Search Results (4,756)

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

In this study, a highly cadmium (II)-resistant bacterium strain, C10-4, identified as Bacillus altitudinis, was isolated from a sediment sample collected from Baiyangdian Lake, China. The minimum inhibitory concentration (MIC) of Cd(II) for strain C10-4 was 1600 mg/L. Factors such as the contact time, pH, Cd(II) concentration, and biomass dosage affected the adsorption of Cd(II) by strain C10-4. The adsorption process fit well to the Langmuir adsorption isotherm model and the pseudo-second-order kinetics model, based on the Cd(II) adsorption data obtained from the cells of strain C10-4. This suggests that Cd(II) is adsorbed by strain C10-4 cells via a single-layer homogeneous chemical adsorption process. According to the Langmuir model, the maximum biosorption capacity was 3.31 mg/g for fresh-strain C10-4 biomass. Cd(II) was shown to adhere to the bacterial cell wall through SEM-EDS analysis. FTIR spectroscopy further indicated that the main functional sites for the binding of Cd(II) ions on the cell surface of strain C10-4 were functional groups such as N-H, -OH, -CH-, C=O, C-O, P=O, sulfate, and phosphate. After the inoculation of strain C10-4 into Cd(II)-contaminated soils, there was a significant reduction (p < 0.01) in the exchangeable fraction of Cd and an increase (p < 0.01) in the sum of the reducible, oxidizable, and residual fractions of Cd. The results show that Bacillus altitudinis C10-4 has good potential for use in the remediation of Cd(II)-contaminated soils. Full article

The high pH and heavy metal leaching of argon oxygen decarburization (AOD) slag limit its application in agriculture. Slag carbonation can aid in decreasing slag alkalinity and inhibit heavy metal release; the environmental safety of utilizing carbonated AOD slag (CAS) as a fertilizer remains a topic of significant debate, however. In this work, pakchoi (Brassica chinensis L.) was planted in CAS-fertilized soil to investigate the accumulation and migration behavior of heavy metals in the soil–plant system and perform an associated risk assessment. Our results demonstrated that CAS addition increases Ca, Si, and Cr concentrations but decreases Mg and Fe concentrations in soil leachates. Low rates (0.25–1%) of CAS fertilization facilitate the growth of pakchoi, resulting in the absence of soil contamination and posing no threat to human health. At the optimal slag addition rate of 0.25%, the pakchoi leaf biomass, stem biomass, leaf area, and seedling height increased by 34.2%, 17.2%, 26.3%, and 8.7%, respectively. The accumulation of heavy metals results in diverging characteristics in pakchoi. Cr primarily accumulates in the roots; in comparison, Pb, Cd, Ni, and Hg preferentially accumulate in the leaves. The migration rate of the investigated heavy metals from the soil to pakchoi follows the order of Cr > Cd > Hg > Ni > Pb; in comparison, that from the roots to the leaves follows the order Cd > Ni > Hg > Cr > Pb. Appropriate utilization of CAS as a mineral fertilizer can aid in improving pakchoi yield, achieving sustainable economic benefits, and preventing environmental pollution. Full article

Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m³ (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article

Background/Objectives: Brain metastasis (BM) is a common and often early manifestation in lung adenocarcinoma (LUAD), yet its tumor microenvironment remains poorly defined at the time of initial diagnosis. This study aims to characterize early immune microenvironmental alterations in synchronous BM using spatial proteomic profiling. Methods: We performed digital spatial proteomic profiling using the NanoString GeoMx platform on formalin-fixed paraffin-embedded tissues from five treatment-naïve LUAD patients in whom BM was the initial presenting lesion. Paired primary lung and brain metastatic samples were analyzed across tumor and stromal compartments using 68 immune- and tumor-related protein markers. Results: Spatial profiling revealed distinct expression patterns between primary tumors and brain metastases. Immune regulatory proteins—including IDO-1, PD-1, PD-L1, STAT3, PTEN, and CD44—were significantly reduced in brain metastases (p < 0.01), whereas pS6, a marker of activation-induced T-cell death, was significantly upregulated (p < 0.01). These alterations were observed in both tumor and stromal regions, suggesting a more immunosuppressive and apoptotic microenvironment in brain lesions. Conclusions: This study provides one of the first spatially resolved proteomic characterizations of synchronous BM at initial LUAD diagnosis. Our findings highlight early immune escape mechanisms and suggest the need for site-specific immunotherapeutic strategies in patients with brain metastasis. Full article

