The 2023 MDPI Annual Report has
been released!
 
20 pages, 2280 KiB  
Article
Revealing Genetic Dynamics: scRNA-seq Unravels Modifications in Human PDL Cells across In Vivo and In Vitro Environments
by Ali T. Abdallah, Michael Peitz and Anna Konermann
Int. J. Mol. Sci. 2024, 25(9), 4731; https://doi.org/10.3390/ijms25094731 (registering DOI) - 26 Apr 2024
Abstract
 The periodontal ligament (PDL) is a highly specialized fibrous tissue comprising heterogeneous cell populations of an intricate nature. These complexities, along with challenges due to cell culture, impede a comprehensive understanding of periodontal pathophysiology. This study aims to address this gap, employing [...] Read more.
 The periodontal ligament (PDL) is a highly specialized fibrous tissue comprising heterogeneous cell populations of an intricate nature. These complexities, along with challenges due to cell culture, impede a comprehensive understanding of periodontal pathophysiology. This study aims to address this gap, employing single-cell RNA sequencing (scRNA-seq) technology to analyze the genetic intricacies of PDL both in vivo and in vitro. Primary human PDL samples (n = 7) were split for direct in vivo analysis and cell culture under serum-containing and serum-free conditions. Cell hashing and sorting, scRNA-seq library preparation using the 10x Genomics protocol, and Illumina sequencing were conducted. Primary analysis was performed using Cellranger, with downstream analysis via the R packages Seurat and SCORPIUS. Seven distinct PDL cell clusters were identified comprising different cellular subsets, each characterized by unique genetic profiles, with some showing donor-specific patterns in representation and distribution. Formation of these cellular clusters was influenced by culture conditions, particularly serum presence. Furthermore, certain cell populations were found to be inherent to the PDL tissue, while others exhibited variability across donors. This study elucidates specific genes and cell clusters within the PDL, revealing both inherent and context-driven subpopulations. The impact of culture conditions—notably the presence of serum—on cell cluster formation highlights the critical need for refining culture protocols, as comprehending these influences can drive the creation of superior culture systems vital for advancing research in PDL biology and regenerative therapies. These discoveries not only deepen our comprehension of PDL biology but also open avenues for future investigations into uncovering underlying mechanisms.  Full article
(This article belongs to the Special Issue Cutting-Edge Insights into Oral Health and Disease)
17 pages, 7250 KiB  
Article
Study on the Adaptability Evaluation of Micro-Dispersed-Gel-Strengthened-Alkali-Compound System and the Production Mechanism of Crude Oil
by Teng Wang, Tianjiang Wu, Yunlong Liu, Chen Cheng and Guang Zhao
Processes 2024, 12(5), 871; https://doi.org/10.3390/pr12050871 (registering DOI) - 26 Apr 2024
Abstract
A novel micro-dispersed-gel (MDG)-strengthened-alkali-compound flooding system was proposed for enhanced oil recovery in high-water-cut mature oilfields. Micro-dispersed gel has different adaptability and application schemes with sodium carbonate and sodium hydroxide. The MDG-strengthened-alkali flooding system can reduce the interfacial tension to an ultra-low interfacial-tension [...] Read more.
A novel micro-dispersed-gel (MDG)-strengthened-alkali-compound flooding system was proposed for enhanced oil recovery in high-water-cut mature oilfields. Micro-dispersed gel has different adaptability and application schemes with sodium carbonate and sodium hydroxide. The MDG-strengthened-alkali flooding system can reduce the interfacial tension to an ultra-low interfacial-tension level of 10−2 mN/m, which can reverse the wettability of rock surface. After 30 days aging, the MDG-strengthened-Na2CO3 flooding system has good viscosity retention of 74.5%, with an emulsion stability of 79.13%. The enhanced-oil-recovery ability of the MDG-strengthened-Na2CO3 (MDGSC) flooding system is 43.91%, which is slightly weaker than the 47.78% of the MDG-strengthened-NaOH (MDGSH) flooding system. The crude-oil-production mechanism of the two systems is different, but they all show excellent performance in enhanced oil recovery. The MDGSC flooding system mainly regulates and seals micro-fractures, forcing subsequent injected water to enter the low-permeability area, and it has the ability to wash the remaining oil in micro-fractures. The MDGSH flooding system mainly removes the remaining oil on the rock wall surface in the micro-fractures by efficient washing, and the MDG particles can also form weak plugging of the micro-fractures. The MDG-strengthened-alkali flooding system can be used as an alternative to enhance oil recovery in high-water-cut and highly heterogeneous mature oilfields. Full article
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23 pages, 612 KiB  
Systematic Review
Korean Hospital Nurses’ Experiences with COVID-19: A Meta-Synthesis of Qualitative Findings
by Suk-Jung Han, Hee-Jung Hong and Bok-Soon Shin
Healthcare 2024, 12(9), 903; https://doi.org/10.3390/healthcare12090903 (registering DOI) - 26 Apr 2024
Abstract
During the COVID-19 pandemic, hospital nurses in South Korea cared for patients amid their own anxiety and fear of infection, armed with a sense of professional duty and overcoming all odds to end the country’s infectious disease pandemic. This study aims to provide [...] Read more.
