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2025
AbstractReactive oxygen species (ROS) of hosts are widely involved in intracellular signaling and against pathogens. Viruses manipulate ROS homeostasis of hosts as a strategy to evade ROS‐mediated negative effects of their infection, but the mechanisms remain unclear. The economically important aquaculture shrimp, Litopenaeus vannamei, is selected to investigate the molecular mechanism of how white spot syndrome virus (WSSV) regulates ROS dynamics and enhances viral replication. WSSV protein wsv220 binds to the repressor of shrimp nuclear factor erythroid 2‐related factor 2 (LvNrf2), called Kelch‐like ECH‐associated protein 1 (LvKeap1), disrupting LvNrf2/LvKeap1 complex and facilitating LvNrf2 nuclear translocation. This activation of LvNrf2 causes up‐regulation of antioxidant genes, including glucose‐6‐phosphate dehydrogenase (LvG6PDH), which increases nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) production, effectively eliminating excessive ROS. Moreover, WSSV exploits LvNrf2 to establish a positive feedback loop by up‐regulating viral immediate early gene wsv051, which further enhances wsv220 expression. Knockdown of LvNrf2 or LvG6PDH reduces WSSV replication and increases host ROS levels. Therefore, WSSV hijacks LvNrf2 pathway to maintain ROS homeostasis and establishes a positive feedback loop to facilitate WSSV replication. These findings reveal a novel molecular mechanism of viral manipulation of host ROS dynamics and suggest potential antiviral strategies targeting LvNrf2 pathway.- Book : ()
- Pub. Date : 2025
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2025
AbstractInnovation in synthesis methodologies is crucial for advancing the discovery of new materials. This work reports the electrosynthesis of a [Au13(4‐tBuPhC≡C)2(Dppe)5]Cl3 nanocluster (Au13 NC) protected by alkynyl and phosphine ligands. From simple precursor, HAuCl4 and ligands, the whole synthesis is driven by a constant potential in single electrolytic cell. X‐ray crystallography determines its total structure. Control experiments, cyclic voltammetry, Proton Nuclear Magnetic Resonance (1H NMR), gas chromatography, and other characterizations demonstrate that a critical tetranuclear Au(I) complex defines the electrochemical redox behavior of the reaction solution. The critical role of a base (e.g., triethylamine) is to suppress the hydrogen evolution reaction at the cathode, paving the way for the reduction of Au ions. To resolve the problem of over‐reduction and deposition of Au on the cathode, pulsed electrolysis, which is specific to electrosynthesis is employed. It significantly improves the reaction rate and the isolated yield of Au13. To extend the application scope, another four NCs protected by different ligands, [Au13(4‐FPhC≡C)2(Dppe)5]Cl3, [Au8(2‐CF3PhC≡C)2(Dppp)4](PF6)2, [Au11(Dppp)5]Cl3, and [Au8(SC2H4Ph)2(Dppp)4]Cl2 are synthesized electrochemically, demonstrating the versatility of the strategy.- Book : ()
- Pub. Date : 2025
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2025
Background: Glutathione (GSH) is an essential antioxidant that protects against oxidative stress, but its oral bioavailability is below 1% due to enzymatic degradation and poor gastrointestinal absorption. Improving the oral bioavailability of GSH could significantly enhance its therapeutic efficacy. Methods: This study synthesised GSH analogues with chemical modifications to improve bioavailability. Seven GSH derivatives were designed: three analogues with altered stereochemistry (1.62, 1.63, and 1.64) and three N-methylated derivatives (1.65, 1.70, and 1.71), alongside a native GSH (1.61). The analogues were synthesised via Fmoc-solid-phase peptide synthesis, and they were characterised using reverse-phase high-performance liquid chromatography (RP-HPLC), electrospray ionisation mass spectrometry (ESI-MS), Fourier-transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR) spectroscopy. Their toxicity was assessed on Caco-2 cells for viability, and their antioxidant activity was assessed on UVA-irradiated fibroblast cells, enzymatic resistance, and interactions with GSH-metabolising enzymes. Results: Among the tested analogues, the N-methylated cysteine Compound (1.70) emerged as the most promising candidate. Compound 1.70 demonstrated superior resistance to enzymatic degradation, as well as showing enhanced cell viability and improved antioxidant activity. In vivo studies revealed a 16.8-fold increase in plasma half-life (t½) and a 16.1-fold increase in oral bioavailability compared to native GSH. Conclusions: Chemical modification strategies, particularly the N-methylation of GSH, present a viable approach to enhancing oral bioavailability. Compound 1.70 showed significant potential for therapeutic applications, warranting further investigation and development in clinical settings.- Book : 17(3)
- Pub. Date : 2025
- Page : pp.385-385
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2025
