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15 pages, 2113 KiB  
Article
Improved Segmented Control Strategy for Continuous Fault Ride-Through of Doubly-Fed Wind Turbines
by Tie Chen, Yifan Xu, Yue Liu, Junlin Ren and Youyuan Fan
Energies 2025, 18(14), 3845; https://doi.org/10.3390/en18143845 - 19 Jul 2025
Viewed by 216
Abstract
Aiming at the transient overcurrent problem faced by doubly-fed induction generators (DFIGs) during continuous voltage fault ride-through, a segmented control strategy based on the rotor side converter (RSC) is proposed. First, through theoretical analysis of the relationship between stator current and transient induced [...] Read more.
Aiming at the transient overcurrent problem faced by doubly-fed induction generators (DFIGs) during continuous voltage fault ride-through, a segmented control strategy based on the rotor side converter (RSC) is proposed. First, through theoretical analysis of the relationship between stator current and transient induced electromotive force (EMF) in each stage of continuous faults, a feedforward control strategy based on the transient component of stator current is proposed. The observable stator current is extracted for its transient component, which is used as a rotor voltage compensation term to effectively counteract the influence of transient EMF. Meanwhile, a fuzzy control algorithm is introduced during the low voltage ride-through (LVRT) stage to dynamically adjust the virtual resistance value, enhancing the system’s damping characteristics. Studies show that this strategy significantly suppresses rotor current spikes in all stages of voltage ride-through. Finally, simulation results verify that the proposed method improves the ride-through performance of DFIG under continuous voltage faults. Full article
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14 pages, 841 KiB  
Article
Evaluation of the Postprandial-Hyperglycemia-Suppressing Effects and Safety of Short-Term Intake of Mulberry Leaf and Water Chestnut Tea: A Randomized Double-Blind Placebo-Controlled Crossover Trial
by Yuya Shinkawa, Midori Yasuda, Yuichiro Nishida, Mikiko Tokiya, Yusuke Takagi, Akiko Matsumoto, Atsushi Kawaguchi and Megumi Hara
Nutrients 2025, 17(14), 2308; https://doi.org/10.3390/nu17142308 - 13 Jul 2025
Viewed by 473
Abstract
Background/Objectives: Postprandial hyperglycemia is a risk factor for diabetes and cardiovascular diseases, even in healthy individuals. Kanzaki mulberry leaf and water chestnut tea (MW tea), a blend of mulberry (Morus alba) leaves and water chestnut (Trapa japonica) leaves [...] Read more.
Background/Objectives: Postprandial hyperglycemia is a risk factor for diabetes and cardiovascular diseases, even in healthy individuals. Kanzaki mulberry leaf and water chestnut tea (MW tea), a blend of mulberry (Morus alba) leaves and water chestnut (Trapa japonica) leaves and husks, is rich in polyphenols and 1-deoxynojirimycin (DNJ) and may suppress postprandial glucose spikes, but evidence regarding its short-term daily intake is limited. This study aimed to evaluate the postprandial glycemic response and safety of two-week MW tea consumption using continuous glucose monitoring (CGM). Methods: We conducted a randomized, double-blind, placebo-controlled, two-period crossover trial involving 31 participants. Each intervention period lasted two weeks, separated by a one-week washout. Participants consumed either MW tea or a placebo before meals. Interstitial glucose levels were measured every 15 min using CGM. Postprandial glucose responses were recorded every 15 min for 180 min after a standardized meal on the first day of each period. The primary outcome was the coefficient of variation (CV) in glucose levels, calculated using data from the central 10 days of each intervention period. Safety was assessed using CGM-derived hypoglycemia metrics and blood test results. Results: The CV of glucose levels during the MW tea period was significantly lower than during the placebo period (mean difference: 0.02, p = 0.0006). A significant reduction in 1 h postprandial glucose area under the curve was also observed. No significant differences were found in hypoglycemia occurrence, liver/renal/inflammatory markers, or self-reported adverse symptoms. Notably, 1,5-anhydroglucitol (1,5-AG) levels significantly increased during MW tea intake, suggesting improved glycemic control. Conclusions: Short-term consumption of Kanzaki MW tea effectively suppressed postprandial glucose variability without safety concerns. These findings support MW tea as a promising natural supplement for glycemic management and the prevention of diabetes. Full article
(This article belongs to the Section Nutrition and Diabetes)
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16 pages, 5447 KiB  
Article
A Gate Driver for Crosstalk Suppression of eGaN HEMT Power Devices
by Longsheng Zhang, Kaihong Wang, Shilong Guo and Binxin Zhu
J. Low Power Electron. Appl. 2025, 15(3), 38; https://doi.org/10.3390/jlpea15030038 - 6 Jul 2025
Viewed by 255
Abstract
The eGaN HEMT power devices face serious crosstalk problems when applied to high-frequency bridge circuits, thereby limiting the switching performance of these devices. To address this issue, a gate driver is proposed in this paper that can suppress both positive and negative crosstalk [...] Read more.
