bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling Divergent Transcriptomic Profiles: A Comparative Single-Cell RNA Sequencing Study of Epithelium, Gingiva, and Periodontal Ligament Tissues
Authors: Abdallah Ali T. , Konermann Anna
Published: May 2024

The periodontium comprising periodontal ligament (PDL), gingiva, and epithelium play crucial roles in maintaining tooth integrity and function. Understanding tissue cellular composition and gene expression is crucial for illuminating periodontal pathophysiology. This study aimed to identify tissue-specific markers via scRNA-Seq. Primary human PDL, gingiva, and epithelium tissues (n = 7) were subjected to cell hashing and sorting. scRNA-Seq library preparation using 10× Genomics protocol and Illumina sequencing was conducted. The analysis was performed using Cellranger (v3.1.0), with downstream analysis via R packages Seurat (v5.0.1) and SCORPIUS (v1.0.9). Investigations identified eight distinct cellular clusters, revealing the ubiquitous presence of epithelial and gingival cells. PDL cells evolved in two clusters with numerical superiority. The other clusters showed varied predominance regarding gingival and epithelial cells or an equitable distribution of both. The cluster harboring most cells mainly consisted of PDL cells and was present in all donors. Some of the other clusters were also tissue-inherent, while the presence of others was environmentally influenced, revealing variability across donors. Two clusters exhibited genetic profiles associated with tissue development and cellular integrity, respectively, while all other clusters were distinguished by genes characteristic of immune responses. Developmental trajectory analysis uncovered that PDL cells may develop after epithelial and gingival cells, suggesting the inherent PDL cell-dominated cluster as a final developmental stage. This single-cell RNA sequencing study delineates the hierarchical organization of periodontal tissue development, identifies tissue-specific markers, and reveals the influence of environmental factors on cellular composition, advancing our understanding of periodontal biology and offering potential insights for therapeutic interventions.
Combination of FOLFOXIRI Drugs with Oncolytic Coxsackie B3 Virus PD-H Synergistically Induces Oncolysis in the Refractory Colorectal Cancer Cell Line Colo320
Authors: Girod Maxim , Geisler Anja , Hinze Luisa , Elsner Leslie , Dieringer Babette , Beling Antje , Kurreck Jens , Fechner Henry
Published: May 2024

FOLFOXIRI chemotherapy is a first-line therapy for advanced or metastatic colorectal cancer (CRC), yet its therapeutic efficacy remains limited. Immunostimulatory therapies like oncolytic viruses can complement chemotherapies by fostering the infiltration of the tumor by immune cells and enhancing drug cytotoxicity. In this study, we explored the effect of combining the FOLFOXIRI chemotherapeutic agents with the oncolytic coxsackievirus B3 (CVB3) PD-H in the CRC cell line Colo320. Additionally, we examined the impact of the drugs on the expression of microRNAs (miRs), which could be used to increase the safety of oncolytic CVB3 containing corresponding miR target sites (miR-TS). The measurement of cytotoxic activity using the Chou–Talalay combination index approach revealed that PD-H synergistically enhanced the cytotoxic activity of oxaliplatin (OX), 5-fluorouracil (5-FU) and SN-38. PD-H replication was not affected by OX and SN-38 but inhibited by high concentrations of 5-FU. MiR expression levels were not or only slightly elevated by the drugs or with drug/PD-H combinations on Colo320 cells. Moreover, the drug treatment did not increase the mutation rate of the miR-TS inserted into the PD-H genome. The results demonstrate that the combination of FOLFOXIRI drugs and PD-H may be a promising approach to enhance the therapeutic effect of FOLFOXIRI therapy in CRC.
Oil Palm AP2 Subfamily Gene EgAP2.25 Improves Salt Stress Tolerance in Transgenic Tobacco Plants
Authors: Zhou Lixia , Cao Hongxing , Zeng Xianhai , Wu Qiufei , Li Qihong , Martin Jerome Jeyakumar John , Fu Dengqiang , Liu Xiaoyu , Li Xinyu , Li Rui , Ye Jianqiu
Published: May 2024

