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17 pages, 17746 KB  
Article
Dual-Tracer Autoradiography and Positron Emission Tomography (PET) Scans Using In-Yolk-Sac Tracer Delivery in the Chicken Chorioallantoic Membrane (CAM) Tumor Model
by Emil L. Villumsen, Signe Bauenmand, Marie B. Thuesen, Mikkel H. Vendelbo, Lars Thrane, Jörg Männer, Niels Bassler, Michael R. Horsman, Michael Pedersen and Morten Busk
Biomedicines 2026, 14(7), 1515; https://doi.org/10.3390/biomedicines14071515 - 6 Jul 2026
Viewed by 65
Abstract
Background: Routine use of the chorioallantoic membrane (CAM) tumor model in nuclear imaging studies is hampered by small tumors, embryonic movements and laborious volume-restricted intravenous tracer/drug administration. We sought a workaround by using fast-growing tumors, high-resolution autoradiography and non-intravenous tracer administration. Methods [...] Read more.
Background: Routine use of the chorioallantoic membrane (CAM) tumor model in nuclear imaging studies is hampered by small tumors, embryonic movements and laborious volume-restricted intravenous tracer/drug administration. We sought a workaround by using fast-growing tumors, high-resolution autoradiography and non-intravenous tracer administration. Methods: Dekalb White chicken eggs were grafted with C3H mammary carcinoma fragments or MOC2 oral squamous cell carcinoma fragments from donor mice. The tumor uptake of 18F-fluorodeoxyglucose (FDG) following in-yolk-sac injection, dripping after CAM scoring or allantoic cavity injection was evaluated using positron emission tomography (PET) and autoradiography. Using in-yolk-sac injection, eggs were administered different tracer mixtures, namely (1) pimonidazole (hypoxia-marker), FDG and 14C-2-deoxyglucose (14C-2DG), (2) pimonidazole, FDG and 14C-acetate or (3) pimonidazole, the hypoxia-selective tracer 18F-fluoroazomycin-arabinoside (FAZA) and 14C-2DG. For comparison, tumor-bearing mice were administered FDG/14C-acetate/pimonidazole. Gross tumor uptake was evaluated using PET. Tumor cryosections were analyzed using dual-tracer autoradiography. Complementary autoradiograms were co-registered, covered by a square grid (0.5 × 0.5 mm). Pearson correlation coefficients (PCC) were calculated from scatterplots. Results: C3H tumors reached a mean weight (with 95% confidence interval) of 0.32 g (0.28–0.37 g), while for MOC2, it was 0.19 g (0.09–0.29 g). In-yolk-sac tracer injection was simple and effective, producing high tracer uptake and contrast 3 h post-administration. Spatial tracer overlap (PCC) was: FDG vs. 14C-2DG, 0.95–0.97; FAZA vs. 14C-2DG, 0.71–0.79 and FDG vs. 14C-acetate, 0.26–0.84 (0.15–0.76 in mice). Pimonidazole revealed tumor hypoxia. Conclusions: Direct-grafting from donor mice generated larger tumors than previously reported. In-yolk-sac tracer administration was practical and allowed larger injected volumes. Autoradiography revealed that: (1) FDG and 14C-2DG can be used interchangeably, (2) 14C-2DG was elevated in FAZA-positive areas, suggesting that in some tumors FDG-PET may provide information on the intratumoral distribution of hypoxic areas, and (3) FDG and 14C-acetate showed variable overlap. We conclude that in-yolk-sac tracer injection and autoradiography simplify and optimize CAM-based nuclear imaging research. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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21 pages, 3206 KB  
Article
Induction of Salt Stress Tolerance in Strawberries Using a Chitosan–Maltodextrin System
by Judith Isabel Torres-de la Cruz, Eneida Adilene Pérez-Velasco, Aida Isabel Leal-Robles and Alonso Méndez-López
Polysaccharides 2026, 7(3), 80; https://doi.org/10.3390/polysaccharides7030080 - 3 Jul 2026
Viewed by 177
Abstract
Salinity is a major abiotic constraint limiting strawberry (Fragaria × ananassa) productivity by disrupting water relations, nutrient uptake, and photosynthetic processes. Biopolymer-based biostimulants have emerged as a sustainable strategy to enhance crop performance under stress conditions. The objective of this study [...] Read more.