The eGaN HEMT power devices face serious crosstalk problems when applied to high-frequency bridge circuits, thereby limiting the switching performance of these devices. To address this issue, a gate driver is proposed in this paper that can suppress both positive and negative crosstalk of eGaN HEMT power devices, offering the advantages of simple control and easy integration. The basic idea is to suppress positive crosstalk by constructing a negative voltage capacitor, and to suppress negative crosstalk by reducing the impedance of the gate loop. To verify the capability of the proposed gate driver, double-pulse and synchronous Buck test platforms are constructed. The experimental results clearly demonstrate that the proposed gate driver reduces the positive and negative crosstalk spikes by 2.03 V and 1.54 V, respectively, ensuring that the positive and negative crosstalk spikes fall within a safe operating range. Additionally, the turn-off speed of the device is enhanced, leading to a reduction in switching loss. Full article
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22 pages, 5021 KiB  
Article
Luteolin-Rich Extract from Harrisonia perforata (Blanco) Merr. Root Alleviates SARS-CoV-2 Spike Protein-Stimulated Lung Inflammation via Inhibition of MAPK/NLRP3 Inflammasome Signaling Pathways
by Warathit Semmarath, Punnida Arjsri, Kamonwan Srisawad, Sonthaya Umsumarng and Pornngarm Dejkriengkraikul
Life 2025, 15(7), 1077; https://doi.org/10.3390/life15071077 - 5 Jul 2025
Viewed by 400
Abstract
The COVID-19-related long-standing effect or Post-Acute Sequelae of COVID-19 (PASC) is often associated with NLRP3 inflammasome activation in pulmonary inflammation elicited by SARS-CoV-2 spike proteins. Spike proteins engage toll-like receptors (TLRs) in respiratory epithelial cells, leading to excessive cytokine production. Given the need [...] Read more.