AP2/ERF transcription factor genes play an important role in regulating the responses of plants to various abiotic stresses, such as cold, drought, high salinity, and high temperature. However, less is known about the function of oil palm AP2/ERF genes. We previously obtained 172 AP2/ERF genes of oil palm and found that the expression of EgAP2.25 was significantly up-regulated under salinity, cold, or drought stress conditions. In the present study, the sequence characterization and expression analysis for EgAP2.25 were conducted, showing that it was transiently over-expressed in Nicotiana tabacum L. The results indicated that transgenic tobacco plants over-expressing EgAP2.25 could have a stronger tolerance to salinity stress than wild-type tobacco plants. Compared with wild-type plants, the over-expression lines showed a significantly higher germination rate, better plant growth, and less chlorophyll damage. In addition, the improved salinity tolerance of EgAP2.25 transgenic plants was mainly attributed to higher antioxidant enzyme activities, increased proline and soluble sugar content, reduced H2O2 production, and lower MDA accumulation. Furthermore, several stress-related marker genes, including NtSOD, NtPOD, NtCAT, NtERD10B, NtDREB2B, NtERD10C, and NtP5CS, were significantly up-regulated in EgAP2.25 transgenic tobacco plants subjected to salinity stress. Overall, over-expression of the EgAP2.25 gene significantly enhanced salinity stress tolerance in transgenic tobacco plants. This study lays a foundation for further exploration of the regulatory mechanism of the EgAP2.25 gene in conferring salinity tolerance in oil palm.
Farnesyl Diphosphate Synthase Gene Associated with Loss of Bone Mass Density and Alendronate Treatment Failure in Patients with Primary Osteoporosis
Authors: Guaraná Werbson Lima , Lima Camilla Albertina Dantas , Barbosa Alexandre Domingues , Crovella Sergio , Sandrin-Garcia Paula
Published: May 2024

Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the FDPS gene, is associated with reduced gene transcription. This study evaluates the FDPS variant rs2297480 (A > C) association with OP patients’ response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) (n = 20) and non-responders (OP-NR) (n = 40). We observed an association of CC genotype with treatment failure (p = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = −2.21% ± 2.56; p = 0.026) and TH (CC = −2.06% ± 1.84; p = 0.015) after two years of alendronate sodium treatment. Relative expression of the FDPS gene was also evaluated in OP-R and OP-NR patients. Higher expression of the FDPS gene was also observed in OP-NR group (FC = 1.84 ± 0.77; p = 0.006) when compared to OP-R. In conclusion, the influence observed of FDPS expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis.
Differences in Metabolite Profiles of Dihydroberberine and Micellar Berberine in Caco-2 Cells and Humans—A Pilot Study
Authors: Chang Chuck , Roh Yoon Seok , Du Min , Kuo Yun Chai , Zhang Yiming , Hardy Mary , Gahler Roland , Solnier Julia
Published: May 2024

We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography–High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group—except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials.
The Characteristics of Structural Properties and Diffusion Pathway of Alkali in Sodium Trisilicate: Nanoarchitectonics and Molecular Dynamic Simulation
Authors: Kien Pham Huu , Trang Giap Thi Thuy
Published: May 2024

Based on nanoarchitectonics and molecular dynamics simulations, we investigate the structural properties and diffusion pathway of Na atoms in sodium trisilicate over a wide temperature range. The structural and dynamics properties are analyzed through the radial distribution function (RDF), the Voronoi Si- and O-polyhedrons, the cluster function fCL(r), and the sets of fastest (SFA) and slowest atoms (SSA). The results indicate that Na atoms are not placed in Si-polyhedrons and bridging oxygen (BO) polyhedrons; instead, Na atoms are mainly placed in non-bridging oxygen (NBO) polyhedrons and free oxygen (FO) polyhedrons. Here BO, NBO, and FO represent O bonded with two, one, and no Si atoms, respectively. The simulation shows that O atoms in sodium trisilicate undergo numerous transformations: NBF0 ↔ NBF1, NBF1 ↔ NBF2, and BO0 ↔ BO1, where NBF is NBO or FO. The dynamics in sodium trisilicate are mainly distributed by the hopping and cooperative motion of Na atoms. We suppose that the diffusion pathway of Na atoms is realized via hopping Na atoms alone in BO-polyhedrons and the cooperative motion of a group of Na atoms in NBO- and FO-polyhedrons.
Effective Radiosensitization of HNSCC Cell Lines by DNA-PKcs Inhibitor AZD7648 and PARP Inhibitors Talazoparib and Niraparib
Authors: Mentzel Jacob , Hildebrand Laura S. , Kuhlmann Lukas , Fietkau Rainer , Distel Luitpold V.
Published: May 2024