During the COVID-19 pandemic, hospital nurses in South Korea cared for patients amid their own anxiety and fear of infection, armed with a sense of professional duty and overcoming all odds to end the country’s infectious disease pandemic. This study aims to provide a meta-synthesis of qualitative studies examining the perceptions and experiences of nurses who cared for patients in dedicated COVID-19 hospitals in South Korea. Electronic databases, including RISS, KISS, KMbase, NDSL, KoreaMed, DBpia, PubMed, CINAHL, and Cochrane, were searched for research published until 2023. The study included research using qualitative approaches. These were reviewed and analyzed using a thematic synthesis approach. The quality of the studies was ascertained using the Critical Appraisal Skills Program checklist for qualitative research. Ultimately, 13 studies involving 219 nurses were included in the final review. Six major themes and thirteen subthemes emerged. The six topics are: “The crisis of a pandemic that suddenly appeared”, “Challenges in nursing patients with infectious diseases”, “A struggle in an unknown time due to a prolonged infectious disease”, “Ethical dilemmas in the face of infectious diseases”, “Duality of the social support system”, and “Professional growth for nurses regarding infectious diseases”. During the unexpected COVID-19 pandemic, nurses were able to overcome difficult situations through their interactions with patients, sense of professional mission, and commitment to nursing. Most importantly, they persevered through their collaboration and closeness with fellow nurses, despite confusion about their professional identity, the ethical dilemmas they faced in patient care, and dual attitudes regarding their social support system. To prepare for future infectious disease outbreaks, a multifaceted support system should be established to enable nurses to have positive interactions with their families, colleagues, and patients, which are central to their resilience. Full article
(This article belongs to the Collection COVID-19: Impact on Public Health and Healthcare)
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15 pages, 3054 KiB  
Article
Assessing the Predictive Accuracy of EORTC, CUETO and EAU Risk Stratification Models for High-Grade Recurrence and Progression after Bacillus Calmette–Guérin Therapy in Non-Muscle-Invasive Bladder Cancer
by Aleksander Ślusarczyk, Karolina Garbas, Patryk Pustuła, Łukasz Zapała and Piotr Radziszewski
Cancers 2024, 16(9), 1684; https://doi.org/10.3390/cancers16091684 (registering DOI) - 26 Apr 2024
Abstract
The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events [...] Read more.
The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette–Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG. Full article
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15 pages, 768 KiB  
Review
Digital Pathology for Better Clinical Practice
by Assia Hijazi, Carlo Bifulco, Pamela Baldin and Jérôme Galon
Cancers 2024, 16(9), 1686; https://doi.org/10.3390/cancers16091686 (registering DOI) - 26 Apr 2024
Abstract
(1) Background: Digital pathology (DP) is transforming the landscape of clinical practice, offering a revolutionary approach to traditional pathology analysis and diagnosis. (2) Methods: This innovative technology involves the digitization of traditional glass slides which enables pathologists to access, analyze, and share high-resolution [...] Read more.
(1) Background: Digital pathology (DP) is transforming the landscape of clinical practice, offering a revolutionary approach to traditional pathology analysis and diagnosis. (2) Methods: This innovative technology involves the digitization of traditional glass slides which enables pathologists to access, analyze, and share high-resolution whole-slide images (WSI) of tissue specimens in a digital format. By integrating cutting-edge imaging technology with advanced software, DP promises to enhance clinical practice in numerous ways. DP not only improves quality assurance and standardization but also allows remote collaboration among experts for a more accurate diagnosis. Artificial intelligence (AI) in pathology significantly improves cancer diagnosis, classification, and prognosis by automating various tasks. It also enhances the spatial analysis of tumor microenvironment (TME) and enables the discovery of new biomarkers, advancing their translation for therapeutic applications. (3) Results: The AI-driven immune assays, Immunoscore (IS) and Immunoscore-Immune Checkpoint (IS-IC), have emerged as powerful tools for improving cancer diagnosis, prognosis, and treatment selection by assessing the tumor immune contexture in cancer patients. Digital IS quantitative assessment performed on hematoxylin–eosin (H&E) and CD3+/CD8+ stained slides from colon cancer patients has proven to be more reproducible, concordant, and reliable than expert pathologists’ evaluation of immune response. Outperforming traditional staging systems, IS demonstrated robust potential to enhance treatment efficiency in clinical practice, ultimately advancing cancer patient care. Certainly, addressing the challenges DP has encountered is essential to ensure its successful integration into clinical guidelines and its implementation into clinical use. (4) Conclusion: The ongoing progress in DP holds the potential to revolutionize pathology practices, emphasizing the need to incorporate powerful AI technologies, including IS, into clinical settings to enhance personalized cancer therapy. Full article
(This article belongs to the Special Issue Predictive Biomarkers for Colorectal Cancer)
20 pages, 8571 KiB  
Technical Note
Airborne Platform Three-Dimensional Positioning Method Based on Interferometric Synthetic Aperture Radar Interferogram Matching
by Lanyu Li, Yachao Wang, Bingnan Wang and Maosheng Xiang
Remote Sens. 2024, 16(9), 1536; https://doi.org/10.3390/rs16091536 (registering DOI) - 26 Apr 2024
Abstract
As the demand for precise navigation of aircraft increases in modern society, researching high-precision, high-autonomy navigation systems is both theoretically valuable and practically significant. Because the inertial navigation system (INS) has systematic and random errors, its output information diverges. Therefore, it is necessary [...] Read more.
