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27 pages, 852 KiB  
Review
Neutralizing Antibodies: Role in Immune Response and Viral Vector Based Gene Therapy
by Tatiana S. Tsaregorodtseva, Aigul A. Gubaidullina, Beata R. Kayumova, Alisa A. Shaimardanova, Shaza S. Issa, Valeriya V. Solovyeva, Albert A. Sufianov, Galina Z. Sufianova and Albert A. Rizvanov
Int. J. Mol. Sci. 2025, 26(11), 5224; https://doi.org/10.3390/ijms26115224 - 29 May 2025
Abstract
Neutralizing antibodies (nAbs) are an important component of the immune system, which plays a dual role in modern medicine. On the one hand, they significantly limit the effectiveness of gene therapy based on viral vectors, reducing the effectiveness of treatment of diseases such [...] Read more.
Neutralizing antibodies (nAbs) are an important component of the immune system, which plays a dual role in modern medicine. On the one hand, they significantly limit the effectiveness of gene therapy based on viral vectors, reducing the effectiveness of treatment of diseases such as spinal muscular atrophy, which is especially evident with repeated administration of therapeutic vectors. On the other hand, nAbs is a promising tool for combating viral infections. This review systematizes current data on the mechanisms of nAbs formation against AAV vectors, analyzes the factors influencing their production, and discusses strategies to overcome this limitation, including modification of vectors and the development of methods to suppress the immune response. Special attention is paid to the prospects of using nAbs as therapeutic agents against viral infections. The key problems and possible directions of research development in this area are considered, which is important for improving approaches to the treatment of both rare genetic and infectious diseases. Full article
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20 pages, 1178 KiB  
Article
Cilantro Photosynthetic Parameters in Response to Different Flows of Nutrient Solutions Prepared with Brackish Waters Dominant in Na+, Cl, or Ca2+
by Uriel Calisto Moura Pessoa, Ênio Farias de França e Silva, Tarcísio Ferreira de Oliveira, Jorge F. S. Ferreira, Edivan Rodrigues de Souza, Mário Monteiro Rolim, Alexsandro Oliveira da Silva and José Amilton Santos Júnior
Water 2025, 17(11), 1640; https://doi.org/10.3390/w17111640 - 28 May 2025
Abstract
Although the NFT (nutrient film technique) solution application rate for cilantro is known for fresh water, the application rate is still debatable when using brackish water. The application rate alone influences flow velocity dynamics, which, when associated with nutrient solution salinity, can impact [...] Read more.
Although the NFT (nutrient film technique) solution application rate for cilantro is known for fresh water, the application rate is still debatable when using brackish water. The application rate alone influences flow velocity dynamics, which, when associated with nutrient solution salinity, can impact plant development when saline water is used. Knowledge of how to best combine solution salinity and application rates will help decide if brackish water can be used to produce cilantro under hydroponic conditions. Thus, two trials were conducted in sequence from November 2019 to February 2020 under a protected environment. Cilantro cv. Verdão was submitted to four levels of electrical conductivity of nutrient solutions (ECns of 1.7, 3.0, 4.5, and 6.0 dS m−1) combined with four flow rates (1.0, 2.0, 3.0, and 4.0 L min−1). Because Na+ and Ca2+ are predominant ions in brackish waters in the crystalline and sedimentary regions in the Brazilian Semiarid region, the first study used brackish waters dominated by NaCl and the second study used waters dominated by CaCl2. We measured gas exchange and other photosynthetic parameters in plants cultivated with nutrient solutions high in Cl and prevalent in Na+ or Ca2+, each combined with different application rates. We concluded that the increment in salinity decreased the gas exchange of cilantro plants, especially when the brackish waters were dominant in Ca2+ and Cl. Up to an ECns of 4.5 dS m−1, plants maintained their leaf chlorophyll concentrations, although with reduced gas exchange. Salt stress compromised chlorophyll a fluorescence, affecting important parameters such as initial, maximum, and variable fluorescence. Besides the effects of salinity on chlorophyll a and b concentrations, the quantum and maximum yields of photosystem II remained stable, indicating that photosystem II may have adapted to the saline conditions applied in this study. The variation in application rates was unable to attenuate the deleterious effects of salinity, regardless of the ionic prevalence. We conclude that cilantro plants can be cultivated under hydroponic conditions, using currently accepted flow rates, with nutrient solutions of up to 3.0 dS m−1 without severe damage to plant photosynthetic parameters. Full article
(This article belongs to the Section Water, Agriculture and Aquaculture)
26 pages, 7354 KiB  
Article
The Improved Remediation Effect of the Combined Use of Earthworms with Bacillus subtilis-Loaded Biochar in Ameliorating Soda Saline–Alkali Soil
by Zhichen Liu, Yingxin Huang, Qibiao Li, Luwen Zhang, Zhenke Liu, Zunhao Zhang and Yuxiang Chen
Microorganisms 2025, 13(6), 1243; https://doi.org/10.3390/microorganisms13061243 - 28 May 2025
Abstract
High pH, Na+, and (CO23+HCO3) are the primary characteristics of soda saline–alkali soil. Current strategies for ameliorating soda saline–alkali soil often involve the combined use of cow manure and maize straw, the [...] Read more.
