bluuebunny/crossref_metadata_2025 huggingface dataset:
The Study on Nondestructive Detection Methods for Internal Quality of Korla Fragrant Pears Based on Near-Infrared Spectroscopy and Machine Learning
Authors: Che Jikai , Liang Qing , Xia Yifan , Liu Yang , Li Hongshan , Hu Ninggang , Cheng Weibo , Zhang Hong , Zhang Hong , Lan Haipeng
Published: November 2024

Quality control and grading of Korla fragrant pears significantly impact their commercial value. Rapid and non-destructive detection of soluble solids content (SSC) and firmness is crucial to improving this. This study proposes a method combining near-infrared spectroscopy (NIRS) with machine learning for the rapid, non-destructive detection of SSC and firmness in Korla pears. By analyzing absorbance in the 900–1800 nm range, six preprocessing methods—Savitzky–Golay derivative (SGD), standard normal variate (SNV), multiplicative scatter correction (MSC), Savitzky–Golay smoothing (SGS), vector normalization (VN), and min-max normalization (MMN)—were applied to the raw spectral data. uninformative variable elimination (UVE) and successive projections algorithm (SPA) were then used to extract effective wavelengths. Partial least squares regression (PLSR) models were developed for SSC and firmness based on the extracted data. The results showed that all preprocessing and wavelength-extraction methods improved model accuracy. The optimal SSC prediction model was MSC-SPA-PLSR (R = 0.93, RMSE = 0.195), and the best hardness prediction model was MSC-UVE-PLSR (R = 0.83, RMSE = 0.249). This research aids in establishing a non-destructive testing system, offering producers a rapid and accurate quality assessment tool, and provides the food industry with better production control measures to enhance standardization and market competitiveness of Korla pears.
Multiscale Modeling and Simulation of Falling Collision Damage Sensitivity of Kiwifruit
Authors: Zhu Yue , Zhu Licheng , Wang Wenbei , Zhao Bo , Han Zhenhao , Wang Ruixue , Yuan Yanwei , Lu Kunlei , Feng Xuguang , Hu Xiaoxi
Published: November 2024

Falling damage is the most common form of damage sustained by kiwifruit during the process of picking and post-processing, and it is difficult to conduct a quantitative analysis of this phenomenon through traditional experimental methods. In order to deeply understand the sensitivity of kiwifruit to falling collision damage, the finite element numerical simulation method was used to evaluate and predict the sensitivity of kiwifruit to falling collision damage during harvesting. First, we obtained the appearance characteristics of kiwifruit through reverse engineering technology and determined the geometric and mechanical property parameters of kiwifruit through physical mechanics experiments. Then, according to the characteristics of fruit tissue structure, a multiscale finite element model, including the skin, pulp, and core, was constructed to simulate the effects of different falling heights, collision angles, and contact surface materials on fruit damage, and the accuracy of the model was verified through falling experiments. Finally, based on the simulation results, the Box–Behnken design was employed within the response surface methodology to establish a sensitivity prediction model for the drop damage sensitivity of kiwifruit across different contact materials. The results showed that the maximum relative error between the speed change obtained using finite element simulation and the speed obtained by the high-speed camera was 5.19%. The model showed high rationality in energy distribution, with the maximum value of hourglass energy not exceeding 0.08% of the internal energy. On the contact surface material with a large elastic modulus, a higher falling height and larger collision angle will significantly increase the risk of fruit bruise. When the contact surface material was a steel plate, the falling height was 1 m, and the collision angle was 90°; the maximum bruise sensitivity of kiwifruit reached 6716.07 mm3 J−1. However, when the contact surface material was neoprene, the falling height was 0.25 m, and the collision angle was 0°, the damage sensitivity was the lowest, at 1570.59 mm3 J−1. The multiscale finite element model of kiwifruit falling collision constructed in this study can accurately predict the damage of kiwifruit during falling collision and provide an effective tool for the quantitative analysis of kiwifruit falling collision damage. At the same time, this study can also provide guidance for the design and optimization of the loss reduction method of the harvesting mechanism, which has important theoretical significance and practical value.
Employing Verbal Divergent Thinking to Mitigate Cognitive Decline: Current State of Research and Reasons to Support Its Use
Authors: Folia Vasiliki , Silva Susana
Published: November 2024

Background/Objectives: Divergent thinking (DT), the ability to generate alternative responses to open-ended problems, has become an increasingly relevant topic in aging research due to its inverse relationship with cognitive decline. Methods: In this narrative review, we explore the latest evidence supporting DT training as a potential strategy for dementia prevention. Results: We identify two pathways through which DT may protect against cognitive decline: (1) by fostering creative cognition and (2) by stimulating DT-related domains. Our findings suggest that verbal DT remains relatively well preserved in older adults, although there is limited empirical evidence to support the idea that DT training enhances creative cognition or DT-related domains in this population. Conclusions: Therefore, while tools designed to enhance DT in older individuals seem promising, it is crucial to rigorously test their effects on the target population to maximize their impact on both the cognitive and psychological domains.
The Efficacy of Telehealth Versus In-Person Management Delivery in Adult Patients with Obesity
Authors: Alolayan Rawan A. , Aldisi Dara A. , Hussain Danish S. , Alafif Nora , Abulmeaty Mahmoud M. A.
Published: November 2024

