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14 pages, 10096 KB  
Article
Protein Kinase C Promotes Notch1 Cleavage Through Both Ligand-Dependent and Hyaluronic Acid–ADAM10-Dependent Mechanisms
by Xin Tang, Yunfei Mu and Hongjun Shi
Cells 2026, 15(15), 1349; https://doi.org/10.3390/cells15151349 - 27 Jul 2026
Viewed by 500
Abstract
Notch1 signaling is essential for endothelial cell fate determination and vascular development. While PKC has been implicated as an upstream activator of Notch1 signaling, the molecular mechanisms by which PKC promotes Notch1 proteolytic cleavage remain poorly defined. Here, using murine endothelial MS1 cells [...] Read more.
Notch1 signaling is essential for endothelial cell fate determination and vascular development. While PKC has been implicated as an upstream activator of Notch1 signaling, the molecular mechanisms by which PKC promotes Notch1 proteolytic cleavage remain poorly defined. Here, using murine endothelial MS1 cells and mouse aortic endothelial cells (MAECs), we identify two cooperative pathways through which PKC drives generation of the Notch1 intracellular domain (NICD). First, PKC activation increases mRNA and protein levels of the Notch1 ligands Jag1 and Dll4. A NICD-Dll4 positive feedback loop further amplifies Notch signaling. Second, PKC upregulates hyaluronic acid synthase 2 (HAS2) mRNA and protein expression, promoting hyaluronan (HA) synthesis. Various genetic (HAS2 knockdown, CD44 knockdown, Hyal2 overexpression) and pharmacological (4-methylumbelliferone, 4-MU) treatments confirmed that HA is required for PKC to activate Notch1. Inhibition of HA production or signaling is associated with downregulation of ADAM10 on the cell surface. Direct phosphorylation of Notch1 at S1791 is dispensable for this effect. Together, these findings reveal a dual pathway model in which PKC coordinates ligand upregulation and HA signaling to promote Notch1 cleavage, identifying the extracellular matrix as a previously unrecognized regulator of Notch1 signal strength in endothelial cells. Full article
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17 pages, 2047 KB  
Article
Lineage-Dependent Regulation of Glutathione Homeostasis by EAAC1 and GTRAP3-18 During Differentiation of Mesenchymal Stem Cells into Neuron-like Cells
by Nobuko Matsumura, Wattanaporn Bhadhprasit and Koji Aoyama
Int. J. Mol. Sci. 2026, 27(12), 5323; https://doi.org/10.3390/ijms27125323 - 12 Jun 2026
Viewed by 400
Abstract
Adult bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent progenitors capable of differentiating into diverse cell lineages, including osteogenic, chondrogenic, adipogenic, and neuronal lineages. In BMSCs, intracellular glutathione (GSH) is a critical determinant of stemness maintenance and differentiation outcomes. However, how intracellular GSH [...] Read more.
Adult bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent progenitors capable of differentiating into diverse cell lineages, including osteogenic, chondrogenic, adipogenic, and neuronal lineages. In BMSCs, intracellular glutathione (GSH) is a critical determinant of stemness maintenance and differentiation outcomes. However, how intracellular GSH homeostasis is regulated during BMSC-to-neuron differentiation remains unclear. In neurons, GSH synthesis critically depends on cysteine uptake mediated by the excitatory amino acid carrier 1 (EAAC1). Here, we investigated the expression, subcellular localization, and functional contribution of EAAC1 and its regulatory protein, glutamate transporter-associated protein 3-18 (GTRAP3-18) in mouse BMSCs and neuron-like BMSCs generated by Notch intracellular domain-based induction (NICD-3F BMSCs). BMSCs exhibited higher intracellular GSH levels than NICD-3F BMSCs, despite comparable levels of EAAC1 protein. In contrast, EAAC1-dependent cysteine uptake and plasma membrane localization of EAAC1 were markedly reduced in BMSCs, indicating differentiation-dependent regulation of EAAC1 trafficking. Treatment with the xCT inhibitor erastin reduced intracellular GSH levels in both BMSCs and NICD-3F BMSCs. GTRAP3-18 expression was high in BMSCs and significantly reduced in NICD-3F BMSCs. Notably, GTRAP3-18 knockout decreased intracellular GSH levels in BMSCs without altering total EAAC1 protein or intracellular cysteine levels, whereas in NICD-3F BMSCs, both GSH and EAAC1 protein levels were increased. These findings demonstrate lineage-dependent divergence in GSH regulatory mechanisms and reveal previously unrecognized functions of GTRAP3-18 in redox control during stem–to–neuron differentiation. Full article
(This article belongs to the Special Issue Current Trends in Redox Physiology Research)
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17 pages, 5467 KB  
Article
Notch Overexpression Potentiates Interferon Signaling in Glioma Cells
by Marina Giannaki, Elena Parmigiani, Karin Burger, Verdon Taylor and Claudio Giachino
Curr. Issues Mol. Biol. 2026, 48(6), 547; https://doi.org/10.3390/cimb48060547 - 23 May 2026
Cited by 1 | Viewed by 915
Abstract
Interferons (IFNs) play fundamental roles in cancer immunity. We have previously shown that conditional ablation of Notch pathway genes in a mouse model of glioma results in impaired IFNγ signaling and immunosuppressive tumors. However, it remained unclear whether the interaction between the Notch [...] Read more.
