bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of the COVID-19 Pandemic on Elite Swimmers and Water Polo Players: Lessons for the Future
Authors: Marinos Georgios , Lamprinos Dimitrios , Papapanou Michail , Sofroni Anastasia , Papaioannou Anastasia , Miletis Dionysios-Nikolaos , Deligiorgi Paraskevi , Papavassiliou Kostas A. , Siasos Gerasimos , Oikonomou Evangelos , Rachiotis George , Tsamakis Konstantinos , Schizas Dimitrios
Published: June 2024

Background: The COVID-19 pandemic has disrupted global daily life, including the world of elite athletes. This paper examines the multifaceted impact the COVID-19 pandemic had on elite swimmers and water polo athletes, specifically their mental health, their concerns over the virus, their intentions of getting vaccinated, and sleep disturbances that they may have faced. Methods: We conducted a cross-sectional study on elite swimmers and water polo players, using an anonymous questionnaire. Results: A total of 200 elite athletes participated. The majority of the participants reported a negative impact on their mental health, screened positive for insomnia (n = 107 (53.5%), with females (n = 101; 57.7%), swimmers (n = 100, 66.7%), and university students (n = 71, 71.7%) being more vulnerable (p < 0.001). Concerns about contracting the disease especially during important training or tournament periods and potential career disruption also affected their psychological well-being. While the majority (75%) had the intention of getting vaccinated, an alarming percentage was yet uncertain over its decision. Conclusions: This study highlights the significant psychological distress faced by elite aquatic athletes during the pandemic. It emphasizes the difficulties faced by elite swimmers and water polo athletes and determines not only the importance of addressing the vaccination intentions of athletes, but also how critical it is to confront the challenges they face both for their personal health and for the restoration of world sports to their pre-pandemic state. More large-scale studies are required to inform policies targeted at minimizing disruption to the athletes’ career, provision of information on preventive measures and vaccination, and improvement in psychological well-being in case of similar major public health issues in the future. Additionally, this study calls for further research to explore the unique challenges faced by aquatic athletes, such as those related to their training environments and fear of contagion, to better support them in future public health crises.
Biomonitoring Environmental Exposure in Syrian Refugees in Lebanon
Authors: Alaouie Malek , Troisi Gera M.
Published: June 2024

Over one million Syrian refugees have been residing in substandard living conditions in Lebanon for the past decade. Non-invasive biomonitoring of fractional exhaled nitric oxide (FeNO) as a pulmonary inflammation biomarker was conducted following and preceding indoor environmental assessments (which revealed elevated mould counts in informal tented settlements and non-residential shelters) to further evaluate effects of environmental exposure to indoor contaminants. Results of biomonitoring (n = 57) provided some insight regarding existing respiratory conditions and the possible implementation of minimally invasive methods to establish susceptibility profiles in Syrian refugees amid limited access to healthcare. The clinical interpretation of FeNO results suggested possible persistent exposure to allergens in addition to significant type 2 inflammation in some subjects. These findings warrant the need to expand this study, investigate other biomarkers, and attempt to correlate findings with environmental conditions to evaluate if a dose–response relationship exists.
An Alternative Proof of Minimum Trace Reconciliation
Authors: Ando Sakai , Narita Futoshi
Published: June 2024

Minimum trace reconciliation, developed by Wickramasuriya et al., 2019, is an innovation in the literature on forecast reconciliation. The proof, however, has a gap, and the idea is not easy to extend to more general situations. This paper fills the gap by providing an alternative proof based on the first-order condition in the space of a non-square matrix and arguing that it is not only simpler but also can be extended to incorporate more general results on minimum weighted trace reconciliation in Panagiotelis et al., 2021. Thus, our alternative proof not only has pedagogical value but also connects the results in the literature from a unified perspective.
Using Machine Learning Algorithms to Investigate the Impact of Temperature Treatment and Salt Stress on Four Forage Peas (Pisum sativum var. arvense L.)
Authors: Okumuş Onur , Say Ahmet , Eren Barış , Demirel Fatih , Uzun Satı , Yaman Mehmet , Aydın Adnan
Published: June 2024