Background: The effectiveness of telehealth in managing obesity in Saudi patients is still under investigation. This study compared the effectiveness of telehealth and in-person obesity management programs for adults. Methods: This clinical trial involved 62 adults, 29 receiving in-person intervention at the clinic and 33 receiving telehealth via videoconference calls. Anthropometric measurements, biochemical parameters, and dietary and lifestyle habits were assessed at baseline and after 12 weeks. Patients have been educated about goal-setting, healthy eating behaviors, personalized meal plans, and increasing physical activity levels. Results: It showed that 45% and 49% of the in-person and telehealth groups lost more than 5% of their initial body weight. Weight, % body fat, and waist circumference were significantly reduced in the in-person and telehealth groups (p < 0.001). No significant differences between the groups were found in the parameters mentioned above. Within-group analysis showed that light physical activity levels improved in both groups significantly (p < 0.001), and the moderate physical activity level improved significantly among the telehealth group (p < 0.039). No significant differences were observed between the groups regarding physical activity level, blood pressure measurement, and biochemical markers, except for the RBC blood level (p = 0.026). The telehealth group had significantly higher attendance rates for counseling sessions (97% vs. 75% for the in-person group, p < 0.01). Participants’ dropout rates were higher for the in-person group 21%, compared to the telehealth group 13%. Telehealth participants’ satisfaction regarding the benefits of the obesity management program in losing weight was higher at 87% compared to the in-person group at 76%. Conclusions: In conclusion, applying a telehealth obesity management program can support patients struggling with obesity who may have limited access to traditional healthcare services, while ensuring that telehealth care replicates the quality of in-person care.
Analysis of Speech Features in Alzheimer’s Disease with Machine Learning: A Case-Control Study
Authors: Noto Shinichi , Sekiyama Yuichi , Nagata Ryo , Yamamoto Gai , Tamura Toshiaki
Published: November 2024

Background: Changes in the speech and language of patients with Alzheimer’s disease (AD) have been reported. Using machine learning to characterize these irregularities may contribute to the early, non-invasive diagnosis of AD. Methods: We conducted cognitive function assessments, including the Mini-Mental State Examination, with 83 patients with AD and 75 healthy elderly participants, and recorded pre- and post-assessment conversations to evaluate participants’ speech. We analyzed the characteristics of the spectrum, intensity, fundamental frequency, and minute temporal variation (∆) of the intensity and fundamental frequency of the speech and compared them between patients with AD and healthy participants. Additionally, we evaluated the performance of the speech features that differed between the two groups as single explanatory variables. Results: We found significant differences in almost all elements of the speech spectrum between the two groups. Regarding the intensity, we found significant differences in all the factors except for the standard deviation between the two groups. In the performance evaluation, the areas under the curve revealed by logistic regression analysis were higher for the center of gravity (0.908 ± 0.036), mean skewness (0.904 ± 0.023), kurtosis (0.932 ± 0.023), and standard deviation (0.977 ± 0.012) of the spectra. Conclusions: This study used machine learning to reveal speech features of patients diagnosed with AD in comparison with healthy elderly people. Significant differences were found between the two groups in all components of the spectrum, paving the way for early non-invasive diagnosis of AD in the future.
Severe Hyperandrogenism in 46,XX Congenital Adrenal Hyperplasia: Molecular Physiopathology, Late Diagnoses, and Personalized Management
Authors: Cera Gianluca , Corsello Andrea , Novizio Roberto , Di Donna Vincenzo , Locantore Pietro , Paragliola Rosa Maria
Published: November 2024

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive endocrine disorders characterized by alteration in adrenal hormonal secretions. The most common form is caused by CYP21A2 mutations that result in 21-hydroxylase deficiency. Clinical features can vary, from salt-wasting forms, characterized by a lack of mineralocorticoid activity with a risk of perinatal-onset adrenal crises, to “simple-virilizing” forms with sufficient aldosterone secretion, up to milder “non-classical” forms, with a variable grade of hyperandrogenism but no severe hormonal deficiencies. During pregnancy, CAH 46,XX fetuses are exposed to elevated androgen levels, leading to a variable grade of virilization and potential central nervous system effects if untreated. These patients are usually (but not always) assigned female at birth, but some cases may be misdiagnosed and assigned male, potentially inducing fertility, gender identity, and sexual behavior issues in adulthood. In these patients, the benefits and risks of a late gender transition should be carefully evaluated. In this paper, we reviewed the literature concerning the most interesting peculiarities of these conditions.
Therapeutic Contribution of Tau-Binding Thiazoloflavonoid Hybrid Derivatives Against Glioblastoma Using Pharmacological Approach in 3D Spheroids
Authors: Relave Emmanuelle T. , Hedna Rayane , Di Maio Attilio , Devred François , Kovacic Hervé , Robin Maxime , Breuzard Gilles
Published: November 2024