Interferons (IFNs) play fundamental roles in cancer immunity. We have previously shown that conditional ablation of Notch pathway genes in a mouse model of glioma results in impaired IFNγ signaling and immunosuppressive tumors. However, it remained unclear whether the interaction between the Notch and IFN signaling pathways could be leveraged to counteract immune evasion in glioma. Here, we investigated whether expression of the intrinsically active Notch intracellular domain (NICD) could enhance IFN responses in glioma cells. Using a doxycycline (Dox)-inducible system, we overexpressed (OE) NICD in U-251MG human glioma cells. NICD-OE dramatically potentiated STAT1 phosphorylation in response to stimulation with either IFNγ or IFNα. Moreover, NICD-OE induced the expression of the transcription factor IRF1, a regulator of IFN signaling responses. Notably, NICD-OE in U-251MG human glioma cells boosted the IFNγ-dependent transcription of the CXCL9 and CXCL10 genes, which encode cytokines that regulate T cell function. Accordingly, NICD-OE in vivo promoted cytotoxic T lymphocyte recruitment to the tumor and reduced tumor cell proliferation in a murine glioma model. Hence, we have identified a signaling network that could be exploited to enhance anti-tumor immunity in glioma subtypes. Full article
(This article belongs to the Special Issue The Molecular Basis of Immunotherapy in Cancer Treatment)
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49 pages, 2415 KB  
Systematic Review
Modulation of Oncogenic NOTCH Signaling in Highly Aggressive Malignancies by Targeting the γ-Secretase Complex: A Systematic Review
by Pablo Martínez-Gascueña, María-Luisa Nueda and Victoriano Baladrón
Cells 2026, 15(5), 468; https://doi.org/10.3390/cells15050468 - 5 Mar 2026
Cited by 3 | Viewed by 1948
Abstract
Background. NOTCH receptors play a pivotal role in carcinogenesis. Upon ligand binding, a cascade of proteolytic cleavages mediated by ADAM proteases and the γ-secretase complex activates the receptor, ultimately releasing the NOTCH intracellular domain (NICD). NICD translocates to the nucleus, where it regulates [...] Read more.
Background. NOTCH receptors play a pivotal role in carcinogenesis. Upon ligand binding, a cascade of proteolytic cleavages mediated by ADAM proteases and the γ-secretase complex activates the receptor, ultimately releasing the NOTCH intracellular domain (NICD). NICD translocates to the nucleus, where it regulates gene expression. This review mainly aims to evaluate γ-secretase inhibitors (GSIs) as anticancer agents in preclinical and clinical settings, with a focus on their ability to block tumor progression, target cancer stem cells, and overcome resistance to standard therapies. Methods. A systematic search was conducted in the ISI Web of Science, PubMed, and Scopus databases, following PRISMA guidelines. The review included preclinical in vitro and in vivo studies, as well as clinical trials, investigating GSIs, either as monotherapy or in combination with other treatments, in TNBC, metastatic melanoma, PDAC, gastric cancer, and NSCLC. Exclusion criteria included duplicates, non-English articles, studies published before 2010, studies on non-cancer conditions, research unrelated to NOTCH signaling, and studies outside the selected cancer types. Overall, 69 articles were included and categorized into the five types of cancer analyzed (20 on NSCLC, 22 on TNBC, 11 on metastatic melanoma, 7 on GC, and 9 on PDAC). Of these, 60 studies corresponded to preclinical research in the types of cancer, and 9 studies corresponded to clinical trials in the types of cancer except for GC. Two independent authors screened and extracted relevant data, with disagreements resolved by the corresponding author. Findings were synthesized qualitatively across cancer types under study. Results. This review summarizes therapeutic advances involving GSIs in cancers driven by oncogenic NOTCH signaling, based on the 69 articles included. Preclinical studies show that GSIs synergize with chemotherapy and radiotherapy, particularly in NSCLC, melanoma, and TNBC, and block EMT, overcome therapeutic resistance, and improve prognosis. Commonly used GSIs include DAPT and RO4929097, which enhance the efficacy of agents, such as gemcitabine (PDAC), paclitaxel, osimertinib, erlotinib, and crizotinib (NSCLC), and 5-FU (gastric cancer, TNBC). Promising strategies include combining GSIs with SAHA, ATRA, CB-103, and other NOTCH signaling targeting molecules, either alone or with chemo- and radiotherapy. Clinical trials with GSIs, however, remain limited. RO4929097 is the most extensively tested GSI in clinical settings. PDAC trials combining GSIs with gemcitabine showed no benefit; melanoma trials yielded modest outcomes; and TNBC trials demonstrated partial responses to GSIs but overall low efficacy and significant adverse events. Discussion and Conclusions. Despite encouraging preclinical evidence, clinical trials with GSIs have underperformed, largely due to tumor heterogeneity, dosing limitations, and the non-selective nature of γ-secretase inhibition. Other NOTCH inhibitors, such as DLL4 antibodies, also resulted in partial responses and secondary effects. Future strategies should prioritize receptor-specific NOTCH inhibitors, patient stratification based on NOTCH pathway activation, and optimized combination regimens. Emerging approaches include integrating immunotherapy with advanced technologies such as CRISPR, CAR-T cells, and bispecific antibodies, as well as targeted delivery systems to enhance efficacy and reduce toxicity. Additional research directions include addressing the tumor microenvironment and EMT-driven resistance, elucidating the mechanisms of immune evasion, and inhibiting tumor angiogenesis. Finally, leveraging artificial intelligence and big-data-driven personalized medicine, including sex-specific considerations, will be essential for improving patient outcomes. Full article