Cadmium (Cd) toxicity destroys plant cells and affects plant growth and development. Due to its unique metallic properties, selenium (Se) has been shown to be effective in antioxidants, cellular immunity, and heavy metal detoxification. When Se and Cd are present together in plants, they antagonize. However, the mechanism of action of the two in the rice cell wall remains to be clarified. In this study, we analyzed the mechanism of Cd detoxification by rice (Oryza sativa L.) cellular polysaccharides mediated by Se, using the cell wall as an entry point. Proteomic and transcriptomic analyses revealed that “Glycosyl hydrolases family 17”, “O-methyltransferase”, and “Polygalacturonase” protein pathways were significantly expressed in the cell wall. The most abundant enzymes involved in polysaccharide biosynthesis were found, including bglB, otsB, HK, PFP, ADH1, and ALDH, which resulted in the synthetic pathway of polysaccharide formation in the rice cell wall. Finally, the essential genes/proteins, such as protein Os03g0170500, were identified. The study showed that Se inhibits Cd uptake and transport when Se (1 mg/kg) is low relative to Cd (3 mg/kg), has little inhibitory effect, and even promotes Cd (3 mg/kg) uptake when Se (5 mg/kg) is relatively high. Full article

Cetraria islandica (L.) Ach. (CI) is a lichen from the Parmeliaceaea family used in medicine. However, the low solubility of CI secondary metabolites in water limits the application of lichen extract and compounds. It prompted us to study the systems of cyclodextrins (CDs) (β-CD, γ-CD, HP-β-CD, and HP-γ-CD) with the CI acetone or CI methanol extracts prepared using grinding and solvent evaporation methods. The content of fumarprotocetraric acid (FPCA), a key CI metabolite, was quantified using HPLC. CD–extract systems were characterized by X-ray powder diffraction (XRPD) and Fourier-transform infrared (FTIR) spectroscopy. Biological activity was evaluated using cell-free assays: a Folin–Ciocalteu analysis, DPPH test, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitions. Dissolution profiles were also assessed. The best biological and physicochemical results were obtained for systems prepared with HP-β-CD and HP-γ-CD via solvent evaporation, showing higher activity and enhanced FPCA release compared to the pure extracts. To the best of our knowledge, this is the first study to report the preparation and characterization of CD-based systems with CI extracts. The obtained results encourage us to continue our research on CI to improve the physicochemical properties of its active compounds. Full article

Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L. var. sylvestris (Lam.) Fiori), the wild cardoon, is known for its culinary applications and potential health benefits. Due to this, and given the growing interest in circular economies, deepening our under-standing of the effects of wild cardoon leaf waste on angiogenesis and collagenase activity represents a valuable opportunity to valorise agricultural byproducts as health-promoting ingredients. In this study, the waste product of wild cardoon leaves was extracted to examine its chemical composition and biological activities. Analytical techniques identified several bioactive compounds, including flavonoids, hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids, and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos and the chick chorioallantoic membrane demonstrated dose-dependent antiangiogenic effects, particularly enhanced by the complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD). Considering the link between angiogenesis and collagenase, the potential effects of the extract on collagenase activity was investigated. The extract alone inhibited collagenase with an IC₅₀ value comparable to that of the standard inhibitor while its complexed form exhibited a 4.5-fold greater inhibitory activity. A molecular docking study examined the interaction between the main compounds and collagenase. In conclusion, wild cardoon leaves can represent a valuable source of bioactive compounds. This study demonstrated that the complexation of the extract with cyclodextrin determines an increase in its biological activity. Full article

Cadmium (Cd) contamination in rice (Oryza sativa L.) poses serious health risks for human, necessitating effective mitigation strategies. This study investigated the effects of Cd stress on iron (Fe), manganese (Mn), zinc (Zn), and Cd accumulation and translocation in rice varieties with high (MY46) or low (ZS97B) Cd accumulation capacities grown in acidic and alkaline soils. Results demonstrated that Cd stress significantly inhibited plant growth, reducing plant height, shoot biomass, and grain yield in both soil types. Cd accumulation increased in roots, shoots, and grains, while Fe, Mn, and Zn concentrations decreased markedly. Molecular analysis revealed upregulation of metal transporter genes (OsIRT1, OsNRAMP1, OsNRAMP5) and the vacuolar sequestration gene (OsHMA3) in roots under Cd exposure. The translocation factor (TF) values of Mn and Zn from root to shoot were reduced in acidic soils, whereas Mn and Zn TFs exhibited an increasing trend in alkaline soils despite Cd exposure. Furthermore, correlation analyses indicated Mn and Zn play crucial roles in suppressing Cd accumulation in both acidic and alkaline soils. These findings provide critical insights for developing soil-specific strategies to reduce Cd accumulation in rice through micronutrient management. Full article