High pH, Na+, and (CO23+HCO3) are the primary characteristics of soda saline–alkali soil. Current strategies for ameliorating soda saline–alkali soil often involve the combined use of cow manure and maize straw, the addition of biochar (BC), and the inoculation of Bacillus subtilis (BS). In this study, B. subtilis-loaded biochar (BSC) was prepared using an adsorption technique. An incubation experiment was conducted. The treatments were as follows: soda saline–alkali soil amended with maize straw and cow manure (T1), which was used as a control; T1 supplemented with earthworms (T2); and T2 supplemented with BS (T3), BC (T4), or BSC (T5). After a 60-day incubation, T5 showed the most significant reduction in pH, ESP, and (HCO3  +  CO23) concentrations, with reductions of 0.24 units, 3.26%, and 120 mg kg−1, respectively, compared to the T1 treatment. The content of soil humic acid, available potassium, and available nitrogen and the activities of β-glucosidase and urease were highest in T5, increasing by 33.5%, 70.1%, 26.1%, 19.0%, and 17.9%, respectively. Microbial sequencing analysis revealed that the Bacillus abundance in T3 was highest during the first 45 days (2.51–3.65%), while the Bacillus abundance in T5 peaked at 3.22% after the 60-day incubation. The soil that was cultivated for 60 days in the experiments was then used for planting alfalfa. T5 showed the highest alfalfa aboveground biomass and peroxidase, increasing by 30.1% and 73.1%, respectively, compared with T1. This study demonstrated that loading onto biochar is beneficial for the survival of B. subtilis in soda saline–alkali soil. When traditional organic materials are used, the combination of earthworms and B. subtilis-loaded biochar significantly alleviates the constraints of soda saline–alkali soil. Full article
(This article belongs to the Section Environmental Microbiology)
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12 pages, 988 KiB  
Article
Association of Pathologic Response and Adjuvant Chemotherapy with Survival in Resected Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy
by James Yu, Jose M. Laborde, Robin Park, Moazzam Shahzad, Youngchul Kim, Jaekyung Cheon, Iman Imanirad, Richard D. Kim, Tiago Biachi de Castria, Nicole L. Nardella, Mokenge Malafa, Jason W. Denbo, Jason B. Fleming, Sarah E. Hoffe, Jessica M. Frakes, Andrew J. Sinnamon, Jose M. Pimiento, Pamela J. Hodul and Dae Won Kim
Cancers 2025, 17(11), 1797; https://doi.org/10.3390/cancers17111797 - 28 May 2025
Abstract
Background: In patients with curatively resected pancreatic adenocarcinoma who have undergone neoadjuvant chemotherapy (NACT), evidence supporting the benefit of additional adjuvant chemotherapy (ACT) remains limited. We aim to identify favorable factors contributing to survival benefits in resected pancreatic adenocarcinoma after NACT. Methods: [...] Read more.
Background: In patients with curatively resected pancreatic adenocarcinoma who have undergone neoadjuvant chemotherapy (NACT), evidence supporting the benefit of additional adjuvant chemotherapy (ACT) remains limited. We aim to identify favorable factors contributing to survival benefits in resected pancreatic adenocarcinoma after NACT. Methods: This is a retrospective cohort study of pancreatic adenocarcinoma patients who underwent NACT followed by curative surgical resection between 2008 and 2023 at a single academic institution. Univariate and multivariable analyses were conducted to identify factors contributing to disease-free survival (DFS) and overall survival (OS). Results: A total of 230 patients with a median age of 68 years (IQR, 62–72 years) were included. All patients underwent curative surgical resection. Of these, 42% received neoadjuvant modified (m) FOLFIRINOX (96/230), 15% received gemcitabine plus nab-paclitaxel (GEM-NAB) (34/230), and 43% received gemcitabine, docetaxel, and capecitabine (GTX) (100/230). In univariate analysis, lower College of American Pathologists (CAP) tumor regression grade (TRG) (0–1 vs. 2–3, median DFS: 29.8 vs. 14.2 months, p = 0.0081) and receipt of ACT (Yes vs. No, median DFS: 22.2 vs. 12.4 months, p < 0.0001) demonstrated significant associations with superior DFS. Multivariable analysis identified receipt of ACT as an independent predictor of superior DFS (HR 0.55, 95% CI: 0.39–0.78, p = 0.0007) and OS (HR 0.49, 95% CI: 0.33–0.71, p = 0.0002). However, the NACT