(This article belongs to the Special Issue New Advances in Anticancer Therapy)
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29 pages, 1732 KB  
Systematic Review
Surveillance of Healthcare-Associated Infections in the WHO African Region: Systematic Review of Literature from 2011 to 2024
by Laetitia Gahimbare, Nathalie K. Guessennd, Claude Mambo Muvunyi, Walter Fuller, Sheick Oumar Coulibaly, Landry Cihambanya, Pierre Claver Kariyo, Olga Perovic, Ambele Judith Mwamelo, Diané Kouao Maxime, Valérie Gbonon, Konan Kouadio Fernique, Babacar Ndoye and Yahaya Ali Ahmed
Antibiotics 2025, 14(12), 1287; https://doi.org/10.3390/antibiotics14121287 - 18 Dec 2025
Viewed by 2516
Abstract
Background: Evidence on HAIs in Africa is fairly common. Objectives: The main objective was to identify the surveillance tools used for healthcare–associated infections (HAIs) in countries in the WHO African Region. Secondary objectives focused on the organization of surveillance, the pathogens involved, and [...] Read more.
Background: Evidence on HAIs in Africa is fairly common. Objectives: The main objective was to identify the surveillance tools used for healthcare–associated infections (HAIs) in countries in the WHO African Region. Secondary objectives focused on the organization of surveillance, the pathogens involved, and the frequency of multidrug–resistant species. Inclusion and exclusion criteria: Observational or interventional studies on healthcare–associated infections in humans, published between January 2011 and December 2024, in French or English, were included. However, the following publications were not included: animal studies, healthcare–associated infections not related to healthcare, literature reviews, studies outside the period or geographical area, and studies in languages other than French or English. Sources of information and search date: The databases consulted were PubMed, Web of Science, EMBASE, Cochrane, African Index Medicus, Google Scholar, and AJOL. The search was conducted between January and March 2025. Risk of bias assessment: The risk of bias was assessed using a specific grid (eleven criteria), scored from one (low) to three (high). The studies were classified into three levels of methodological quality. The results of the bias assessment showed that the publications were excellent (strong and moderate) with a cumulative rate of 99.9%. Methods of synthesizing results: Data were extracted using a standardized grid and synthesized narratively. No meta–analysis was performed. Number of studies and characteristics: 95 studies were included, mostly cross–sectional studies (82.1%), cohorts (10.4%), and a few case reports. Most were from West Africa (60.0%), particularly Nigeria (16.8%) and South Africa (14.7%). Main results: • Most common pathogens: Staphylococcus aureus (53.7%), Escherichia coli (43.2%), Klebsiella pneumoniae (32.6%). • Resistance profile: ESBL (27.4%), MRSA (21.1%), multidrug resistance (13.7%). • Sources of HAIs: mainly exogenous (83.2%). • Laboratory methods: phenotypic (70.5%), genotypic or genomic rare (3.1%). • Scope of studies: local (96.8%), national (3.2%). Limitations of evidence: Risk of bias due to underreporting of HAIs, methodological heterogeneity, predominance of cross–sectional studies, low use of molecular methods, lack of modeling, and uneven geographical coverage. Overall interpretation and implications: surveillance of HAIs in Africa remains fragmented and poorly standardized. There is a need to strengthen national systems, integrate molecular methods, train professionals, and promote interventional research. The WHO GLASS program can serve as a framework for harmonizing surveillance. Full article
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18 pages, 2197 KB  
Article
Long-Term Impact of Pneumococcal Conjugate Vaccines on the Burden of Pneumococcal Meningitis in Mozambique, 2013–2023
by Aquino Albino Nhantumbo, Goitom Weldegebriel, Linda de Gouveia, Reggis Katsande, Charlotte Elizabeth Comé, Alcides Moniz Munguambe, Vlademir Cantarelli, Cícero Dias, Rachid Muleia, Ezequias Fenias Sitoe, Eunice Veronica Zeca, Amir Seni, Ana Nicolau Tambo, Ana Cristina de Faria Neves Mussagi, Plácida Iliany Maholela, Ivano de Filippis and Eduardo Samo Gudo
Vaccines 2025, 13(12), 1246; https://doi.org/10.3390/vaccines13121246 - 15 Dec 2025
Viewed by 1041
Abstract
Background: Mozambique introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in 2013 using a three-dose primary series with no booster dose (3p+0) and later switched to the PCV13 using a schedule of two primary doses with one booster (2p+1). We aimed to describe the [...] Read more.