Growing evidence has unveiled the pathological significance of Tau in many cancers, including the most aggressive and lethal brain tumor glioblastoma multiform (GBM). In this regard, we have recently examined the structure–activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau-overexpressing GBM cells. Here, we evaluated the anticancer activities of the two lead compounds 2 and 9 using multi-cellular spheroids (MCSs) which represent an easy 3D human cell model to mimic GBM organization, physical constraints and drug penetration. The two compounds reduced cell evasion from spheroids up to three times, especially for Tau-expressing cells. As a first step towards a therapeutic approach, we quantified the effects of these compounds on MCS growth using two complementary protocols: single and repeated treatments. A single injection with compound 9 slowed down the growth of MCSs formed with U87 shCTRL cells by 40% at 10 µM. More interestingly, multiple treatment with compound 9 slowed the growth of U87 shCTRL spheroids by 40% at a concentration of 5 µM, supporting the increased bioavailability of compound 9 within MCSs. In conclusion, compound 9 deserves particular attention as promising candidate for specifically targeting Tau-expressing cancers such as GBM.
Nlrp3 Deficiency Does Not Substantially Affect Femoral Fracture Healing in Mice
Authors: Menger Maximilian M. , Speicher Rouven , Hans Sandra , Histing Tina , El Kayali Moses K. D. , Ehnert Sabrina , Menger Michael D. , Ampofo Emmanuel , Wrublewsky Selina , Laschke Matthias W.
Published: November 2024

Inflammation has been recognized as major factor for successful bone regeneration. On the other hand, a prolonged or overshooting inflammatory response can also cause fracture healing failure. The nucleotide-binding oligomerization domain (NOD)-like receptor protein (NLRP)3 inflammasome plays a crucial role in inflammatory cytokine production. However, its role during fracture repair remains elusive. We investigated the effects of Nlrp3 deficiency on the healing of closed femoral fractures in Nlrp3−/− and wildtype mice. The callus tissue was analyzed by means of X-ray, biomechanics, µCT and histology, as well as immunohistochemistry and Western blotting at 2 and 5 weeks after surgery. We found a significantly reduced trabecular thickness at 2 weeks after fracture in the Nlrp3−/− mice when compared to the wildtype animals. However, the amount of bone tissue did not differ between the two groups. Additional immunohistochemical analyses showed a reduced number of CD68-positive macrophages within the callus tissue of the Nlrp3−/− mice at 2 weeks after fracture, whereas the number of myeloperoxidase (MPO)-positive granulocytes was increased. Moreover, we detected a significantly lower expression of vascular endothelial growth factor (VEGF) and a reduced number of microvessels in the Nlrp3−/− mice. The expression of the absent in melanoma (AIM)2 inflammasome was increased more than 2-fold in the Nlrp3−/− mice, whereas the expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 was not affected. Our results demonstrate that Nlrp3 deficiency does not markedly affect femoral fracture healing in mice. This is most likely due to the unaltered expression of pro-inflammatory cytokines and pro-osteogenic growth factors.
Genome-Wide Identification and Analysis of Gene Family of Carbohydrate-Binding Modules in Ustilago crameri
Authors: Zhai Dongyu , Xu Deze , Xiang Ting , Zhang Yu , Wu Nianchen , Nie Fuqing , Yin Desuo , Wang Aijun
Published: November 2024

Ustilago crameri is a pathogenic basidiomycete fungus that causes foxtail millet kernel smut (FMKS), a devastating grain disease in most foxtail millet growing regions of the world. Carbohydrate-Binding Modules (CBMs) are one of the important families of carbohydrate-active enzymes (CAZymes) in fungi and play a crucial role in fungal growth and development, as well as in pathogen infection. However, there is little information about the CBM family in U. crameri. Here, 11 CBM members were identified based on complete sequence analysis and functional annotation of the genome of U. crameri. According to phylogenetic analysis, they were divided into six groups. Gene structure and sequence composition analysis showed that these 11 UcCBM genes exhibit differences in gene structure and protein motifs. Furthermore, several cis-regulatory elements involved in plant hormones were detected in the promoter regions of these UcCBM genes. Gene ontology (GO) enrichment and protein–protein interaction (PPI) analysis showed that UcCBM proteins were involved in carbohydrate metabolism, and multiple partner protein interactions with UcCBM were also detected. The expression of UcCBM genes during U. crameri infection is further clarified, and the results indicate that several UcCBM genes were induced by U. crameri infection. These results provide valuable information for elucidating the features of U. crameri CBMs’ family proteins and lay a crucial foundation for further research into their roles in interactions between U. crameri and foxtail millet.
AMPA and NMDA Receptors in Hippocampus of Rats with Fluoride-Induced Cognitive Decline
Authors: Nadei Olga Vladimirovna , Agalakova Natalia Ivanovna
Published: November 2024

This experimental study was performed to evaluate the alterations in the expression of a few subunits composing glutamate AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors in the hippocampal cells of Wistar rats in response to long-term fluoride (F-) exposure. The animals were given water with background 0.4 (control), 5, 20, and 50 ppm F- (as NaF) for 12 months. The cognitive capacities of rats were examined by novel object recognition (NOR), Y-maze test, and Morris water maze tests. RT-qPCR and Western blotting techniques were used to evaluate the expression of different AMPA and NMDA subunits at transcriptional and translational levels, respectively. Long-term F- poisoning disturbed the formation of hippocampus-dependent working spatial and long-term non-spatial memory. The expression of Gria1, Gria2, and Gria3 genes encoding different subunits of AMPA receptors were comparable in hippocampi of control and F--exposed animals, although the levels of both Grin2a and Grin2b mRNA increased. Long-term F- intake enhanced the ratio of phospho-GluA1/total-GluA1 proteins in subcellular fraction enriched with cytosolic proteins, while decreased content of GluA2 but elevated level of GluA3 were observed in subcellular fraction enriched with membrane proteins. Such changes were accompanied by increased phosphorylation of GluN2A and GluN2B subunits, higher ratios of GluN2A/GluN1 and GluN2B/GluN1 proteins in the cytosol, and GluN2A/GluN2B ratio in membranes. These changes indicate the predominance of Ca2+-permeable AMPARs in membranes and a shift between different NMDARs subunits in hippocampal cells of F--exposed rats, which is typical for neurodegeneration and can at least partially underly the observed disturbances in cognitive capacities of animals.
Vitamin K2 Protects Against SARS-CoV-2 Envelope Protein-Induced Cytotoxicity in Chronic Myeloid Leukemia Cells and Enhances Imatinib Activity
Authors: Okabe Seiichi , Arai Yuya , Gotoh Akihiko
Published: November 2024

