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10 pages, 1191 KiB  
Article
RNA Sequencing on Muscle Biopsies from Exertional Rhabdomyolysis Patients Revealed Down-Regulation of Mitochondrial Function and Enhancement of Extracellular Matrix Composition
by Mingqiang Ren, Luke P. Michaelson, Ognoon Mungunsukh, Peter Bedocs, Liam Friel, Kristen Cofer, Carolyn E. Dartt, Nyamkhishig Sambuughin and Francis G. O’Connor
Genes 2025, 16(8), 930; https://doi.org/10.3390/genes16080930 (registering DOI) - 2 Aug 2025
Abstract
Background/Objective: Exertional rhabdomyolysis (ER) is primarily driven by mechanical stress on muscles during strenuous or unaccustomed exercise, often exacerbated by environmental factors like heat and dehydration. While the general cellular pathway involving energy depletion and calcium overload is understood in horse ER models, [...] Read more.
Background/Objective: Exertional rhabdomyolysis (ER) is primarily driven by mechanical stress on muscles during strenuous or unaccustomed exercise, often exacerbated by environmental factors like heat and dehydration. While the general cellular pathway involving energy depletion and calcium overload is understood in horse ER models, the underlying mechanisms specific to the ER are not universally known within humans. This study aimed to evaluate whether patients with ER exhibited transcriptional signatures that were significantly different from those of healthy individuals. Methods: This study utilized RNA sequencing on skeletal muscle samples from 19 human patients with ER history, collected at a minimum of six months after the most recent ER event, and eight healthy controls to investigate the transcriptomic landscape of ER. To identify any alterations in biological processes between the case and control groups, functional pathway analyses were conducted. Results: Functional pathway enrichment analyses of differentially expressed genes revealed strong suppression of mitochondrial function. This suppression included the “aerobic electron transport chain” and “oxidative phosphorylation” pathways, indicating impaired energy production. Conversely, there was an upregulation of genes associated with adhesion and extracellular matrix-related pathways, indicating active restoration of muscle function in ER cases. Conclusions: The study demonstrated that muscle tissue exhibited signs of suppressed mitochondrial function and increased extracellular matrix development. Both of these facilitate muscle recovery within several months after an ER episode. Full article
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16 pages, 2407 KiB  
Article
Transcriptional Analysis of Spodoptera frugiperda Sf9 Cells Infected with Daphnis nerii Cypovirus-23
by Wendong Kuang, Jian Yang, Jinchang Wang, Chenghua Yan, Junhui Chen, Xinsheng Liu, Chunhua Yang, Zhigao Zhan, Limei Guan, Jianghuai Li, Tao Deng, Feiying Yang, Guangqiang Ma and Liang Jin
Int. J. Mol. Sci. 2025, 26(15), 7487; https://doi.org/10.3390/ijms26157487 (registering DOI) - 2 Aug 2025
Abstract
Daphnis nerii cypovirus-23 (DnCPV-23) is a new type of cypovirus that has a lethal effect on many species of Sphingidae pests. DnCPV-23 can replicate in Spodoptera frugiperda Sf9 cells, but the replication characteristics of the virus in this cell line are still unclear. [...] Read more.