Salinity is a major abiotic constraint limiting strawberry (Fragaria × ananassa) productivity by disrupting water relations, nutrient uptake, and photosynthetic processes. Biopolymer-based biostimulants have emerged as a sustainable strategy to enhance crop performance under stress conditions. The objective of this study was to evaluate the effect of a chitosan–maltodextrin (CHTMD) formulation on growth, physiological response, and fruit quality in strawberry plants under saline conditions at the Universidad Autonoma Agraria Antonio Narro in Saltillo, Mexico. A randomized complete block design with a 2 × 4 factorial arrangement was established, including two salinity levels (0 and 45 mM NaCl) and four CHTMD concentrations (0, 250, 500, and 1000 mg L−1). The application of CHTMD significantly mitigated the adverse effects of salinity and improved plant growth, biomass accumulation, gas exchange, yield, and fruit quality. Under saline conditions, 250 mg L−1 increased total fresh weight by 148.5% compared with the saline control, while root length increased by up to 58.5% under non-saline conditions. Yield was enhanced by 87.3% and 71.4% with 250 and 1000 mg L−1, respectively, whereas fruit number increased by up to 63.8% under salinity. Photosynthetic rate increased from 12.58 to 16.19 μmol CO2 m−2 s−1 and stomatal conductance from 0.235 to 0.325 mol H2O m−2 s−1. Fruit quality was also enhanced, with soluble solids increasing from 5.9 to 7.1 °Brix, vitamin C from 50.58 to 115.42 mg 100 g−1 FW, and total anthocyanins from 65.7 to 106.2 C3G 100 g−1 FW, indicating a substantial enhancement to the fruit’s nutraceutical quality, particularly at 500 mg L−1 and 1000 mg L−1. These findings demonstrate that the CHTMD system is an effective biostimulant capable of improving tolerance to salt stress by modulating key physiological and biochemical responses, as well as enhancing the functional quality of the fruit. This approach represents a promising and sustainable strategy for strawberry production in agricultural systems affected by salinity. Full article
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10 pages, 1402 KB  
Article
Indoxyl Sulfate, a Gut Microbiota-Derived Metabolite, Modulates Hepatic Cholesterol Metabolism via SREBP-2/HMG-CoA Reductase Upregulation in Rats
by Mateusz Szudzik, Mikołaj Zajdel, Anna Laskowska, Tomasz Hutsch and Marcin Ufnal
Nutrients 2026, 18(13), 2160; https://doi.org/10.3390/nu18132160 - 3 Jul 2026
Viewed by 137
Abstract
Background: A high-fat diet (HFD) contributes to cardiometabolic disease. Gut microbiota-derived metabolites may participate in this process, but their contribution to lipid regulation is not well defined. Indoxyl sulfate (IS), a microbiota-derived metabolite, has been linked to vascular and metabolic dysfunction. Its role [...] Read more.
Background: A high-fat diet (HFD) contributes to cardiometabolic disease. Gut microbiota-derived metabolites may participate in this process, but their contribution to lipid regulation is not well defined. Indoxyl sulfate (IS), a microbiota-derived metabolite, has been linked to vascular and metabolic dysfunction. Its role in lipid metabolism remains unclear. Methods: In Part A, plasma and urinary concentrations of IS were measured in plasma and urine from HFD-fed rats in which dyslipidemia had developed, together with controls. In Part B, HepG2 cells were exposed to IS, and cell viability and selected cholesterol metabolism-related transcripts and proteins were assessed. In Part C, 10-week-old, male Sprague–Dawley rats maintained on a standard diet received vehicle or IS at two doses for 8 weeks. Hepatic expression of LDLR, SREBP-2, HMG-CoA reductase, and related cholesterol metabolism markers were measured by quantitative real-time PCR and Western blotting. Results: In Part A, higher plasma IS concentrations and higher daily urinary IS excretion were found in samples collected from HFD-fed rats compared to controls. In HepG2 cells, IS reduced cell viability at higher concentrations and increased LDLR mRNA and protein expression. In IS-treated rats, total cholesterol, LDL-cholesterol, and triglycerides increased in a dose-dependent manner. Hepatic SREBP-2 and HMG-CoA reductase protein levels were increased at both IS doses, whereas LDLR protein abundance was increased at the higher dose. Moreover, serum PCSK9 levels were reduced in IS-treated rats. Conclusion: IS increased in HFD-fed rats. IS altered cholesterol metabolism-related pathways in HepG2 cells and in rats. In vivo IS administration increased circulating lipids and hepatic proteins involved in cholesterol synthesis and uptake. These findings indicate that IS may contribute to disturbed lipid homeostasis, although its role in HFD-induced dyslipidemia requires further mechanistic confirmation. Full article
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21 pages, 2625 KB  
Article
Evaluating Nitrogen Reduction Under Combined Rice Straw Biochar and Milk Vetch Application: A Multi-Objective Assessment of Rice Yield, Grain Quality, and Partial Factor Productivity of Nitrogen Fertilizer in a Double-Rice Cropping System
by Zhijian Xie, Hanghang Wang, Kun Zhang and Ye Lu
Foods 2026, 15(13), 2354; https://doi.org/10.3390/foods15132354 - 2 Jul 2026
Viewed by 179
Abstract
Co-incorporating rice straw biochar (RSB) and milk vetch (MV) is a promising strategy for sustainable rice production. However, the appropriate nitrogen (N) reduction rate under RSB + MV, particularly when balancing multiple production objectives, remains unclear. This study evaluated five N-reduction rates (0–70% [...] Read more.