The combination of high or low temperatures and high salt may cause significant harm to the yield, quality, and overall productivity of forage pea crops. The germination process, a crucial phase in the life cycle of forage peas, may be greatly influenced by varying temperature and salinity conditions. To comprehend the influence of these elements on the germination of forage peas, one must use many tactics, including the choice of resilient forage pea cultivars. The experiment aimed to evaluate the response of four forage pea cultivars (Arda, Ozkaynak, Taskent, and Tore) caused by various temperature (10 °C, 15 °C, and 20 °C) and salt (0, 5, 10, 15, and 20 dS m−1) conditions at the germination stage using multivariate analysis and machine learning methods. An observation of statistical significance (p < 0.01) was made regarding the variations between genotypes, temperature–salt levels, and the interaction of the observed factors: germination percentage (GP), shoot length (SL), root length (RL), fresh weight (FW), and dry weight (DW). The cultivar Tore had the best values for SL (1.63 cm), RL (5.38 cm), FW (1.10 g), and DW (0.13 g) among all the cultivars. On the other hand, the Ozkaynak cultivar had the highest value for GP (89.13%). The values of all of the parameters that were investigated decreased as the salt level rose, whereas the values increased when the temperature level increased. As a result, the Tore cultivar exhibited the highest values for shoot length, root length, fresh weight, and dry weight variables when exposed to a maximum temperature of 20 °C and a saline level of 0 dS m−1. It was determined that temperature treatment of fodder peas can reduce salt stress if kept at optimum levels. The effects of temperature and salt treatments on the germination data of several fodder pea cultivars were analyzed and predicted. Three distinct machine learning algorithms were used to create predictions. Based on R2 (0.899), MSE (5.344), MAPE (6.953), and MAD (4.125) measures, the MARS model predicted germination power (GP) better. The GPC model performed better in predicting shoot length (R2 = 0.922, MSE = 0.602, MAPE = 11.850, and MAD = 0.326) and root length (R2 = 0.900, MSE = 0.719, MAPE = 12.673, and MAD = 0.554), whereas the Xgboost model performed better in estimating fresh weight (R2 = 0.966, MSE = 0.130, MAPE = 11.635, and MAD = 0.090) and dry weight (R2 = 0.895, MSE = 0.021, MAPE = 12.395, and MAD = 0.013). The results of the research show that the techniques and analyses used can estimate stress tolerance, susceptibility levels, and other plant parameters, making it a cost-effective and reliable way to quickly and accurately study forage peas and related species.
In Vitro and Molecular Docking Studies of Antiglycation Potential of Phenolic Compounds in Date Palm (Phoenix dactylifera L.) Fruit: Exploring Local Varieties in the Food Industry
Authors: Ouamnina Abdoussadeq , Alahyane Abderrahim , Elateri Imane , Ouhammou Mourad , Abderrazik Mohamed
Published: June 2024

The Moroccan date-growing sector is rich in a wide diversity of varieties but faces major challenges, notably the undervaluation of certain varieties intended mainly for animal feed. In this study, our objective was to evaluate the antiglycation activity of four date varieties, including three low-market-value varieties and one high-market-value variety, harvested during two seasons (2021 and 2022). In addition, to improve our knowledge of the antiglycation potential, molecular docking analyses were carried out. The results of the antiglycation activity of the date extracts showed strong activity, particularly for the ‘Khalt Khal’ variety, which showed a 50% inhibition concentration (IC50) of 1.83 mg/mL and 2 mg/mL in 2021 and 2022, respectively. In addition, the molecular docking analysis also showed the possible link between the bioactive compounds identified and their mechanisms of action. Our findings suggest new evidence for the antiglycation properties of the bioactive compounds present in dates. These results suggest the use of these varieties as a source of bioactive molecules or as a food additive. This could make it possible to create medicines or food products with a high commercial value using dates, which could help to treat the complications associated with glycation.
Improvement of Physiological Features and Essential Oil Content of Thymus vulgaris after Soil Amendment with Chitosan Nanoparticles under Chromium Toxicity
Authors: Haghaninia Mohammad , Rasouli Farzad , Javanmard Abdollah , Mahdavinia Gholamreza , Azizi Sahar , Nicoletti Rosario , Murariu Otilia Cristina , Tallarita Alessio Vincenzo , Caruso Gianluca
Published: June 2024

An excessive amount of chromium in soil has detrimental effects on plant processes, and impairs food security, and public health. The application of nanoparticles may be a suitable solution and an innovative strategy by which to reduce plant abiotic stresses and pollution in the agricultural ecosystems. This research focuses on the effects of chitosan nanoparticles (CS-NPs) on thyme (Thymus vulgaris L.) plants grown in Cr-contaminated soil. The effects of CS-NPs as a soil amendment at four concentrations were investigated on plant nutrient uptake, photosynthesis parameters, antioxidant system, and essential oil (EO) content under soil Cr stress. The results show that chromium stress reduced fresh and dry weight of shoots, the uptake of macro-, and micro-elements, chlorophyll and carotenoids. The application of CS-NPs improved the antioxidant enzyme activity, reduced malondialdehyde, and increased the content of nutrients, EOs, photosynthetic pigments, and chlorophyll fluorescence parameters. The intermediate dose of chitosan nanoparticles (0.1% w/v) best valorized the content and yield of thyme EOs under chromium stress. These results are indicative that the application of CS-NPs can represent a supportive approach for plant production in soils contaminated with heavy metals.
Pilot Study by Liquid Biopsy in Gastrointestinal Stromal Tumors: Analysis of PDGFRA D842V Mutation and Hypermethylation of SEPT9 Presence by Digital Droplet PCR
Authors: Olivera-Salazar Rocío , Salcedo Cabañas Gabriel , Vega-Clemente Luz , Alonso-Martín David , Castellano Megías Víctor Manuel , Volward Peter , García-Olmo Damián , García-Arranz Mariano
Published: June 2024

Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists’ diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes.
Key Regulators of Angiogenesis and Inflammation Are Dysregulated in Patients with Varicose Veins
Authors: Zalewski Daniel , Chmiel Paulina , Kołodziej Przemysław , Kocki Marcin , Feldo Marcin , Kocki Janusz , Bogucka-Kocka Anna
Published: June 2024

Varicose veins (VVs) are the most common manifestation of chronic venous disease (CVD) and appear as abnormally enlarged and tortuous superficial veins. VVs result from functional abnormalities in the venous circulation of the lower extremities, such as venous hypertension, venous valve incompetence, and venous reflux. Previous studies indicate that enhanced angiogenesis and inflammation contribute to the progression and onset of VVs; however, dysregulations in signaling pathways associated with these processes in VVs patients are poorly understood. Therefore, in our study, we aimed to identify key regulators of angiogenesis and inflammation that are dysregulated in patients with VVs. Expression levels of 18 genes were analyzed in peripheral blood mononuclear cells (PBMC) using real-time PCR, as well as plasma levels of 6 proteins were investigated using ELISA. Higher levels of CCL5, PDGFA, VEGFC, TGF-alpha, TGF-beta 1, and VEGF-A, as well as lower levels of VEGFB and VEGF-C, were found to be statistically significant in the VV group compared to the control subjects without VVs. None of the analyzed factors was associated with the venous localization of the varicosities. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors in PBMC and plasma from VVs patients, providing new insight into molecular mechanisms that could contribute to the development of VVs and point out promising candidates for circulatory biomarkers of this disease.
Triphenylphosphonium-Conjugated Palmitic Acid for Mitochondrial Targeting of Pancreatic Cancer Cells: Proteomic and Molecular Evidence
Authors: Siragusa Giuliana , Brandi Jessica , Rawling Tristan , Murray Michael , Cecconi Daniela
Published: June 2024

Pancreatic ductal adenocarcinoma (PDAC)’s resistance to therapies is mainly attributed to pancreatic cancer stem cells (PCSCs). Mitochondria-impairing agents can be used to hamper PCSC propagation and reduce PDAC progression. Therefore, to develop an efficient vector for delivering drugs to the mitochondria, we synthesized tris(3,5-dimethylphenyl)phosphonium-conjugated palmitic acid. Triphenylphosphonium (TPP) is a lipophilic cationic moiety that promotes the accumulation of conjugated agents in the mitochondrion. Palmitic acid (PA), the most common saturated fatty acid, has pro-apoptotic activity in different types of cancer cells. TPP-PA was prepared by the reaction of 16-bromopalmitic acid with TPP, and its structure was characterized by 1H and 13C NMR and HRMS. We compared the proteomes of TPP-PA-treated and untreated PDAC cells and PCSCs, identifying dysregulated proteins and pathways. Furthermore, assessments of mitochondrial membrane potential, intracellular ROS, cardiolipin content and lipid peroxidation, ER stress, and autophagy markers provided information on the mechanism of action of TPP-PA. The findings showed that TPP-PA reduces PDAC cell proliferation through mitochondrial disruption that leads to increased ROS, activation of ER stress, and autophagy. Hence, TPP-PA might offer a new approach for eliminating both the primary population of cancer cells and PCSCs, which highlights the promise of TPP-derived compounds as anticancer agents for PDAC.
Identification and Validation of Tumor Microenvironment-Associated Signature in Clear-Cell Renal Cell Carcinoma through Integration of DNA Methylation and Gene Expression
Authors: Ye Zijian , Xu Jialiang , Zhang Xin , Zhang Yifan , Ivanova Deyana , Lu Weiyu , Zhang Jianning , Li Fangfang , Chen Xuemei , Wang Yingxiong , Wang Meijiao , Xie Biao
Published: June 2024