Daphnis nerii cypovirus-23 (DnCPV-23) is a new type of cypovirus that has a lethal effect on many species of Sphingidae pests. DnCPV-23 can replicate in Spodoptera frugiperda Sf9 cells, but the replication characteristics of the virus in this cell line are still unclear. To determine the replication characteristics of DnCPV-23 in Sf9 cells, uninfected Sf9 cells and Sf9 cells at 24 and 72 h after DnCPV-23 infection were collected for transcriptome analysis. Compared to uninfected Sf9 cells, a total of 188 and 595 differentially expressed genes (DEGs) were identified in Sf9 cells collected at 24 hpi and 72 h, respectively. KEGG analyses revealed that 139 common DEGs in two treatment groups were related to nutrition and energy metabolism-related processes, cell membrane integrity and function-related pathways, detoxification-related pathways, growth and development-related pathways, and so on. We speculated that these cellular processes might be manipulated by viruses to promote replication. This study provides an important basis for further in-depth research on the mechanism of interaction between viruses and hosts. It provides additional basic information for the future exploitation of DnCPV-23 as a biological insecticide. Full article
21 pages, 3686 KiB  
Article
Genome-Wide Analyses of the XTH Gene Family in Brachypodium distachyon and Functional Analyses of the Role of BdXTH27 in Root Elongation
by Hongyan Shen, Qiuping Tan, Wenzhe Zhao, Mengdan Zhang, Cunhao Qin, Zhaobing Liu, Xinsheng Wang, Sendi An, Hailong An and Hongyu Wu
Int. J. Mol. Sci. 2025, 26(15), 7457; https://doi.org/10.3390/ijms26157457 (registering DOI) - 1 Aug 2025
Abstract
Xyloglucan endotransglucosylase/hydrolases (XTHs) are a class of cell wall-associated enzymes involved in the construction and remodeling of cellulose/xyloglucan crosslinks. However, knowledge of this gene family in the model monocot Brachypodium distachyon is limited. A total of 29 BdXTH genes were identified from the [...] Read more.
Xyloglucan endotransglucosylase/hydrolases (XTHs) are a class of cell wall-associated enzymes involved in the construction and remodeling of cellulose/xyloglucan crosslinks. However, knowledge of this gene family in the model monocot Brachypodium distachyon is limited. A total of 29 BdXTH genes were identified from the whole genome, and these were further divided into three subgroups (Group I/II, Group III, and the Ancestral Group) through evolutionary analysis. Gene structure and protein motif analyses indicate that closely clustered BdXTH genes are relatively conserved within each group. A highly conserved amino acid domain (DEIDFEFLG) responsible for catalytic activity was identified in all BdXTH proteins. We detected three pairs of segmentally duplicated BdXTH genes and five groups of tandemly duplicated BdXTH genes, which played vital roles in the expansion of the BdXTH gene family. Cis-elements related to hormones, growth, and abiotic stress responses were identified in the promoters of each BdXTH gene, and when roots were treated with two abiotic stresses (salinity and drought) and four plant hormones (IAA, auxin; GA3, gibberellin; ABA, abscisic acid; and BR, brassinolide), the expression levels of many BdXTH genes changed significantly. Transcriptional analyses of the BdXTH genes in 38 tissue samples from the publicly available RNA-seq data indicated that most BdXTH genes have distinct expression patterns in different tissues and at different growth stages. Overexpressing the BdXTH27 gene in Brachypodium led to reduced root length in transgenic plants, which exhibited higher cellulose levels but lower hemicellulose levels compared to wild-type plants. Our results provide valuable information for further elucidation of the biological functions of BdXTH genes in the model grass B. distachyon. Full article
(This article belongs to the Section Molecular Plant Sciences)
22 pages, 7156 KiB  
Communication
Water Management, Environmental Challenges, and Rehabilitation Strategies in the Khyargas Lake–Zavkhan River Basin, Western Mongolia: A Case Study of Ereen Lake
by Tseren Ochir Soyol-Erdene, Ganbat Munguntsetseg, Zambuu Burmaa, Ulziibat Bilguun, Shagijav Oyungerel, Soninkhishig Nergui, Nyam-Osor Nandintsetseg, Michael Walther and Ulrich Kamp
Geographies 2025, 5(3), 38; https://doi.org/10.3390/geographies5030038 (registering DOI) - 1 Aug 2025
Abstract
The depletion of water resources caused by climate change and human activities is a pressing global issue. Lake Ereen is one of the ten natural landmarks of the Gobi-Altai of western Mongolia is included in the list of “important areas for birds” recognized [...] Read more.