Co-incorporating rice straw biochar (RSB) and milk vetch (MV) is a promising strategy for sustainable rice production. However, the appropriate nitrogen (N) reduction rate under RSB + MV, particularly when balancing multiple production objectives, remains unclear. This study evaluated five N-reduction rates (0–70% conventional N fertilizer) under RSB + MV. Grain yield, quality, nutrient uptake, and partial factor productivity of N fertilizer (PFPN) were assessed in early and late rice. Entropy-weighted Technique for Order Preference by Similarity to Ideal Solution (EW-TOPSIS) model was used to integrate all indicators, when Gaussian model was applied to estimate the appropriate N-reduction rate. Pearson correlation and random forest analysis identified primary predictors of grain quality. Results showed that appropriate N-reduction (≤30%) under RSB + MV maintained or increased grain yield, quality, and PFPN compared to conventional N fertilization alone. Among all treatments, N80BM and N70BM achieved the highest comprehensive scores in EW-TOPSIS analysis, and Gaussian model-estimated N-reduction of 18.2% and 21.0% for early and late rice, respectively. Nutrient uptake, effective panicle number and filled grains per panicle were identified as primary predictors of grain quality. Therefore, under the tested condition, RSB + MV with 20% N-reduction achieved the highest overall performance. However, these findings require further validation across multiple-year and multi-location. Full article
(This article belongs to the Section Grain)
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18 pages, 1930 KB  
Systematic Review
COACH Study: COVID-19 Influence on Cardiorespiratory Fitness in Athletes—A Systematic Review and Meta-Analysis
by Przemysław Kasiak and Grzegorz Procyk
J. Clin. Med. 2026, 15(13), 5133; https://doi.org/10.3390/jcm15135133 - 1 Jul 2026
Viewed by 266
Abstract
Objectives: We aimed to systematically review and meta-analyze the impact of COVID-19 infection on cardiorespiratory fitness (CRF): (1) within-athlete (the same participants before and after infection), and (2) between-athlete (infected vs. healthy reference participants). Methods: In this systematic review (PROSPERO Registry: [...] Read more.
Objectives: We aimed to systematically review and meta-analyze the impact of COVID-19 infection on cardiorespiratory fitness (CRF): (1) within-athlete (the same participants before and after infection), and (2) between-athlete (infected vs. healthy reference participants). Methods: In this systematic review (PROSPERO Registry: CRD42024540430) we included observational studies enrolling recreational or competitive athletes ≥18 years old with laboratory confirmation of SARS-CoV-2 infection. The primary outcome was change in relative maximal oxygen uptake (VO2max). Secondary outcomes included changes in absolute VO2max, maximal ventilation (VEmax), and maximal heart rate (HRmax). We searched Embase, PubMed, Medline, Scopus, and Web of Science up to August 9th, 2025. Risk of bias was assessed with the JBI critical appraisal tool. Meta-analyses were performed with a random-effects model. Results: Twelve studies enrolling a total of 1595 participants met the eligibility criteria. COVID-19 infection was associated with lower relative VO2max (MD = −1.83 mL·kg−1·min−1; 95%CI [−3.16, −0.49]; p = 0.007; I2 = 54%) and absolute VO2max (MD = −0.15 L·min−1; 95%CI [−0.29, −0.01]; p = 0.03; I2 = 0%). COVID-19 infection was associated with lower VEmax (MD = −7.99 L·min−1; 95%CI [−12.94, −3.04]; p = 0.002; I2 = 0%) but not with HRmax (MD = −0.34 bpm; 95%CI [−1.54, 0.86]; p = 0.58; I2 = 0%). High heterogeneity of included studies was addressed with subgroup analyses. The risk of bias in most studies was high. The certainty of evidence was very low for each outcome. Conclusions: COVID-19 infection in athletes was associated with reduced VO2max and VEmax. The relationships were highly dependent on the quality of the studies. CRF and athlete profile should be considered when making shared decisions regarding safe return to sport after infection. Full article
(This article belongs to the Special Issue Insights and Innovations in Sports Cardiology)
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28 pages, 9038 KB  
Article
Does Metformin Interfere with Cardiorespiratory and Substrate Oxidation Adaptations to Exercise Training in Metabolic Syndrome Patients? A Randomized Placebo-Controlled Trial
by Jabeur Methnani, Amira Moussa, Wissem Dhahbi, Halil İbrahim Ceylan, Ismail Dergaa, Aymen ElHraiech, Taieb Ach, Imed Latiri, Monia Zaouali, Ali Bouslama, Valentina Stefanica, Asma Omezzine and Ezdine Bouhlel
Biomolecules 2026, 16(7), 971; https://doi.org/10.3390/biom16070971 - 1 Jul 2026
Viewed by 554
Abstract
Metformin and aerobic exercise are routinely co-prescribed in the management of metabolic syndrome, yet evidence regarding their interaction on cardiorespiratory fitness and substrate oxidation adaptations remains inconsistent. This study aimed to investigate the effects of combined metformin and aerobic training on peak oxygen [...] Read more.