The tumor microenvironment (TME) is crucial in tumor development, metastasis, and response to immunotherapy. DNA methylation can regulate the TME without altering the DNA sequence. However, research on the methylation-driven TME in clear-cell renal cell carcinoma (ccRCC) is still lacking. In this study, integrated DNA methylation and RNA-seq data were used to explore methylation-driven genes (MDGs). Immune scores were calculated using the ESTIMATE, which was employed to identify TME-related genes. A new signature connected with methylation-regulated TME using univariate, multivariate Cox regression and LASSO regression analyses was developed. This signature consists of four TME-MDGs, including AJAP1, HOXB9, MYH14, and SLC6A19, which exhibit high methylation and low expression in tumors. Validation was performed using qRT-PCR which confirmed their downregulation in ccRCC clinical samples. Additionally, the signature demonstrated stable predictive performance in different subtypes of ccRCC. Risk scores are positively correlated with TMN stages, immune cell infiltration, tumor mutation burden, and adverse outcomes of immunotherapy. Interestingly, the expression of four TME-MDGs are highly correlated with the sensitivity of first-line drugs in ccRCC treatment, especially pazopanib. Molecular docking indicates a high affinity binding between the proteins and pazopanib. In summary, our study elucidates the comprehensive role of methylation-driven TME in ccRCC, aiding in identifying patients sensitive to immunotherapy and targeted therapy, and providing new therapeutic targets for ccRCC treatment.
The Role of TPM3 in Protecting Cardiomyocyte from Hypoxia-Induced Injury via Cytoskeleton Stabilization
Authors: Huang Ke , Yang Weijia , Shi Mingxuan , Wang Shiqi , Li Yi , Xu Zhaoqing
Published: June 2024

Ischemic heart disease (IHD) remains a major global health concern, with ischemia-reperfusion injury exacerbating myocardial damage despite therapeutic interventions. In this study, we investigated the role of tropomyosin 3 (TPM3) in protecting cardiomyocytes against hypoxia-induced injury and oxidative stress. Using the AC16 and H9c2 cell lines, we established a chemical hypoxia model by treating cells with cobalt chloride (CoCl2) to simulate low-oxygen conditions. We found that CoCl2 treatment significantly upregulated the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in cardiomyocytes, indicating the successful induction of hypoxia. Subsequent morphological and biochemical analyses revealed that hypoxia altered cardiomyocyte morphology disrupted the cytoskeleton, and caused cellular damage, accompanied by increased lactate dehydrogenase (LDH) release and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity, indicative of oxidative stress. Lentivirus-mediated TPM3 overexpression attenuated hypoxia-induced morphological changes, cellular damage, and oxidative stress imbalance, while TPM3 knockdown exacerbated these effects. Furthermore, treatment with the HDAC1 inhibitor MGCD0103 partially reversed the exacerbation of hypoxia-induced injury caused by TPM3 knockdown. Protein–protein interaction (PPI) network and functional enrichment analysis suggested that TPM3 may modulate cardiac muscle development, contraction, and adrenergic signaling pathways. In conclusion, our findings highlight the therapeutic potential of TPM3 modulation in mitigating hypoxia-associated cardiac injury, suggesting a promising avenue for the treatment of ischemic heart disease and other hypoxia-related cardiac pathologies.
Role of Adipose-Derived Mesenchymal Stem Cells in Bone Regeneration
Authors: Lau Chau Sang , Park So Yeon , Ethiraj Lalith Prabha , Singh Priti , Raj Grace , Quek Jolene , Prasadh Somasundaram , Choo Yen , Goh Bee Tin
Published: June 2024

Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.
Unveiling the Secrets of Acinetobacter baumannii: Resistance, Current Treatments, and Future Innovations
Authors: Marino Andrea , Augello Egle , Stracquadanio Stefano , Bellanca Carlo Maria , Cosentino Federica , Spampinato Serena , Cantarella Giuseppina , Bernardini Renato , Stefani Stefania , Cacopardo Bruno , Nunnari Giuseppe
Published: June 2024

Acinetobacter baumannii represents a significant concern in nosocomial settings, particularly in critically ill patients who are forced to remain in hospital for extended periods. The challenge of managing and preventing this organism is further compounded by its increasing ability to develop resistance due to its extraordinary genomic plasticity, particularly in response to adverse environmental conditions. Its recognition as a significant public health risk has provided a significant impetus for the identification of new therapeutic approaches and infection control strategies. Indeed, currently used antimicrobial agents are gradually losing their efficacy, neutralized by newer and newer mechanisms of bacterial resistance, especially to carbapenem antibiotics. A deep understanding of the underlying molecular mechanisms is urgently needed to shed light on the properties that allow A. baumannii enormous resilience against standard therapies. Among the most promising alternatives under investigation are the combination sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, xeruborbactam, and the newest molecules such as novel polymyxins or zosurabalpin. Furthermore, the potential of phage therapy, as well as deep learning and artificial intelligence, offer a complementary approach that could be particularly useful in cases where traditional strategies fail. The fight against A. baumannii is not confined to the microcosm of microbiological research or hospital wards; instead, it is a broader public health dilemma that demands a coordinated, global response.
Increasing the Survival of a Neuronal Model of Alzheimer’s Disease Using Docosahexaenoic Acid, Restoring Endolysosomal Functioning by Modifying the Interactions between the Membrane Proteins C99 and Rab5
Authors: Vigier Maxime , Uriot Magalie , Djelti-Delbarba Fathia , Claudepierre Thomas , El Hajj Aseel , Yen Frances T. , Oster Thierry , Malaplate Catherine
Published: June 2024