The mechano-responsiveness of osteocytes is critical for maintaining bone health and associated with a reduced oxidative stress defense, yet the precise molecular mechanisms remain incompletely understood. Here, we address the gap by investigating the epigenetic reprogramming that drives osteocyte responses to mechanical loading. We found overall remodeling of antioxidant response under mechanical loading and identified NRF2, a key transcription factor in oxidative stress response, which plays a vital role in the epigenetic remodeling of osteocytes. The results showed that mechanical loading enhanced NRF2 protein stability, promoted its nuclear translocation, and activated osteocyte-specific transcriptional programs. In contrast, pharmacological stabilization of NRF2 failed to fully replicate these effects, underscoring the unique role of mechanical stimuli in modulating NRF2 activity and antioxidant function. Our findings highlight the potential therapeutic limitations of NRF2-stabilizing drugs and suggest that combining pharmacological approaches with mechanical interventions could offer more effective treatments to maintain oxidative homeostasis.- Book : 14(3)
- Pub. Date : 2025
- Page : pp.346-346
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2025
Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterised by multiorgan pathological histiocytic infiltration. Cardiac involvement occurs in 40–75% of patients and increases mortality. A 55-year-old woman with chest pain and dyspnoea was found to have an interatrial septal mass and aortitis suspicious for ECD without other organ involvement. After two inadequate transcatheter interatrial biopsies were obtained using ultrasound guidance alone, diagnostic samples were successfully obtained using intraprocedural frozen section examination. The patient started genotype-targeted treatment with good response. Biopsy confirmation of ECD is required to guide treatment; however, cardiac biopsies are uncommonly performed when other organs are affected. Our unique case of isolated cardiovascular involvement highlights how frozen sectioning with multimodal intraprocedural imaging guidance can improve diagnostic yield of endomyocardial biopsies. It also highlights how diagnosis of rare conditions requires careful multidisciplinary evaluation of affected organs, procedural risk and diagnostic yield. The use of frozen sectioning can improve diagnostic yield of endomyocardial biopsies.- Book : 20()
- Pub. Date : 2025
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2025
Abstract
Background
While canonical anabolic and proteolytic pathways have been well examined in the context of skeletal muscle proteostasis, the roles of endoplasmic reticulum stress (ERS) and the induced unfolded protein response (UPR) are underappreciated. Thus, we aimed to determine whether aging and/or disuse atrophy in rats altered skeletal muscle ERS/UPR markers.
Methods and Results
Soleus (SOL) and plantaris (PLT) muscles of 3-month-old (mo), 6 mo, 12 mo, 18 mo, and 24 mo rats (9–10 per group, 48 in total) were analyzed for UPR proteins with further analysis performed on the protein CHOP. The gastrocnemius muscles of 4 mo rats that had undergone hindlimb immobilization (HLI, n = 12) or sham casting (CTL, n = 12) were analyzed for similar targets as well as more extensive CHOP-related targets. CHOP protein was greater in the PLT and SOL of 18 and 24 mo rats versus other age groups (P < 0.05). Moreover, negative correlations existed between CHOP expression and normalized PLT (R=-0.702, P < 0.001) and SOL (R=-0.658, P < 0.001) muscle weights in all rats analyzed at different ages. CHOP protein expression was also greater in the gastrocnemius of HLI versus CTL rats (P < 0.001), and a negative correlation existed between CHOP protein expression and normalized muscle weights in these rats (R=-0.814, P < 0.001). Nuclear CHOP protein levels (P < 0.010) and genes transcriptionally regulated by CHOP were also greater in HLI versus CTL rats (P < 0.001) implicating transcriptional activity of CHOP is elevated during disuse atrophy.
Conclusions
CHOP is operative during aging- and disuse-induced skeletal muscle atrophy in rodents, and more research is needed to determine if CHOP is a key mechanistic driver of these processes.
- Book : 52(1)
- Pub. Date : 2025
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2025
ABSTRACTThis paper presents a 4 4 millimeter‐wave (mm‐wave) phased array antenna operating in the Ka‐band (27–34 GHz) fabricated using low‐temperature co‐fired ceramic (LTCC) technology. The proposed array employs several innovative design features to achieve superior performance. An oversized aperture, combined with a parasitic patch and an embedded air cavity, significantly enhances the gain and bandwidth. Additionally, an asymmetric stripline feed structure minimises back radiation and facilitates multi‐layer integration, enabling seamless compatibility with beamforming systems. The antenna demonstrates a measured impedance bandwidth of 27% and a realised gain of 17.5 dBi at 29 GHz, with a scanning angle of . These results establish the design as a compact, high‐efficiency, and broadband solution for mm‐wave phased array applications in 5G and beyond. Experimental validation using a 16‐channel beamformer module further highlights the practicality of the design for real‐world deployment.- Book : 19(1)
- Pub. Date : 2025
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2025
Abstract
Purpose
To compare cone-beam computed tomography (CBCT) with photon-counting detector computed tomography (PCD-CT) at equivalent radiation doses, focusing on qualitative and quantitative parameters relevant to dental implant surgery.