regimen (mFOLFIRINOX vs. GEM-NAB) and the transition between neoadjuvant and adjuvant therapy (de-escalation vs. continuation vs. change) did not correlate with DFS or OS. The duration of perioperative chemotherapy showed a trend toward improved survival outcomes, though not statistically significant (6 months vs. <6 months: DFS, 19.4 vs. 16.2 months, p = 0.1448; OS, 49.6 vs. 30.4 months, p = 0.0623). In the following subgroup analyses, receipt of ACT provided DFS/OS benefits in patients who did not achieve a major pathologic response, pN0, or R0 resection (DFS: p = 0.0003; OS: p < 0.0001). However, it did not provide DFS/OS benefits in those who achieved a major pathologic response with pN0/R0 to NACT (DFS: p = 0.8036; OS: p = 0.1877). Conclusions: In resected pancreatic adenocarcinoma following NACT, receiving ACT was associated with favorable survival outcomes. Additional ACT appears to benefit patients who did not achieve a major pathologic response (pN0 or R0) to neoadjuvant therapy, with limited benefit for those who achieved a major response with pN0/R0. The specific NACT regimen (mFOLFIRINOX vs. GEM-NAB) and changes in ACT from NACT did not significantly influence survival outcomes in our cohort. Full article
(This article belongs to the Collection Oncology: State-of-the-Art Research in the USA)
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19 pages, 2215 KiB  
Article
Multi-Method Combined Screening of Agarase-Secreting Fungi from Sea Cucumber and Preliminary Analyses on Their Agarases and Agar-Oligosaccharide Products
by Shuting He, Tiantian Lu, Xiaoyu Sun, Fangfang Ban, Longjian Zhou, Yayue Liu, Yan Feng and Yi Zhang
Microorganisms 2025, 13(6), 1235; https://doi.org/10.3390/microorganisms13061235 - 28 May 2025
Abstract
Agar can be degraded into agar-oligosaccharides by physical, chemical, and biological methods, but the further industrial application of agar-oligosaccharides has been limited by the environmental pollution of traditional agar-oligosaccharides preparation methods and the lack of novel agarase. In this study, we reported the [...] Read more.
Agar can be degraded into agar-oligosaccharides by physical, chemical, and biological methods, but the further industrial application of agar-oligosaccharides has been limited by the environmental pollution of traditional agar-oligosaccharides preparation methods and the lack of novel agarase. In this study, we reported the screening of 12 strains with agar-degrading activity from sea cucumber intestine and mucus using a combination of Gram’s iodine staining and 3,5-dinitrosalicylic acid (DNS) method, during which five fungal strains exhibited high agarase activity. Their production of different agarases and agar-oligosaccharides could be visualized by zymogram assay and thin-layer chromatography. A strain ACD-11-B with the highest agarase activity showed 99.79% similarity to Aspergillus sydowii CBS593.65 for ITS rDNA sequence. Strain ACD-11-B produced five possible agarases with predicted molecular weights of 180, 95, 43, 33, and 20 kDa, approximately. The optimal temperature and pH of the crude enzyme production by strain ACD-11-B were 40 °C and 6.0. The crude enzyme was stable at 30 °C, and Ca2+, K+, and Na+ could increase the activity of the crude enzyme. Its agarases demonstrated remarkable salt tolerance and substrate specificity, with neoagarobiose (NA2) identified as the main degradation product. These results indicate that the fungal strain ACD-11-B can secrete agarases with potential in industrial applications, making it a new producer strain for agarase production. Full article
(This article belongs to the Section Microbial Biotechnology)
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17 pages, 1550 KiB  
Article
Influence of Reduced Molar Mass of Low-Acyl Gellan Gum on Weak Gel Formation and Rheological Properties
by Nina G. Mikusheva, Ivan M. Zorin, Alexander S. Gubarev, Alexandr V. Ievlev, Olga V. Volina and Nikolai V. Tsvetkov
Gels 2025, 11(6), 398; https://doi.org/10.3390/gels11060398 - 27 May 2025
Abstract
Reduced-molar-mass low-acyl gellan gum was obtained by the centrifugation of an aqueous solution of commercially available food-grade gellan gum. The derived sample was characterized by NMR, FTIR, ICPE, and viscometry methods. The characteristics were compared with commercially available gellan gum Gelzan™. The main [...] Read more.