(1) Head and neck squamous cell carcinoma (HNSCC) is common, while treatment is difficult, and mortality is high. Kinase inhibitors are promising to enhance the effects of radiotherapy. We compared the effects of the PARP inhibitors talazoparib and niraparib and that of the DNA-PKcs inhibitor AZD7648, combined with ionizing radiation. (2) Seven HNSCC cell lines, including Cal33, CLS-354, Detroit 562, HSC4, RPMI2650 (HPV-negative), UD-SCC-2 and UM-SCC-47 (HPV-positive), and two healthy fibroblast cell lines, SBLF8 and SBLF9, were studied. Flow cytometry was used to analyze apoptosis and necrosis induction (AnnexinV/7AAD) and cell cycle distribution (Hoechst). Cell inactivation was studied by the colony-forming assay. (3) AZD7648 had the strongest effects, radiosensitizing all HNSCC cell lines, almost always in a supra-additive manner. Talazoparib and niraparib were effective in both HPV-positive cell lines but only consistently in one and two HPV-negative cell lines, respectively. Healthy fibroblasts were not affected by any combined treatment in apoptosis and necrosis induction or G2/M-phase arrest. AZD7648 alone was not toxic to healthy fibroblasts, while the combination with ionizing radiation reduced clonogenicity. (4) In conclusion, talazoparib, niraparib and, most potently, AZD7648 could improve radiation therapy in HNSCC. Healthy fibroblasts tolerated AZD7648 alone extremely well, but irradiation-induced effects might occur. Our results justify in vivo studies.
Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker
Authors: Malvasi Antonio , Baldini Giorgio Maria , Cicinelli Ettore , Di Naro Edoardo , Baldini Domenico , Favilli Alessandro , Quellari Paola Tiziana , Sabbatini Paola , Fioretti Bernard , Malgieri Lorenzo E. , Damiani Gianluca Raffaello , Dellino Miriam , Trojano Giuseppe , Tinelli Andrea
Published: May 2024

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women’s mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles’ activation, which could cause an aberrant mechano-sensitive pacemaker activation–deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.
Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes
Authors: Pontifex Carly S. , Zaman Mashiat , Fanganiello Roberto D. , Shutt Timothy E. , Pfeffer Gerald
Published: May 2024

In this review we examine the functionally diverse ATPase associated with various cellular activities (AAA-ATPase), valosin-containing protein (VCP/p97), its molecular functions, the mutational landscape of VCP and the phenotypic manifestation of VCP disease. VCP is crucial to a multitude of cellular functions including protein quality control, endoplasmic reticulum-associated degradation (ERAD), autophagy, mitophagy, lysophagy, stress granule formation and clearance, DNA replication and mitosis, DNA damage response including nucleotide excision repair, ATM- and ATR-mediated damage response, homologous repair and non-homologous end joining. VCP variants cause multisystem proteinopathy, and pathology can arise in several tissue types such as skeletal muscle, bone, brain, motor neurons, sensory neurons and possibly cardiac muscle, with the disease course being challenging to predict.
Anti-Idiotypic VHHs and VHH-CAR-T Cells to Tackle Multiple Myeloma: Different Applications Call for Different Antigen-Binding Moieties
Authors: Hanssens Heleen , Meeus Fien , Gesquiere Emma L. , Puttemans Janik , De Vlaeminck Yannick , De Veirman Kim , Breckpot Karine , Devoogdt Nick
Published: May 2024

CAR-T cell therapy is at the forefront of next-generation multiple myeloma (MM) management, with two B-cell maturation antigen (BCMA)-targeted products recently approved. However, these products are incapable of breaking the infamous pattern of patient relapse. Two contributing factors are the use of BCMA as a target molecule and the artificial scFv format that is responsible for antigen recognition. Tackling both points of improvement in the present study, we used previously characterized VHHs that specifically target the idiotype of murine 5T33 MM cells. This idiotype represents one of the most promising yet challenging MM target antigens, as it is highly cancer- but also patient-specific. These VHHs were incorporated into VHH-based CAR modules, the format of which has advantages compared to scFv-based CARs. This allowed a side-by-side comparison of the influence of the targeting domain on T cell activation. Surprisingly, VHHs previously selected as lead compounds for targeted MM radiotherapy are not the best (CAR-) T cell activators. Moreover, the majority of the evaluated VHHs are incapable of inducing any T cell activation. As such, we highlight the importance of specific VHH selection, depending on its intended use, and thereby raise an important shortcoming of current common CAR development approaches.
Antiproliferative and Anti-Inflammatory Effects of the Polyphenols Phloretin and Balsacone C in a Coculture of T Cells and Psoriatic Keratinocytes
Authors: Ruel Yasmine , Moawad Fatma , Alsarraf Jérôme , Pichette André , Legault Jean , Brambilla Davide , Pouliot Roxane
Published: May 2024

Plaque psoriasis is a chronic inflammatory skin disease causing red inflamed lesions covered by scales. Leukocytes, including dendritic cells and T cells, participate in the inflammation of the skin by producing multiple cytokines, thus contributing to the hyperproliferation of keratinocytes. Lack of effectiveness and toxic side effects are the main concerns with conventional treatments, and research involving new antipsoriatic molecules is essential. In this study, the anti-inflammatory and antiproliferative effects of two natural polyphenols, phloretin and balsacone C, were investigated using the coculture of T cells and psoriatic keratinocytes. Phloretin exerted antiproliferative activity by regulating the expression of antigen Ki67 and proliferating cell nuclear antigen (PCNA). These effects were comparable to those of methotrexate, a reference treatment for moderate to severe psoriasis. With balsacone C, the expression of Ki67 was also reduced. Additionally, phloretin decreased the levels of multiple pro-inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1α (MIP-1α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17A (IL-17A), and tumor necrosis factor alpha (TNF-α). The increased interleukin-2 (IL-2) levels with phloretin and methotrexate also represented anti-inflammatory activity. Balsacone C and methotrexate decreased the levels of IL-1α and IL-1β, but methotrexate exerted a higher reduction. In summary, the anti-inflammatory effects of phloretin were more pronounced than those of methotrexate and balsacone C. In addition, the expression of lymphocyte common antigen (CD45) was more similar to that of the healthy condition after using phloretin or methotrexate. Finally, phloretin stood out from the other compounds and appears promising for psoriasis treatment.
Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options
Authors: Portincasa Piero , Khalil Mohamad , Mahdi Laura , Perniola Valeria , Idone Valeria , Graziani Annarita , Baffy Gyorgy , Di Ciaula Agostino
Published: May 2024