The depletion of water resources caused by climate change and human activities is a pressing global issue. Lake Ereen is one of the ten natural landmarks of the Gobi-Altai of western Mongolia is included in the list of “important areas for birds” recognized by the international organization Birdlife. However, the construction of the Taishir Hydroelectric Power Station, aimed at supplying electricity to the western provinces of Mongolia, had a detrimental effect on the flow of the Zavkhan River, resulting in a drying-up and pollution of Lake Ereen, which relies on the river as its water source. This study assesses the pollution levels in Ereen Lake and determines the feasibility of its rehabilitation by redirecting the flow of the Zavkhan River. Field studies included the analysis of water quality, sediment contamination, and the composition of flora. The results show that the concentrations of ammonium, chlorine, fluorine, and sulfate in the lake water exceed the permissible levels set by the Mongolian standard. Analyses of elements from sediments revealed elevated levels of arsenic, chromium, and copper, exceeding international sediment quality guidelines and posing risks to biological organisms. Furthermore, several species of diatoms indicative of polluted water were discovered. Lake Ereen is currently in a eutrophic state and, based on a water quality index (WQI) of 49.4, also in a “polluted” state. Mass balance calculations and box model analysis determined the period of pollutant replacement for two restoration options: drying-up and complete removal of contaminated sediments and plants vs. dilution-flushing without direct interventions in the lake. We recommend the latter being the most efficient, eco-friendly, and cost-effective approach to rehabilitate Lake Ereen. Full article
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17 pages, 5553 KiB  
Article
Effects of Interspecific Competition on Habitat Shifts of Sardinops melanostictus (Temminck et Schlegel, 1846) and Scomber japonicus (Houttuyn, 1782) in the Northwest Pacific
by Siyuan Liu, Hanji Zhu, Jianhua Wang, Famou Zhang, Shengmao Zhang and Heng Zhang
Biology 2025, 14(8), 968; https://doi.org/10.3390/biology14080968 (registering DOI) - 1 Aug 2025
Abstract
As economically important sympatric species in the Northwest Pacific, the Japanese sardine (Sardinops melanostictus) and Chub mackerel (Scomber japonicus) exhibit significant biological interactions. Understanding the impact of interspecies competition on their habitat dynamics can provide crucial insights for the [...] Read more.
As economically important sympatric species in the Northwest Pacific, the Japanese sardine (Sardinops melanostictus) and Chub mackerel (Scomber japonicus) exhibit significant biological interactions. Understanding the impact of interspecies competition on their habitat dynamics can provide crucial insights for the sustainable development and management of these interconnected species resources. This study utilizes fisheries data of S. melanostictus and S. japonicus from the Northwest Pacific, collected from June to November between 2017 and 2020. We integrated various environmental parameters, including temperature at different depths (0, 50, 100, 150, and 200 m), eddy kinetic energy (EKE), sea surface height (SSH), chlorophyll-a concentration (Chl-a), and the oceanic Niño index (ONI), to construct interspecific competition species distribution model (icSDM) for both species. We validated these models by overlaying the predicted habitats with fisheries data from 2021 and performing cross-validation to assess the models’ reliability. Furthermore, we conducted correlation analyses of the habitats of these two species to evaluate the impact of interspecies relationships on their habitat dynamics. The results indicate that, compared to single-species habitat models, the interspecific competition species distribution model (icSDM) for these two species exhibit a significantly higher explanatory power, with R2 values increasing by up to 0.29; interspecific competition significantly influences the habitat dynamics of S. melanostictus and S. japonicus, strengthening the correlation between their habitat changes. This relationship exhibits a positive correlation at specific stages, with the highest correlations observed in June, July, and October, at 0.81, 0.80, and 0.88, respectively; interspecific competition also demonstrates stage-specific differences in its impact on the habitat dynamics of S. melanostictus and S. japonicus, with the most pronounced differences occurring in August and November. Compared to S. melanostictus, interspecific competition is more beneficial for the expansion of the optimal habitat (HIS ≥ 0.6) for S. japonicus and, to some extent, inhibits the habitat expansion of S. melanostictus. The variation in migratory routes and predatory interactions (with larger individuals of S. japonicus preying on smaller individuals of S. melanostictus) likely constitutes the primary factors contributing to these observed differences. Full article
(This article belongs to the Special Issue Adaptation of Living Species to Environmental Stress)
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29 pages, 3958 KiB  
Article
Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy
by Somaiyeh Azmoun, Freeman C. Lewis, Daniel Shoieb, Yan Jin, Elena Colicino, Isha Mhatre-Winters, Haiwei Gu, Hari Krishnamurthy, Jason R. Richardson, Donatella Placidi, Luca Lambertini and Roberto G. Lucchini
Brain Sci. 2025, 15(8), 829; https://doi.org/10.3390/brainsci15080829 (registering DOI) - 31 Jul 2025
Abstract
Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on [...] Read more.
Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m3 (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article
(This article belongs to the Special Issue From Bench to Bedside: Motor–Cognitive Interactions—2nd Edition)
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42 pages, 3564 KiB  
Review
A Review on Sustainable Upcycling of Plastic Waste Through Depolymerization into High-Value Monomer
by Ramkumar Vanaraj, Subburayan Manickavasagam Suresh Kumar, Seong Cheol Kim and Madhappan Santhamoorthy
Processes 2025, 13(8), 2431; https://doi.org/10.3390/pr13082431 - 31 Jul 2025
Viewed by 3
Abstract
Plastic waste accumulation is one of the most pressing environmental challenges of the 21st century, owing to the widespread use of synthetic polymers and the limitations of conventional recycling methods. Among available strategies, chemical upcycling via depolymerization has emerged as a promising circular [...] Read more.
Plastic waste accumulation is one of the most pressing environmental challenges of the 21st century, owing to the widespread use of synthetic polymers and the limitations of conventional recycling methods. Among available strategies, chemical upcycling via depolymerization has emerged as a promising circular approach that converts plastic waste back into valuable monomers and chemical feedstocks. This article provides an in-depth narrative review of recent progress in the upcycling of major plastic types such as PET, PU, PS, and engineering plastics through thermal, chemical, catalytic, biological, and mechanochemical depolymerization methods. Each method is critically assessed in terms of efficiency, scalability, energy input, and environmental impact. Special attention is given to innovative catalyst systems, such as microsized MgO/SiO2 and Co/CaO composites, and emerging enzymatic systems like engineered PETases and whole-cell biocatalysts that enable low-temperature, selective depolymerization. Furthermore, the conversion pathways of depolymerized products into high-purity monomers such as BHET, TPA, vanillin, and bisphenols are discussed with supporting case studies. The review also examines life cycle assessment (LCA) data, techno-economic analyses, and policy frameworks supporting the adoption of depolymerization-based recycling systems. Collectively, this work outlines the technical viability and sustainability benefits of depolymerization as a core pillar of plastic circularity and monomer recovery, offering a path forward for high-value material recirculation and waste minimization. Full article
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24 pages, 1117 KiB  
Article
Comparative Analysis of Pesticide Residues in Hive Products from Rapeseed (Brassica napus subsp. napus) and Sunflower (Helianthus annuus) Crops Under Varying Agricultural Practices in Romania During the 2020–2021 Beekeeping Seasons
by Dan Bodescu, Viorel Fătu, Agripina Şapcaliu, Elena Luiza Bădic, Roxana Zaharia, Dana Tăpăloagă, Alexandru-Dragoș Robu and Radu-Adrian Moraru
Agriculture 2025, 15(15), 1648; https://doi.org/10.3390/agriculture15151648 - 31 Jul 2025
Viewed by 34
Abstract
Over the past years, increasing attention has been drawn to the adverse effects of agricultural pesticide use on pollinators, with honeybees being especially vulnerable. The aim of this study was to evaluate the levels of residues detectable and/or quantifiable of neonicotinoid pesticides and [...] Read more.