Reduced-molar-mass low-acyl gellan gum was obtained by the centrifugation of an aqueous solution of commercially available food-grade gellan gum. The derived sample was characterized by NMR, FTIR, ICPE, and viscometry methods. The characteristics were compared with commercially available gellan gum Gelzan™. The main focus of the investigation is on the rheological properties of low-molar-mass-gellan ion-induced gels and the influence of reduced molar mass on gelling of gellan. The gels were prepared by adding 0.2–0.3 M of NaCl or KCl to the 0.6 g/dL gellan gum aqueous solution in a 1:1 ratio. The kinetics of gelling at room temperature, studied by rheological methods, strongly depends on molar mass and is practically independent of the temperature (up to 37 °C) and the type of ions. Analysis of the mechanical spectra characterized the obtained gels as weak gels. The gelling temperature achieved upon cooling for low-molar-mass gellan with a 0.1 M NaCl concentration was 39.0 °C (rheology) and 43.5–42.5 °C (visual observation). In summary, this study complements the existing knowledge about how the reduced molar mass of low-acyl gellan gum influences its rheological properties and gelling behavior in ion-induced systems and provides insights into the formulation of gellan-based gels, which can be effectively utilized in various food and pharmaceutical applications. Full article
(This article belongs to the Special Issue Physical and Mechanical Properties of Polymer Gels (2nd Edition))
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24 pages, 2777 KiB  
Article
Phytochemical Profiling of Processed Açaí Pulp (Euterpe oleracea) Through Mass Spectrometry and Its Protective Effects Against Oxidative Stress in Cardiomyocytes and Rats
by Jefferson Romáryo Duarte da Luz, Eder Alves Barbosa, Rubiamara Mauricio de Sousa, Maria Lúcia de Azevedo Oliveira, Marcela Fabiani Silva Dias, Ingrid Reale Alves, Gisele Custódio de Souza, Elenilze Figueiredo Batista Ferreira, Carla Guzmán-Pincheira, Maria das Graças Almeida and Gabriel Araujo-Silva
Antioxidants 2025, 14(6), 642; https://doi.org/10.3390/antiox14060642 - 27 May 2025
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Abstract
The antioxidant capacity and modulation of oxidative stress by industrially processed açaí pulp extract from the Amazon (APEA) and its major anthocyanins, cyanidin 3-glucoside (C3G) and cyanidin-3-O-rutinoside (C3R), were evaluated as potential strategies for preventing cardiovascular diseases. The APEA was chemically characterized using [...] Read more.
The antioxidant capacity and modulation of oxidative stress by industrially processed açaí pulp extract from the Amazon (APEA) and its major anthocyanins, cyanidin 3-glucoside (C3G) and cyanidin-3-O-rutinoside (C3R), were evaluated as potential strategies for preventing cardiovascular diseases. The APEA was chemically characterized using ultrafast liquid chromatography-mass spectrometry (UFLC-MS), which revealed six main phenolic compounds. Notably, 9-(2,3-dihydroxypropoxy)-9-oxononanoic acid, acanthoside B, roseoside, cinchonine, and nonanedioate were identified for the first time in açaí extracts. In vitro antioxidant assays demonstrated that APEA exhibited strong DPPH- and ABTS-radical-scavenging activities (up to 80% inhibition and 65 mmol TE/100g DW, respectively) and showed ferrous- and copper-ion-chelating activities comparable to those of EDTA-Na2 at higher concentrations (up to 95% inhibition). Hydroxyl and superoxide radical scavenging activities reached 80% inhibition, similar to that of ascorbic acid. In H2O2-treated H9c2 cardiomyocytes, APEA significantly reduced the intracellular ROS levels by 46.9%, comparable to the effect of N-acetylcysteine. APEA also attenuated menadione-induced oxidative stress in H9c2 cells, as shown by a significant reduction in CellROX fluorescence (p < 0.05). In vivo, APEA (100 mg/kg) significantly reduced CCl-induced hepatic lipid peroxidation (MDA levels), restored glutathione (GSH), and increased the antioxidant enzymes CAT, GPx, and SOD, demonstrating superior effects to C3G and C3R, especially after 21 days of treatment (p < 0.001). These findings suggest that Amazonian açaí pulp (APEA) retains potent antioxidant activity after industrial processing, with protective effects against oxidative damage in cardiomyocytes and hepatic tissue, highlighting its potential as a functional food ingredient with cardioprotective and hepatoprotective properties. Full article
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15 pages, 1002 KiB  
Article
Isolation and Functional Characterization of Yeasts from Fermented Plant Based Products
by Dilara Devecioglu, Anı Kuscu and Funda Karbancioglu-Guler
Fermentation 2025, 11(6), 305; https://doi.org/10.3390/fermentation11060305 - 26 May 2025
Viewed by 165
Abstract
Yeasts isolated from fermented plant-based sources—boza, pickles, and chickpeas—were evaluated for probiotic potential. Among 18 colonies, seven isolates showing no hemolytic activity were selected and identified: Pichia kudriavzevii (four isolates), Kazachstania exigua, Hanseniaspora uvarum, and Saccharomyces cerevisiae. Most isolates were able [...] Read more.