The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression of liver damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk of cardio-metabolic diseases and cancer. In recent years, the terminological evolution from “nonalcoholic fatty liver disease” (NAFLD) to “metabolic dysfunction-associated fatty liver disease” (MAFLD) and, finally, “metabolic dysfunction-associated steatotic liver disease” (MASLD) has been paralleled by increased knowledge of mechanisms linking local (i.e., hepatic) and systemic pathogenic pathways. As a consequence, the need for an appropriate classification of individual phenotypes has been oriented to the investigation of innovative therapeutic tools. Besides the well-known role for lifestyle change, a number of pharmacological approaches have been explored, ranging from antidiabetic drugs to agonists acting on the gut–liver axis and at a systemic level (mainly farnesoid X receptor (FXR) agonists, PPAR agonists, thyroid hormone receptor agonists), anti-fibrotic and anti-inflammatory agents. The intrinsically complex pathophysiological history of MASLD makes the selection of a single effective treatment a major challenge, so far. In this evolving scenario, the cooperation between different stakeholders (including subjects at risk, health professionals, and pharmaceutical industries) could significantly improve the management of disease and the implementation of primary and secondary prevention measures. The high healthcare burden associated with MASLD makes the search for new, effective, and safe drugs a major pressing need, together with an accurate characterization of individual phenotypes. Recent and promising advances indicate that we may soon enter the era of precise and personalized therapy for MASLD/MASH.
The Significant Role of PA28αβ in CD8+ T Cell-Mediated Graft Rejection Contrasts with Its Negligible Impact on the Generation of MHC-I Ligands
Authors: Inholz Katharina , Bader Ulrika , Mundt Sarah , Basler Michael
Published: May 2024

The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the proteasome activator (PA)28 alpha beta (PA28αβ). In particular, several immunogenic peptides have been reported to be PA28αβ-dependent. In contrast, we did not observe a major impact of PA28αβ on the generation of different major histocompatibility complex (MHC) classI ligands. PA28αβ-knockout mice infected with the lymphocytic choriomeningitis virus (LCMV) or vaccinia virus showed a normal cluster of differentiation (CD) 8 response and viral clearance. However, we observed that the adoptive transfer of wild-type cells into PA28αβ-knockout mice led to graft rejection, but not vice versa. Depletion experiments showed that the observed rejection was mediated by CD8+ cytotoxic T cells. These data indicate that PA28αβ might be involved in the development of the CD8+ T cell repertoire in the thymus. Taken together, our data suggest that PA28αβ is a crucial factor determining T cell selection and, therefore, impacts graft acceptance.
Neurotoxicity and Developmental Neurotoxicity of Copper Sulfide Nanoparticles on a Human Neuronal In-Vitro Test System
Authors: Stern Michael , Botha Nandipha , Cloete Karen J. , Maaza Malik , Tan Saime , Bicker Gerd
Published: May 2024

Nanoparticles (NPs) are becoming increasingly important novel materials for many purposes, including basic research, medicine, agriculture, and engineering. Increasing human and environmental exposure to these promising compounds requires assessment of their potential health risks. While the general direct cytotoxicity of NPs is often routinely measured, more indirect possible long-term effects, such as reproductive or developmental neurotoxicity (DNT), have been studied only occasionally and, if so, mostly on non-human animal models, such as zebrafish embryos. In this present study, we employed a well-characterized human neuronal precursor cell line to test the concentration-dependent DNT of green-manufactured copper sulfide (CuS) nanoparticles on crucial early events in human brain development. CuS NPs turned out to be generally cytotoxic in the low ppm range. Using an established prediction model, we found a clear DNT potential of CuS NPs on neuronal precursor cell migration and neurite outgrowth, with IC50 values 10 times and 5 times, respectively, lower for the specific DNT endpoint than for general cytotoxicity. We conclude that, in addition to the opportunities of NPs, their risks to human health should be carefully considered.
In Vitro Screening of Ecotoxic and Cytotoxic Activities of Ailanthus altissima Leaf Extract against Target and Non-Target Plant and Animal Cells
Authors: Cocîrlea Maria Denisa , Simionescu Natalia , Petrovici Anca Roxana , Silion Mihaela , Biondi Barbara , Lastella Luana , Oancea Simona
Published: May 2024