The COVID-19-related long-standing effect or Post-Acute Sequelae of COVID-19 (PASC) is often associated with NLRP3 inflammasome activation in pulmonary inflammation elicited by SARS-CoV-2 spike proteins. Spike proteins engage toll-like receptors (TLRs) in respiratory epithelial cells, leading to excessive cytokine production. Given the need for effective therapeutic strategies to mitigate spike protein-stimulated lung inflammation, we examined the anti-inflammatory properties of luteolin and ethanolic extract from Harrisonia perforata (Blanco) Merr. root. The ethanolic extract of H. perforata root (HPEE) contained a high concentration of luteolin flavonoid (143.53 ± 1.58 mg/g extract). Both HPEE (25–100 μg/mL) and luteolin (4.5–36 μM) significantly inhibited inflammation stimulated by the Wuhan (W) and Omicron (O) spike protein S1, as evidenced by a dose-dependent significant decrease in IL-6, IL-1β, and IL-18 secretion in A549 lung epithelial cells (p < 0.05). Furthermore, pretreatment with HPEE or luteolin prior to spike protein exposure (100 ng/mL) significantly, in a dose-dependent manner, repressed the inflammatory mRNA expression (p < 0.05). Mechanistic study revealed that HPEE and luteolin suppressed NLRP3 inflammasome signaling activation by reducing their machinery protein expressions. Additionally, they inhibited the ERK/JNK/p38 MAPK signaling activation, resulting in decreased inflammatory mRNA expression and cytokine release. These findings suggest that H. perforata root extract and its major flavonoid luteolin exert potent anti-inflammatory effects and may offer therapeutic potential against spike protein-induced lung inflammation. Full article
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19 pages, 4184 KiB  
Article
Host–Virus Interface in Persistent SARS-CoV-2 Infections: Viral Characteristic Evolution and Gene Expression Profiling Analysis
by Athok Shofiudin Maarif, Yukari Nishikawa, Miyako Takata, Kyosuke Kanai, Edo Riyandani, Kengo Mukuda, Momone Mimura, Kosuke Yamaguchi, Hiroyuki Kato, Ryo Okamoto, Kensaku Okada, Tsuyoshi Kitaura, Masaki Nakamoto, Akira Yamasaki, Seiji Kageyama and Hiroki Chikumi
Int. J. Mol. Sci. 2025, 26(13), 6221; https://doi.org/10.3390/ijms26136221 - 27 Jun 2025
Viewed by 490
Abstract
Persistent SARS-CoV-2 infections involve prolonged viral replication and immune system interactions, potentially driving viral evolution and immune escape. This study examines viral characteristics and host gene expression changes in persistent infections. The nasopharyngeal samples from four patients with persistent SARS-CoV-2 infections at Tottori [...] Read more.
Persistent SARS-CoV-2 infections involve prolonged viral replication and immune system interactions, potentially driving viral evolution and immune escape. This study examines viral characteristics and host gene expression changes in persistent infections. The nasopharyngeal samples from four patients with persistent SARS-CoV-2 infections at Tottori University Hospital, Japan, were analyzed. Viral isolates were cultured, and infectivity was assessed using TCID50 assays. To investigate host responses, RNA sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs), and Gene Ontology (GO) enrichment analysis mapped affected biological pathways. Viral genome sequencing detected mutations associated with prolonged infection. The results showed significant infectivity differences between early- and late-phase infection. Gene expression analysis revealed a strong early phase of pro-inflammatory response (IL6, TNF, IL1B, CXCL10) followed by immune suppression. GO enrichment analysis highlighted inflammation and cytokine-mediated immune pathways. Genomic sequencing identified mutations in ORF1ab and the spike (S) protein, potentially aiding immune escape. The findings underscore that SARS-CoV-2 adapts during persistent infections, altering infectivity and immune responses. These highlight the need for continued monitoring of prolonged infections to mitigate immune escape and viral evolution. Full article
(This article belongs to the Special Issue Advanced Perspectives on Virus–Host Interactions)
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15 pages, 744 KiB  
Article
Influence of Acute and Chronic Load on Perceived Wellbeing, Neuromuscular Performance, and Immune Function in Male Professional Football Players
by Alastair Harris, Tim J. Gabbett, Rachel King, Stephen P. Bird and Peter Terry
Sports 2025, 13(6), 176; https://doi.org/10.3390/sports13060176 - 31 May 2025
Viewed by 1621
Abstract
Objectives: The purpose of the present study was to investigate the relationship between acute and chronic loads, and the fatigue response within male elite professional football players. Design: 40-week longitudinal study across the 2021–2022 season in the English Championship. Methods: Twenty-three outfield football [...] Read more.