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by excessive proliferation of myeloid cells. The COVID-19 pandemic has raised concerns regarding the impact of SARS-CoV-2 on patients with malignancies, particularly those with CML. This study aimed to investigate the effects of SARS-CoV-2 proteins on CML cell viability and the protective role of vitamin K2 (VK2) in conjunction with imatinib. Experiments conducted on K562 CML cells demonstrated that the SARS-CoV-2 envelope protein induces cytotoxicity and activates caspase 3/7, which are key markers of apoptosis. VK2 mitigated these cytotoxic effects and decreased cytokine production while inhibiting colony formation. Furthermore, the combination of VK2 with imatinib significantly reduced cellular proliferation, diminished mitochondrial membrane potential, and markedly suppressed colony formation. These findings suggest that VK2 protects CML cells from SARS-CoV-2-induced cytotoxicity and enhances the therapeutic efficacy of imatinib, presenting a potential strategy to improve CML treatment during the COVID-19 pandemic.
Epigenetic Mechanisms Induced by Mycobacterium tuberculosis to Promote Its Survival in the Host
Authors: Thomas Shwetha Susan , Abhinand Kuniyil , Menon Arjun M. , Nair Bipin G. , Kumar Geetha B. , Arun K. B. , Edison Lekshmi K. , Madhavan Aravind
Published: November 2024

Tuberculosis caused by the obligate intracellular pathogen, Mycobacterium tuberculosis, is one among the prime causes of death worldwide. An urgent remedy against tuberculosis is of paramount importance in the current scenario. However, the complex nature of this appalling disease contributes to the limitations of existing medications. The quest for better treatment approaches is driving the research in the field of host epigenomics forward in context with tuberculosis. The interplay between various host epigenetic factors and the pathogen is under investigation. A comprehensive understanding of how Mycobacterium tuberculosis orchestrates such epigenetic factors and favors its survival within the host is in increasing demand. The modifications beneficial to the pathogen are reversible and possess the potential to be better targets for various therapeutic approaches. The mechanisms, including histone modifications, DNA methylation, and miRNA modification, are being explored for their impact on pathogenesis. In this article, we are deciphering the role of mycobacterial epigenetic regulators on various strategies like cytokine expression, macrophage polarization, autophagy, and apoptosis, along with a glimpse of the potential of host-directed therapies.
Special Issue “Biochemical and Molecular Approaches to Postharvest Research”: An Overview
Authors: Lara Isabel , Puche Fontanilles Josep M.
Published: November 2024

“O fortunatos nimium, sua si bona norint agricolas!” [...]
Space Travel: The Radiation and Microgravity Effects on the Cardiovascular System
Authors: Mircea Andrei Alexandru , Pistritu Dan Valentin , Fortner Andra , Tanca Antoanela , Liehn Elisa Anamaria , Bucur Octavian
Published: November 2024

Space flight modulates the functions of the cardiovascular system. The exposure to space conditions can alter the cerebral blood flow, as well as the venous return. Anemia, cardiac output changes, and increased activity of the sympathetic nervous system can also be seen. Understanding cardiac changes prepares astronauts for both better in-flight adaptations and long-term protection against cardiovascular diseases. The heart could undergo radio-degenerative effects when exposed to space radiation, increasing the risk of cardiovascular diseases in the long run. A high frequency of arrhythmias, such as ventricular/atrial premature complexes, have been reported during the Gemini and Apollo missions. Additionally, microgravity can lead to progressive degeneration of the myocytes and muscle atrophy with altered gene expression and calcium handling, along with impaired contractility. This review summarizes the potential cardiovascular effects of spaceflight and prevention measures.
NFSA-DTI: A Novel Drug–Target Interaction Prediction Model Using Neural Fingerprint and Self-Attention Mechanism
Authors: Liu Feiyang , Xu Huang , Cui Peng , Li Shuo , Wang Hongbo , Wu Ziye
Published: November 2024

Existing deep learning methods have shown outstanding performance in predicting drug–target interactions. However, they still have limitations: (1) the over-reliance on locally extracted features by some single encoders, with insufficient consideration of global features, and (2) the inadequate modeling and learning of local crucial interaction sites in drug–target interaction pairs. In this study, we propose a novel drug–target interaction prediction model called the Neural Fingerprint and Self-Attention Mechanism (NFSA-DTI), which effectively integrates the local information of drug molecules and target sequences with their respective global features. The neural fingerprint method is used in this model to extract global features of drug molecules, while the self-attention mechanism is utilized to enhance CNN’s capability in capturing the long-distance dependencies between the subsequences in the target amino acid sequence. In the feature fusion module, we improve the bilinear attention network by incorporating attention pooling, which enhances the model’s ability to learn local crucial interaction sites in the drug–target pair. The experimental results on three benchmark datasets demonstrated that NFSA-DTI outperformed all baseline models in predictive performance. Furthermore, case studies illustrated that our model could provide valuable insights for drug discovery. Moreover, our model offers molecular-level interpretations.
Inhibition of Cancer Cell Migration and Invasion In Vitro by Recombinant Tyrosine-Sulfated Haemathrin, A Thrombin Inhibitor
Authors: Jo Guk Heui , Jung Sun Ah , Yoon Jin Sook , Lee Joon H.
Published: November 2024