As the demand for precise navigation of aircraft increases in modern society, researching high-precision, high-autonomy navigation systems is both theoretically valuable and practically significant. Because the inertial navigation system (INS) has systematic and random errors, its output information diverges. Therefore, it is necessary to combine them with other navigation systems for real-time compensation and correction of these errors. The SAR matching positioning and navigation system uses synthetic aperture radar (SAR) image matching for platform positioning and compensates for the drift caused by errors in the inertial measurement unit (IMU). Images obtained by SAR are matched with digital landmark data, and the platform’s position is calculated based on the SAR imaging geometry. However, SAR matching positioning faces challenges due to seasonal variations in SAR images, the need for typical landmarks for matching, and the lack of elevation information in two-dimensional SAR image matching. This paper proposes an airborne platform positioning method based on interferometric SAR (InSAR) interferogram matching. InSAR interferograms contain terrain elevation information, are less affected by seasonal changes, and provide higher positioning accuracy and robustness. By matching real-time InSAR-processed interferograms with simulated interferograms using a digital elevation model (DEM), three-dimensional position information about the matching points has been obtained. Subsequently, a three-dimensional positioning model for the platform has bene established using the unit line-of-sight vector decomposition method. In actual flight experiments using an FMCW Ku-band Interferometric SAR system, the proposed platform positioning framework demonstrated its ability to achieve precise positioning in the absence of signals from the global navigation satellite system (GNSS). Full article
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32 pages, 3528 KiB  
Article
Identifying Characteristic Fire Properties with Stationary and Non-Stationary Fire Alarm Systems
by Michał Wiśnios, Sebastian Tatko, Michał Mazur, Jacek Paś, Jarosław Mateusz Łukasiak and Tomasz Klimczak
Sensors 2024, 24(9), 2772; https://doi.org/10.3390/s24092772 (registering DOI) - 26 Apr 2024
Abstract
The article reviews issues associated with the operation of stationary and non-stationary electronic fire alarm systems (FASs). These systems are employed for the fire protection of selected buildings (stationary) or to monitor vast areas, e.g., forests, airports, logistics hubs, etc. (non-stationary). An FAS [...] Read more.
The article reviews issues associated with the operation of stationary and non-stationary electronic fire alarm systems (FASs). These systems are employed for the fire protection of selected buildings (stationary) or to monitor vast areas, e.g., forests, airports, logistics hubs, etc. (non-stationary). An FAS is operated under various environmental conditions, indoor and outdoor, favourable or unfavourable to the operation process. Therefore, an FAS has to exhibit a reliable structure in terms of power supply and operation. To this end, the paper discusses a representative FAS monitoring a facility and presents basic tactical and technical assumptions for a non-stationary system. The authors reviewed fire detection methods in terms of fire characteristic values (FCVs) impacting detector sensors. Another part of the article focuses on false alarm causes. Assumptions behind the use of unmanned aerial vehicles (UAVs) with visible-range cameras (e.g., Aviotec) and thermal imaging were presented for non-stationary FASs. The FAS operation process model was defined and a computer simulation related to its operation was conducted. Analysing the FAS operation process in the form of models and graphs, and the conducted computer simulation enabled conclusions to be drawn. They may be applied for the design, ongoing maintenance and operation of an FAS. As part of the paper, the authors conducted a reliability analysis of a selected FAS based on the original performance tests of an actual system in operation. They formulated basic technical and tactical requirements applicable to stationary and mobile FASs detecting the so-called vast fires. Full article
(This article belongs to the Section Environmental Sensing)
15 pages, 2030 KiB  
Article
Berberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1
by Kei Goto, Rina Fujiwara-Tani, Shota Nukaga, Yoshihiro Miyagawa, Isao Kawahara, Ryoichi Nishida, Ayaka Ikemoto, Rika Sasaki, Ruiko Ogata, Shingo Kishi, Yi Luo, Kiyomu Fujii, Hitoshi Ohmori and Hiroki Kuniyasu
Int. J. Mol. Sci. 2024, 25(9), 4735; https://doi.org/10.3390/ijms25094735 (registering DOI) - 26 Apr 2024
Abstract
Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat [...] Read more.
Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor κB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in a cachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppression and modulation of the signaling system. Full article
16 pages, 555 KiB  
Article
Feasibility and Acute Toxicity of Hypo-Fractionated Radiotherapy on 0.35T MR-LINAC: The First Prospective Study in Spain
by Daniela Gonsalves, Abrahams Ocanto, Eduardo Meilan, Alberto Gomez, Jesus Dominguez, Lisselott Torres, Castalia Fernández Pascual, Macarena Teja, Miguel Montijano Linde, Marcos Guijarro, Daniel Rivas, Jose Begara, Jose Antonio González, Jon Andreescu, Esther Holgado, Diego Alcaraz, Escarlata López, Maia Dzhugashvli, Fernando Lopez-Campos, Filippo Alongi and Felipe Couñagoadd Show full author list remove Hide full author list
Cancers 2024, 16(9), 1685; https://doi.org/10.3390/cancers16091685 (registering DOI) - 26 Apr 2024
Abstract
This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors [...] Read more.
This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies. Full article
(This article belongs to the Special Issue MRI-Guided Real-Time Adaptive Radiotherapy)
22 pages, 2464 KiB  
Article
The Impact of Internet Addiction on Mental Health: Exploring the Mediating Effects of Positive Psychological Capital in University Students
by Girum Tareke Zewude, Derib Gosim Bereded, Endris Abera, Goche Tegegne, Solomon Goraw and Tesfaye Segon
Adolescents 2024, 4(2), 200-221; https://doi.org/10.3390/adolescents4020014 (registering DOI) - 26 Apr 2024
Abstract
Introduction: The widespread use of the internet has brought numerous benefits, but it has also raised concerns about its potential negative impact on mental health, particularly among university students. This study aims to investigate the relationship between internet addiction (IA) and mental [...] Read more.