Over the past years, increasing attention has been drawn to the adverse effects of agricultural pesticide use on pollinators, with honeybees being especially vulnerable. The aim of this study was to evaluate the levels of residues detectable and/or quantifiable of neonicotinoid pesticides and other pesticides in biological materials (bees, bee brood, etc.) and beehive products (honey, pollen, etc.) applied as seed dressings in rapeseed and sunflower plants in two growing seasons (2020–2021) in fields located in three agro-climatic regions in Romania. The study involved the comparative sampling of hive products (honey, pollen, adult bees, and brood) from experimental and control apiaries, followed by pesticide residue analysis in an accredited laboratory (Primoris) using validated chromatographic techniques (LC-MS/MS and GC-MS). Toxicological analyses of 96 samples, including bees, bee brood, honey, and pollen, confirmed the presence of residues in 46 samples, including 10 bee samples, 10 bee brood samples, 18 honey samples, and 8 pollen bread samples. The mean pesticide residue concentrations detected in hive products were 0.032 mg/kg in honey, 0.061 mg/kg in pollen, 0.167 mg/kg in bees, and 0.371 mg/kg in bee brood. The results highlight the exposure of honeybee colonies to multiple sources of pesticide residue contamination, under conditions where legal recommendations for the controlled application of agricultural treatments are not followed. The study provides relevant evidence for strengthening the risk assessment framework and underscores the need for adopting stricter monitoring and regulatory measures to ensure the protection of honeybee colony health. Full article
(This article belongs to the Section Agricultural Product Quality and Safety)
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31 pages, 638 KiB  
Systematic Review
Exploring the Autistic Brain: A Systematic Review of Diffusion Tensor Imaging Studies on Neural Connectivity in Autism Spectrum Disorder
by Giuseppe Marano, Georgios D. Kotzalidis, Maria Benedetta Anesini, Sara Barbonetti, Sara Rossi, Miriam Milintenda, Antonio Restaino, Mariateresa Acanfora, Gianandrea Traversi, Giorgio Veneziani, Maria Picilli, Tommaso Callovini, Carlo Lai, Eugenio Maria Mercuri, Gabriele Sani and Marianna Mazza
Brain Sci. 2025, 15(8), 824; https://doi.org/10.3390/brainsci15080824 (registering DOI) - 31 Jul 2025
Viewed by 41
Abstract
Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article
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14 pages, 3747 KiB  
Article
Biocontrol Activity of Volatile Organic Compounds Emitted from Bacillus paralicheniformis 2-12 Against Fusarium oxysporum Associated with Astragalus membranaceus Root Rot
by Yan Wang, Jiaqi Yuan, Rui Zhao, Shengnan Yuan, Yaxin Su, Wenhui Jiao, Xinyu Huo, Meiqin Wang, Weixin Fan and Chunwei Wang
Microorganisms 2025, 13(8), 1782; https://doi.org/10.3390/microorganisms13081782 - 31 Jul 2025
Viewed by 192
Abstract
Root rot, mainly caused by Fusarium oxysporum, is one of the most destructive diseases and leads to significant economic loss of Astragalus membranaceus. To develop an effective strategy for the management of this serious disease, a bacterial strain 2-12 was screened [...] Read more.