Docosahexaenoic acid (DHA, C22:6 ω3) may be involved in various neuroprotective mechanisms that could prevent Alzheimer’s disease (AD). Its influence has still been little explored regarding the dysfunction of the endolysosomal pathway, known as an early key event in the physiopathological continuum triggering AD. This dysfunction could result from the accumulation of degradation products of the precursor protein of AD, in particular the C99 fragment, capable of interacting with endosomal proteins and thus contributing to altering this pathway from the early stages of AD. This study aims to evaluate whether neuroprotection mediated by DHA can also preserve the endolysosomal function. AD-typical endolysosomal abnormalities were recorded in differentiated human SH-SY5Y neuroblastoma cells expressing the Swedish form of human amyloid precursor protein. This altered phenotype included endosome enlargement, the reduced secretion of exosomes, and a higher level of apoptosis, which confirmed the relevance of the cellular model chosen for studying the associated deleterious mechanisms. Second, neuroprotection mediated by DHA was associated with a reduced interaction of C99 with the Rab5 GTPase, lower endosome size, restored exosome production, and reduced neuronal apoptosis. Our data reveal that DHA may influence protein localization and interactions in the neuronal membrane environment, thereby correcting the dysfunction of endocytosis and vesicular trafficking associated with AD.
Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective
Authors: Vavallo Marica , Cingolani Sophia , Cozza Giulio , Schiavone Francesco P. , Dottori Ludovica , Palumbo Carla , Lahner Edith
Published: June 2024

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological–psychiatric up to gastrointestinal and less commonly to gynecological–obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.
Comprehensive Proteome and Acetylome Analysis of Needle Senescence in Larix gmelinii
Authors: Zhang Xuting , Shan Jinyuan , Wang Jiaxiu , Zhang Yanxia , Yang Feiyun , Liu Bin , Zhang Lifeng , Li Guojing , Wang Ruigang
Published: June 2024

Leaf senescence is essential for the growth and development of deciduous trees in the next season. Larix gmelinii, a deciduous coniferous tree, exhibits its most distinctive feature by turning yellow in the autumn and eventually shedding its leaves, resulting in significant changes in its appearance during the fall. Lysine acetylation plays an important role in diverse cellular processes; however, limited knowledge is available regarding acetylations in the needle senescence of L. gmelinii. In this study, the proteomics and acetylated modification omics of two phenotypic leaves, yellow and green (senescent and non-senescent) needles, were analyzed before autumn defoliation. In total, 5022 proteins and 4469 unique acetylation sites in 2414 lysine acylated proteins were identified, and this resulted in the discovery of 1335 differentially expressed proteins (DEPs) and 605 differentially expressed acetylated proteins (DAPs) in yellow versus green needles. There are significant differences between the proteome and acetylome; only 269 proteins were found to be DEP and DAP, of which 136 proteins were consistently expressed in both the DEP and DAP, 91 proteins were upregulated, and 45 proteins were down-regulated. The DEPs participate in the metabolism of starch and sucrose, while the DAPs are involved in glycolysis and the tricarboxylic acid cycle. Among them, DEPs underwent significant changes in glycolysis and citric acid cycling. Most of the enzymes involved in glycolysis and the citrate cycle were acetylated. DAPs were down-regulated in glycolysis and up-regulated in the citrate cycle. In all, the results of this study reveal the important role of lysine acetylation in the senescence of L. gmelinii needles and provide a new perspective for understanding the molecular mechanism of leaf senescence and tree seasonal growth.
Serotonin Influences Insulin Secretion in Rat Insulinoma INS-1E Cells
Authors: Yoo Yeong-Min , Joo Seong Soo
Published: June 2024

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine that plays a critical role in insulin secretion, energy metabolism, and mitochondrial biogenesis. However, the action of serotonin in insulin production and secretion by pancreatic β cells has not yet been elucidated. Here, we investigated how exogenous nanomolar serotonin concentrations regulate insulin synthesis and secretion in rat insulinoma INS-1E cells. Nanomolar serotonin concentrations (10 and 50 nM) significantly increased insulin protein expression above the constant levels in untreated control cells and decreased insulin protein levels in the media. The reductions in insulin protein levels in the media may be associated with ubiquitin-mediated protein degradation. The levels of membrane vesicle trafficking-related proteins including Rab5, Rab3A, syntaxin6, clathrin, and EEA1 proteins were significantly decreased by serotonin treatment compared to the untreated control cells, whereas the expressions of Rab27A, GOPC, and p-caveolin-1 proteins were significantly reduced by serotonin treatment. In this condition, serotonin receptors, Gαq-coupled 5-HT2b receptor (Htr2b), and ligand-gated ion channel receptor Htr3a were significantly decreased by serotonin treatment. To confirm the serotonylation of Rab3A and Rab27A during insulin secretion, we investigated the protein levels of Rab3A and Rab27A, in which transglutaminase 2 (TGase2) serotonylated Rab3A but not Rab27A. The increases in ERK phosphorylation levels were consistent with increases in the expression of p-Akt. Also, the expression level of the Bcl-2 protein was significantly increased by 50 and 100 nM serotonin treatment compared to the untreated control cells, whereas the levels of Cu/Zn-SOD and Mn-SOD proteins decreased. These results indicate that nanomolar serotonin treatment regulates the insulin protein level but decreases this level in media through membrane vesicle trafficking-related proteins (Rab5, Rab3A, syntaxin6, clathrin, and EEA1), the Akt/ERK pathway, and Htr2b/Htr3a in INS-1E cells.
Advancements in Immunotherapeutic Treatments for Hepatocellular Carcinoma: Potential of Combination Therapies
Authors: Zarlashat Yusra , Mushtaq Hassan , Pham Linh , Abbas Wasim , Sato Keisaku
Published: June 2024