Metformin and aerobic exercise are routinely co-prescribed in the management of metabolic syndrome, yet evidence regarding their interaction on cardiorespiratory fitness and substrate oxidation adaptations remains inconsistent. This study aimed to investigate the effects of combined metformin and aerobic training on peak oxygen uptake (VO2peak), maximal fat oxidation (MFO), submaximal substrate utilization, and perceived exertion in metformin-naïve adults with metabolic syndrome. In this randomized, placebo-controlled trial, 24 metformin-naïve adults with metabolic syndrome were allocated to receive either metformin (1000 mg/day; MET-EX) or a matched placebo (PLA-EX) combined with supervised aerobic training (5 sessions/week, 60% VO2peak, 500 kcal/session) for five weeks; 22 participants (n = 11 per group) completed the protocol. VO2peak, MFO, fat and carbohydrate oxidation, energy expenditure, and rating of perceived exertion (Borg 6–20) were assessed before and after the intervention. The absolute VO2peak gain was modestly attenuated in MET-EX relative to PLA-EX (group × time interaction p = 0.042; +0.11 vs. +0.26 L·min−1), whereas the interaction for relative VO2peak did not reach significance (p = 0.088). In contrast, MFO increased substantially more in MET-EX than in PLA-EX (+0.13 vs. +0.04 g·min−1; p = 0.001), accompanied by greater fat oxidation, energy expenditure, and perceived exertion during moderate-to-high submaximal exercise intensities. Moreover, VO2peak improvement was negatively correlated with age exclusively in MET-EX (r = −0.87, p < 0.001). These findings suggest that metformin induces a dissociated adaptation profile during aerobic training in metabolic syndrome, characterized by enhanced lipid oxidation alongside attenuated cardiorespiratory adaptations and greater perceived effort, particularly in older individuals. Full article
(This article belongs to the Section Molecular Medicine)
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14 pages, 3941 KB  
Article
Torrefaction as a Strategy for Solid Fuel Production from Wastewater Sludge of the Meat Industry
by Marjana Simonič and Danijela Urbancl
Processes 2026, 14(13), 2143; https://doi.org/10.3390/pr14132143 - 1 Jul 2026
Viewed by 145
Abstract
Waste sludge from the treatment of meat processing wastewater poses significant environmental concerns. This study examines the viability of upgrading two sludge fractions, screenings (S) and flotation sludge (FS), into solid fuel through torrefaction. The materials were thermally treated at temperatures ranging from [...] Read more.
Waste sludge from the treatment of meat processing wastewater poses significant environmental concerns. This study examines the viability of upgrading two sludge fractions, screenings (S) and flotation sludge (FS), into solid fuel through torrefaction. The materials were thermally treated at temperatures ranging from 250 to 450 °C under an inert nitrogen atmosphere. The effects of torrefaction on physicochemical properties, thermal behaviour, and functional group composition were systematically evaluated using proximate analysis, higher heating value (HHV) determination, thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). The results indicate that increasing torrefaction temperature leads to a substantial enhancement in mass loss due to progressive devolatilization. Concurrently, there is a reduction in moisture uptake and an improvement in hydrophobicity. Proximate analysis revealed a decrease in volatile matter (35% for FS and 31% for S) and a corresponding increase in fixed carbon (from 0.46 to 1.80% for FS and from 6.43 to 20.60% for S). The S fraction demonstrated a better fuel ratio (1.27%) compared to the FS one (0.06%), indicating more favourable fuel properties. TGA results demonstrated improved thermal stability of torrefied samples. FTIR analysis confirmed the progressive removal of polar functional groups (O–H, C=O, N–O) and the formation of more carbon-rich and hydrophobic structures. Torrefaction at temperatures of at least 350 °C effectively upgrades both sludge fractions into more stable and energy-dense materials. The findings indicate that torrefaction is a promising pathway for the valorisation of meat processing wastewater sludge and its conversion into a sustainable solid fuel. Full article
(This article belongs to the Special Issue Advanced Biofuel Production Processes and Technologies)
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27 pages, 14319 KB  
Article
Optimizing Irrigation and Nitrogen Inputs for Balancing Greenhouse Gas Mitigation, Productivity, and Profitability in an Intercropping System of Wolfberry and Alfalfa
by Junkui Jia, Boda Li, Yuanbo Jiang, Huile Lv, Yaya Duan, Yanbiao Wang and Jinxi Chen
Plants 2026, 15(13), 2038; https://doi.org/10.3390/plants15132038 - 1 Jul 2026
Viewed by 175
Abstract
Water and nitrogen management influences farmland productivity and greenhouse gas emissions by regulating the soil micro-environment. However, the synergistic optimization strategy among yield improvement, economic benefit, and emission reduction in intercropping systems in arid regions remains unclear. Based on a two-year field experiment [...] Read more.