Objectives: The purpose of the present study was to investigate the relationship between acute and chronic loads, and the fatigue response within male elite professional football players. Design: 40-week longitudinal study across the 2021–2022 season in the English Championship. Methods: Twenty-three outfield football players had workload measured using global positioning system (Distance, High-Intensity Distance and Sprint Distance) and perceived exertion. Load-response was measured via a perceived wellbeing questionnaire, counter-movement jump (CMJ) and salivary immunoglobulin A. Results: General estimating equation models identified 18 significant interactions between workload and load-response markers. Thirteen significant interactions were found between acute and chronic workloads and CMJ variables, jump height, eccentric duration and flight contraction time. A poor CMJ was observed when acute sprint workload was >+1 standard deviation and chronic distance increased. However, when chronic perceived exertion increased, and acute sprint workload was >+1 standard deviation an advantageous response was detected on counter movement jump variables. The S-IgA response to acute and chronic workload was more variable; when chronic loads were >+1 standard deviation above mean values and acute workload increased, salivary immunoglobulin A was both suppressed and elevated depending on the interacting acute variable. Higher chronic workload was associated with better perceived wellbeing, even when acute workload was >+1 standard deviation above the mean. Conclusion: In general, low chronic workloads and acute spikes in workload were associated with poorer neuromuscular and immune function. Furthermore, CMJ performance and perceived wellbeing improved when chronic workloads were higher, despite the occurrence of acute spikes in workload. Full article
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15 pages, 1113 KiB  
Article
Reactivity of Z-3-Hexenal with Amino Groups Provides a Potential Mechanism for Its Direct Effects on Insect Herbivores
by Jurgen Engelberth and Marie Engelberth
Insects 2025, 16(6), 582; https://doi.org/10.3390/insects16060582 - 31 May 2025
Viewed by 515
Abstract
Green leaf volatiles (GLV) have been shown in the past to significantly affect herbivore performance in plants by activating direct and indirect defense measures. At the same time, insect herbivores have developed multiple mechanisms to reduce the quantities of Z-3-hexenal, the first product [...] Read more.
Green leaf volatiles (GLV) have been shown in the past to significantly affect herbivore performance in plants by activating direct and indirect defense measures. At the same time, insect herbivores have developed multiple mechanisms to reduce the quantities of Z-3-hexenal, the first product of the pathway. Among the various measures is the abundance of a molecule named hexenal trapping molecule (HALT), which appears to bind large quantities of freshly produced Z-3-hexenal (Z3al). Functional groups like -NH2 within HALT may be responsible for the binding of Z3al. To test for this potential interaction, we tested different amino acids in various binding assays for their capacity to bind Z3al. We found a significant reduction in Z3al production in the presence of these amino acids, presumably through Schiff base formation. In a feeding assay with beet armyworm (Spodoptera exigua), we found a significant impact of a Z3al- or E2al-spiked artificial diet on growth and development. Together, these data indicate that the presence of Z3al in a diet can harm insect herbivores, which may help to further explain the efforts insect herbivores undertake to suppress the biosynthesis of this compound. Full article
(This article belongs to the Collection Plant Responses to Insect Herbivores)
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14 pages, 1835 KiB  
Article
Dual Mechanisms of the Diazepine-Benzimidazole Derivative, DAB-19, in Modulating Glutamatergic Neurotransmission
by Maxim V. Nikolaev, Irina M. Fedorova, Oxana V. Chistyakova, Tatiana Yu. Postnikova, Kira Kh. Kim, Mikhail Yu. Dron, Aleksey V. Zaitsev and Denis B. Tikhonov
Int. J. Mol. Sci. 2025, 26(11), 5299; https://doi.org/10.3390/ijms26115299 - 30 May 2025
Viewed by 519
Abstract
The search for novel compounds with anticonvulsant properties remains a key focus in neuropharmacology. Recently, the diazepine-benzimidazole derivative, DAB-19, has emerged as a promising candidate due to its demonstrated anxiolytic and analgesic effects. In this study, we investigate the mechanisms underlying DAB-19’s activity, [...] Read more.