Introduction: The widespread use of the internet has brought numerous benefits, but it has also raised concerns about its potential negative impact on mental health, particularly among university students. This study aims to investigate the relationship between internet addiction (IA) and mental health (MH) in university students, as well as explore the mediating effects of positive psychological capital (PsyCap) in this relationship. Objective: The main goal of this study was to examine the psychometric properties of the measures and to determine whether internet addiction could negatively predict university students’ mental health, mediated through PsyCap. Method: A cross-sectional design with an inferential approach was employed to address this objective. The data were collected using the Psychological Capital Questionnaire (PCQ-24), Internet Addiction Scale (IAS), and Keyes’ Mental Health Continuum-Short Form (MHC-SF). The total sample of this study comprised 850 students from two large public higher education institutions in Ethiopia, of whom 334 (39.3%) were female and 516 (60.7%) were male, with a mean age of 22.32 (SD = 4.04). Several analyses were performed to achieve the stated objectives, such as Cronbach’s alpha and composite reliabilities, bivariate correlation, discriminant validity, common method biases, and structural equation modeling (confirmatory factor analysis, path analysis, and mediation analysis). Confirmatory factor analysis was conducted to test the construct validity of IAS, PCQ-24, and MHC-SF. Additionally, the mediating model was examined using structural equation modeling with the corrected biased bootstrap method. Results: The preliminary study results found that the construct validity of IAS, PCQ-24, and MHC-SF was excellent and appropriate. Furthermore, the findings demonstrate that internet addiction had a negative and direct effect on PsyCap and MH. Moreover, PsyCap fully mediated the relationship between IA and MH. Additionally, this study confirmed that all the scales exhibited strong internal consistency and good psychometric properties. Conclusion: This study contributes to a better understanding of the complex interplay between IA, PsyCap, and MH among university students, confirming previous findings. Recommendation: The findings, discussed in relation to the recent and relevant literature, will be valuable for practitioners and researchers aiming to improve mental health and reduce internet addiction by utilizing positive psychological resources as protective factors for university students. Full article
(This article belongs to the Section Adolescent Health and Mental Health)
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15 pages, 1499 KiB  
Article
Gallic Acid Can Promote Low-Density Lipoprotein Uptake in HepG2 Cells via Increasing Low-Density Lipoprotein Receptor Accumulation
by Dongying Zhang, Qixing Zhou, Xiangxuan Yang, Zhen Zhang, Dongxue Wang, Dandan Hu, Yewei Huang, Jun Sheng and Xuanjun Wang
Molecules 2024, 29(9), 1999; https://doi.org/10.3390/molecules29091999 (registering DOI) - 26 Apr 2024
Abstract
Gallic acid (GA) is a type of polyphenolic compound that can be found in a range of fruits, vegetables, and tea. Although it has been confirmed it improves non-alcoholic fatty liver disease (NAFLD), it is still unknown whether GA can improve the occurrence [...] Read more.
Gallic acid (GA) is a type of polyphenolic compound that can be found in a range of fruits, vegetables, and tea. Although it has been confirmed it improves non-alcoholic fatty liver disease (NAFLD), it is still unknown whether GA can improve the occurrence of NAFLD by increasing the low-density lipoprotein receptor (LDLR) accumulation and alleviating cholesterol metabolism disorders. Therefore, the present study explored the effect of GA on LDLR and its mechanism of action. The findings indicated that the increase in LDLR accumulation in HepG2 cells induced by GA was associated with the stimulation of the epidermal growth factor receptor–extracellular regulated protein kinase (EGFR-ERK1/2) signaling pathway. When the pathway was inhibited by EGFR mab cetuximab, it was observed that the activation of the EGFR-ERK1/2 signaling pathway induced by GA was also blocked. At the same time, the accumulation of LDLR protein and the uptake of LDL were also suppressed. Additionally, GA can also promote the accumulation of forkhead box O3 (FOXO3) and suppress the accumulation of hepatocyte nuclear factor-1α (HNF1α), leading to the inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) mRNA expression and protein accumulation. This ultimately results in increased LDLR protein accumulation and enhanced uptake of LDL in cells. In summary, the present study revealed the potential mechanism of GA’s role in ameliorating NAFLD, with a view of providing a theoretical basis for the dietary supplementation of GA. Full article
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17 pages, 5807 KiB  
Article
Cinnamaldehyde Protects against P. gingivalis Induced Intestinal Epithelial Barrier Dysfunction in IEC-6 Cells via the PI3K/Akt-Mediated NO/Nrf2 Signaling Pathway
by Chethan Sampath, Sasanka S. Chukkapalli, Abhinav V. Raju, Leela Subhashini C. Alluri, Dollada Srisai and Pandu R. Gangula
Int. J. Mol. Sci. 2024, 25(9), 4734; https://doi.org/10.3390/ijms25094734 (registering DOI) - 26 Apr 2024
Abstract
Porphyromonas gingivalis (Pg), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the pathogenesis of intestinal and systemic diseases. In this study, we sought to elucidate the protective role of cinnamaldehyde (CNM, an [...] Read more.