Water and nitrogen management influences farmland productivity and greenhouse gas emissions by regulating the soil micro-environment. However, the synergistic optimization strategy among yield improvement, economic benefit, and emission reduction in intercropping systems in arid regions remains unclear. Based on a two-year field experiment using an intercropping system of wolfberry and alfalfa, this study established four irrigation levels [full irrigation (W0), mild water deficit (W1), moderate water deficit (W2), and severe water deficit (W3)] and four nitrogen application levels [0 (N0), 150 (N1), 300 (N2), and 450 kg·ha−1 (N3)]. The effects of water and nitrogen regulation on soil hydrothermal conditions, greenhouse gas emissions, crop yield, and economic benefits were systematically analyzed. The results showed that soil water content increased with higher nitrogen application rates but decreased with a more severe water deficit. In contrast, soil temperature exhibited the opposite trend, with the W3 treatment increasing by 2.23–2.41 °C compared to W0 during the full fruiting period. The emission fluxes of CO2 and N2O increased with higher nitrogen application rates but decreased with a more severe water deficit. CH4 acted as a sink, with its uptake decreasing as nitrogen application increased and the water deficit intensified. CO2 was the dominant contributor to the global warming potential of the intercropping system of wolfberry and alfalfa, accounting for 85.3–94.6% of the total. The emission fluxes of CO2 and N2O were significantly positively correlated with the soil water content, while the CH4 emission flux was significantly positively correlated with the soil temperature. The W0N2 treatment achieved the highest system yield and net profit, whereas the W1N2 treatment exhibited the highest return on investment. A comprehensive evaluation using the entropy weight–TOPSIS model identified W1N2 as the optimal treatment. An integrated water–nitrogen decision model determined that the optimal water and nitrogen combination for achieving a high yield, a high efficiency, and low emissions was an irrigation amount of 4245–4413 m3·ha−1 and a nitrogen application rate of 290–323 kg·ha−1. The findings of this study can provide a scientific basis for the sustainable water and nitrogen management of characteristic cash crop intercropping systems in arid regions. Full article
(This article belongs to the Special Issue Water and Nutrient Management for Sustainable Crop Production)
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23 pages, 768 KB  
Article
Application of Biofertilizers as a Strategy to Reduce P-Mineral Fertilization in the Production of Eucalyptus globulus Labill.
by Paula Alvarenga, Margarida Braguês, Margarida Mota, José Rafael, Amaia Nogales, Henrique Ribeiro and M. Glória Esquível
Forests 2026, 17(7), 780; https://doi.org/10.3390/f17070780 - 30 Jun 2026
Viewed by 162
Abstract
Eucalyptus (Eucalyptus globulus Labill.) plays a fundamental role in the Portuguese forestry sector, highlighting the need for sustainable practices that contribute to maintain soil fertility and biodiversity, without compromising productivity. An experiment was conducted, with a low extractable-P soil (<10 mg P₂O₅ [...] Read more.
Eucalyptus (Eucalyptus globulus Labill.) plays a fundamental role in the Portuguese forestry sector, highlighting the need for sustainable practices that contribute to maintain soil fertility and biodiversity, without compromising productivity. An experiment was conducted, with a low extractable-P soil (<10 mg P₂O₅ kg⁻¹), to evaluate the use of biofertilizers as a strategy to reduce mineral fertilizers dependency. Eucalyptus trees were inoculated at transplantation, with two commercial inoculants based on Glomus iranicum (an arbuscular mycorrhizal fungus, AMF) and inorganic phosphate-solubilizing bacteria (Pseudomonas putida and Pseudomonas fluorescens), under differential P fertilization conditions. Reducing P fertilization to 70% and 40% of the reference dose did not significantly reduce final aboveground biomass, under the studied conditions. Biofertilizer application enhanced soil P availability, particularly when AMF and Pseudomonas were co-inoculated, suggesting synergistic effects on P mobilization and uptake. Plant physiological performance, assessed through vegetation indices, remained stable across treatments, indicating effective acclimation to reduced P supply, while stomatal conductance suggested improved tolerance to P deficiency in Pseudomonas-inoculated plants. The widespread presence of a well-established native mycorrhizal community, which led to a higher root colonization under low P conditions, highlights the importance of plant–microbe interactions in nutrient-limited environments. Overall, these findings underscore the potential of integrating reduced P fertilization with microbial inoculants to improve P use efficiency and support sustainable eucalyptus production. Full article
(This article belongs to the Special Issue Forest Growth, Soil Properties and Climate)
24 pages, 2194 KB  
Review
Advancing Global Hepatitis B Elimination: The Case for Using Maize as a Low-Cost, Heat-Stable, and Scalable Oral Vaccine
by Muneaki Watanabe and John A. Howard
Vaccines 2026, 14(7), 578; https://doi.org/10.3390/vaccines14070578 - 30 Jun 2026
Viewed by 274
Abstract
Because hepatitis B virus (HBV) remains a major global health burden, innovative strategies are essential to achieve the World Health Organization’s goal of eliminating viral hepatitis and closing persistent coverage gaps for injectable vaccines. While parenteral administration remains the gold standard for immunization, [...] Read more.