The search for novel compounds with anticonvulsant properties remains a key focus in neuropharmacology. Recently, the diazepine-benzimidazole derivative, DAB-19, has emerged as a promising candidate due to its demonstrated anxiolytic and analgesic effects. In this study, we investigate the mechanisms underlying DAB-19’s activity, focusing on its impact on glutamatergic transmission, a key target in the pathophysiology of various central nervous system disorders. Intriguingly, while DAB-19 suppressed evoked glutamatergic transmission in rat brain slices, it simultaneously enhanced spontaneous neurotransmission. Further experiments on glutamatergic neuromuscular synapses in fly larvae revealed two distinct mechanisms: calcium-dependent potentiation of glutamate release and inhibition of spike propagation via blockade of voltage-gated sodium channels. The latter effect was directly confirmed in rat brain neurons. Given its action on sodium channels, we tested DAB-19 in the pentylenetetrazole model, where it delayed seizure onset but did not prevent seizures. These findings position DAB-19 as a multifaceted compound with significant therapeutic potential. Full article
(This article belongs to the Special Issue Epilepsy: From Molecular Basis to Therapy, 2nd Edition)
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18 pages, 1091 KiB  
Article
SARS-CoV-2 Antibodies in Response to COVID-19 Vaccination in Underserved Racial/Ethnic Minority People Living with HIV
by Yongjun Huang, Haley R. Fonseca, Leonardo Acuna, Wensong Wu, Xuexia Wang, Samantha Gonzales, Manuel Barbieri, David R. Brown and Marianna K. Baum
Vaccines 2025, 13(5), 517; https://doi.org/10.3390/vaccines13050517 - 13 May 2025
Viewed by 753
Abstract
Background: Understanding immune response is essential for preparing for public health crises. COVID-19 vaccination provides robust immunity against SARS-CoV-2, but immunocompromised populations may have weaker immune responses. We assessed SARS-CoV-2 spike (trimer) total IgG/IgM/IgA (total Ig) to investigate immune response to COVID-19 [...] Read more.
Background: Understanding immune response is essential for preparing for public health crises. COVID-19 vaccination provides robust immunity against SARS-CoV-2, but immunocompromised populations may have weaker immune responses. We assessed SARS-CoV-2 spike (trimer) total IgG/IgM/IgA (total Ig) to investigate immune response to COVID-19 vaccination in people living with HIV (PLWH), considering CD4+ T cell count, viral load, substance use, and comorbidities. Methods: This cross-sectional study was conducted in Miami, Florida, between May 2021 and December 2021 as part of the NIH Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative (3U01DA040381-05S1) and the Miami Adult Studies on HIV (MASH) cohort (U01DA040381). Blood samples were collected and SARS-CoV-2 spike (trimer) total Ig was quantified. HIV serostatus, viral load, CD4+ T cell count, and COVID-19 vaccinations were abstracted from medical records. Substance use (tobacco, alcohol, and drug use [marijuana, cocaine, heroin, fentanyl, methamphetamine, amphetamine, hallucinogens, ecstasy, or misuse of prescription drugs]), and comorbidities (hypertension, diabetes, autoimmune disease, obesity, chronic kidney disease, and substance use disorders) were assessed via validated questionnaires. Drug use was confirmed via urine toxicology. Multivariable linear regression was conducted. Results: Median age (n = 1317) was 57.8 years, 49.8% were male, 50% were Black non-Hispanic, 66.2% had received ≥1 dose of a COVID-19 vaccine, and 29.6% were PLWH (71.3% virally suppressed and median CD4+ T cell count > 500 cells/µL). PLWH, compared to people without HIV, were more likely to have received ≥1 dose of a COVID-19 vaccine (76.2% vs. 62.0%, p < 0.001) and present with substance use (77.2% vs. 42.9%, p < 0.001) and comorbidities (72.8% vs. 48.2%, p < 0.001). Vaccinated PLWH, compared to unvaccinated PLWH, had higher CD4+ T cell counts (577.5 vs. 517.5, p = 0.011) and were more likely to be virally suppressed (76.4% vs. 54.8%, p < 0.001). A lower CD4+ T cell count (<200 vs. ≥500, β = −0.400, p = 0.033) and higher HIV viral load (≥200–<5000 vs. <200, β = −0.275, p < 0.001) were associated with lower spike (trimer) total Ig titers, indicating a diminished response to COVID-19 vaccination. Conclusions: A lower CD4+ T cell count and higher HIV viremia were linked to reduced SARS-CoV-2 immunogenicity in racial/ethnic minority PLWH, a population underrepresented in vaccine clinical trials. HIV care providers should target efforts to maintain viral suppression to avoid diminished responses to COVID-19 vaccination. Full article
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15 pages, 6274 KiB  
Article
Research on the Speckle Effect Suppression Technology of a Laser Vibrometer Based on the Dual-Wavelength Detection Principle
by Xiangyi Jin, Yangyi Shen, Yahao Wang, Xinxin Kong and Wenxi Zhang
Appl. Sci. 2025, 15(9), 4858; https://doi.org/10.3390/app15094858 - 27 Apr 2025
Viewed by 488
Abstract
Laser vibrometers are known for their high precision, long-range capabilities, and non-contact measurement characteristics. However, in long-range applications, spike noise often arises, primarily due to the laser speckle effect induced by rough targets. To address this challenge, this paper develops a light field [...] Read more.
