud sampling techniques have been researched to improve deep learning networks. As many conventional models use point clouds directly, the consideration of computational complexity has become critical for practicality. One of the representative ways to decrease computations is downsampling, which also affects the performance in terms of precision. Existing classic sampling methods have adopted a standardized way regardless of the task-model property in learning. However, this limits the improvement of the point cloud sampling network’s performance. That is, the performance of such task-agnostic methods is too low when the sampling ratio is high. Therefore, this paper proposes a novel downsampling model based on the transformer-based point cloud sampling network (TransNet) to efficiently perform downsampling tasks. The proposed TransNet utilizes self-attention and fully connected layers to extract meaningful features from input sequences and perform downsampling. By introducing attention techniques into downsampling, the proposed network can learn about the relationships between point clouds and generate a task-oriented sampling methodology. The proposed TransNet outperforms several state-of-the-art models in terms of accuracy. It has a particular advantage in generating points from sparse data when the sampling ratio is high. We expect that our approach can provide a promising solution for downsampling tasks in various point cloud applications.
Extensive Gaseous Emissions Reduction of Firewood-Fueled Low Power Fireplaces by a Gas Sensor Based Advanced Combustion Airflow Control System and Catalytic Post-Oxidation
Authors: Zhang Xin , Ojha Binayak , Bichlmaier Hermann , Hartmann Ingo , Kohler Heinz
Published: May 2023

In view of the tremendous emissions of toxic gases and particulate matter (PM) by low-power firewood-fueled fireplaces, there is an urgent need for effective measures to lower emissions to keep this renewable and economical source for private home heating available in the future. For this purpose, an advanced combustion air control system was developed and tested on a commercial fireplace (HKD7, Bunner GmbH, Eggenfelden, Germany), complemented with a commercial oxidation catalyst (EmTechEngineering GmbH, Leipzig, Germany) placed in the post-combustion zone. Combustion air stream control of the wood-log charge combustion was realized by five different control algorithms to describe all situations of combustion properly. These control algorithms are based on the signals of commercial sensors representing catalyst temperature (thermocouple), residual oxygen concentration (LSU 4.9, Bosch GmbH, Gerlingen, Germany) and CO/HC-content in the exhaust (LH-sensor, Lamtec Mess- und Regeltechnik für Feuerungen GmbH & Co. KG, Walldorf (Germany)). The actual flows of the combustion air streams, as calculated for the primary and secondary combustion zone, are adjusted by motor-driven shutters and commercial air mass flow sensors (HFM7, Bosch GmbH, Gerlingen, Germany) in separate feedback control loops. For the first time, the residual CO/HC-content (CO, methane, formaldehyde, etc.) in the flue gas is in-situ monitored with a long-term stable AuPt/YSZ/Pt mixed potential high-temperature gas sensor, which allows continuous estimation of the flue gas quality with an accuracy of about ±10%. This parameter is not only an essential input for advanced combustion air stream control but also provides monitoring of the actual combustion quality and logging of this value over a whole heating period. By many firing experiments in the laboratory and by field tests over four months, it could be demonstrated that with this long-term stable and advanced automated firing system, depression of the gaseous emissions by about 90% related to manually operated fireplaces without catalyst could be achieved. In addition, preliminary investigations at a firing appliance complemented by an electrostatic precipitator yielded PM emission depression between 70% and 90%, depending on the firewood load.
ECG-Free Heartbeat Detection in Seismocardiography Signals via Template Matching
Authors: Centracchio Jessica , Parlato Salvatore , Esposito Daniele , Bifulco Paolo , Andreozzi Emilio
Published: May 2023

Cardiac monitoring can be performed by means of an accelerometer attached to a subject’s chest, which produces the Seismocardiography (SCG) signal. Detection of SCG heartbeats is commonly carried out by taking advantage of a simultaneous electrocardiogram (ECG). SCG-based long-term monitoring would certainly be less obtrusive and easier to implement without an ECG. Few studies have addressed this issue using a variety of complex approaches. This study proposes a novel approach to ECG-free heartbeat detection in SCG signals via template matching, based on normalized cross-correlation as heartbeats similarity measure. The algorithm was tested on the SCG signals acquired from 77 patients with valvular heart diseases, available from a public database. The performance of the proposed approach was assessed in terms of sensitivity and positive predictive value (PPV) of the heartbeat detection and accuracy of inter-beat intervals measurement. Sensitivity and PPV of 96% and 97%, respectively, were obtained by considering templates that included both systolic and diastolic complexes. Regression, correlation, and Bland–Altman analyses carried out on inter-beat intervals reported slope and intercept of 0.997 and 2.8 ms (R2 > 0.999), as well as non-significant bias and limits of agreement of ±7.8 ms. The results are comparable or superior to those achieved by far more complex algorithms, also based on artificial intelligence. The low computational burden of the proposed approach makes it suitable for direct implementation in wearable devices.
Sequential Fusion Filter for State Estimation of Nonlinear Multi-Sensor Systems with Cross-Correlated Noise and Packet Dropout Compensation
Authors: Tan Liguo , Wang Yibo , Hu Changqing , Zhang Xinbin , Li Liyi , Su Haoxiang
Published: May 2023

This paper is concerned with the problem of state estimation for nonlinear multi-sensor systems with cross-correlated noise and packet loss compensation. In this case, the cross-correlated noise is modeled by the synchronous correlation of the observation noise of each sensor, and the observation noise of each sensor is correlated with the process noise at the previous moment. Meanwhile, in the process of state estimation, since the measurement data may be transmitted in an unreliable network, data packet dropout will inevitably occur, leading to a reduction in estimation accuracy. To address this undesirable situation, this paper proposes a state estimation method for nonlinear multi-sensor systems with cross-correlated noise and packet dropout compensation based on a sequential fusion framework. Firstly, a prediction compensation mechanism and a strategy based on observation noise estimation are used to update the measurement data while avoiding the noise decorrelation step. Secondly, a design step for a sequential fusion state estimation filter is derived based on an innovation analysis method. Then, a numerical implementation of the sequential fusion state estimator is given based on the third-degree spherical-radial cubature rule. Finally, the univariate nonstationary growth model (UNGM) is combined with simulation to verify the effectiveness and feasibility of the proposed algorithm.