Root rot, mainly caused by Fusarium oxysporum, is one of the most destructive diseases and leads to significant economic loss of Astragalus membranaceus. To develop an effective strategy for the management of this serious disease, a bacterial strain 2-12 was screened from A. membranaceus rhizosphere soil and identified as Bacillus paralicheniformis based on the phylogenetic analyses of gyrase subunit B gene (gyrB) and RNA polymerase gene (rpoB) sequences. Interestingly, the volatile organic compounds (VOCs) produced by B. paralicheniformis 2-12 exhibited potent antifungal activities against F. oxysporum, as well as fifteen other plant pathogens. Under scanning electron microscopy observation, hyphae treated with the VOCs exhibited abnormal variation such as distortion, twist, and vesiculation, leading to distinctive protoplasm shrinkage. After treatment with B. paralicheniformis 2-12 VOCs, the lesion diameter and disease incidence both reduced significantly compared to control (p < 0.05), thus demonstrating prominent biological efficiency. Moreover, B. paralicheniformis 2-12 VOCs were composed of 17 VOCs, including 9 alkanes, 3 alcohols, 3 acids and esters, 1 aromatic compound, and 1 alkyne compound. A total of 1945 DEGs, including 1001 up-regulated and 944 down-regulated genes, were screened via transcriptome analysis. These DEGs were mainly associated with membranes and membrane parts, amino acid metabolism, and lipid metabolism. The findings in this work strongly suggested that B. paralicheniformis 2-12 VOCs could be applied as a new candidate for the control of A. membranaceus root rot. Full article
(This article belongs to the Section Microbial Biotechnology)
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14 pages, 290 KiB  
Article
Patterns of Reverse Transcriptase Inhibitor Resistance Mutations in People Living with Human Immunodeficiency Virus in Libreville, Gabon
by Guy Francis Nzengui-Nzengui, Gaël Mourembou, Euloge Ibinga, Ayawa Claudine Kombila-Koumavor, Hervé M’boyis-Kamdem, Edmery Muriel Mpouho-Ntsougha, Alain Mombo-Mombo and Angélique Ndjoyi-Mbiguino
Trop. Med. Infect. Dis. 2025, 10(8), 216; https://doi.org/10.3390/tropicalmed10080216 - 30 Jul 2025
Viewed by 166
Abstract
Objective: To characterize the profiles of resistance mutations to HIV reverse transcriptase inhibitors in Gabon. Design: Cross-sectional study conducted over 37 months, from October 2019 to October 2022, at the IST/HIV/AIDS Reference Laboratory, a reference center for the biological monitoring of people living [...] Read more.
Objective: To characterize the profiles of resistance mutations to HIV reverse transcriptase inhibitors in Gabon. Design: Cross-sectional study conducted over 37 months, from October 2019 to October 2022, at the IST/HIV/AIDS Reference Laboratory, a reference center for the biological monitoring of people living with the human immunodeficiency virus (PWHIV) in Gabon. Methods: Plasma from 666 PWHIV receiving antiretroviral treatment was collected, followed by RNA extraction, amplification, and reverse transcriptase gene sequencing. Statistical analyses were performed using Stata® 14.0 software (USA). Results: Six hundred and sixty-six (666) PWHIV plasma collected from 252 male and 414 female patients were analyzed and 1654 mutations were detected in 388 patients, including 849 (51.3%) associated with nucleoside reverse transcriptase inhibitors (NRTIs) and 805 (48.7%) with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Three of the most prescribed treatment regimens were associated to the appearance of both NRTIs and NNRTIs resistance mutations: TDF + 3TC + EFV (24.02%; 160/666); TDF + FTC + EFV) (17.2%; 114/666) and AZT + 3TC + EFV (14.6%; 97/666). Additionally, stage 3 of CD4 T-lymphocyte deficiency, the higher viral load, and treatment duration are risk factors influencing the appearance of virus mutations. Also, treatment containing TDF-3TC + DTG is more protective against mutations. Conclusions: Drug resistance mutations are common in Gabon and compromise the efficacy of ART. Further study must search for other causes of therapeutic failure in Gabon in PWHIV. Full article
(This article belongs to the Special Issue HIV Testing, Prevention and Care Interventions, 2nd Edition)
20 pages, 8914 KiB  
Article
Assessment of Low-Dose rhBMP-2 and Vacuum Plasma Treatments on Titanium Implants for Osseointegration and Bone Regeneration
by Won-Tak Cho, Soon Chul Heo, Hyung Joon Kim, Seong Soo Kang, Se Eun Kim, Jong-Ho Lee, Gang-Ho Bae and Jung-Bo Huh
Materials 2025, 18(15), 3582; https://doi.org/10.3390/ma18153582 (registering DOI) - 30 Jul 2025
Viewed by 140
Abstract
This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated [...] Read more.