Laser vibrometers are known for their high precision, long-range capabilities, and non-contact measurement characteristics. However, in long-range applications, spike noise often arises, primarily due to the laser speckle effect induced by rough targets. To address this challenge, this paper develops a light field transmission model for laser vibrometers. By exploiting the differences in speckle patterns formed by lasers of different wavelengths on the same rough target, a dual-wavelength laser vibrometry technique utilizing wavelength division multiplexing devices is proposed, along with a dual-channel signal enhancement method based on orthogonal demodulation. This approach effectively reduces the likelihood of spike noise and enhances the system’s velocity measurement resolution. The experimental results demonstrate that, compared to the single-wavelength system, the dual-wavelength system significantly suppresses laser speckle noise, mitigates measurement spike noise, and improves the stability of micro-vibration measurements. Additionally, the system’s velocity resolution improves from 0.165 μm/s/Hz1/2 in the single-wavelength system to 0.122 μm/s/Hz1/2 in the dual-wavelength system, thereby enhancing the system’s sensitivity to micro-vibrations. In engineering applications, the dual-wavelength approach provides higher stability and resolution for micro-vibration signal measurements. Full article
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20 pages, 6141 KiB  
Article
Optimization of Snubber Circuit Parameters for AC–AC Chopper Converter
by Zhenyu Shi, Liyang Wei, Jinlong He, Gang Li and Chunwei Song
Electronics 2025, 14(9), 1733; https://doi.org/10.3390/electronics14091733 - 24 Apr 2025
Viewed by 520
Abstract
The AC-AC chopper converter, as a direct power conversion device without DC intermediate stages, has garnered significant attention due to its advantages of high efficiency and fast dynamic response. However, the voltage spikes induced by switching device turn-off transients (reaching 143% of the [...] Read more.
The AC-AC chopper converter, as a direct power conversion device without DC intermediate stages, has garnered significant attention due to its advantages of high efficiency and fast dynamic response. However, the voltage spikes induced by switching device turn-off transients (reaching 143% of the reference voltage) severely threaten system reliability, while traditional RC snubber circuit parameter design methods (e.g., empirical formula-based approaches) exhibit limited suppression effectiveness. To address this issue, this paper proposes an optimized parameter design method for RC snubber circuits in AC-AC chopper converters by establishing a turn-off transient energy transfer model to optimize snubber resistor and capacitor parameters. Experimental results from the prototype based on the TMS320F28335 digital controller demonstrate that the optimized method suppresses voltage spikes to <10% and, even under a 40% step load variation from the nominal value, maintains output voltage fluctuations stably below 5%. Full article
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17 pages, 3167 KiB  
Article
Research on a Three-Phase Digital Inverter Power Supply Based on Gallium Nitride
by Yannan Yu, Xiao Zhu and Jichi Yan
Electronics 2025, 14(8), 1599; https://doi.org/10.3390/electronics14081599 - 15 Apr 2025
Viewed by 476
Abstract
In this study, GaN devices are implemented in low-power three-phase inverters to achieve high-frequency operation and a compact design. A 500 W power-rated prototype operating at a switching frequency of 200 kHz was designed. A linear active disturbance rejection control (LADRC) strategy was [...] Read more.