Background: Mozambique introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in 2013 using a three-dose primary series with no booster dose (3p+0) and later switched to the PCV13 using a schedule of two primary doses with one booster (2p+1). We aimed to describe the burden and serotype distribution of pneumococcal meningitis in children under 5 years of age in Mozambique over an eleven-year period starting with the year of PCV10 introduction, and assess the impact of the PCV vaccine and schedule changes. Methods: We analysed meningitis surveillance data in Mozambique from March 2013 through to December 2023. Cerebrospinal fluid (CSF) samples were collected from eligible children in three referral hospitals (Maputo Central Hospital [south], Beira Central Hospital [central], and Nampula Central Hospital [north]). Culture and polymerase chain reaction assay (qPCR) were performed on each sample. S. pneumoniae-positive samples were subsequently serotyped using multiplex assay. We estimated annual incidence rates for pneumococcal meningitis in children under 5 years old following the PCVs’ introduction (2013–2023). The impact of the product switch and schedule change from PCV10/3p+0 to PCV13/2p+1 on the burden and serotype distribution of pneumococcal meningitis was assessed. Results: Of the 4075 CSF samples tested, 7.4% (301/4075) were positive for S. pneumoniae, 2.5% (103/4075) for H. influenzae, and 1.0% (42/4075) for N. meningitidis. Pneumococcal meningitis incidence in children under five reduced from 44.7 cases per 100,000 in 2013 to 4.6 cases per 100,000 in 2023, an 89.7% reduction. In the PCV13/2p+1 period (2020–2023), pneumococcal meningitis incidence was 51.2% lower than the PCV10/3p+0 period (2013–2017) (IRR 0.49, 95% CI 0.4–0.6; p < 0.001). PCV10-serotype pneumococcal meningitis incidence among children under five decreased by 65.6% in the PCV13/2p+1 period (IRR 0.34, 95% CI 0.2–0.6; p < 0.001). We detected zero cases of pneumococcal meningitis due to the PCV13-serotype in 2020–2023, whereas non-PCV10/13-serotypes increased by 76% (IRR 1.76, 95% CI 1.2–2.6; p = 0.004). The case–fatality proportion decreased by 71.9% (95% CI 62.9–84.8%) in the PCV13/2p+1 period. Conclusions: Since the introduction of PCVs in Mozambique, the burden of pneumococcal meningitis and deaths in children under 5 years of age has substantially decreased, as well as the prevalence of PCV13-serotypes. Higher valency PCVs are needed due to the increased prevalence of non-PCV10/13-serotypes. Funding: Gavi, The Vaccine Alliance, reference number: MOZ-HSS-2-INS; WHO Reference: 2014405143-0, creation DFC to support HIB & Surveillance System. Full article
(This article belongs to the Special Issue Pneumococcal Vaccines: Current Status and Future Prospects)
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18 pages, 6928 KB  
Article
Split Ends Inhibits the Dedifferentiation of imINP to Prevent the Generation of Supernumerary Type II Neuroblasts in Drosophila
by Qingxia Zhou, Fuhao Zhang, Sifan Gong, Shuliu Zhang, Wenting Gong, Menglong Rui and Su Wang
Cells 2025, 14(23), 1926; https://doi.org/10.3390/cells14231926 - 4 Dec 2025
Viewed by 978
Abstract
Investigating the mechanisms that maintain different types of neural stem cells is essential for brain development. While factors maintaining distinct Drosophila melanogaster neuroblasts (NBs) have been identified, additional factors remain unidentified. In this paper, we find knockdown of split ends (spen) [...] Read more.
Investigating the mechanisms that maintain different types of neural stem cells is essential for brain development. While factors maintaining distinct Drosophila melanogaster neuroblasts (NBs) have been identified, additional factors remain unidentified. In this paper, we find knockdown of split ends (spen) increases in nuclear Notch intracellular domain (NICD) level, which in turn activates Notch signaling in type II NBs. This activation causes the intermediate neural progenitors (imINPs) to dedifferentiate into type II NBs, thereby increasing the number of type II NBs specifically. Additionally, we find that knockdown of both spen and a co-repressor of the Notch signaling pathway, Hairless, in type II NBs exacerbates the increase in type II NBs number, compared to spen knockdown alone. Furthermore, we observe that loss of Spen results in more severe phenotypes than loss of Hairless in type II NBs and their lineages. We reveal that Spen may indeed function as a functional homolog of its mammalian homolog, SHARP, acting as a novel Notch signaling co-repressor in type II NBs specifically. This highlights the potential for multiple co-repressors to collaboratively regulate the same signaling pathway within the type II NBs lineage. The distinct regulatory mechanism of type I and II NBs offers new insights into the study of neural stem cell homeostasis. Full article
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21 pages, 1669 KB  
Article
Comparison of the CO2 Balance in Electroslag Reduction of Cadmium with Pyrometallurgical and Hydrometallurgical Recovery Methods
by Ervīns Blumbergs, Michail Maiorov, Artūrs Brēķis, Ernests Platacis, Sergei Ivanov, Jekaterina Nikitina, Artur Bogachov and Vladimir Pankratov
Metals 2025, 15(11), 1197; https://doi.org/10.3390/met15111197 - 27 Oct 2025
Cited by 1 | Viewed by 947
Abstract
This study presents a carbon footprint assessment of a novel electroslag method for cadmium (Cd) recovery from spent nickel–cadmium (Ni-Cd) batteries in comparison with the carbon footprints of pyrometallurgical and hydrometallurgical cadmium recovery methods. A comparison of CO2 emissions in three types [...] Read more.