Thrombin, a key enzyme in the regulation of hemostasis, has been implicated in cancer progression. This study explored the effect of recombinant tyrosine-sulfated haemathrin on cancer cell behavior and signaling pathways compared to wild-type (WT) haemathrin 2. The recombinant proteins, tyrosine-sulfated haemathrin 2 (haemathrin 2S), and WT haemathrin 2 were produced in Escherichia coli and subsequently purified and applied to SKOV3 and MDA-MB-231 cells with and without thrombin stimulation. Cell migration and invasion were assessed using wound healing and Transwell assays, respectively. Haemathrin 2S treatment significantly diminished cell migration and invasion promoted by thrombin in both SKOV3 and MDA-MB-231 cells (p < 0.05). Additionally, haemathrin 2S effectively inhibited thrombin-induced phosphorylation of serine/threonine kinase (Akt) in both cell lines (p < 0.05), while WT haemathrin 2 had this effect only in MDA-MB-231 cells. Furthermore, haemathrin 2S significantly reduced thrombin-activated phosphorylation of extracellular signal-regulated kinases (ERK) and p38 in both cell lines (p < 0.05) and reversed E/N-cadherin expression in thrombin-treated MDA-MB-231 cells (p < 0.05), which were not observed with WT haemathrin 2. Overall, haemathrin 2S was more effective than WT haemathrin 2 in reducing cancer cell migration and invasion, indicating that targeting thrombin with sulfated haemathrin is a promising strategy for cancer therapy. However, further in vivo studies are needed to confirm these results.
Natural Antimicrobial Agents from Algae: Current Advances and Future Directions
Authors: Zuorro Antonio , Lavecchia Roberto , Contreras-Ropero Jefferson E. , Martínez Janet B. García , Barajas-Ferreira Crisóstomo , Barajas-Solano Andrés F.
Published: November 2024

Infectious diseases have significantly shaped human history, leading to significant advancements in medical science. The discovery and development of antibiotics represented a critical breakthrough, but the rise of antibiotic-resistant pathogens now presents a serious global health threat. Due to the limitations of current synthetic antimicrobials, such as toxicity and environmental concerns, it is essential to explore alternative solutions. Algae, particularly microalgae and cyanobacteria, have emerged as promising sources of bioactive antimicrobial compounds. This review provides a comprehensive analysis of the antimicrobial properties of algal-derived compounds, including polysaccharides, fatty acids, and phenols, which have shown effectiveness against multi-drug-resistant bacteria. A co-occurrence bibliometric analysis using VOSviewer highlighted five key research clusters: antibiotic resistance, algal extracts, biosynthesis, water treatment, and novel pharmacological compounds. Furthermore, the primary mechanisms of action of these bioactive compounds, such as the inhibition of protein synthesis and cell membrane disruption, were identified, demonstrating their potential against both common and multi-resistant pathogens. Future research should prioritize optimizing algal biomass production, utilizing genetic and metabolic engineering, and creating innovative delivery systems to enhance the efficient production of bioactive compounds.
Development and Evaluation of ABI-171, a New Fluoro-Catechin Derivative, for the Treatment of Idiopathic Pulmonary Fibrosis
Authors: Araldi Gian Luca , Hwang Yu-Wen , Raghu Ganesh
Published: November 2024

The persistent challenge of idiopathic pulmonary fibrosis (IPF), characterized by disease progression and high mortality, underscores the urgent need for innovative therapeutic strategies. We have developed a novel small molecule—catechin derivative ABI-171—selectively targeting dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) and proviral integration site for Moloney murine leukemia virus 1 (PIM1) kinases, crucial in the pathogenesis of fibrotic processes. We employed the Bleomycin-induced (intratracheal) mouse model of pulmonary fibrosis (PF) to evaluate the therapeutic efficacy of ABI-171. Mice with induced PF were treated QD with ABI-171, either prophylactically or therapeutically, using oral and intranasal routes. Pirfenidone (100 mg/kg, TID) and Epigallocatechin gallate (EGCG, 100 mg/kg, QD), a natural catechin currently in a Phase 1 clinical trial, were used as reference compounds. ABI-171, administered prophylactically, led to a significant reduction in hydroxyproline levels and fibrotic tissue formation compared to the control group. Treatment with ABI-171 improved body weight, indicating mitigation of disease-related weight loss. Additionally, ABI-171 demonstrated anti-inflammatory activity, reducing lymphocyte and neutrophil infiltration. In the therapeutic setting, ABI-171, administered 7 days post-induction, reduced mortality rates (p = 0.04) compared with the bleomycin and EGCG control groups. ABI-171 also ameliorated the severity of lung injuries assessed by improved Masson’s trichrome scores when administered both orally and intranasally. ABI-171 significantly decreases bleomycin-induced PF and improves survival in mice, showcasing promising therapeutic potential beyond current medications like pirfenidone and EGCG for patients with IPF. Based on these results, further studies with ABI-171 are ongoing in preclinical studies.
Matrix Background Screening of an ssDNA Aptamer and Its Identification Against Lactopontin
Authors: Zhu Chao , Feng Ziru , Yan Mengmeng , Du Hongxia , Li Tengfei , Mao Jiangsheng
Published: November 2024