Ailanthus altissima, an invasive plant species, exhibits pharmacological properties, but also some allergic effects on humans. This study aimed to evaluate the potential toxicity of A. altissima leaves, using a complex approach towards different organisms. The ecotoxic impact of a crude extract was investigated on seeds germination and brine shrimp lethality. Cytotoxicity was studied in vitro using non-target (haemolysis, liposomal model, fibroblast), and target (cancer cells) assays. Leaf extract at 1000 µg/mL significantly inhibited wheat and tomato germination, while no significant effects were found on parsley germination. A slight stimulatory effect on wheat and tomato germination was found at 125 µg/mL. In a brine shrimp-test, the extract showed a low toxicity at 24 h post-exposure (LC50 = 951.04 ± 28.26 μg/mL), the toxic effects increasing with the exposure time and extract concentration. Leaf extract caused low hematotoxicity. The extract was biocompatible with human gingival fibroblasts. No anti-proliferative effect was found within the concentration range of 10–500 µg/mL on malignant melanoma (MeWo) and hepatocellular carcinoma (HepG2). In a liposomal model-test, the extract proved to possess low capability to alter the eukaryotic cell-mimicking membranes within the tested concentration range. Given the low to moderate toxicity on tested organisms/cells, the A. altissima autumn leaves may find useful applications.
The Influence of Mesotrione on Human Colorectal Adenocarcinoma Cells and Possibility of Its Toxicity Mitigation by Cichoric Acid
Authors: Jabłońska-Trypuć Agata , Wydro Urszula , Wołejko Elżbieta , Kalinowska Monika , Świderski Grzegorz , Krętowski Rafał , Naumowicz Monika , Kondzior Paweł , Cechowska-Pasko Marzanna , Lewandowski Włodzimierz
Published: May 2024

Mesotrione, as a widely used herbicide, is present in the environment in detectable amounts, causing serious damage. Here, we aimed to investigate the effect of mesotrione on Caco-2 cells and the possibility of its toxicity mitigation by cichoric acid. Therefore, we analyzed the cytotoxicity of both these compounds and the selected oxidative stress parameters, apoptosis and interaction of both the tested compounds with the cell membrane and their accumulation within the cells. In cytotoxicity studies, the stimulating activity of mesotrione was observed, and simultaneously, the inhibitory effect of cichoric acid was noticed. This effect was related to the results of oxidative stress analysis and apoptosis measurements. The activity level of key enzymes (glutathione peroxidase, catalase and superoxide dismutase) in Caco-2 cells exposed to cichoric acid was higher as compared to that of the control. The treatment with mesotrione did not induce apoptosis in the Caco-2 cells. The penetration of the studied compounds into the Caco-2 cells was measured by using an HPLC methodology, and the results indicate mesotrione’s high penetration capacity. The distribution of charge on the surface of the cell membranes changed under the influence of both compounds. Considering the mutual interactions of beneficial and potentially toxic food ingredients, it should be noted that, despite the observed favorable trend, cichoric acid is not able to overcome the toxic and cancer-stimulating effects of this pesticide.
Object Tracking Based on Optical Flow Reconstruction of Motion-Group Parameters
Authors: Karpuzov Simeon , Petkov George , Ilieva Sylvia , Petkov Alexander , Kalitzin Stiliyan
Published: May 2024

Rationale. Object tracking has significance in many applications ranging from control of unmanned vehicles to autonomous monitoring of specific situations and events, especially when providing safety for patients with certain adverse conditions such as epileptic seizures. Conventional tracking methods face many challenges, such as the need for dedicated attached devices or tags, influence by high image noise, complex object movements, and intensive computational requirements. We have developed earlier computationally efficient algorithms for global optical flow reconstruction of group velocities that provide means for convulsive seizure detection and have potential applications in fall and apnea detection. Here, we address the challenge of using the same calculated group velocities for object tracking in parallel. Methods. We propose a novel optical flow-based method for object tracking. It utilizes real-time image sequences from the camera and directly reconstructs global motion-group parameters of the content. These parameters can steer a rectangular region of interest surrounding the moving object to follow the target. The method successfully applies to multi-spectral data, further improving its effectiveness. Besides serving as a modular extension to clinical alerting applications, the novel technique, compared with other available approaches, may provide real-time computational advantages as well as improved stability to noisy inputs. Results. Experimental results on simulated tests and complex real-world data demonstrate the method’s capabilities. The proposed optical flow reconstruction can provide accurate, robust, and faster results compared to current state-of-the-art approaches.
Impact of the Transboundary Interference Inhibitor on RNAi and the Baculovirus Expression System in Insect Cells
Authors: Zheng Hao , Zhao Hengfeng , Xiong Haifan , Awais Mian Muhammad , Zeng Songrong , Sun Jingchen
Published: May 2024