This study presents a carbon footprint assessment of a novel electroslag method for cadmium (Cd) recovery from spent nickel–cadmium (Ni-Cd) batteries in comparison with the carbon footprints of pyrometallurgical and hydrometallurgical cadmium recovery methods. A comparison of CO2 emissions in three types of technological processes during the recovery of 1 kg of cadmium is carried out. Energy inputs and CO2 emissions are calculated for the electroslag process and compared to conventional methods, such as pyrometallurgical and hydrometallurgical reduction methods. The electroslag process eliminates cadmium vaporization by using molten KCl–NaCl flux and carbon under electromagnetic stirring. Cadmium reduction occurs under a layer of flux, which prevents the contact of the reduced cadmium with the atmosphere. The electroslag process temperature is limited to 700 °C, which is lower than the boiling point of cadmium (767 °C). The electroslag remelting process uses molten KCl–NaCl flux and carbon as a reductant under electrovortex flow stirring. The pyrometallurgical method for extracting cadmium from nickel–cadmium batteries is based on the reduction of cadmium with carbon at high temperatures. In the pyrometallurgical process, coal (anthracite) is used as the carbonaceous material, which can extract 99.92% of cadmium at 900 °C. Cadmium is separated using a vacuum at temperatures ranging from 800 °C to 950 °C for several hours. Hydrometallurgy is a metal extraction process involving chemical reactions that occur in organic or aqueous solutions at low temperatures. The hydrometallurgical process involves a series of acid or alkaline leaches, followed by separation and purification methods such as absorption, cementation, ion exchange, and solvent extraction to separate and concentrate metals from leach solutions. Full article
(This article belongs to the Section Extractive Metallurgy)
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22 pages, 6310 KB  
Article
A Green Electroslag Technology for Cadmium Recovery from Spent Ni-Cd Batteries Under Protective Flux with Electromagnetic Stirring by Electrovortex Flows
by Ervīns Blumbergs, Michail Maiorov, Artur Bogachov, Ernests Platacis, Sergei Ivanov, Pavels Gavrilovs and Vladimir Pankratov
Metals 2025, 15(9), 959; https://doi.org/10.3390/met15090959 - 29 Aug 2025
Cited by 3 | Viewed by 1525
Abstract
The recycling of nickel–cadmium batteries poses a significant environmental challenge due to cadmium’s high biotoxicity. This study proposes a green method for recovering cadmium from cadmium oxide (CdO) using carbon (coal) in the presence of a molten binary flux (KCl:NaCl = 0.507:0.493, melting [...] Read more.
The recycling of nickel–cadmium batteries poses a significant environmental challenge due to cadmium’s high biotoxicity. This study proposes a green method for recovering cadmium from cadmium oxide (CdO) using carbon (coal) in the presence of a molten binary flux (KCl:NaCl = 0.507:0.493, melting point 667 °C). The flux’s relatively low density and conductivity enable cadmium reduction beneath and through the flux layer. Brown coal (5–25 mm) served as the reductant. The reduction of cadmium from cadmium oxide with carbon (brown coal) took place in the temperature range from 667 °C to 700 °C. To enhance the process, electrovortex flows (EVF) were employed—generated by the interaction between non-uniform AC electric currents and their self-induced magnetic fields resembling conditions in a fluidised bed reactor. The graphite crucible acted as both one of the electrodes, with a graphite rod as the second electrode. As Cd and CdO are denser than both the flux and coal, the reduction proceeded below the flux layer. The flux facilitated CdO transport to the reductant, speeding up the reaction. X-ray diffraction (XRD) and scanning electron microscopy (SEM) confirmed the formation of metallic cadmium beneath and within the flux layer. This method demonstrates the feasibility of flux-assisted cadmium recovery without prior mixing and offers a foundation for further optimisation of sustainable battery recycling. Full article
(This article belongs to the Special Issue Green Technologies in Metal Recovery)
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19 pages, 2396 KB  
Article
Alleviation of Ovalbumin-Allergic Reactions in Mice by Eucommia ulmoides Polysaccharides via Modulation of Intestinal Microbiota
by Xuelei Zhang, Ketong Bi, Chuansheng Zhao, Yuxin Cao, Yuxuan Yang, Jingxuan Jia, Yong Zhang, Dandan Zhai, Yu Yang and Peng Li
Foods 2025, 14(16), 2913; https://doi.org/10.3390/foods14162913 - 21 Aug 2025
Cited by 6 | Viewed by 1830
Abstract
Food allergy represents a prevalent immunological disorder, with current clinical management primarily emphasizing allergen avoidance and emergency pharmacological intervention. Eucommia ulmoides polysaccharides, the principal bioactive constituents of the traditional Chinese medicinal plant Eucommia ulmoides, have demonstrated anti-inflammatory and antioxidant properties; however, their [...] Read more.