Yeasts isolated from fermented plant-based sources—boza, pickles, and chickpeas—were evaluated for probiotic potential. Among 18 colonies, seven isolates showing no hemolytic activity were selected and identified: Pichia kudriavzevii (four isolates), Kazachstania exigua, Hanseniaspora uvarum, and Saccharomyces cerevisiae. Most isolates were able to survive under low pH and bile salt conditions, simulating the environment of the gastrointestinal tract (5.62–8.59 log CFU/mL) and tolerated NaCl concentrations up to 6–8% (w/v). All isolates exhibited antibiotic resistance; however, their susceptibility to antifungals varied. While P. kudriavzevii DD_B_M88 exhibited the highest hydrophobicity (63.07%), isolate auto-aggregation increased to 53–95% after 24 h. Most isolates showed a great capability to co-aggregate with pathogens and inhibited them significantly (up to 98.72%), except for S. cerevisiae DD_NB_M90. The selected three isolates and their cell-free supernatants, up to a certain concentration, showed no significant cytotoxicity on Caco-2 cell line. Eventually, six isolates, excluding S. cerevisiae DD_NB_M90, fulfilled the probiotic criteria, and can serve as probiotic starter cultures for alternative food production. Full article
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14 pages, 1380 KiB  
Article
Impact of Tumor Location on Survival Outcomes in Pancreatic Head Versus Body/Tail Cancer: Institutional Experience
by Abdullah Esmail, Vikram Dhillon, Ebtesam Al-Najjar, Bayan Khasawneh, Mohammed Alghamdi, Fahad Ibnshamsah and Maen Abdelrahim
Cancers 2025, 17(11), 1777; https://doi.org/10.3390/cancers17111777 - 26 May 2025
Viewed by 150
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits variable survival outcomes based on tumor location, with pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) differing in prognosis and treatment response. This study investigates the correlation between tumor location and survival outcomes in PDAC patients [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits variable survival outcomes based on tumor location, with pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) differing in prognosis and treatment response. This study investigates the correlation between tumor location and survival outcomes in PDAC patients treated with standard chemotherapy regimens. Methods: A retrospective analysis of 604 PDAC patients (400 PHC, 204 PBTC) diagnosed between January 2015 and May 2024 at Houston Methodist Neal Cancer Center was conducted. Patients received either mFOLFIRINOX or gemcitabine/nab-paclitaxel as first-line therapy. Clinical data, including demographics, tumor stage, treatment modalities, and molecular profiles, were extracted from electronic records. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier analyses and Cox proportional hazards models. Latent class analysis (LCA) identified patient subgroups based on shared clinical, demographic, and survival characteristics. Results: PHC patients demonstrated superior median OS (12 months) compared to PBTC (9 months, p = 0.012) and PFS (8 months vs. 5 months, p = 0.0008). Across both subtypes, mFOLFIRINOX was associated with significantly longer OS than gem/nab-paclitaxel (PHC: 18.8 vs. 12.7 months, p < 0.0001; PBTC: 14 vs. 6 months, p = 0.011). LCA revealed distinct clusters: in PHC, a curative-intent class (median OS > 24 months) contrasted with a palliative class (<6 months); in PBTC, an aggressive treatment class (median OS > 18 months) differed from a limited treatment class (<6 months). Cluster differences were linked to treatment intensity, stage, and radiation use. Conclusions: PHC is associated with better survival outcomes than PBTC, with mFOLFIRINOX outperforming gem/nab-paclitaxel in both subtypes. LCA highlights heterogeneous patient subgroups, suggesting opportunities for personalized treatment strategies in PDAC management. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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20 pages, 7314 KiB  
Article
Zoharite, (Ba,K)6 (Fe,Cu,Ni)25S27, and Gmalimite, K6□Fe2+24S27—New Djerfisherite Group Minerals from Gehlenite-Wollastonite Paralava, Hatrurim Complex, Israel
by Irina O. Galuskina, Biljana Krüger, Evgeny V. Galuskin, Hannes Krüger, Yevgeny Vapnik, Mikhail Murashko, Kamila Banasik and Atali A. Agakhanov
Minerals 2025, 15(6), 564; https://doi.org/10.3390/min15060564 - 26 May 2025
Viewed by 141
Abstract
Zoharite (IMA 2017-049), (Ba,K)6 (Fe,Cu,Ni)25S27, and gmalimite (IMA 2019-007), ideally K6□Fe2+24S27, are two new sulfides of the djerfisherite group. They were discovered in an unusual gehlenite–wollastonite paralava with pyrrhotite nodules located [...] Read more.