RNA interference inhibitors were initially discovered in plant viruses, representing a unique mechanism employed by these viruses to counteract host RNA interference. This mechanism has found extensive applications in plant disease resistance breeding and other fields; however, the impact of such interference inhibitors on insect cell RNA interference remains largely unknown. In this study, we screened three distinct interference inhibitors from plant and mammal viruses that act through different mechanisms and systematically investigated their effects on the insect cell cycle and baculovirus infection period at various time intervals. Our findings demonstrated that the viral suppressors of RNA silencing (VSRs) derived from plant and mammal viruses significantly attenuated the RNA interference effect in insect cells, as evidenced by reduced apoptosis rates, altered gene regulation patterns in cells, enhanced expression of exogenous proteins, and improved production efficiency of recombinant virus progeny. Further investigations revealed that the early expression of VSRs yielded superior results compared with late expression during RNA interference processes. Additionally, our results indicated that dsRNA-binding inhibition exhibited more pronounced effects than other modes of action employed by these interference inhibitors. The outcomes presented herein provide novel insights into enhancing defense mechanisms within insect cells using plant and mammal single-stranded RNA virus-derived interference inhibitors and have potential implications for expanding the scope of transformation within insect cell expression systems.
Looking at the Mental Health of Children and Adolescents with Cleft Lip and/or Palate through Neuroticism and Emotional Regulation Strategies: A Case-Controlled Observational Study
Authors: Ruiz-Guillén Ana , González-Olmo María José , Castañeda-López Esther , Romero-Maroto Martín , Peñacoba-Puente Cecilia
Published: May 2024

Background: Children and adolescents with cleft lip and/or palate (CL/P) are at an increased risk of developing emotional disorders. This study aims to explore this question in greater depth by addressing three objectives: (1) the presence of neuroticism as an indicator of emotional symptomatology, (2) the use of adaptive and non-adaptive emotional regulation strategies, and (3) the relationship between these strategies and neuroticism. Methods: A case–control correlational methodology was employed, with 60 children and adolescents with CL/P (mean age = 12.80 years; 33 females) and 60 non-clinical equivalent children and adolescents. Results: The CL/P group has higher scores on neuroticism (t = −7.74; p ≤ 0.001, d Cohen = 1.43) and lower scores in almost all emotional regulation strategies. The presence of CL/P moderated the relationship between neuroticism and self-blame (Beta = −0.46, t = −2.81, p = 0.005), rumination (Beta = −0.49, t = −3.73, p < 0.001), catastrophizing (Beta = −0.61, t = −4.26, p < 0.001), and blaming others (Beta = −0.45, t = −2.84, p = 0.005). This model predicted a significant variance of neuroticism (all p < 0.005), which ranged from 39% to 41%. Conclusions: The CL/P group has worse mental health indicators. Particularly novel results about the CL/P group are the lower scores on regulation strategies (both adaptive and non-adaptive) and the fact that non-adaptive strategies contribute, contrary to their effect in the general population, to a decrease in neuroticism. It supports the need to incorporate mental health indicators in the diagnosis and treatment of children and adolescents with CL/P.
Bilateral Uveal Melanoma: An Insight into Genetic Predisposition in Four New Unrelated Patients and Review of Published Cases
Authors: Silva-Rodríguez Paula , Bande Manuel , Pardo María , Domínguez Fernando , Loidi Lourdes , Blanco-Teijeiro María José
Published: May 2024

Background: Primary bilateral uveal melanoma (BUM) is an exceptionally rare form of uveal melanoma (UM). This study aimed to explore the potential existence of a genetic predisposition towards the development of BUM. Methods: We employed an exome sequencing approach on germline DNA from four unrelated patients diagnosed with BUM, seeking pathogenic or likely pathogenic variants indicative of a genetic predisposition to UM. Results: None of the patients exhibited pathogenic variants in the BAP1 gene. However, loss-of-function (LoF) variants in the TERF2IP and BAX genes were identified in two of the BUM patients. For patients BUM1 and BUM2, no pathogenic/likely pathogenic variants of significant clinical relevance to BUM were found to warrant inclusion in this report. Conclusions: Our findings suggest the presence of yet-to-be-discovered genes that may contribute to UM predisposition, as evidenced by the absence of pathogenic variants in known UM predisposition genes among the four BUM patients studied. The TERF2IP and BAX genes emerge as noteworthy candidates for further investigation regarding their role in genetic predisposition to UM. Specifically, the potential role of UM as a candidate cancer within the spectrum of cancers linked to pathogenic variants in the TERF2IP gene and other genes associated with the shelterin complex warrants further examination. Additional functional studies are necessary to support or challenge this hypothesis.
Effects of Exercise on Frailty in Older People Based on ACSM Recommendations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Pan Neng , Ossowski Zbigniew , Tong Jun , Li Dan , Gao Shan
Published: May 2024