Food allergy represents a prevalent immunological disorder, with current clinical management primarily emphasizing allergen avoidance and emergency pharmacological intervention. Eucommia ulmoides polysaccharides, the principal bioactive constituents of the traditional Chinese medicinal plant Eucommia ulmoides, have demonstrated anti-inflammatory and antioxidant properties; however, their specific effects on food allergies remain inadequately characterized. A total of thirty-six female BALB/c mice were randomly allocated into three groups (n = 12 per group): the control group (CON group, receiving saline treatment), the allergic model group (OVA group, subjected to ovalbumin sensitization), and the intervention group (OVA+PS group, undergoing OVA sensitization followed by Eucommia ulmoides polysaccharides administration via gavage). The anti-allergic efficacy of Eucommia ulmoides polysaccharides was comprehensively evaluated through clinical allergy symptom scoring, histological and pathological tissue analysis, real-time fluorescence quantitative PCR (qRT-PCR) for the assessment of key gene expression, and 16S rDNA sequencing. The findings indicated the following: (1) The allergy scores in the OVA+PS group were significantly lower than those in the OVA group (p < 0.01). Following OVA stimulation, the rectal temperature of mice in the OVA group decreased sharply, whereas the temperature decline in the OVA+PS group was more gradual compared to the model group. (2) The liver, kidney, spleen, and intestinal tissues of mice in the OVA+PS group exhibited normal morphology, consistent with the CON group, which suggests that Eucommia ulmoides polysaccharides effectively mitigates the local inflammatory response induced by food allergy. (3) The expression of NICD in the spleen of mice in the OVA+PS group was significantly higher than in the OVA group (p < 0.05), while the expression of the Hes1 gene was significantly elevated in the OVA group compared to both the CON and OVA+PS groups (p < 0.05). In the OVA group, the expression level of Gata-3 was significantly elevated compared to both the CON group and the OVA+PS group (p < 0.05). Similarly, the expression of STAT5 in the OVA group was markedly higher than in the other groups (p < 0.05). (4) Eucommia ulmoides polysaccharides were found to modulate the intestinal microbiota composition in allergic mice, notably increasing the expression abundance of Enterobacter, Oscillibacter, and Butyricicoccus, while decreasing the expression abundance of Clostridium sensu stricto 1 and Turicibacter. (5) There was a correlation between alterations in the intestinal microbiota of mice and the expression of key genes. Specifically, the relative abundance of Blautia was negatively correlated with the expression of NICD and Gata-3 genes (p < 0.05), and the relative abundance of the Lachnospiraceae_FCS020_group was negatively correlated with the expression of the Hes1 gene (p < 0.05). In conclusion, Eucommia ulmoides polysaccharides demonstrate potential in alleviating allergic symptoms, providing a scientific foundation for the development of novel natural anti-allergic functional foods. Full article
(This article belongs to the Special Issue Natural Polysaccharides: Structure and Health Functions)
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23 pages, 16399 KB  
Article
Design and Implementation of a Full SiC-Based Phase-Shifted Full-Bridge DC-DC Converter with Nanocrystalline-Cored Magnetics for Railway Battery Charging Applications
by Fatih Enes Gocen, Salih Baris Ozturk, Mehmet Hakan Aksit, Gurkan Dugan, Benay Cakmak and Caner Demir
Energies 2025, 18(15), 3945; https://doi.org/10.3390/en18153945 - 24 Jul 2025
Cited by 8 | Viewed by 3323
Abstract
This paper presents the design and implementation of a high-efficiency, full silicon carbide (SiC)-based center-tapped phase-shifted full-bridge (PSFB) converter for NiCd battery charging applications in railway systems. The converter utilizes SiC MOSFET modules on the primary side and SiC diodes on the secondary [...] Read more.
This paper presents the design and implementation of a high-efficiency, full silicon carbide (SiC)-based center-tapped phase-shifted full-bridge (PSFB) converter for NiCd battery charging applications in railway systems. The converter utilizes SiC MOSFET modules on the primary side and SiC diodes on the secondary side, resulting in significant efficiency improvements due to the superior switching characteristics and high-temperature tolerance inherent in SiC devices. A nanocrystalline-cored center-tapped transformer is optimized to minimize voltage stress on the rectifier diodes. Additionally, the use of a nanocrystalline core provides high saturation flux density, low core loss, and excellent permeability, particularly at high frequencies, which significantly enhances system efficiency. The converter also compensates for temperature fluctuations during operation, enabling a wide and adjustable output voltage range according to the temperature differences. A prototype of the 10-kW, 50-kHz PSFB converter, operating with an input voltage range of 700–750 V and output voltage of 77–138 V, was developed and tested both through simulations and experimentally. The converter achieved a maximum efficiency of 97% and demonstrated a high power density of 2.23 kW/L, thereby validating the effectiveness of the proposed design for railway battery charging applications. Full article
(This article belongs to the Special Issue Advancements in Electromagnetic Technology for Electrical Engineering)
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11 pages, 2330 KB  
Article
Separations of Strategic Metals from Spent Electronic Waste Using “Green Methods”
by Urszula Domańska, Anna Wiśniewska and Zbigniew Dąbrowski
Separations 2025, 12(6), 167; https://doi.org/10.3390/separations12060167 - 18 Jun 2025
Cited by 2 | Viewed by 1869
Abstract
Next-generation recycling technologies must be urgently innovated to tackle huge volumes of spent batteries, photovoltaic panels or printed circuit boards (WPCBs). Current e-waste recycling industrial technology is dominated by traditional recycling technologies. Herein, ionic liquids (ILs), deep eutectic solvents (DESs) and promising oxidizing [...] Read more.