Methods
This ex vivo comparative study of porcine specimens assessed five imaging protocols with both CBCT and PCD-CT at three effective radiation dose levels (high: 360µSv, standard: 145µSv, low: 20µSv) to evaluate image quality, artifact burden, metal artifact susceptibility, and quantitative bone measurements in the mandibular region. Three blinded readers analyzed the data using a 5-point Likert scale (5 = highest to 1 = lowest rating) and performed linear bone measurements at implant planning sites. Statistical analysis included descriptive statistics and inter-reader reliability assessment using intraclass correlation coefficients (ICC).
Results
Each reader evaluated 30 data sets (12 CBCT, 18 PCD-CT), with 24 implant planning sites per imaging protocol. High-dose PCD-CT demonstrated the best image quality and diagnostic interpretability (4.89 ± 0.27), followed by standard-dose PCD-CT and CBCT (4.50 ± 0.73; 4.33 ± 0.61), with low-dose protocols showing intermediate quality with higher artifact burden. In comparison to CBCT, PCD-CT demonstrated superior performance in reducing implant-induced artifacts across all protocols. Quantitative bone measurements showed minimal variability, meeting clinical precision requirements for computer-assisted implant surgery. Both qualitative (ICCs:0.70–0.89; p < 0.001) and quantitative (ICCs:0.79–1; p < 0.001) analyses demonstrated high reliability, regardless of the reader’s experience.
Conclusions
PCD-CT demonstrated superior image quality and reduced artifacts compared with CBCT at all radiation dose levels. These findings highlight PCD-CT’s potential to enhance implant planning and improve clinical outcomes with reduced radiation exposure while maintaining diagnostic accuracy.
- Book : 11(1)
- Pub. Date : 2025
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2025
Kefir, a traditional probiotic beverage with significant cultural, social, and health relevance, has garnered increasing scientific interest for its functional properties. Here, we synthesized findings from 14 studies investigating the bacterial and fungal diversity in artisanal cow’s milk kefir through metagenomic analysis. Following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), a comprehensive search was conducted in databases including Portal BVS, Scopus, Scielo, and Web of Science. From an initial pool of 522 articles, 14 were selected based on stringent inclusion and exclusion criteria, focusing on English-written studies. Key terms such as “kefir milk”, “artisanal kefir”, “milk”, “metagenomics”, and “cow” were identified through Boolean searches over the last five years. This review addresses the growing need for research on the microbial diversity of artisanal cow’s milk kefir from various global regions. The results indicate a remarkable diversity in microbial communities, primarily dominated by bacteria from the phylum Firmicutes (notably Lactobacillus) and yeasts from the genera Saccharomyces and Kluyveromyces. These microbial compositions are shaped by factors such as milk type, production methods, and grain handling practices, reflecting regional adaptations and influencing kefir’s sensory, probiotic, and functional properties. We argue that a full understanding of these microbial dynamics is critical for standardizing production processes and enhancing quality control measures, ultimately ensuring artisanal kefir’s consistency and health benefits.- Book : 11(3)
- Pub. Date : 2025
- Page : pp.150-150
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2025
ABSTRACTBackgroundIntraductal papillomas of the breast (IDPs) are typically small benign lesions characterized by pathologic discharge, a palpable mass, or an occult presentation. Giant IDPs (> 5 cm) are a rare entity. The few existing cases of giant IDPs describe grossly apparent exam findings and concerning features on imaging. While surgical excision is the standard of care for most IDPs, there is a scarcity of evidence to guide management of giant papillary tumors.CaseWe describe a case of a 64‐year‐old female presenting with pathologic nipple discharge and no discrete palpable breast mass who was routinely diagnosed with ductal carcinoma in situ (DCIS). Imaging findings of mass calcifications and intraductal mass debris correlated with biopsy results, and the patient underwent central lumpectomy with oncoplastic reconstruction. At the time of surgery, the DCIS was incidentally found to be contained within a large solitary papilloma. The specimen pathology showed DCIS spanning a large area in a multifocal pattern that involved a 7 cm giant intraductal papilloma. Though margins were negative for malignancy, the benign papillary lesion was incompletely excised. A multidisciplinary review opted to pursue whole breast radiation therapy followed by adjuvant endocrine treatment over re‐excision.ConclusionThis unusual case highlights the potential for giant IDP to remain clinically occult in the background of known ductal carcinoma in situ and emphasizes the value of multidisciplinary care discussion and a patient‐centered approach to surgical decision making in the absence of existing guidelines.- Book : 8(3)
- Pub. Date : 2025
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