In this study, GaN devices are implemented in low-power three-phase inverters to achieve high-frequency operation and a compact design. A 500 W power-rated prototype operating at a switching frequency of 200 kHz was designed. A linear active disturbance rejection control (LADRC) strategy was introduced to solve the issue of high-frequency inverter oscillation. Additionally, the driving circuit was optimized to address the issue of voltage spikes in the drive voltage. Subsequently, the feasibility and effectiveness of the control strategy were validated through a system simulation model built in Simulink. Lastly, a digital control algorithm was developed by leveraging the capabilities of DSP28034. During testing at an operating frequency of 200 kHz, it was found that the drive voltage waveform was excellent and that the three-phase inverter output remained stable, with no signs of oscillation. The implemented design effectively suppresses peak drive voltage levels, demonstrating optimized gate drive circuitry performance. The output waveform of three-phase inverter proves the effectiveness of the control strategy. Full article
(This article belongs to the Section Power Electronics)
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26 pages, 2312 KiB  
Article
Impact of SARS-CoV-2 Wuhan and Omicron Variant Proteins on Type I Interferon Response
by Marija Janevska, Evelien Naessens and Bruno Verhasselt
Viruses 2025, 17(4), 569; https://doi.org/10.3390/v17040569 - 15 Apr 2025
Viewed by 932
Abstract
SARS-CoV-2 has demonstrated a remarkable capacity for immune evasion. While initial studies focused on the Wuhan variant and adaptive immunity, later emerging strains such as Omicron exhibit mutations that may alter their immune-modulatory properties. We performed a comprehensive review of immune evasion mechanisms [...] Read more.
SARS-CoV-2 has demonstrated a remarkable capacity for immune evasion. While initial studies focused on the Wuhan variant and adaptive immunity, later emerging strains such as Omicron exhibit mutations that may alter their immune-modulatory properties. We performed a comprehensive review of immune evasion mechanisms associated with SARS-CoV-2 viral proteins to focus on the evolutionary dynamics of immune modulation. We systematically analyzed and compared the impact of all currently known Wuhan and Omicron SARS-CoV-2 proteins on type I interferon (IFN) responses using a dual-luciferase reporter assay carrying an interferon-inducible promoter. Results revealed that Nsp1, Nsp5, Nsp14, and ORF6 are potent type I IFN inhibitors conserved across Wuhan and Omicron strains. Notably, we identified strain-specific differences, with Nsp6 and Spike proteins exhibiting enhanced IFN suppression in Omicron, whereas the Envelope protein largely retained this function. To extend these findings, we investigated selected proteins in primary human endothelial cells and also observed strain-specific differences in immune response with higher type I IFN response in cells expressing the Wuhan strain variant, suggesting that Omicron’s adaptational mutations may contribute to a damped type I IFN response in the course of the pandemic’s trajectory. Full article
(This article belongs to the Section Coronaviruses)
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14 pages, 2245 KiB  
Article
Vasoactive Intestinal Peptide (VIP) in COVID-19 Therapy—Shedding of ACE2 and TMPRSS2 via ADAM10
by Charlotte Gutzler, Kerstin Höhne, Daniele Bani, Gian Kayser, Sebastian Fähndrich, Michael Ambros, Martin J. Hug, Siegbert Rieg, Valeria Falcone, Joachim Müller-Quernheim, Gernot Zissel and Björn C. Frye
Int. J. Mol. Sci. 2025, 26(6), 2666; https://doi.org/10.3390/ijms26062666 - 16 Mar 2025
Viewed by 957
Abstract
Patients infected with SARS-CoV-2 may develop mild respiratory symptoms but also Acute Respiratory Distress Syndrome (ARDS). Additionally, severe systemic inflammation contributes to morbidity and mortality. The SARS-CoV-2 virus enters the cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, followed by cleavage [...] Read more.