Porphyromonas gingivalis (Pg), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the pathogenesis of intestinal and systemic diseases. In this study, we sought to elucidate the protective role of cinnamaldehyde (CNM, an activator of Nrf2) against P. gingivalis (W83) and Pg-derived lipopolysaccharide (Pg-LPS) induced intestinal epithelial barrier dysfunction via antioxidative mechanisms in IEC-6 cells. IEC-6 (ATCC, CRL-1592) cells were pretreated with or without CNM (100 µM), in the presence or absence of P. gingivalis (strain W83, 109 MOI) or Pg-LPS (1, 10, and 100 µg/mL), respectively, between 0–72 h time points by adopting a co-culture method. Intestinal barrier function, cytokine secretion, and intestinal oxidative stress protein markers were analyzed. P. gingivalis or Pg-LPS significantly (p < 0.05) increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels expressing oxidative stress damage. Pg-LPS, as well as Pg alone, induces inflammatory cytokines via TLR-4 signaling. Furthermore, infection reduced Nrf2 and NAD(P)H quinone dehydrogenase 1 (NQO1). Interestingly, inducible nitric oxide synthase (iNOS) protein expression significantly (p < 0.05) increased with Pg-LPS or Pg infection, with elevated levels of nitric oxide (NO). CNM treatment suppressed both Pg- and Pg-LPS-induced intestinal oxidative stress damage by reducing ROS, MDA, and NO production. Furthermore, CNM treatment significantly upregulated the expression of tight junction proteins via increasing the phosphorylation levels of PI3K/Akt/Nrf2 suppressing inflammatory cytokines. CNM protected against Pg infection-induced intestinal epithelial barrier dysfunction by activating the PI3K/Akt-mediated Nrf2 signaling pathway in IEC-6 cells. Full article
(This article belongs to the Special Issue Nitric Oxide Synthases: Function and Regulation 2.0)
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16 pages, 7031 KiB  
Article
Complete Plastomes of Ten Rorippa Species (Brassicaceae): Comparative Analysis and Phylogenetic Relationships
by Ting Ren, Lulu Xun, Yun Jia and Bin Li
Agronomy 2024, 14(5), 913; https://doi.org/10.3390/agronomy14050913 (registering DOI) - 26 Apr 2024
Abstract
The genus Rorippa belongs to the family Brassicaceae, and its members usually have high medicinal value. The genus consists of approximately 75 species and mainly grows in the Northern Hemisphere, occurring in every continent except Antarctica. The taxonomy and phylogenetic relationships of Rorippa [...] Read more.
The genus Rorippa belongs to the family Brassicaceae, and its members usually have high medicinal value. The genus consists of approximately 75 species and mainly grows in the Northern Hemisphere, occurring in every continent except Antarctica. The taxonomy and phylogenetic relationships of Rorippa are still unsettled, largely due to complex morphological variations in Rorippa, which were caused by frequent hybridization events. Here, we sequenced four complete plastid genomes of Rorippa species by Illumina paired-end sequencing. The four new plastid genomes of Rorippa ranged in total size from 154,671 bp for R. palustris to 154,894 bp for R. sylvestris. There are 130 genes in the four plastomes, embodying 8 rRNA, 37 tRNA, and 85 protein-coding genes. Combining with six published plastid genomes, we carried on comparative and phylogenetic analyses. We found that the ten Rorippa plastid genomes were conservative in gene number and order, total size, genomic structure, codon usage, long repeat sequence, and SSR. Fourteen mutational hotspot regions could be selected as candidate DNA barcoding to distinguish Rorippa plants. The phylogenetic trees clearly identified that ten Rorippa species displayed monophyletic relationships within the tribe Cardamineae based on plastomes and nrDNA ITS sequences. However, there are significant cytonuclear discordances in the interspecific relationships within Rorippa, as well as the intergeneric relationships between Rorippa and its related genera. We inferred that the cytonuclear discordance is most likely a result of interspecific hybridization within Rorippa, as well as intergeneric hybridization with its related genera. These plastid genomes can offer precious information for studies of species authentication, evolutionary history, and the phylogeny of Rorippa. Full article
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19 pages, 4779 KiB  
Article
Hispidulin Alleviates Mast Cell-Mediated Allergic Airway Inflammation through FcεR1 and Nrf2/HO-1 Signaling Pathway
by Seungwon Jeong, Yeon-Yong Kim, Dongwon Lee, Sang-Hyun Kim and Soyoung Lee
Antioxidants 2024, 13(5), 528; https://doi.org/10.3390/antiox13050528 (registering DOI) - 26 Apr 2024
Abstract
Allergic asthma is a type 2 immune-response-mediated chronic respiratory disease. Mast cell activation influences the pathogenesis and exacerbation of allergic asthma. Therefore, the development of mast cell-targeting pharmacotherapy is important for managing allergic airway inflammation. We investigated the efficacy of hispidulin (HPD), natural [...] Read more.
Allergic asthma is a type 2 immune-response-mediated chronic respiratory disease. Mast cell activation influences the pathogenesis and exacerbation of allergic asthma. Therefore, the development of mast cell-targeting pharmacotherapy is important for managing allergic airway inflammation. We investigated the efficacy of hispidulin (HPD), natural flavone, in a mast-cell-mediated ovalbumin (OVA)-induced allergic airway inflammation model. HPD alleviated symptoms of allergic asthma and decreased the levels of immunoglobulin (Ig) E, type 2 inflammation, immune cell infiltration, and mast cell activation in the lung. Furthermore, in vivo analysis confirmed the efficacy of HPD through the evaluation of IgE-mediated allergic responses in a mast cell line. HPD treatment inhibited mast cell degranulation through inhibition of the FcεR1 signaling pathway and suppressed the expression of inflammatory cytokines (TNF-α, IL-4, IL-6, and IL-13) through suppression of the NF-κB signaling pathway. The antioxidant effects of HPD in activated mast cells were identified through modulation of antioxidant enzymes and the Nrf2/HO-1 signaling pathway. In conclusion, HPD may be a potential therapeutic candidate for allergic airway inflammation of asthma and acts by suppressing mast cell activation and oxidative stress. Full article
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20 pages, 2168 KiB  
Article
Optimally Splitting Solar Spectrums by Concentrating Solar Spectrums Splitter for Hydrogen Production via Solid Oxide Electrolysis Cell
by Shaocheng Lang, Jinliang Yuan and Houcheng Zhang
Energies 2024, 17(9), 2067; https://doi.org/10.3390/en17092067 (registering DOI) - 26 Apr 2024
Abstract
The concentrating solar spectrums splitter (CSSS)-driven solid oxide electrolysis cell (SOEC) is an attractive technology for green hydrogen production. The CSSS mainly comprises a concentrating photovoltaic (CPV), which converts sunlight with shorter wavelengths into electricity, and a concentrating solar collector (CSC), which converts [...] Read more.