Zoharite (IMA 2017-049), (Ba,K)6 (Fe,Cu,Ni)25S27, and gmalimite (IMA 2019-007), ideally K6□Fe2+24S27, are two new sulfides of the djerfisherite group. They were discovered in an unusual gehlenite–wollastonite paralava with pyrrhotite nodules located in the Hatrurim pyrometamorphic complex, Negev Desert, Israel. Zoharite and gmalimite build grained aggregates confined to the peripheric parts of pyrrhotite nodules, where they associate with pentlandite, chalcopyrite, chalcocite, digenite, covellite, millerite, heazlewoodite, pyrite and rudashevskyite. The occurrence and associated minerals indicate that zoharite and gmalimite were formed at temperatures below 800 °C, when sulfides formed on external zones of the nodules have been reacting with residual silicate melt (paralava) locally enriched in Ba and K. Macroscopically, both minerals are bronze in color and have a dark-gray streak and metallic luster. They are brittle and have a conchoidal fracture. In reflected light, both minerals are optically isotropic and exhibit gray color with an olive tinge. The reflectance values for zoharite and gmalimite, respectively, at the standard COM wavelengths are: 22.2% and 21.5% at 470 nm, 25.1% and 24.6% at 546 nm, 26.3% and 25.9% at 589 nm, as well as 27.7% and 26.3% at 650 nm. The average hardness for zoharite and for gmalimite is approximately 3.5 of the Mohs hardness. Both minerals are isostructural with owensite, (Ba,Pb)6(Cu,Fe,Ni)25S27. They crystallize in cubic space group Pm¯3m with the unit-cell parameters a = 10.3137(1) Å for zoharite and a = 10.3486(1) Å for gmalimite. The calculated densities are 4.49 g·cm−3 for the zoharite and 3.79 g·cm−3 for the gmalimite. The primary structural units of these minerals are M8S14 clusters, composed of MS4 tetrahedra surrounding a central MS6 octahedron. The M site is occupied by transition metals such as Fe, Cu, and Ni. These clusters are further connected via the edges of the MS4 tetrahedra, forming a close-packed cubic framework. The channels within this framework are filled by anion-centered polyhedra: SBa9 in zoharite and SK9 in gmalimite, respectively. In the M8S14 clusters, the M atoms are positioned so closely that their d orbitals can overlap, allowing the formation of metal–metal bonds. As a result, the transition metals in these clusters often adopt electron configurations that reflect additional electron density from their local bonding environment, similar to what is observed in pentlandite. Due to the presence of shared electrons in these metal–metal bonds, assigning fixed oxidation states—such as Fe2+/Fe3+ or Cu+/Cu2+—becomes challenging. Moreover, modeling the distribution of mixed-valence cations (Fe2+/3+, Cu+/2+, and Ni2+) across the two distinct M sites—one located in the MS6 octahedron and the other in the MS4 tetrahedra—often results in ambiguous outcomes. Consequently, it is difficult to define an idealized end-member formula for these minerals. Full article
(This article belongs to the Collection New Minerals)
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14 pages, 14940 KiB  
Article
Optimization of Scanning Protocol for AI-Integrated Assessment of HER2 Dual Bright-Field In-Situ Hybridization Application in Breast Cancer
by Nilay Bakoglu Malinowski, Takashi Ohnishi, Emine Cesmecioglu, Dara S. Ross, Tetsuya Tsukamoto and Yukako Yagi
Bioengineering 2025, 12(6), 569; https://doi.org/10.3390/bioengineering12060569 - 26 May 2025
Viewed by 141
Abstract
Accurately determining HER2 status is essential for breast cancer treatment. We developed an AI-integrated in-house application for automated Dual bright-field (BF) in situ hybridization (ISH) analysis on whole slide images (WSIs), although optimal scanning conditions remain unclear. We evaluated scanners and optimized scanning [...] Read more.
Accurately determining HER2 status is essential for breast cancer treatment. We developed an AI-integrated in-house application for automated Dual bright-field (BF) in situ hybridization (ISH) analysis on whole slide images (WSIs), although optimal scanning conditions remain unclear. We evaluated scanners and optimized scanning protocols for clinical application. Ten de-identified invasive breast carcinoma cases, with HER2 immunohistochemistry and FISH results, were analyzed using three scanners and six scanning protocols. WSIs scanned by Scanner ‘A’ have 0.12 µm/pixel with 0.95 NA (A1) and 1.2 NA (A2); Scanner ‘B’ have 0.08 µm/pixel (B1); 0.17 µm/pixel (B2); and 0.17 µm/pixel with extended focus (1.4 µm step size and three layers) (B3); Scanner ‘C’ has 0.26 µm/pixel (C1) resolution. Results showed scanning protocols A1, A2, B2, and B3 yielded HER2 gene amplification status and ASCO/CAP ISH group results consistent with manual FISH as the ground truth. However, protocol C demonstrated poor concordance due to nuclei detection failure in six cases. The AI-integrated application achieved the best performance using scanning protocols with optimized resolutions of 0.12 µm/pixel and 0.17 µm/pixel with extended focus. This study highlights the importance of scanner selection in AI-based HER2 assessment and demonstrates that optimized scanning parameters enhance the accuracy and reliability of automated Dual BF ISH analysis. Full article
(This article belongs to the Special Issue AI-Driven Innovations in Computational Histology/Pathology)
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18 pages, 4401 KiB  
Article
Computational Fluid Dynamics Investigation of Flow and Flame Behavior in Natural Gas Burners for Borax Pentahydrate Furnaces
by Mehmed Rafet Ozdemir, Ramazan Sener, İlker Solakoglu and Bahadır Tunaboylu
Processes 2025, 13(6), 1660; https://doi.org/10.3390/pr13061660 - 26 May 2025
Viewed by 218
Abstract
The combustion behavior and thermal performance of industrial-scale borax pentahydrate (Na2B4O7·5H2O) melting furnaces remain underexplored despite their critical role in boric oxide (B2O3) production, a key input for high-performance manufacturing. This [...] Read more.