Objectives: The objective of the study was to carry out an analysis of the methodological quality of clinical trials (effects of exercise on frailty in older people) based on ACSM recommendations. Methods: The search scope included PubMed, Embase, Web of Science, Cochrane, and literature that cannot be retrieved from the database. The topic was the impact of exercise on frailty in elderly people. Changes in five outcome measures (FP, BI, SPPB, GS, and BMI) were assessed using mean differences (MD) and 95% confidence intervals (95% CI). A random effects model (RE) was used to conduct a meta-analysis and compare the results between subgroups. Results: The intervention effects of exercise on the five outcome indicators of frailty in elderly people were all significant (p < 0.05). The effect of a high-consistency subgroup on outcome indicators FP and GS was more significant than that of the low- or uncertain-consistency subgroup (MD: −1.09 < −0.11, MD: 2.39 >1.1). There was no significant difference in the intervention effect as reflected in the outcome measures SPPB and BMI in the high-consistency subgroup (p = 0.07, p = 0.34). There was no significant difference in the impact of the intervention on the outcome measure BI between the two subgroups (p = 0.06, p = 0.14). Conclusions: Exercise prescriptions with high consistency with ACSM recommendations may be more effective in both FP and GS interventions than those with uncertain or low consistency. However, it is essential to note that the data derived from the meta-analysis is still subject to the small number of studies, the unknown degree of consistency of participants in individual studies, and the different mix of cases in the studies.
Risk Factors for Progression of Cervical Congenital Scoliosis and Associated Compensatory Curve Behavior
Authors: Amanullah Amir A. , Oh Taemin , Toll Brandon J. , Patel Akul , Samdani Amer F. , Pahys Joshua M. , Kim Andrew Jeongyoon , Vellanki Aniketh , Steindler Jessica , Ishmael Terrence G. , Hwang Steven W.
Published: May 2024

Background: This study investigated risk factors for progression of deformity in pediatric congenital cervical scoliosis (CCS) and evaluated the correlation between congenital cervical curves and compensatory thoracic and lumbar curves. Methods: Medical records were retrospectively reviewed for 38 pediatric patients with CCS with a minimum 2-year follow-up. Curve progression was defined as >10° increase in cervical coronal curve angle between presentation and last follow-up. Results: A total of 38 patients (16 girls, 22 boys) with a mean age at presentation of 5.6 ± 4.1 years met the inclusion criteria. Sixteen patients (42%) had curve progression with a mean follow-up of 3.1 ± 3.0 years. At presentation, T1 slope was significantly larger among children with progressive deformities (p = 0.041). A total of 18 of the 38 patients with strictly cervical spine deformity were then selected for subanalysis to evaluate the progression of compensatory curves. Cervical major coronal curves were found to significantly correlate with lumbar major coronal curves (r = 0.409), C2 central sacral vertical line (CSVL) (r = 0.407), and C7-CSVL (r = 0.403) (p < 0.05). Thoracic major coronal curves did not significantly correlate with cervical major coronal curves (r = 0.218) (p > 0.05). Conclusion: In conclusion, 42% of osseous CCS curves progressed over time in the overall cohort, and high initial T1 slope was found to be most highly correlated with progression of cervical deformity. Cervical major coronal curves significantly correlated with lumbar curve magnitude but not with thoracic curve size in isolated CCS, possibly due to the increased flexibility of the lumbar spine which may allow greater compensatory balance and thus have a greater correlation with cervical curve magnitude and possibly progression.
Cardiac Dysfunction and Exercise Tolerance in Patients after Complex Treatment for Cranial and Craniospinal Tumors in Childhood
Authors: Novikova Alena , Poltavskaya Maria , Pavlova Maria , Chomakhidze Petr , Bykova Aleksandra , Potemkina Nadezhda , Chashkina Maria , Fashafsha Zaki Z. A. , Mesitskaya Dinara , Gogiberidze Nana , Levshina Anna , Giverts Ilya , Shchekochikhin Dmitry , Andreev Denis
Published: May 2024