The concentrating solar spectrums splitter (CSSS)-driven solid oxide electrolysis cell (SOEC) is an attractive technology for green hydrogen production. The CSSS mainly comprises a concentrating photovoltaic (CPV), which converts sunlight with shorter wavelengths into electricity, and a concentrating solar collector (CSC), which converts the remaining sunlight into heat. However, the optimal splitting of the solar spectrums is a critical challenge that directly impacts the efficiency and normal operation of the SOEC. To address this challenge, a mathematical model integrating the CSSS with the SOEC is developed based on principles from thermodynamics and electrochemistry. By analyzing the requirements of electricity and heat for the SOEC, the model determines the optimal configuration and operational parameters. The results show that the anode-supported type, higher operating temperature, larger inlet flow rate of water, higher operating pressure of the SOEC, higher operating temperature of the CSC, and larger electric current of the CPV contribute to allocating more solar spectrums to the CSC for heat generation. However, the greater effectiveness of the heat exchangers, higher operating temperature, and larger optical concentration ratio of the CPV exhibit contrasting effects on the spectrum allocation. The obtained results provide valuable theoretical guidance for designing and running the CSSS for hydrogen production through SOEC. Full article
(This article belongs to the Special Issue Solar Cells, Circuits and Systems for PV Conversion)
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15 pages, 988 KiB  
Article
Effects of sn-2 Palmitic Triacylglycerols and the Ratio of OPL to OPO in Human Milk Fat Substitute on Metabolic Regulation in Sprague-Dawley Rats
by Lin Zhu, Shuaizhen Fang, Yaqiong Zhang, Xiangjun Sun, Puyu Yang, Weiying Lu and Liangli Yu
Nutrients 2024, 16(9), 1299; https://doi.org/10.3390/nu16091299 (registering DOI) - 26 Apr 2024
Abstract
In this study, the influence of total sn-2 palmitic triacylglycerols (TAGs) and ratio of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO) in human milk fat substitute (HMFS) on the metabolic changes were investigated in Sprague–Dawley rats. Metabolomics and lipidomics profiling analysis indicated that increasing [...] Read more.
In this study, the influence of total sn-2 palmitic triacylglycerols (TAGs) and ratio of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO) in human milk fat substitute (HMFS) on the metabolic changes were investigated in Sprague–Dawley rats. Metabolomics and lipidomics profiling analysis indicated that increasing the total sn-2 palmitic TAGs and OPL to OPO ratio in HMFS could significantly influence glycine, serine and threonine metabolism, glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid metabolism, bile acid biosynthesis, and taurine and hypotaurine metabolism pathways in rats after 4 weeks of feeding, which were mainly related to lipid, bile acid and energy metabolism. Meanwhile, the up-regulation of taurine, L-tryptophan, and L-cysteine, and down-regulations of lysoPC (18:0) and hypoxanthine would contribute to the reduction in inflammatory response and oxidative stress, and improvement of immunity function in rats. In addition, analysis of targeted biochemical factors also revealed that HMFS-fed rats had significantly increased levels of anti-inflammatory factor (IL-4), immunoglobulin A (IgA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px), and decreased levels of pro-inflammatory factors (IL-6 and TNF-α) and malondialdehyde (MDA), compared with those of the control fat-fed rats. Collectively, these observations present new in vivo nutritional evidence for the metabolic regulatory effects of the TAG structure and composition of human milk fat substitutes on the host. Full article
(This article belongs to the Special Issue Functional Components and Their Modulation of Metabolism)
16 pages, 1001 KiB  
Article
Sustainable Utilization of Mushroom By-Products Processed with a Combined Osmotic Dehydration Pretreatment and a Hot-Air-Drying Step
by Natalia A. Stavropoulou, Andriana E. Lazou and Maria C. Giannakourou
Foods 2024, 13(9), 1339; https://doi.org/10.3390/foods13091339 (registering DOI) - 26 Apr 2024
Abstract
Mushroom production and consumption are gaining increased interest due to their unique flavor and nutritional value. However, in the mushroom industry, large amounts of by-products are generated, which have a high negative environmental and economic impact. In this study, an osmotic dehydration process [...] Read more.