Lactopontin (LPN) is a highly phosphorylated O-glycosylated acidic protein closely associated with infant gut, brain, and immune development, and its recognition is urgent due to its rising application in fortified dairy products and infant formula. In this study, an ssDNA aptamer against LPN was obtained, among which two kinds of matrix-background-assisted systematic evolution of ligands via exponential enrichment (SELEX) approaches were performed and compared. The direct approach was to utilize the sample matrix as the mixing-incubation background between the ssDNA library and LPN that can theoretically increase screening pressure and simulate practical application scenarios. The indirect approach was to utilize a PBS buffer as a screening background and to include counter-screening steps that adopt the “sample matrix” as a whole as the counter-screening target. Their screening evolutions were monitored through qPCR assays from sequence diversity convergences of each sub-library based on the change in the proportion of hetero- and homo-duplexes from the dissociation curve and melting temperature, which were also verified from the sequence statistics of high-throughput sequencing. The common sequence of Seq.I1II3 from the two approaches was finally fished out as the aptamer through multiple analyses of combining the sequence frequency, secondary structures, homology, and binding assessments, which was demonstrated good specificity and low-nanomolar affinity by qPCR assay (KD, 5.9 nM). In addition, molecular docking and a dynamics simulation were performed for their binding site prediction and affinity confirmation. This study provides a potential identifying element and a basis for accelerating the development of methods for LPN detection in dairy products.
Identification of a Novel Biomarker Panel for Breast Cancer Screening
Authors: Vaida Maria , Arumalla Kamala K. , Tatikonda Pavan Kumar , Popuri Bharadwaj , Bux Rashid A. , Tappia Paramjit S. , Huang Guoyu , Haince Jean-François , Ford W. Randolph
Published: November 2024

Breast cancer remains a major public health concern, and early detection is crucial for improving survival rates. Metabolomics offers the potential to develop non-invasive screening and diagnostic tools based on metabolic biomarkers. However, the inherent complexity of metabolomic datasets and the high dimensionality of biomarkers complicates the identification of diagnostically relevant features, with multiple studies demonstrating limited consensus on the specific metabolites involved. Unlike previous studies that rely on singular feature selection techniques such as Partial Least Square (PLS) or LASSO regression, this research combines supervised and unsupervised machine learning methods with random sampling strategies, offering a more robust and interpretable approach to feature selection. This study aimed to identify a parsimonious and robust set of biomarkers for breast cancer diagnosis using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (from the Cooperative Human Tissue Network, USA) were analyzed. This study also overcomes the common issue of dataset imbalance by using propensity score matching (PSM), which ensures reliable comparisons between cancer and control groups. We employed Univariate Naïve Bayes, L2-regularized Support Vector Classifier (SVC), Principal Component Analysis (PCA), and feature engineering techniques to refine and select the most informative features. Our best-performing feature set comprised 11 biomarkers, including 9 metabolites (SM(OH) C22:2, SM C18:0, C0, C3OH, C14:2OH, C16:2OH, LysoPC a C18:1, PC aa C36:0 and Asparagine), a metabolite ratio (Kynurenine-to-Tryptophan), and 1 demographic variable (Age), achieving an area under the ROC curve (AUC) of 98%. These results demonstrate the potential for a robust, cost-effective, and non-invasive breast cancer screening and diagnostic tool, offering significant clinical value for early detection and personalized patient management.
Exploring Genomic Regions Associated with Fruit Traits in Pepper: Insights from Multiple GWAS Models
Authors: Ro Nayoung , Oh Hyeonseok , Ko Ho-Cheol , Yi Jungyoon , Na Young-Wang , Haile Mesfin
Published: November 2024

This study utilized 303 pepper accessions from diverse Capsicum species to explore fruit traits, including length, width, wall thickness, and weight. Descriptive statistics revealed a mean fruit length of 66.19 mm, width of 23.48 mm, wall thickness of 1.89 mm, and weight of 15.29 g, with significant variability, particularly in fruit weight. Correlation analysis demonstrated strong positive relationships between fruit width, weight, and fruit wall thickness (r = 0.89 and r = 0.86, respectively), while fruit length showed weaker correlations with these traits. Analysis of fruit positions revealed that the majority of accessions had a pendent fruit position (156), followed by erect (85) and intermediate (8). In terms of fruit shape, triangular and narrow triangular shapes were the most common, observed in 102 and 98 accessions, respectively. Genome-wide association studies (GWAS) identified significant single nucleotide polymorphisms (SNPs) associated with fruit traits across four models (Blink, FarmCPU, MLM, MLMM). The number of significantly associated SNPs were as follows: fruit length (89), fruit width (55), fruit weight (63), fruit wall thickness (48), fruit shape (151), and fruit position (51). Several genes were also identified where the SNPs are located or adjacent to, providing candidate genes for further exploration of the genetic basis of fruit morphology. Notably, genes such as E3 ubiquitin-protein ligase RGLG1 (associated with fruit width), Homeobox-leucine zipper protein HDG11 (involved in fruit width), Auxin response factor 23 (linked to fruit shape), and ATP-dependent zinc metalloprotease FtsH (related to fruit weight) were identified. These findings enhance our understanding of the genetic basis of fruit morphology in Capsicum, offering valuable insights for breeding and agricultural practices.
Diterpenoid from Croton tonkinensis as a Potential Radiation Sensitizer in Oral Squamous Cell Carcinoma: An In Vitro Study
Authors: Lee Hui-Ming , Kuo Ping-Chung , Chen Wen-Hui , Chen Po-Jen , Lam Sio-Hong , Su Yu-Chieh , Chen Chih-Hao
Published: November 2024