The combustion behavior and thermal performance of industrial-scale borax pentahydrate (Na2B4O7·5H2O) melting furnaces remain underexplored despite their critical role in boric oxide (B2O3) production, a key input for high-performance manufacturing. This study addressed this gap by employing three-dimensional computational fluid dynamics (CFD) simulations to model two operational natural gas-fired furnaces with distinct burner configurations (four-burner and six-burner systems). The analysis focused on optimizing burner placement, specifically, the axial distance and inclination angle, to enhance thermal uniformity and reduce refractory wall damage caused by aggressive high-temperature borate corrosion. A comprehensive parametric study of twelve burner configurations revealed that tilting the burners at 5–10° significantly improved temperature uniformity while reducing peak wall temperatures and mitigating localized hot spots. The optimal design, incorporating a 10° burner angle and a staggered burner arrangement (Case 11), attained a melt pool temperature of 1831.3 K and a charging average wall temperature of 1812.0 K. These values represent essential benchmarks for maximizing furnace efficiency and operational stability. The modified designs for the four- and six-burner systems led to improved temperature distributions and a notable reduction in maximum wall temperatures, directly contributing to longer maintenance intervals and improved refractory durability. The findings of this study confirm that minor geometrical and angular adjustments in burner placement can yield significant performance gains. The validated CFD approach and proposed design modifications offer a scalable, low-cost strategy for improving combustion efficiency and furnace lifespan in borax processing facilities. Full article
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22 pages, 5356 KiB  
Article
Mucosal and Serum Neutralization Immune Responses Elicited by COVID-19 mRNA Vaccination in Vaccinated and Breakthrough-Infection Individuals: A Longitudinal Study from Louisville Cohort
by Lalit Batra, Divyasha Saxena, Triparna Poddar, Maryam Zahin, Alok Amraotkar, Megan M. Bezold, Kathleen T. Kitterman, Kailyn A. Deitz, Amanda B. Lasnik, Rachel J. Keith, Aruni Bhatnagar, Maiying Kong, Jon D. Gabbard, William E. Severson and Kenneth E. Palmer
Vaccines 2025, 13(6), 559; https://doi.org/10.3390/vaccines13060559 - 24 May 2025
Viewed by 269
Abstract
Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the [...] Read more.
Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the USA. We conducted a prospective longitudinal study to analyze the immune response elicited by two/three and four doses of monovalent mRNA vaccines in both vaccinated individuals and those who experienced breakthrough infections. Participants were stratified into different age groups: 18–40, 41–60, and over 60 years. Methods: We assessed cross-variant neutralization responses in two cohorts—Cohort I: n = 167 (serum), Cohort II: n = 92 (serum and nasal swab) samples—using infectious virus microneutralization assay (MN) and antibody (IgG or IgA) binding ELISA titers to the spike protein receptor binding domain (RBD). Samples were collected from the Louisville Metro–Jefferson County Co-Immunity Project, a federally funded, population-based study for the surveillance of SARS-CoV-2 in Jefferson County, Kentucky during 2020–2022, involving both health care workers and a local community. Results: Individuals who received two doses of the mRNA vaccine exhibited reduced neutralization against Beta, Delta, and Omicron BA.1 variants compared to wildtype Wuhan, with further decline observed six months post-booster vaccination. However, individuals who experienced natural COVID-19 infection (breakthrough) after receiving two vaccine doses showed enhanced neutralization and antibody responses, particularly against Omicron BA.1. Following the 3rd dose, antibodies and neutralization responses were restored. Among triple-vaccinated individuals, reduced neutralization was observed against Omicron variants BA.1, BA.5, and BA.2 compared to Wuhan. Neutralization responses were better against BA.2 variant compared to BA.1 and BA.5. However, individuals who received three doses of vaccine and experienced a breakthrough infection (n = 45) elicited significantly higher neutralizing antibodies responses against all Omicron subvariants compared to vaccinated individuals. Interestingly, nasal swab samples collected from volunteers with breakthrough infection showed significantly elevated spike-reactive mucosal IgA antibodies and enhanced cross neutralization against BA.1, BA.2, and BA.5 compared to individuals who received only three vaccine doses. Conclusions: mRNA vaccination elicits a strong systemic immune response by boosting serum neutralizing antibodies (NAb), although this protection wanes over time, allowing new variants to escape neutralization. Breakthrough individuals have extra enrichment in nasal NAb offering protection against emerging variants. This longitudinal immune profiling underscores the strengthening of pandemic preparedness and supports the development of durable mucosal vaccines against respiratory infectious disease. Full article