This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated that plasma treatment increased surface energy, promoting cell adhesion and proliferation. Additionally, it facilitated sustained rhBMP-2 release by enhancing protein binding to the implant surface. In vivo experiments using the four-beagle mandibular defect model were conducted with the following four groups: un-treated implants, rhBMP-2–coated implants, plasma-treated implants, and implants treated with both rhBMP-2 and plasma. Micro-computed tomography (micro-CT) and medical CT analyses revealed a significantly greater volume of newly formed bone in the combined treatment group (p < 0.05). Histological evaluation further confirmed superior outcomes in the combined group, showing significantly higher bone-to-implant contact (BIC), new bone area (NBA), and inter-thread bone density (ITBD) compared to the other groups (p < 0.05). These findings indicate that vacuum plasma treatment enhances the biological efficacy of low-dose rhBMP-2, representing a promising strategy to improve implant integration in compromised conditions. Further studies are warranted to determine the optimal clinical dosage. Full article
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9 pages, 2757 KiB  
Article
Externally Triggered Activation of Nanostructure-Masked Cell-Penetrating Peptides
by Gayong Shim
Molecules 2025, 30(15), 3205; https://doi.org/10.3390/molecules30153205 - 30 Jul 2025
Viewed by 161
Abstract
Cell-penetrating peptides offer a promising strategy for intracellular delivery; however, non-specific uptake and off-target cytotoxicity limit their clinical utility. To address these limitations, a cold atmospheric plasma-responsive delivery platform was developed in which the membrane activity of a peptide was transiently suppressed upon [...] Read more.
Cell-penetrating peptides offer a promising strategy for intracellular delivery; however, non-specific uptake and off-target cytotoxicity limit their clinical utility. To address these limitations, a cold atmospheric plasma-responsive delivery platform was developed in which the membrane activity of a peptide was transiently suppressed upon complexation with a DNA-based nanostructure. Upon localized plasma exposure, DNA masking was disrupted, restoring the biological functions of the peptides. Transmission electron microscopy revealed that the synthesized DNA nanoflower structures were approximately 150–250 nm in size. Structural and functional analyses confirmed that the system remained inert under physiological conditions and was rapidly activated by plasma treatment. Fluorescence recovery, cellular uptake assays, and cytotoxicity measurements demonstrated that the peptide activity could be precisely controlled in both monolayer and three-dimensional spheroid models. This externally activatable nanomaterial-based system enables the spatial and temporal regulation of peptide function without requiring biochemical triggers or permanent chemical modifications. This platform provides a modular strategy for the development of potential peptide therapeutics that require precise control of activation in complex biological environments. Full article
(This article belongs to the Special Issue Nanomaterials for Advanced Biomedical Applications, 2nd Edition)
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12 pages, 402 KiB  
Article
SBRT in the Very Elderly: A Viable Option for Pulmonary Oligometastases?
by Samuel M. Vorbach, Meinhard Nevinny-Stickel, Ute Ganswindt and Thomas Seppi
Cancers 2025, 17(15), 2512; https://doi.org/10.3390/cancers17152512 - 30 Jul 2025
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Abstract
Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in [...] Read more.
Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in clinical analyses. This study aimed to evaluate clinical outcomes and toxicity of SBRT for pulmonary oligometastases in octogenarians. Methods: This retrospective, single-centre analysis included 34 patients aged ≥ 80 years treated with SBRT for histologically confirmed pulmonary oligometastases between 2010 and 2024. Results: A total of 46 pulmonary metastases were treated with curative intent using fractionation schemes of 3 × 15 Gy, 6 × 8 Gy, or 10 × 6 Gy. Median biologically effective dose (BED10) was 112.5 Gy. Follow-up included regular CT imaging and toxicity assessment according to CTCAE. With a median follow-up of 22.6 months, 1-, 2-, and 3-year local control (LC) rates were 95.2%, 95.2%, and 90.2%, respectively. Median overall survival (OS) was 46.6 months, with 1-, 2-, and 3-year OS rates of 78.4%, 71.4%, and 59.5%. Progression-free survival (PFS) at 1, 2, and 3 years was 63.4%, 51.6%, and 47.3%, respectively. No grade ≥ 3 toxicities were observed. Grade 2 pneumonitis and dermatitis occurred in 2.9% each and were well managed. Asymptomatic rib fractures were detected in 5.9% of patients. No significant predictors for LC, PFS, or OS were identified in univariate analysis. Conclusions: SBRT for pulmonary oligometastases in patients ≥ 80 years is feasible, safe, and effective. High local control, favourable cancer-specific survival, and minimal toxicity support its use as a curative-intent treatment in this growing patient population. These findings contribute important site- and age-specific evidence and support the inclusion of very elderly patients in future prospective SBRT trials. Full article
(This article belongs to the Special Issue Treatment Outcomes in Older Adults with Cancer)
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Article
Sex-Specific Differences in Antidepressant and Antipsychotic Treatment Outcomes and Serum Levels in Children and Adolescents
by Maike Scherf-Clavel, Stefanie Fekete, Manfred Gerlach, Christoph U. Correll, Paul Plener, Jörg M. Fegert, Andreas Karwautz, Peter Heuschmann, Tobias Banaschewski, Wolfgang Briegel, Christian Fleischhaker, Tobias Hellenschmidt, Hartmut Imgart, Michael Kaess, Michael Kölch, Karl Reitzle, Tobias J. Renner, Christian Rexroth, Gerd Schulte-Körne, Frank Theisen, Susanne Walitza, Christoph Wewetzer, Franca Keicher, Stefan Unterecker, Sebastian Walther, Marcel Romanos, Karin M. Egberts, Timo Vloet and Regina Taurinesadd Show full author list remove Hide full author list
Pharmaceutics 2025, 17(8), 983; https://doi.org/10.3390/pharmaceutics17080983 - 30 Jul 2025
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Abstract
Introduction: Sex-specific differences in psychopharmacological treatment have gained increasing attention in adults, with studies showing that women often have higher serum concentrations of psychotropic drugs due to biological differences. However, despite recognition of these differences in adults, reference ranges for therapeutic drug monitoring [...] Read more.
Introduction: Sex-specific differences in psychopharmacological treatment have gained increasing attention in adults, with studies showing that women often have higher serum concentrations of psychotropic drugs due to biological differences. However, despite recognition of these differences in adults, reference ranges for therapeutic drug monitoring (TDM) in general, but even more sex-specific therapeutic windows for psychotropic drugs, are lacking in children and adolescents, who may metabolize and respond to medications differently. Aim: The study aimed to investigate sex-specific differences in antidepressant (AD) and antipsychotic (AP) -treatment outcomes, and pharmacokinetics in childhood/adolescence. In particular, we examined differences in AD and AP serum levels and clinical effects, including adverse drug effects (ADEs) and therapeutic effectiveness. Methods: This study is part of the multicenter “TDM-VIGIL” pharmacovigilance project, which prospectively followed patients aged 6–18 years treated with AD and AP across 18 child psychiatric centers in German-speaking countries from 2014 to 2018. Clinical data, including drug concentrations (AD: fluoxetine, mirtazapine, (es)citalopram, sertraline; AP: aripiprazole, quetiapine, olanzapine, risperidone), were collected using an internet-based registry, and treatment outcomes and ADEs were assessed during routine visits. Statistical analyses were performed to examine sex differences in pharmacokinetics and clinical responses, adjusting for age, weight, and other confounders. Results: A total of 705 patients (66.5% girls, 24.7% <14 years, mean age of 14.6 years) were included. Female patients were slightly older, had lower body weight, and were more often diagnosed with depression and anorexia nervosa, while boys were more frequently diagnosed with hyperkinetic disorders and atypical autism. We found no sex differences in the serum concentrations of investigated drugs when adjusted for age and weight. In fluoxetine treatment in patients diagnosed with mood (affective) disorders, female sex was associated with the probability for very good therapy response (p = 0.04), as well as with moderate treatment response (p = 0.02) compared to no treatment response. Discussion: Our findings suggest that sex may not affect serum levels of investigated AD and AP in children/adolescents. However, treatment outcome of fluoxetine was associated with sex, with higher probability for a better outcome in female patients diagnosed with mood (affective) disorders. Full article
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