Radiotherapy combined with a radiosensitizer represents an important treatment for head and neck squamous cell carcinoma (HNSCC). Only a few chemotherapy agents are currently approved as radiosensitizers for targeted therapy. Oral squamous cell carcinoma is one of the deadliest cancers, with approximately ~500,000 new diagnosed cases and 145,000 deaths worldwide per year. The incidence of new cases continues to increase in developing countries. This study aimed to investigate the effect of Croton tonkinensis and Curcuma longa on cell viability in OSCC cells. The HNSCC cell line OML1 and its radiation-resistant clone OML1-R were used. The anticancer effect and the mechanism of action of Croton tonkinensis and Curcuma longa in OSCC cells were analyzed by using cell viability assays, Western blot analysis, and Tranwell migration assays. The results showed that Croton tonkinensis concentration-dependently reduced the viability of OML1 and OML1-R (radioresistant) cells by downregulating the levels of AKT/mTOR mediators, such as p110α, p85, pAKT (ser473), p-mTOR (ser2448), and p-S6 Ribosomal (ser235/236). We found that cotreatment of OML1 and OML1R cells with either zVAD-FMK (apoptosis inhibitor), Ferrostatin-1 (Fer-1, a ferroptosis inhibitor), or chloroquine (CQ, an autophagy inhibitor) markedly reduced cell death. These results demonstrate that Croton tonkinensis exhibits anti-proliferation activity and highlight the therapeutic potential of small-molecule inhibitors against PI3K/mTOR signaling for radiosensitization in HNC treatment.
Prohibited Olympic Medalist with PIEZO1 VUS Who Claims Innocence
Authors: Sonkodi Balázs , Kováts Tímea , Gálik Bence , Tompa Márton , Urbán Péter , Nagy Zsófia Flóra , Ács Pongrác , Tóth Miklós , Gyenesei Attila
Published: November 2024

Competitive athletes are often exposed to extreme physiological loading, resulting in over excessive mechanotransduction during their acute intensive training sessions and competitions. Individual differences in their genetics often affect how they cope with these challenges, as reflected in their high performances. Olympic Medalists are prohibited from providing atypical values in the Hematological Module of the Athlete Biological Passport. Since there was no aphysiological result and the Athlete maintained his innocence, a whole genome sequence analysis was carried out on him and his parents, with the primary focus on the PIEZO ion channels encoding gene. PIEZO1 is known to participate in homeostatic regulation even on a whole-body level, including the regulation of physical performance, circulatory longevity of red blood cells and cell fate determination of mesenchymal stem cells in relation to hydrostatic pressure. However, PIEZO2 was found to be the principal mechanosensory ion channel for proprioception. These regulatory mechanisms play a pivotal role in mechanotransduction and intensive exercise moments. Interestingly, two variances of uncertain significance of PIEZO1 were found that may explain the atypical values of the Athlete. Furthermore, two additional variances in SDC2, the syndcan-2 encoding gene, were identified in trans position that may influence the crosstalk between PIEZO2 and PIEZO1, with more likely relevance to the detected atypical values. After all, based on the found variances of PIEZO1 and syndecan-2, it cannot be ruled out that these VUS variants may have caused or impacted the exhibited outlier findings of the ABP Hematological Module of the Athlete.
Uncovering Metal-Decorated TiO2 Photocatalysts for Ciprofloxacin Degradation—A Combined Experimental and DFT Study
Authors: Kovačević Marija , Simić Marija , Živković Sanja , Milović Miloš , Tolić Stojadinović Ljiljana , Relić Dubravka , Vasić Anićijević Dragana
Published: November 2024

Optimization of the efficiency of the photocatalytic degradation of organic and pharmaceutical pollutants represents a matter of fundamental and practical interest. The present experimental and DFT study deals with evaluation of OH radical binding energy as a simple computational descriptor of the catalytic activity of d-metal-decorated TiO2 photocatalysts for the photodegradation of the widely used antibiotic ciprofloxacin. Five d-metals commonly used in catalytic materials (Zr, Pt, Pd, Fe, and Cu) were deposited on the TiO2 surface, and the obtained photocatalysts were characterized experimentally (XRPD, ICP-OES, and SEM) and theoretically (DFT). Attention was also paid to the mechanistic insights and degradation byproducts (based on UV-Vis spectrometry and LC/MS analysis) in order to obtain systematic insight into their structure/performance relationships and confirm the proposed model of the degradation process based on OH radical reactivity.
Germline Variants in DNA Interstrand-Cross Link Repair Genes May Contribute to Increased Susceptibility for Serrated Polyposis Syndrome
Authors: Silva Patrícia , Francisco Inês , Filipe Bruno , Lage Pedro , Rosa Isadora , Fernandes Sofia , Fonseca Ricardo , Rodrigues Paula , Parreira Joana , Claro Isabel , Albuquerque Cristina
Published: November 2024