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31 pages, 7040 KiB  
Article
Dietary Probiotic Bacillus subtilis AAHM-BS2360 and Its Postbiotic Metabolites Enhance Growth, Immunity, and Resistance to Edwardsiellosis in Pangasianodon hypophthalmus
by Nugroho Wiratama, Pakapon Meachasompop, Benchawan Kumwan, Yosapon Adisornprasert, Prapansak Srisapoome, Phornphan Phrompanya, Patcharapong Thangsunan, Pattanapong Thangsunan, Kanokporn Saenphet, Supap Saenphet, Wararut Buncharoen and Anurak Uchuwittayakul
Antioxidants 2025, 14(6), 629; https://doi.org/10.3390/antiox14060629 - 23 May 2025
Viewed by 250
Abstract
Edwardsiellosis, caused by Edwardsiella tarda, poses a significant threat to the aquaculture industry, particularly in pangasius farming. This study investigates the effects of probiotic Bacillus subtilis AAHM-BS2360 and its postbiotic metabolites on growth performance, immune responses, antioxidative activity, and disease resistance against [...] Read more.
Edwardsiellosis, caused by Edwardsiella tarda, poses a significant threat to the aquaculture industry, particularly in pangasius farming. This study investigates the effects of probiotic Bacillus subtilis AAHM-BS2360 and its postbiotic metabolites on growth performance, immune responses, antioxidative activity, and disease resistance against E. tarda infection. A total of 240 healthy pangasius (37.0 ± 4.9 g) were divided into four treatment groups with four replicate tanks each, as follows: (1) the Control group, which received feed top-dressed with 100 mL of 0.85% NaCl/kg diet; (2) the Probiotic group, which received feed supplemented with 100 mL of B. subtilis AAHM-BS2360 cells at the concentration of 1 × 1012 CFU/kg diet; (3) the Postbiotic group, which received feed supplemented with B. subtilis AAHM-BS2360 cell-free supernatant 100 mL/kg diet; and (4) the Pro + Post group, which received a combination of B. subtilis AAHM-BS2360 cells and cell-free supernatant. After 30 days of feeding treatment, biochemical serum analysis revealed a significant increase in the AST/ALT ratio in the Postbiotic group. The Probiotic and Postbiotic treatments increased lysozyme activity in mucus, indicating an innate immune response to pathogens. The Pro + Post group exhibited the highest levels of catalase (CAT) in serum and upregulated antioxidant-related genes. All treatment groups receiving B. subtilis AAHM-BS2360, metabolites, and their combinations showed significant upregulation of immune-related genes, like lygl1, tgfb, b2ml, and tnf. The expression of proinflammatory genes (litaf, ifngr1l, c3, il13, and il1b) increased, with the most pronounced effects observed in the Pro + Post group. The Probiotic group showed significant upregulation of the growth-related gene igf1. Meanwhile, the Pro + Post group showed significantly higher values in SGR and ADG parameters, with values of 3.29 ± 0.98%/day and 1.42 ± 0.52 g/day respectively (p < 0.05). Survival rates were significantly higher in the Pro + Post (87.5%), Postbiotic (84.37%), and Probiotic (81.25%) groups when challenged with E. tarda. Dietary supplementation with B. subtilis AAHM-BS2360, its metabolites, and their combination enhanced immune response, reduced oxidative stress, and improved growth performance in pangasius, highlighting its potential as a functional feed additive for sustainable aquaculture. Full article
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23 pages, 2262 KiB  
Review
The Role of Nanoparticles in Therapy of Real-World Patients with Pancreatic Cancer: A Scoping Review
by Ioannis Konstantinidis, Sophia Tsokkou, Dimitrios Katsikeros, Paraskevi Chatzikomnitsa, Menelaos Papakonstantinou, Eftychia Liampou, Evdokia Toutziari, Dimitrios Giakoustidis, Petros Bageas, Vasileios Papadopoulos, Alexandros Giakoustidis and Theodora Papamitsou
Cancers 2025, 17(10), 1726; https://doi.org/10.3390/cancers17101726 - 21 May 2025
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Abstract
Pancreatic cancer (PC) is one of the most aggressive and fatal malignancies worldwide, posing a significant global health challenge due to its high mortality rates, late-stage diagnosis, and limited therapeutic efficacy [...] Full article
(This article belongs to the Special Issue Management of Pancreatic Cancer)
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