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and a significant global health burden, with increasing incidence rates and limited treatment options. Immunotherapy has become a promising approach due to its ability to affect the immune microenvironment and promote antitumor responses. The immune microenvironment performs an essential role in both the progression and the development of HCC, with different characteristics based on specific immune cells and etiological factors. Immune checkpoint inhibitors, including programmed death-1/programmed death-ligand 1 inhibitors (pembrolizumab, nivolumab, and durvalumab) and cytotoxic T lymphocyte antigen-4 inhibitors (tremelimumab and ipilimumab), have the potential to treat advanced HCC and overcome adverse effects, such as liver failure and chemoresistance. Phase II and phase III clinical trials highlight the efficacy of pembrolizumab and nivolumab, respectively, in advanced HCC patients, as demonstrated by their positive effects on overall survival and progression-free survival. Tremelimumab has exhibited modest response rates, though it does possess antiviral activity. Thus, it is still being investigated in ongoing clinical trials. Combination therapies with multiple drugs have demonstrated potential benefits in terms of survival and tumor response rates, improving patient outcomes compared to monotherapy, especially for advanced-stage HCC. This review addresses the clinical trials of immunotherapies for early-, intermediate-, and advanced-stage HCC. Additionally, it highlights how combination therapy can significantly enhance overall survival, progression-free survival, and objective response rate in advanced-stage HCC, where treatment options are limited.
STAT5 Is Necessary for the Metabolic Switch Induced by IL-2 in Cervical Cancer Cell Line SiHa
Authors: Valle-Mendiola Arturo , Rocha-Zavaleta Leticia , Maldonado-Lagunas Vilma , Morelos-Laguna Diego , Gutiérrez-Hoya Adriana , Weiss-Steider Benny , Soto-Cruz Isabel
Published: June 2024

The tumor cells reprogram their metabolism to cover their high bioenergetic demands for maintaining uncontrolled growth. This response can be mediated by cytokines such as IL-2, which binds to its receptor and activates the JAK/STAT pathway. Some reports show a correlation between the JAK/STAT pathway and cellular metabolism, since the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of genes related to energetic metabolism. However, the role of STAT proteins in the metabolic switch induced by cytokines in cervical cancer remains poorly understood. In this study, we analyzed the effect of IL-2 on the metabolic switch and the role of STAT5 in this response. Our results show that IL-2 induces cervical cancer cell proliferation and the tyrosine phosphorylation of STAT5. Also, it induces an increase in lactate secretion and the ratio of NAD+/NADH, which suggest a metabolic reprogramming of their metabolism. When STAT5 was silenced, the lactate secretion and the NAD+/NADH ratio decreased. Also, the expression of HIF1α and GLUT1 decreased. These results indicate that STAT5 regulates IL-2-induced cell proliferation and the metabolic shift to aerobic glycolysis by regulating genes related to energy metabolism. Our results suggest that STAT proteins modulate the metabolic switch in cervical cancer cells to attend to their high demand of energy required for cell growth and proliferation.
Hematopoietic Stem Cells and Their Niche in Bone Marrow
Authors: Kwon Munju , Kim Byoung Soo , Yoon Sik , Oh Sae-Ock , Lee Dongjun
Published: June 2024

Extensive research has explored the functional correlation between stem cells and progenitor cells, particularly in blood. Hematopoietic stem cells (HSCs) can self-renew and regenerate tissues within the bone marrow, while stromal cells regulate tissue function. Recent studies have validated the role of mammalian stem cells within specific environments, providing initial empirical proof of this functional phenomenon. The interaction between bone and blood has always been vital to the function of the human body. It was initially proposed that during evolution, mammalian stem cells formed a complex relationship with the surrounding microenvironment, known as the niche. Researchers are currently debating the significance of molecular-level data to identify individual stromal cell types due to incomplete stromal cell mapping. Obtaining these data can help determine the specific activities of HSCs in bone marrow. This review summarizes key topics from previous studies on HSCs and their environment, discussing current and developing concepts related to HSCs and their niche in the bone marrow.
Sound Matrix Shaping of Living Matter: From Macrosystems to Cell Microenvironment, Where Mitochondria Act as Energy Portals in Detecting and Processing Sound Vibrations
Authors: Valenti Daniela , Atlante Anna
Published: June 2024