Patients infected with SARS-CoV-2 may develop mild respiratory symptoms but also Acute Respiratory Distress Syndrome (ARDS). Additionally, severe systemic inflammation contributes to morbidity and mortality. The SARS-CoV-2 virus enters the cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, followed by cleavage by transmembrane serine protease 2 (TMPRSS2). Vasoactive intestinal peptide (VIP) is known for its immune-modulating effects by suppressing the release of pro-inflammatory cytokines and enhancing regulatory T-cells. Furthermore, it has been tested in SARS-CoV-2-related clinical trials. We set out to investigate its role in the setting of SARS-CoV-2 infection in vitro. Epithelial cells (CaCo-2) were stimulated with SARS-CoV-2 spike protein, treated with native VIP and analyzed to investigate the mRNA and surface expression of ACE2 and TMPRSS2, the enzyme activity of TMPRSS2 and the infection rate by a SARS-CoV-2 pseudovirus. VIP downregulated ACE2 and TMPRSS2 mRNA and surface expression. Beyond these direct effects, VIP mediates the shedding of surface-expressed ACE2 and TMPRSS2 via upregulation of a sheddase protease (ADAM10). Functionally, these dual mechanisms of VIP-mediated downregulation of proteins involved in SARS-CoV-2 cell entry resulted in a reduced infection rate by the SARS-CoV-2 pseudovirus. These data imply that VIP hampers viral entry mechanisms based on SARS-CoV-2 and the linkage to ADAM10 may stimulate research in other indications beyond SARS-CoV-2. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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12 pages, 1622 KiB  
Article
Rapid Sterilization of Clinical Apheresis Blood Products Using Ultra-High Dose Rate Radiation
by Stavros Melemenidis, Khoa D. Nguyen, Rosella Baraceros-Pineda, Cherie K. Barclay, Joanne Bautista, Hubert D. Lau, M. Ramish Ashraf, Rakesh Manjappa, Suparna Dutt, Luis A. Soto, Nikita Katila, Brianna Lau, Vignesh Viswanathan, Amy S. Yu, Murat Surucu, Lawrie B. Skinner, Edgar G. Engleman, Billy W. Loo and Tho D. Pham
Int. J. Mol. Sci. 2025, 26(6), 2424; https://doi.org/10.3390/ijms26062424 - 7 Mar 2025
Viewed by 914
Abstract
Blood products, including apheresis platelets and plasma, are essential for medical use but pose risks of bacterial contamination and viral transmission. Platelets are prone to bacterial growth due to their storage conditions, while plasma requires extensive screening. This study explores rapid irradiation as [...] Read more.
Blood products, including apheresis platelets and plasma, are essential for medical use but pose risks of bacterial contamination and viral transmission. Platelets are prone to bacterial growth due to their storage conditions, while plasma requires extensive screening. This study explores rapid irradiation as an innovative pathogen reduction method. A clinical linear accelerator was configured to deliver ultra-high dose rate (6 kGy/min) irradiation to platelet and plasma components. Platelets spiked with Escherichia coli (E. coli; 10⁵ colony-forming units) were irradiated at 0.1–20 kGy, followed by bacterial growth and platelet count analysis. COVID-19 convalescent plasma (CCP) was irradiated at 25 kGy, and receptor-binding domain (RBD)-specific immunoglobulins (Ig) were assessed. Irradiation at 1 kGy reduced E. coli growth by 2.7-log without significant platelet loss, while 5 kGy achieved complete suppression. The estimated 6-log bacterial reduction dose (2.3 kGy) led to a 31% platelet count drop. Administering a 25 kGy virus-sterilizing dose to CCP resulted in a 9.2% decrease in RBD-specific IgG binding. This study demonstrates the proof-of-concept for rapid blood sterilization using a clinical linear accelerator. The method maintains platelet counts and CCP antibody binding at sterilizing doses, highlighting its potential as a point-of-care blood product sterilization solution. Full article
(This article belongs to the Section Biochemistry)
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