State-of-the-art therapy improves the five-year survival rate of patients under the age of 20 with cranial and craniospinal tumors by up to 74%. The urgency of dealing effectively with late treatment-associated cardiovascular complications is rising. Objective: We aimed to assess echocardiographic parameters and exercise performance in subjects with a history of complex treatment for cranial and craniospinal tumors in childhood. Methods: the study of 48 subjects who underwent cranial and craniospinal irradiation for CNS tumors in childhood and 20 healthy age- and sex-matched volunteers was conducted. The examination included hormone studies, cardiopulmonary exercise testing, and, in the main group, echocardiography (ECHO). Results: In five (10.4%) patients, ECHO changes were detected after complex anti-cancer treatment: thickening and calcification of the aortic valve leaflets (2%), and reduction in the systolic LV and RV function (8% and 6%, respectively). Irradiation of various areas was a significant predictor for reduced exercise tolerance, hyperventilation at rest and upon exertion, and an increased ventilatory equivalent for carbon dioxide. Low exercise tolerance was associated with a younger age at the time of treatment initiation. Significant differences were noted between the control group and the childhood cancer survivors with endocrine disorders. Conclusions: The obtained data confirm the importance of regular cardiovascular and endocrine monitoring of this group of cancer survivors.
Coordination of SRF-PLL and Grid Forming Inverter Control in Microgrid with Solar PV and Energy Storage
Authors: Babu V. Vignesh , Roselyn J. Preetha , Sundaravadivel Prabha
Published: May 2024

Recently, there has been a huge advancement in renewable energy integration in power systems. Power converters with grid-forming or grid-following topologies are typically employed to link these decentralized power sources to the grid. However, because distributed generation has less inertia than synchronous generators, their use of renewable energy sources threatens the electrical grid’s reliability. Suitable control approaches for ensuring frequency and voltage stability in the grid-connected form of operation are established in this study, which offers dynamic, seamless power switching in the islanded mode of operation. In this research, effective Phase Locked Loop (PLL) techniques for grid-forming (GFM) and grid-following (GFL) converters are designed to achieve a smooth transition from grid-tied to islanded mode of operation. In this work, PLL configurations are implemented while considering the active and reactive power, frequency, voltage, and current parameters of the system, and ensuring voltage and frequency stability. The simulation results in a microgrid network that ensures a smooth transition of power transfer while switching between modes of operation, and supports the voltage and frequency stability of the system.
Experimental Evidence on Incremental Formed Polymer Sheets Using a Stair Toolpath Strategy
Authors: Formisano Antonio , Boccarusso Luca , De Fazio Dario , Durante Massimo
Published: May 2024

Incremental sheet forming represents a relatively recent technology, similar to the layered manufacturing principle of the rapid prototype approach; it is very suitable for small series production and guarantees cost-effectiveness because it does not require dedicated equipment. Research has initially shown that this process is effective in metal materials capable of withstanding plastic deformation but, in recent years, the interest in this technique has been increasing for the manufacture of complex polymer sheet components as an alternative to the conventional technologies, based on heating–shaping–cooling manufacturing routes. Conversely, incrementally formed polymer sheets can suffer from some peculiar defects, like, for example, twisting. To reduce the risk of this phenomenon, the occurrence of failures and poor surface quality, a viable way is to choose toolpath strategies that make the tool/sheet contact conditions less severe; this represents one of the main goals of the present research. Polycarbonate sheets were worked using incremental forming; in detail, cone frusta with a fixed-wall angle were manufactured with different toolpaths based on a reference and a stair strategy, in lubricated and dry conditions. The forming forces, the forming time, the twist angle, and the mean roughness were monitored. The analysis of the results highlighted that a stair toolpath involving an alternation of diagonal up and vertical down steps represents a useful strategy to mitigate the occurrence of the twisting phenomenon in incremental formed thermoplastic sheets and a viable way of improving the process towards a green manufacturing process.
Experimental and Numerical Study of Suspended Inter-Array Cable Configurations for Floating Offshore Wind Farm
Authors: Li Di-Rong , Su Yu-Shiou , Yang Ray-Yeng
Published: May 2024

The present study evaluates the feasibility of using a fully suspended inter-array cable system for an offshore wind farm. It includes both numerical simulations and a scaled-down experiment, conducted at a 1:49 scale, to validate the numerical results. To achieve the goal, a 15 MW floating offshore wind turbine (FOWT) and a floating offshore substation (FOSS) are involved to simulate the wind farm array. This study incorporates the 50-year return period conditions of the Taiwan Hsinchu offshore area, which has a water depth of about 100 m, to validate the specifications related to the platform motion and mooring line tension. Additionally, an analysis of the tension, curvature, and fatigue damage of the dynamic cable system is discussed in this research. Because a fully suspended cable is a relatively new concept and may be more frequently considered in a deeper water depth area, numerical simulation software Orcina Orcaflex 11.4 has been chosen to conduct the fully coupled simulation, determining whether the fully suspended cable system could effectively withstand the challenges posed by extreme sea conditions. This is due to the reason that a fully suspended cable would occupy a larger space in the ocean, which may pose a risk by influencing the navigation of the vessels. Therefore, the cable laying depth under normal sea states is also discussed to evaluate the influence over vessel navigation. This study also collects the long-term environmental data from the Central Weather Bureau, Taiwan, to calculate the accumulative cable fatigue damage under different sea states. To integrate the results, this research applies fitness parameters to evaluate the feasibility of each cable configuration. Covering the cable performance under extreme sea states and regular operating sea states offers valuable insights for applications in ocean engineering.