Next-generation recycling technologies must be urgently innovated to tackle huge volumes of spent batteries, photovoltaic panels or printed circuit boards (WPCBs). Current e-waste recycling industrial technology is dominated by traditional recycling technologies. Herein, ionic liquids (ILs), deep eutectic solvents (DESs) and promising oxidizing additives that can overcome some traditional recycling methods of metal ions from e-waste, used in our works from last year, are presented. The unique chemical environments of ILs and DESs, with the application of low-temperature extraction procedures, are important environmental aspects known as “Green Methods”. A closed-loop system for recycling zinc and manganese from the “black mass” (BM) of waste, Zn-MnO2 batteries, is presented. The leaching process achieves a high efficiency and distribution ratio using the composition of two solvents (Cyanex 272 + diethyl phosphite (DPh)) for Zn(II) extraction. High extraction efficiency with 100% zinc and manganese recovery is also achieved using DESs (cholinum chloride/lactic acid, 1:2, DES 1, and cholinum chloride/malonic acid, 1:1, DES 2). New, greener recycling approaches to metal extraction from the BM of spent Li-ion batteries are presented with ILs ([N8,8,8,1][Cl], (Aliquat 336), [P6,6,6,14][Cl], [P6,6,6,14][SCN] and [Benzet][TCM]) eight DESs, Cyanex 272 and D2EHPA. A high extraction efficiency of Li(I) (41–92 wt%) and Ni(II) (37–52 wt%) using (Cyanex 272 + DPh) is obtained. The recovery of Ni(II) and Cd(II) from the BM of spent Ni-Cd batteries is also demonstrated. The extraction efficiency of DES 1 and DES 2, contrary to ILs ([P6,6,6,14][Cl] and [P6,6,6,14][SCN]), is at the level of 30 wt% for Ni(II) and 100 wt% for Cd(II). In this mini-review, the option to use ILs, DESs and Cyanex 272 for the recovery of valuable metals from end-of-life WPCBs is presented. Next-generation recycling technologies, in contrast to the extraction of metals from acidic leachate preceded by thermal pre-treatment or from solid material only after thermal pre-treatment, have been developed with ILs and DESs using the ABS method, as well as Cyanex 272 (only after the thermal pre-treatment of WPCBs), with a process efficiency of 60–100 wt%. In this process, four new ILs are used: didecyldimethylammonium propionate, [N10,10,1,1][C2H5COO], didecylmethylammonium hydrogen sulphate, [N10,10,1,H][HSO4], didecyldimethylammonium dihydrogen phosphate, [N10,10,1,1][H2PO4], and tetrabutylphosphonium dihydrogen phosphate, [P4,4,4,4][H2PO4]. The extraction of Cu(II), Ag(I) and other metals such as Al(III), Fe(II) and Zn(II) from solid WPCBs is demonstrated. Various additives are used during the extraction processes. The Analyst 800 atomic absorption spectrometer (FAAS) is used for the determination of metal content in the solid BM. The ICP-OES method is used for metal analysis. The obtained results describe the possible application of ILs and DESs as environmental media for upcycling spent electronic wastes. Full article
(This article belongs to the Section Materials in Separation Science)
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17 pages, 3168 KB  
Article
Notch Is Required for Neural Progenitor Proliferation During Embryonic Eye Regrowth
by Dylan J. Guerin, Belen Gutierrez, Baoyi Zhang and Kelly Ai-Sun Tseng
Int. J. Mol. Sci. 2025, 26(6), 2637; https://doi.org/10.3390/ijms26062637 - 14 Mar 2025
Cited by 2 | Viewed by 2461
Abstract
The ability of an organism to regrow tissues is regulated by various signaling pathways. One such pathway that has been studied widely both in the context of regeneration and development is the Notch signaling pathway. Notch is required for the development of the [...] Read more.
The ability of an organism to regrow tissues is regulated by various signaling pathways. One such pathway that has been studied widely both in the context of regeneration and development is the Notch signaling pathway. Notch is required for the development of the eye and regeneration of tissues in multiple organisms, but it is unknown if Notch plays a role in the regulation of Xenopus laevis embryonic eye regrowth. We found that Notch1 is required for eye regrowth and regulates retinal progenitor cell proliferation. Chemical and molecular inhibition of Notch1 significantly decreased eye regrowth by reducing retinal progenitor cell proliferation without affecting retinal differentiation. Temporal inhibition studies showed that Notch function is required during the first day of regrowth. Interestingly, Notch1 loss-of-function phenocopied the effects of the inhibition of the proton pump, vacuolar-type ATPase (V-ATPase), where retinal proliferation but not differentiation was blocked during eye regrowth. Overexpression of a form of activated Notch1, the Notch intracellular domain (NICD) rescued the loss of eye regrowth due to V-ATPase inhibition. These findings highlight the importance of the Notch signaling pathway in eye regeneration and its role in inducing retinal progenitor cell proliferation in response to injury. Full article
(This article belongs to the Special Issue Notch Signaling Pathways)
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35 pages, 9472 KB  
Review
The Safety Engineering of Sodium-Ion Batteries Used as an Energy Storage System for the Military
by Agnieszka Iwan, Krzysztof A. Bogdanowicz, Robert Pich, Agnieszka Gonciarz, Jacek Miedziak, Ireneusz Plebankiewicz and Wojciech Przybyl
Energies 2025, 18(4), 978; https://doi.org/10.3390/en18040978 - 18 Feb 2025
Cited by 16 | Viewed by 8890
Abstract
The main idea of this work is based on the latest achievements in the commercialization of sodium-ion (Na-ion) batteries, which constitute a basis of analysis for military applications as energy storage systems. Technical, engineering, and ecological aspects were analyzed to find the optimal [...] Read more.