Vibration and sound are the shaping matrix of the entire universe. Everything in nature is shaped by energy vibrating and communicating through its own sound trail. Every cell within our body vibrates at defined frequencies, generating its peculiar “sound signature”. Mitochondria are dynamic, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. Novel research has shown that the mitochondrial function of mammalian cells can be modulated by various energetic stimuli, including sound vibrations. Regarding acoustic vibrations, definite types of music have been reported to produce beneficial impacts on human health. In very recent studies, the effects of different sound stimuli and musical styles on cellular function and mitochondrial activity were evaluated and compared in human cells cultured in vitro, investigating the underlying responsible molecular mechanisms. This narrative review will take a multilevel trip from macro to intracellular microenvironment, discussing the intimate vibrational sound activities shaping living matter, delving deeper into the molecular mechanisms underlying the sound modulation of biological systems, and mainly focusing our discussion on novel evidence showing the competence of mitochondria in acting as energy portals capable of sensing and transducing the subtle informational biofields of sound vibration.
Impaired Tertiary Dentin Secretion after Shallow Injury in Tgfbr2-Deficient Dental Pulp Cells Is Rescued by Extended CGRP Signaling
Authors: Stanwick Monica , Fenesha Fatma , Hamid Ahmed , Kang Khushroop , Kanniard Dane , Kim Irene , Mandarano Nicholas , Schumacher Fernanda L. , Peters Sarah B.
Published: June 2024

The transforming growth factor β (TGFβ) superfamily is a master regulator of development, adult homeostasis, and wound repair. Dysregulated TGFβ signaling can lead to cancer, fibrosis, and musculoskeletal malformations. We previously demonstrated that TGFβ receptor 2 (Tgfbr2) signaling regulates odontoblast differentiation, dentin mineralization, root elongation, and sensory innervation during tooth development. Sensory innervation also modulates the homeostasis and repair response in adult teeth. We hypothesized that Tgfbr2 regulates the neuro-pulpal responses to dentin injury. To test this, we performed a shallow dentin injury with a timed deletion of Tgfbr2 in the dental pulp mesenchyme of mice and analyzed the levels of tertiary dentin and calcitonin gene-related peptide (CGRP) axon sprouting. Microcomputed tomography imaging and histology indicated lower dentin volume in Tgfbr2cko M1s compared to WT M1s 21 days post-injury, but the volume was comparable by day 56. Immunofluorescent imaging of peptidergic afferents demonstrated that the duration of axon sprouting was longer in injured Tgfbr2cko compared to WT M1s. Thus, CGRP+ sensory afferents may provide Tgfbr2-deficient odontoblasts with compensatory signals for healing. Harnessing these neuro-pulpal signals has the potential to guide the development of treatments for enhanced dental healing and to help patients with TGFβ-related diseases.
Exploring the Structurally Conserved Regions and Functional Significance in Bacterial N-Terminal Nucleophile (Ntn) Amide-Hydrolases
Authors: Quiroga Israel , Hernández-González Juan Andrés , Bautista-Rodríguez Elizabeth , Benítez-Rojas Alfredo C.
Published: June 2024

The initial adoption of penicillin as an antibiotic marked the start of exploring other compounds essential for pharmaceuticals, yet resistance to penicillins and their side effects has compromised their efficacy. The N-terminal nucleophile (Ntn) amide-hydrolases S45 family plays a key role in catalyzing amide bond hydrolysis in various compounds, including antibiotics like penicillin and cephalosporin. This study comprehensively analyzes the structural and functional traits of the bacterial N-terminal nucleophile (Ntn) amide-hydrolases S45 family, covering penicillin G acylases, cephalosporin acylases, and D-succinylase. Utilizing structural bioinformatics tools and sequence analysis, the investigation delineates structurally conserved regions (SCRs) and substrate binding site variations among these enzymes. Notably, sixteen SCRs crucial for substrate interaction are identified solely through sequence analysis, emphasizing the significance of sequence data in characterizing functionally relevant regions. These findings introduce a novel approach for identifying targets to enhance the biocatalytic properties of N-terminal nucleophile (Ntn) amide-hydrolases, while facilitating the development of more accurate three-dimensional models, particularly for enzymes lacking structural data. Overall, this research advances our understanding of structure–function relationships in bacterial N-terminal nucleophile (Ntn) amide-hydrolases, providing insights into strategies for optimizing their enzymatic capabilities.
Video-Based Sign Language Recognition via ResNet and LSTM Network
Authors: Huang Jiayu , Chouvatut Varin
Published: June 2024