Because hepatitis B virus (HBV) remains a major global health burden, innovative strategies are essential to achieve the World Health Organization’s goal of eliminating viral hepatitis and closing persistent coverage gaps for injectable vaccines. While parenteral administration remains the gold standard for immunization, constraints such as cold-chain dependence and needle-associated barriers limit its reach, particularly in resource-constrained environments. This review summarizes work aimed at a plant-produced orally delivered vaccine as a transformative, scalable step towards global hepatitis B elimination. Early studies demonstrated proof of concept for the oral delivery of plant-produced hepatitis B vaccine candidates, including human trials using lettuce and potato as the host, but they were limited by low antigen yields and instability. In contrast, maize-produced antigens represent a significant advancement, achieving high levels of accumulation and utilizing the seed’s natural desiccation physiology for bioencapsulation to protect the antigen from digestion in the gastrointestinal tract. Mechanistically, this platform enables timed antigen release in the duodenum, promoting M-cell uptake and CD103+ (cells expressing CD103 known as integrin alpha E) dendritic cell (DC) presentation, thus encouraging immunogenic programming over oral tolerance. In addition, defatting the grain by supercritical fluid extraction further improves antigen thermostability up to 45 °C for one month and ambient temperatures for one year, maintaining structural integrity under extreme conditions in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) stability guidelines. Current recommendations for immunization are for three parenteral administrations using the hepatitis B surface antigen (HBsAg). The primary dose is usually given shortly after birth as a part of a multivalent vaccine. Therefore, initial studies for the oral plant-based vaccine have focused on using an oral boost after the parenteral prime. Data to support this premise are summarized along with co-administration of an oral and parental administration to elicit a stronger immune response. By overcoming past issues related to dose density and stability, this scalable, needle-free platform offers a practical way to eliminate global hepatitis B virus (HBV) transmission, especially in resource-constrained environments. Full article
(This article belongs to the Special Issue Production of Plant-Based Vaccines and Therapeutics)
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17 pages, 18615 KB  
Article
Hollow Mesoporous Silica Nanoparticles Co-Loaded with Docetaxel and Indocyanine Green for Synergistic Chemo–Photothermal Therapy
by Guangru Chu, Kaiyi Zhang, Yaru Wu, Siqi He, Zhongkai Liu, Aijiao Wang, Hongji Wang, Liying Cui, Shengkai Liu, Jin Huang, Jinsong Peng and Zhiguo Liu
Nanomaterials 2026, 16(13), 805; https://doi.org/10.3390/nano16130805 - 30 Jun 2026
Viewed by 263
Abstract
Hollow mesoporous silica nanoparticles (HSNs) were synthesized via the Stöber method using resorcinol–formaldehyde resin as a template and further developed as a multifunctional nanocarrier for synergistic chemo–photothermal therapy. Docetaxel (DTX) and indocyanine green (ICG) were co-loaded into HSNs as the prodrug and photothermal [...] Read more.
Hollow mesoporous silica nanoparticles (HSNs) were synthesized via the Stöber method using resorcinol–formaldehyde resin as a template and further developed as a multifunctional nanocarrier for synergistic chemo–photothermal therapy. Docetaxel (DTX) and indocyanine green (ICG) were co-loaded into HSNs as the prodrug and photothermal agent. The loading sequence of these agents can critically affect encapsulation efficiency. Preloading DTX followed by ICG incorporation achieved the highest drug loading (38.65%) and preserved the photoactivity of ICG. The resulting ICG&DTX@NH2-HSNs exhibited strong and stable near-infrared photothermal conversion, as well as pH- and laser-responsive drug release behavior. In vitro studies confirmed efficient cellular uptake by 4T1 tumor cells and enhanced cytotoxicity compared with single treatments. In vivo experiments demonstrated significant tumor growth suppression in 4T1 tumor-bearing mice, with the greatest effect observed under combined ICG&DTX@NH2-HSNs and laser irradiation. Importantly, histological analysis of major organs revealed no obvious toxicity, confirming the biosafety of the present nanoplatform. This study confirmed the potential of hollow mesoporous silica-based nanocarriers as safe and effective platforms for combined chemotherapy and photothermal cancer therapy. Full article
(This article belongs to the Section Biology and Medicines)
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30 pages, 978 KB  
Article
Assessing Geographic Inequalities in Childhood Immunisation Coverage: A Critical Scoping Review of Spatial Analysis Methods
by Adrien Allorant, Nicole Bergen, M. Carolina Danovaro-Holliday, Joshua Lorin, Gustavo Caetano Corrêa, Danielle Boyda, Johanna Lee Belanger, Ravi Shankar Santhana Gopala Krishnan, Rocco Panciera and Ahmad Reza Hosseinpoor
Vaccines 2026, 14(7), 572; https://doi.org/10.3390/vaccines14070572 - 29 Jun 2026
Viewed by 367
Abstract
Background: Spatial analysis methods, including model-based geostatistics (MBG), small-area estimation (SAE), and cluster detection, are increasingly used to map subnational immunisation coverage and identify geographic inequalities in low- and middle-income countries. However, the extent to which these methods capture the multidimensional determinants of [...] Read more.