Mushroom production and consumption are gaining increased interest due to their unique flavor and nutritional value. However, in the mushroom industry, large amounts of by-products are generated, which have a high negative environmental and economic impact. In this study, an osmotic dehydration process followed by hot-air-drying was applied to mushroom stems to produce dried mushrooms as the end product. The osmotic dehydration conditions (concentration of hypertonic solution, specifically, 10–30% maltodextrin and 20–40% oligofructose; a treatment time of 40–80 min; and a temperature range of 30–50 °C) were optimized using response surface methodology (RSM). The results showed that a four-factor three-level Box–Behnken experimental design was effectively implemented to evaluate the effect of the process parameters and identify the optimal osmotic dehydration conditions for producing osmotically dehydrated mushrooms. The main factor affecting mass transfer was the osmosis temperature, and the optimal conditions were found to be 38 °C, 40% oligofructose and 19.3% maltodextrin as the osmotic agents, and 80 min of immersion time. Moreover, the results showed that osmotic pretreatment, in the optimal conditions, significantly reduced the required drying time of the by-products compared to traditional hot-air-drying, especially at milder drying temperatures. Consequently, the required energy was also reduced by at least 40% at 50 °C. Full article
19 pages, 7713 KiB  
Article
Bayesian Updating for Random Tensile Force Identification of Ancient Tie Rods Using Modal Data
by Chiara Pepi and Massimiliano Gioffrè
Appl. Sci. 2024, 14(9), 3698; https://doi.org/10.3390/app14093698 (registering DOI) - 26 Apr 2024
Abstract
Tie rods play a crucial role in civil engineering, particularly in controlling lateral thrusts in arches and vaults, and enhancing the structural integrity of masonry buildings, both historic and contemporary. Accurately assessing the tensile axial forces in tie rods is challenging due to [...] Read more.
Tie rods play a crucial role in civil engineering, particularly in controlling lateral thrusts in arches and vaults, and enhancing the structural integrity of masonry buildings, both historic and contemporary. Accurately assessing the tensile axial forces in tie rods is challenging due to the limitations of existing methodologies. These methodologies often rely on indirect measurements, computational models, and optimization procedures, resulting in single-point solutions and neglecting both modeling and measurement uncertainties. This study introduces a novel Bayesian updating framework to effectively address these limitations. The framework aims to accurately identify the structural parameters influencing tie rod behavior and estimate uncertainties using natural frequencies as references. A key innovation lies in the mathematical formulation of Bayesian updating, which is founded upon the definition of computational models integrating uncertain updating parameters and latent random variables derived from a rigorous sensitivity analysis aimed at quantifying the impact of the updating parameters on the natural frequencies. Notably, the application of Bayesian updating to the structural identification problem of ancient tie rods represents a significant advancement. The framework provides a comprehensive description of the uncertainties associated with computational models, offering valuable insights for practitioners and researchers alike. Moreover, the results of the sensitivity analysis serve as a valuable tool for setting up inverse problems geared towards accurately identifying tensile axial forces. Full article
26 pages, 5919 KiB  
Article
Diversified Filtering Mechanism for Evaluation Indicators of Urban Road Renewal Schemes
by Juan Du, Bing Liu, Yimeng Wu, Xiufang Li and Vijayan Sugumaran
Sustainability 2024, 16(9), 3638; https://doi.org/10.3390/su16093638 (registering DOI) - 26 Apr 2024
Abstract
As global urban infrastructure renewal progresses, the urgent need for sustainability-driven urban renewal intensifies amidst resource scarcity and environmental concerns. Effective evaluation and decision making regarding urban road renewal schemes are prerequisites for their successful implementation. However, variation in the prioritization of indicators [...] Read more.
As global urban infrastructure renewal progresses, the urgent need for sustainability-driven urban renewal intensifies amidst resource scarcity and environmental concerns. Effective evaluation and decision making regarding urban road renewal schemes are prerequisites for their successful implementation. However, variation in the prioritization of indicators in project evaluations and the poor adaptability of existing frameworks hinder the quick assessment of diverse projects. To address this issue, this paper proposes a scheme evaluation framework with embedded renewal project features comprising four modules. Following the initial construction of a sustainability-driven evaluation system, an indicator-filtering mechanism combining the Latent Dirichlet Allocation (LDA) model with a text similarity algorithm is developed. The Entropy Weight-–TOPSIS method is then employed to derive the final optimal decision based on selected indicators. Applying the decision framework to the G15 Jialiu Widening and Reconstruction Project in Shanghai, China, indicators are reduced by 48.3%, with the optimal scheme decision consistent with the traditional Entropy Weight–TOPSIS method. The framework is robust and enhances decision efficiency, filling theoretical gaps in existing indicator-filtering mechanisms. Full article
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24 pages, 2123 KiB  
Article
Mathematical Modeling of SOIC Package Dynamics in Dielectric Fluids during High-Voltage Insulation Testing
by Yohan A. Aparicio and Manuel Jimenez
Appl. Sci. 2024, 14(9), 3693; https://doi.org/10.3390/app14093693 (registering DOI) - 26 Apr 2024
Abstract
The efficient testing and validation of the high-voltage (HV) insulation of small-outline integrated circuit (SOIC) packages presents numerous challenges when trying to achieve faster and more accurate processes. The complex behavior these packages when submerged in diverse physical media with varying densities requires [...] Read more.