The main idea of this work is based on the latest achievements in the commercialization of sodium-ion (Na-ion) batteries, which constitute a basis of analysis for military applications as energy storage systems. Technical, engineering, and ecological aspects were analyzed to find the optimal solution for using Na-ion batteries for military purposes. When selecting batteries for military applications, the following criteria are required: (a) they are more durable than standard batteries, (b) resistant to fire, (c) cannot explode, (d) cannot emit heat so as not to reveal their position, (e) equipped with safety elements and protective circuits to ensure safety, and (f) have the highest possible energy density, defined as the ratio of capacity to weight. The advantages and challenges of Na-ion batteries are discussed and compared to typical lithium-ion batteries, and also lithium iron phosphate, Ni-Cd, and Ni-MH batteries. The prospects for expanding the practical applications of Na-ion batteries in the military are presented. The unique properties of Na-ion batteries, such as their lower risk of ignition, more excellent thermal stability, and ability to work in extreme conditions, are essential from the point of view of military operations. Additionally, when considering environmental and logistical aspects, sodium-ion batteries may offer more sustainable and cost-effective solutions for the military. Therefore, this work aims not only to present the technological potential of these systems but also to draw attention to their strategic importance for the future of military operations. Battery discharge can result from leaving current receivers switched on or even from a drop in temperature. The discharge current should not exceed 1/10 of the battery capacity (1C). Discharging below the discharge voltage may result in irreversible damage. Sodium-ion batteries are safer to use than their lithium counterparts and allow for discharge to 0 V, eliminating the possibility of uncontrolled thermal discharge due to a short circuit (explosion, ignition), which is particularly important in the military. Full article
(This article belongs to the Section D2: Electrochem: Batteries, Fuel Cells, Capacitors)
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22 pages, 18467 KB  
Article
Co-Optimization of Operational and Intelligent Completion Parameters of CO2 Water-Alternating-Gas Injection Processes in Carbonate Reservoirs
by Xili Deng, Jingxuan Wang, Xiangguo Zhao, Liangyu Rao, Yongbin Zhao and Xiaofei Sun
Energies 2025, 18(2), 375; https://doi.org/10.3390/en18020375 - 16 Jan 2025
Cited by 1 | Viewed by 1768
Abstract
Recently, maximum reservoir contacting (MRC) wells have attracted more and more attention and have been gradually applied to CO2 WAG injections. During the use of MRC wells for CO2 WAG injections, intelligent completions are commonly considered to control CO2 breakthroughs. [...] Read more.
Recently, maximum reservoir contacting (MRC) wells have attracted more and more attention and have been gradually applied to CO2 WAG injections. During the use of MRC wells for CO2 WAG injections, intelligent completions are commonly considered to control CO2 breakthroughs. However, the design of the operational and intelligent completion parameters is a complicated process and there are no studies on the co-optimization of the operational and intelligent completion parameters for CO2 WAG processes. This study outlines an approach to enhance the oil recovery from CO2 WAG injection processes through the co-optimization of the operational and intelligent completion parameters of MRC wells in a carbonate reservoir. First, a simulation method is developed by using Petrel and Intersect. Then, a series of simulations are performed to prove the viability of intelligent completions and to investigate the effects of the timing and duration of the CO2 WAG injection, as well as the type, number, and placement of intelligent completion devices on the performance of a CO2 WAG injection by MRC wells. Finally, the imperialist competitive algorithm is used to co-optimize the operational and intelligent completion parameters for MRC wells. The results show that compared with the spiral inflow control device (SICD), autonomous inflow control device (AICD), labyrinth inflow control device (LICD), and annular interval control valve (AICV), the nozzle inflow control device (NICD) is the best type of intelligent completion device for MRC wells. There is an optimal installation timing, inflow area, and number of NICDs for a CO2 WAG injection by MRC wells. The NICDs need to be placed based on the permeability distribution. The oil recovery for the optimal case with the NICDs reached 46.43%, which is an increase of 3.8% over that of the base case with a conventional completion. In addition, compared with the non-uniformity coefficient of the base case (11.7), the non-uniformity coefficient of the optimal case with the NICDs decreased to 4.21. This is the first time that the co-optimization of the operational and intelligent completion parameters of a CO2 WAG injection has been reported, which adds more information about the practical applications of MRC wells in CO2 WAG injections for enhancing oil recovery in carbonate reservoirs. Full article
(This article belongs to the Special Issue Failure and Multiphysical Fields in Geo-Energy)
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