Background: Spatial analysis methods, including model-based geostatistics (MBG), small-area estimation (SAE), and cluster detection, are increasingly used to map subnational immunisation coverage and identify geographic inequalities in low- and middle-income countries. However, the extent to which these methods capture the multidimensional determinants of immunisation uptake, and whether their outputs inform programme decisions in practice, remains unclear. Methods: We conducted a critical scoping review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines, systematically searching PubMed and Google Scholar for studies applying spatial statistical methods to childhood immunisation coverage or equity. Findings were synthesised using a combination of descriptive summary and thematic and interpretive synthesis. Results: We included 50 studies from the 421 papers identified. Spatial methods have successfully revealed subnational coverage inequalities that national averages obscure, and studies developed in collaboration with national programme teams, integrating routine health system data alongside household surveys, produced the most operationally relevant outputs. However, most studies relied exclusively on survey data with a limited incorporation of supply-side determinants, and few discussed how uncertainty in estimates should constrain downstream use. Although a growing number of studies articulated clear implementation pathways, confirmed programmatic uptake of spatial outputs remained largely undocumented. The emergence of machine learning approaches (8 of 50 studies) offers predictive gains but introduces additional challenges around transparency and quality assurance for governance use. Conclusions: Spatial methods are becoming more frequently used for immunisation but are more likely to contribute to immunisation equity goals when co-produced with programme teams, matched to decision-relevant geographies, and accompanied by transparent documentation of model assumptions and limitations. Future research should prioritise quality frameworks for algorithm-assisted health estimates and systematic evaluation of whether spatial outputs improve decision-making relative to existing data sources. Full article
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24 pages, 1759 KB  
Review
Arming Inactivated Enveloped Virus Vaccines with the GGTA1 Gene: A Potent Method for Amplification of Viral Vaccines Effectiveness and Protection Against Variants
by Uri Galili
Vaccines 2026, 14(7), 571; https://doi.org/10.3390/vaccines14070571 - 29 Jun 2026
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Abstract
This review describes a novel method for increasing the effectiveness of inactivated enveloped whole-virus vaccines by targeting them for extensive uptake by antigen-presenting cells (APCs). Several inactivated whole-virus vaccines with dense glycan shields display suboptimal effectiveness because the multiple carbohydrate chains (glycans) on [...] Read more.
This review describes a novel method for increasing the effectiveness of inactivated enveloped whole-virus vaccines by targeting them for extensive uptake by antigen-presenting cells (APCs). Several inactivated whole-virus vaccines with dense glycan shields display suboptimal effectiveness because the multiple carbohydrate chains (glycans) on the virus mask immunogenic peptides and surround the virus with a negative electrostatic charge that decreases uptake by APCs. It is postulated that engineering such vaccinating viruses to present the carbohydrate antigen “α-gal epitope” on the glycan shields will immunocomplex them with the anti-Gal antibody; thus, it will target them for robust uptake by APCs. Anti-Gal is an abundant natural antibody in humans, constituting ~1% of human circulating immunoglobulins. The ligand of anti-Gal is the α-gal epitope, which is naturally synthesized in non-primate mammals and New World monkeys by the glycosylation enzyme α1,3galactosyltransferase. This enzyme is encoded by the GGTA1-gene. Viral vaccines presenting multiple α-gal epitopes on their glycan shield bind anti-Gal and activate the complement system to produce complement chemotactic cleavage peptides C5a and C3a that induce extensive recruitment of APCs to vaccine injection sites. The virion-bound anti-Gal further targets the viral vaccine for robust uptake by APCs, following binding of its Fc “tail” to Fcγ-receptors on APCs. The efficacy of this method was studied in anti-Gal-producing mice with α-gal presenting inactivated influenza virus vaccine and with gp120 of HIV presenting this epitope. These studies indicated that virus vaccines engineered to present α-gal epitopes increase anti-virus antibody production and virus-specific T-cell activation by 15- to 100-fold in comparison to the same vaccines lacking α-gal epitopes. It is suggested that α-gal presenting inactivated SARS-CoV-2 virus vaccines can induce a similar protective long-term immune memory against S- M-, E-, and N-viral proteins. Furthermore, immune-escaping variants of the mutated S-protein may be destroyed by antibodies to M and E proteins, and cells infected with such variants may be killed by cytotoxic T cells specific to peptides of the N-protein. Such an anti-M-, E-, and N-protein immune protection may prevent expansion of these variants and thus may avoid the need for immunization with COVID-19 vaccines every 6 months or following the appearance of new variants. A similar potent immunization may be achieved with an inactivated Ebolavirus vaccine engineered to present α-gal epitopes on the glycan shield. The resulting immune response to the various Ebolavirus proteins also may contribute to cross-reactive protection against other Ebolavirus species containing proteins with evolutionarily conserved structures. An effective method for the preparation of a whole-virus vaccine presenting α-gal epitopes is by arming it with the GGTA1-gene inserted into the viral genome. Such virions will present multiple α-gal epitopes on their glycan shield, which will amplify their immunogenicity instead of reducing it in the wild-type virus. Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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21 pages, 9409 KB  
Article
Synergistic Effects of Carbonated and Hydrophobically Modified Municipal Solid Waste Incineration Fly Ash on Mortar Performance and Heavy-Metal Immobilisation
by Jingwei Zhang, Yi Zheng, Kangjie Zhang and Jia Li
Buildings 2026, 16(13), 2593; https://doi.org/10.3390/buildings16132593 - 29 Jun 2026
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Abstract
Municipal solid waste incineration (MSWI) fly ash contains soluble salts and heavy metals, which may cause leaching risks and durability deterioration when directly used in cement-based materials. This study aimed to investigate the synergistic effects of carbonated and hydrophobically modified municipal solid waste [...] Read more.