Serrated polyposis syndrome (SPS) is characterized by the development of multiple colorectal serrated polyps and increased predisposition to colorectal cancer (CRC). However, the molecular basis of SPS, especially in cases presenting family history of SPS and/or polyps and/or CRC in first-degree relatives (SPS-FHP/CRC), is still poorly understood. In a previous study, we proposed the existence of two molecular entities amongst SPS-FHP/CRC families, proximal/whole-colon and distal SPS-FHP/CRC, according to the preferential location of lesions and somatic events involved in tumor initiation. In the present study, we aimed to investigate these distinct subgroups of SPS patients in a larger cohort at the germline level and to identify the genetic defects underlying an inherited susceptibility for these two entities. Next-generation sequencing was performed using multigene analysis with a custom-designed panel in a Miseq platform in 60 SPS patients (with and without/unknown FHP/CRC). We found germline pathogenic variants in 6/60 patients (ATM, FANCM, MITF, RAD50, RAD51C, and RNF43). We also found variants of unknown significance (VUS), with prediction of probable damaging effect in 23/60 patients (ATM, BLM, BRCA1, FAN1, ERCC2, ERCC3, FANCA, FANCD2, FANCL, MSH2, MSH6, NTHL1, PALB2, PDGFRA, PMS2, PTCH1, RAD51C, RAD51D, RECQL4, TSC2, WRN, and XRCC5 genes). Most variants were detected in gene coding for proteins of the Fanconi Anemia (FA) pathway involved in the DNA Interstrand-Cross Link repair (ICLR). Notably, variants in ICLR genes were significantly more frequent in the proximal/whole-colon than in the distal subgroup [15/44 (34%) vs 1/16 (6%), p = 0.025], as opposed to the non-ICLR genes that were slightly more frequent in the distal group [8/44 (18%) vs. 5/16 (31%), p > 0.05]. Germline defects in the DNA-ICLR genes may contribute to increased serrated colorectal polyps/carcinoma risk in SPS patients, particularly in proximal/whole-colon SPS. The inclusion of DNA-ICLR genes in the genetic diagnosis of SPS patients, mainly in those with proximal/whole-colon lesions, should be considered and validated by other studies. In addition, patients with germline defects in the DNA-ICLR genes may be more sensitive to treatment with platinum-based therapeutics, which can have implications in the clinical management of these patients.
Potential Cryptic Diversity in the Genus Scoliodon (Carcharhiniformes: Carcharhinidae): Insights from Mitochondrial Genome Sequencing
Authors: Ye Peiyuan , Miao Yuanxiang , Wang Chen , Sonchaeng Pichai , Siriwong Sarawut , Chen Shaobo , Wang Junjie , Chen Xiao
Published: November 2024

Scoliodon is a genus of small placental sharks living in offshore waters. For a long time, the genus was considered a monotypic genus until a valid species, Scoliodon macrorhynchos, was confirmed in 2010. However, S. muelleri in the same study was not widely recognized because of the lack of evidence. In this study, we obtained the complete mitochondrial genome of the genus Scoliodon from Ranong, Thailand, and tentatively named it Scoliodon sp. By comparing the complete mitochondrial genome with those of two other Scoliodon species and conducting phylogenetic and divergence time analyses, we determined that Scoliodon sp. diverged from the other species. These findings indicate the potential for a new cryptic species (Scoliodon sp.) in the Scoliodon genus. This conclusion was further supported by a subsequent analysis of the published S. laticaudus control region sequences from previous studies. Finally, based on these conclusions, we used machine learning to derive a new identification method for the cryptic species. This approach may be useful for the discovery of new species or cryptic species in other organisms.
Ecto-NOX Disulfide-Thiol Exchanger 2 (ENOX2/tNOX) Is a Potential Prognostic Marker in Primary Malignant Melanoma and May Serve as a Therapeutic Target
Authors: Böcker Matti , Chatziioannou Eftychia , Niessner Heike , Hirn Constanze , Busch Christian , Ikenberg Kristian , Kalbacher Hubert , Handgretinger Rupert , Sinnberg Tobias
Published: November 2024

With an increasing incidence of malignant melanoma, new prognostic biomarkers for clinical decision making have become more important. In this study, we evaluated the role of ecto-NOX disulfide-thiol exchanger 2 (ENOX2/tNOX), a cancer- and growth-associated protein, in the prognosis and therapy of primary malignant melanoma. We conducted a tissue microarray analysis of immunohistochemical ENOX2 protein expression and The Cancer Genome Atlas (TCGA) ENOX2 RNA expression analysis, as well as viability assays and Western blots of melanoma cell lines treated with the ENOX2 inhibitor phenoxodiol (PXD) and BRAF inhibitor (BRAFi) vemurafenib. We discovered that high ENOX2 expression is associated with decreased overall (OS), disease-specific (DSS) and metastasis-free survival (MFS) in primary melanoma (PM) and a reduction in electronic tumor-infiltrating lymphocytes (eTILs). A gradual rise in ENOX2 expression was found with an increase in malignant potential from benign nevi (BNs) via PMs to melanoma metastases (MMs), as well as with an increasing tumor thickness and stage. These results highlight the important role of ENOX2 in cancer growth, progression and metastasis. The ENOX2 expression was not limited to malignant cell lines but could also be found in keratinocytes, fibroblasts and melanocytes. The viability of melanoma cell lines could be inhibited by PXD. A reduced induction of phospho-AKT under PXD could prevent the development of acquired BRAFi resistance. In conclusion, ENOX2 may serve as a potential prognostic marker and therapeutic target in malignant melanoma.