The efficient testing and validation of the high-voltage (HV) insulation of small-outline integrated circuit (SOIC) packages presents numerous challenges when trying to achieve faster and more accurate processes. The complex behavior these packages when submerged in diverse physical media with varying densities requires a detailed analysis to understand the factors influencing their behavior. We propose a systematic and scalable mathematical model based on trapezoidal motion patterns and a deterministic analysis of hydrodynamic forces to predict SOIC package misalignment during automated high-voltage testing in a dielectric fluid. Our model incorporates factors known to cause misalignment during the maneuvering of packages, such as surface tension forces, sloshing, cavity formation, surface waves, and bubbles during the insertion, extraction, and displacement of devices while optimizing test speed for minimum testing time. Our model was validated via a full-factorial statistical experiment for different SOIC package sizes on a pick-and-place (PNP) machine with preprogrammed software and a zero-insertion force socket immersed in different dielectric fluids under controlled thermal conditions. Results indicate the model achieves 99.64% reliability with a margin of error of less than 4.78%. Our research deepens the knowledge and understanding of the physical and hydrodynamic factors that impact the automated testing processes of high-voltage insulator SOIC packages of different sizes for different dielectric fluids. It enables improved testing times and higher reliability than traditional trial-and-error methods for high-voltage SOIC packages, leading to more efficient and accurate processes in the electronics industry. Full article
(This article belongs to the Special Issue Disruptive Trends in Automation Technology)
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19 pages, 1881 KiB  
Article
Unravelling the Role of Candida albicans Prn1 in the Oxidative Stress Response through a Proteomics Approach
by Victor Arribas, Lucia Monteoliva, María Luisa Hernáez, Concha Gil and Gloria Molero
Antioxidants 2024, 13(5), 527; https://doi.org/10.3390/antiox13050527 (registering DOI) - 26 Apr 2024
Abstract
Candida albicans Prn1 is a protein with an unknown function similar to mammalian Pirin. It also has orthologues in other pathogenic fungi, but not in Saccharomyces cerevisiae. Prn1 highly increases its abundance in response to H2O2 treatment; thus, to [...] Read more.
Candida albicans Prn1 is a protein with an unknown function similar to mammalian Pirin. It also has orthologues in other pathogenic fungi, but not in Saccharomyces cerevisiae. Prn1 highly increases its abundance in response to H2O2 treatment; thus, to study its involvement in the oxidative stress response, a C. albicans prn1∆ mutant and the corresponding wild-type strain SN250 have been studied. Under H2O2 treatment, Prn1 absence led to a higher level of reactive oxygen species (ROS) and a lower survival rate, with a higher percentage of death by apoptosis, confirming its relevant role in oxidative detoxication. The quantitative differential proteomics studies of both strains in the presence and absence of H2O2 indicated a lower increase in proteins with oxidoreductase activity after the treatment in the prn1∆ strain, as well as an increase in proteasome-activating proteins, corroborated by in vivo measurements of proteasome activity, with respect to the wild type. In addition, remarkable differences in the abundance of some transcription factors were observed between mutant and wild-type strains, e.g., Mnl1 or Nrg1, an Mnl1 antagonist. orf19.4850, a protein orthologue to S. cerevisiae Cub1, has shown its involvement in the response to H2O2 and in proteasome function when Prn1 is highly expressed in the wild type. Full article
(This article belongs to the Topic Redox in Microorganisms, 2nd Edition)
26 pages, 1123 KiB  
Article
Transformation of Energy Resources in the Visegrad Group: Strategies, Results, and Climate Effectiveness
by Izabela Jonek-Kowalska and Sara Rupacz
Resources 2024, 13(5), 64; https://doi.org/10.3390/resources13050064 (registering DOI) - 26 Apr 2024
Abstract
The climate challenges posed by the European Union are particularly difficult for emerging and developing economies. This causes reluctance to undertake them and even denial of their validity. For this reason, this article seeks to answer the question of whether it is possible [...] Read more.
The climate challenges posed by the European Union are particularly difficult for emerging and developing economies. This causes reluctance to undertake them and even denial of their validity. For this reason, this article seeks to answer the question of whether it is possible to carry out an effective transformation of energy resources in the developing economies of the Visegrad Group. Analyses in this area are conducted in a long-term, 58-year research perspective (1965–2022) and concern the Czech Republic, Hungary, Poland, and Slovakia. The effectiveness of the examined transformation is assessed in two dimensions as follows: (1) resource and (2) emission, which are then synthesized using a multi-criteria analysis. This research shows that an effective resource transformation aimed at a zero-emission economy is possible even in emerging and developing economies, although it undoubtedly requires time and consistency in the implementation of the once-chosen energy policy. Hungary—a leader in assessed climate effectiveness—has systematically decarbonized while reducing the use of total non-renewable resources. The Hungarian resource transition strategy assumed the use of nuclear energy and an increase in the share of renewable resources. The result of these activities is a quite diversified energy mix, which is greater resource self-sufficiency and low carbon dioxide emissions. The Czech Republic also achieved a similar strategy and results. Poland and Slovakia coped much worse with the climate challenge: although they gave up coal, they replaced it largely with other non-renewable resources. It is worth emphasizing that Poland has managed to significantly increase the use of renewable resources, and nuclear energy and hydropower have also appeared in the Slovak mix. Nevertheless, this did not allow for achieving good climatic results. Full article
19 pages, 6840 KiB  
Article
Preparation of a Novel Oat β-Glucan–Chromium(III) Complex and Its Hypoglycemic Effect and Mechanism
by Pengshou Li, Yunlu Wang, Xiaoting Wang, Rui Li, Kaihui Wang, Yu Jiang, Mingyuan Zhang, Chuhan Huang, Qixiang Ma, Jian Sun and Jianye Quan
Molecules 2024, 29(9), 1998; https://doi.org/10.3390/molecules29091998 (registering DOI) - 26 Apr 2024
Abstract
This study synthesized a novel oat β-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found [...] Read more.
This study synthesized a novel oat β-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits. Full article

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