Municipal solid waste incineration (MSWI) fly ash contains soluble salts and heavy metals, which may cause leaching risks and durability deterioration when directly used in cement-based materials. This study aimed to investigate the synergistic effects of carbonated and hydrophobically modified municipal solid waste incineration fly ashes on the engineering performance and heavy-metal immobilisation of mortar. Mortars containing modified fly ashes were evaluated in terms of hydration behavior, compressive strength, water absorption, electrically accelerated corrosion resistance, heavy metal leaching, and microstructure. Carbonated fly ash promoted hydration through the nucleation and filling effects of CaCO3, shortened setting time, increased cumulative hydration heat, and improved compressive strength by up to 4.5 MPa. Hydrophobic fly ash reduced particle wettability and capillary water transport, thereby reducing water uptake and mitigating visible corrosion-induced deterioration under accelerated conditions, although excessive dosage delayed hydration and reduced strength. The combined modification showed a clear synergistic effect, reducing water absorption by up to 39.9%. In particular, the C3H3 specimen, containing 75 kg·m−3 carbonated MSWI fly ash and 75 kg·m−3 hydrophobically modified MSWI fly ash, exhibited the lowest water absorption of 3.92% and effectively suppressed crack propagation and corrosion-product migration. The leaching concentrations of Cr, Cu, Zn, As, Cd, and Pb were below the GB 18598—2019 limits. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), and low-field nuclear magnetic resonance (NMR) results indicated that the improved performance originated from a composite barrier involving carbonate filling, hydrophobic interfacial blocking, and heavy metal solidification/stabilization. Full article
(This article belongs to the Section Building Materials, and Repair & Renovation)
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28 pages, 7723 KB  
Article
Thermal Conversion of Paulownia tomentosa Leaves into Carbonaceous Materials: Effects on Physicochemical Properties and Sorption of Metribuzin and Tebuconazole from Water
by Margita Ščasná, Michal Hebnár, Alexandra Kucmanová, Maroš Sirotiak, Veronika Kvorková, Maroš Soldán, Jan Hajzler, Barbora Ludrovcová and Marián Palcut
Technologies 2026, 14(7), 396; https://doi.org/10.3390/technologies14070396 - 29 Jun 2026
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Abstract
This study investigated carbonaceous materials prepared from Paulownia tomentosa leaves by hydrothermal carbonization, slow pyrolysis, and HCl post-treatment for the adsorption of metribuzin and tebuconazole from water. Hydrochars were prepared at 180–220 °C, pyrochars at 400–600 °C, and the pyrochar produced at 600 [...] Read more.
This study investigated carbonaceous materials prepared from Paulownia tomentosa leaves by hydrothermal carbonization, slow pyrolysis, and HCl post-treatment for the adsorption of metribuzin and tebuconazole from water. Hydrochars were prepared at 180–220 °C, pyrochars at 400–600 °C, and the pyrochar produced at 600 °C was further treated with HCl. The materials were characterized by yield, ash content, active and exchangeable pH, oxidizable organic carbon content, FTIR, SEM, and CO2-derived surface and pore properties. Increasing processing temperature reduced the yield in both conversion routes. Hydrochars retained more oxygen-containing and oxidizable organic structures, whereas pyrochars showed stronger carbonization, higher ash content, and higher CO2-derived surface area. HCl treatment decreased the ash residue, thereby resulting in improved CO2-accessible surface and pore properties and more fragmented morphology. Metribuzin adsorption was better described by the pseudo-second-order kinetic model across all sorbents, with the highest fitted equilibrium adsorbed amount observed following HCl treatment. Tebuconazole showed higher initial uptake toward most untreated materials, but its kinetic profiles were non-monotonic, with a decrease in the adsorbed amount at longer contact times. Consequently, the conventional PFO and PSO models did not adequately describe its complete kinetic behavior. Nonlinear isotherm modeling showed predominantly Freundlich-type fitting for metribuzin, suggesting heterogeneous adsorption sites, whereas tebuconazole was formally better described by Langmuir-type fitting, although with poorer fit quality for several materials. The results show that Paulownia tomentosa leaves are a suitable precursor for carbonaceous sorbents and that HCl-treated pyrochar is the most promising material for metribuzin adsorption. Full article
(This article belongs to the Section Environmental Technology)
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