Sign language recognition technology can help people with hearing impairments to communicate with non-hearing-impaired people. At present, with the rapid development of society, deep learning also provides certain technical support for sign language recognition work. In sign language recognition tasks, traditional convolutional neural networks used to extract spatio-temporal features from sign language videos suffer from insufficient feature extraction, resulting in low recognition rates. Nevertheless, a large number of video-based sign language datasets require a significant amount of computing resources for training while ensuring the generalization of the network, which poses a challenge for recognition. In this paper, we present a video-based sign language recognition method based on Residual Network (ResNet) and Long Short-Term Memory (LSTM). As the number of network layers increases, the ResNet network can effectively solve the granularity explosion problem and obtain better time series features. We use the ResNet convolutional network as the backbone model. LSTM utilizes the concept of gates to control unit states and update the output feature values of sequences. ResNet extracts the sign language features. Then, the learned feature space is used as the input of the LSTM network to obtain long sequence features. It can effectively extract the spatio-temporal features in sign language videos and improve the recognition rate of sign language actions. An extensive experimental evaluation demonstrates the effectiveness and superior performance of the proposed method, with an accuracy of 85.26%, F1-score of 84.98%, and precision of 87.77% on Argentine Sign Language (LSA64).
Scope and Prosody in Multiple Wh-Questions
Authors: Lee So-Young
Published: June 2024

The prosodic marking of the wh-scope has been a good testing ground to shed light on syntax-prosody mapping. Many accounts have been proposed based on various theoretical models, including the E-feature agreement system, the Multiple Spell-Out Model, Contiguity Theory, and the Wrap-XP Model. However, most previous studies focused on the constructions with a single wh-phrase, and few studies paid attention to multiple wh-questions. This paper presents novel data from production experiments to show the prosodic patterns of multiple wh-questions in Korean, for which none of the previous accounts makes correct predictions. This study proposes a new alignment constraint considering the scope relations between wh-words. The necessity of such a constraint suggests that the prosodic structures for wh-scope interpretations are not the direct outcome of syntax and phonology but the aggregation of syntax, phonology, and semantics.
Microstructural and Electrochemical Study: Pitting Corrosion Mechanism on A390 Al–Si Alloy and Ce–Mo Treatment as a Better Corrosion Protection
Authors: Herrera Hernández Héctor , Mandujano Ruiz Araceli , González Morán Carlos Omar , Miranda Hernández José Guadalupe , Flores Cuautle José de Jesús Agustín , Morales Hernández Jorge , Hernández Casco Irma
Published: June 2024

Sulfuric acid anodizing assisted by a hydrothermal sealing with inhibitors [Ce3+-Mo6+] was used to prevent pitting corrosion on spray-deposited hypereutectic Al–Si alloy (A390). An investigation concerning the evaluation of pitting corrosion resistance on the anodic oxide thin film with ions incorporated was carried out in NaCl solution using electrochemical measurements (i.e., potentiodynamic polarization and electrochemical impedance spectroscopy, EIS). The influence of Si phase morphology and size on the growth mechanism of an anodic oxide film was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results were then compared with those for its equivalent IM390 alloy (Al-17Si-4.5Cu-0.6Mg) produced through a conventional process ingot metallurgy, IM. The electrochemical findings indicate that sulfuric acid anodizing followed by a simple hot water sealing treatment was ineffective. In this manner, an intense attack was localized by pitting corrosion that occurred on the anodic oxide film in less than three days, as denoted by characteristic changes in the EIS spectra at the lowest frequencies. Improved results were achieved for Ce–Mo surface modification, which can provide better corrosion resistance on the aluminum alloys because no signs of pits were observed during the corrosion testing.
Analysis of Energy and Material Consumption for the Manufacturing of an Aeronautical Tooling: An Experimental Comparison between Pure Machining and Big Area Additive Manufacturing
Authors: Marqués Alejandro , Dieste Jose Antonio , Monzón Iván , Laguía Alberto , Javierre Carlos , Elduque Daniel
Published: June 2024

Additive manufacturing (AM) has been fully incorporated into both the academic and the industrial world. This technology has been shown to lower costs and environmental impacts. Moreover, AM-based technologies, such as wire arc additive manufacturing (WAAM), have been proven suitable for the manufacturing of large products with significant mechanical requirements. This study examines the manufacture of two aeronautical toolings: first, using conventional techniques, and second, using a big area additive manufacturing (BAAM) process, specifically WAAM technology, followed by second-stage hybrid machining. Both toolings can be considered interchangeable in terms of design and performance. Energy and material consumption were analysed and compared throughout both tooling procedures. The results show the important optimisation of both procedures in manufacturing WAAM tooling, encompassing the additive process and second-stage hybrid machining. Nevertheless, the time required for WAAM tooling manufacturing increased significantly compared to conventional manufacturing tooling. Moreover, based on metrology data from the AM process, a theoretical study was conducted to assess different design optimisations for WAAM tooling manufacturing and determine their influence on material and energy consumption. These theoretical results improve those already obtained regarding energy and raw material savings.