The leaf diseases of Panax notoginseng (Panax notoginseng (Burk) F. H. Chen) are mainly spread by spores. To enable rapid and sensitive detection of spores for early warning of disease spread, we developed a carbon dot-based fluorescent probe encapsulated by MIL-101 using wax apple as a green carbon source (WA-CDs@MIL-101). The WA-CDs@MIL-101 was thoroughly characterized, and the detection conditions were optimized. The interaction mechanism between WA-CDs@MIL-101 and spores was investigated. The fluorescence of WA-CDs@MIL-101 was recovered due to electrostatic adsorption between spores and WA-CDs@MIL-101. Under the optimized detection conditions, the probe exhibited excellent sensing performance, showing a strong linear relationship (R² = 0.9978) between spore concentration (0.0025–5.0 mg/L) and fluorescence recovery ratio, with a detection limit of 5.15 μg/L. The WA-CDs@MIL-101 was successfully applied to detect spores on Panax notoginseng leaves, achieving satisfactory recoveries (94–102%) with relative standard deviations of 1.3–3.4%. The WA-CDs@MIL-101 shows great promise for detecting spores on Panax notoginseng leaves. Full article

Background: Fowl typhoid (FT), a septicemic infection caused by Salmonella Gallinarum (SG), and H9N2 avian influenza are two economically important diseases that significantly affect the global poultry industry. Methods: We exploited the live attenuated Salmonella Gallinarum (SG) mutant JOL3062 (SG: ∆lon ∆pagL ∆asd) as a delivery system for H9N2 antigens to induce an immunoprotective response against both H9N2 and FT. To enhance immune protection against H9N2, a prokaryotic and eukaryotic dual expression plasmid, pJHL270, was employed. The hemagglutinin (HA) consensus sequence from South Korean avian influenza A virus (AIV) was cloned under the Ptrc promoter for prokaryotic expression, and the B cell epitope of neuraminidase (NA) linked with matrix protein 2 (M2e) was placed for eukaryotic expression. In vitro and in vivo expressions of the H9N2 antigens were validated by qRT-PCR and Western blot, respectively. Results: Oral immunization with JOL3121 induced a significant increase in SG and H9N2-specific serum IgY and cloacal swab IgA antibodies, confirming humoral and mucosal immune responses. Furthermore, FACS analysis showed increased CD4+ and CD8+ T cell populations. On day 28 post-immunization, there was a substantial rise in the hemagglutination inhibition titer in the immunized birds, demonstrating neutralization capabilities of immunization. Both IFN-γ and IL-4 demonstrated a significant increase, indicating a balance of Th1 and Th2 responses. Intranasal challenge with the H9N2 Y280 strain resulted in minimal to no clinical signs with significantly lower lung viral titer in the JOL3121 group. Upon SG wildtype challenge, the immunized birds in the JOL3121 group yielded 20% mortality, while 80% mortality was recorded in the PBS control group. Additionally, bacterial load in the spleen and liver was significantly lower in the immunized birds. Conclusions: The current vaccine model, designed with a host-specific pathogen, SG, delivers a robust immune boost that could enhance dual protection against FT and H9N2 infection, both being significant diseases in poultry, as well as ensure public health. Full article

Monkeypox virus (MPXV) has caused 148,892 confirmed cases and 341 deaths from 137 countries worldwide, as reported by the World Health Organization (WHO), highlighting the urgent need for effective vaccines to prevent the spread of MPXV. Traditional vaccine development is low-throughput, expensive, time consuming, and susceptible to reversion to virulence. Alternatively, a reverse vaccinology approach offers a rapid, efficient, and safer alternative for MPXV vaccine design. Here, MPXV proteins associated with viral infection were analyzed for immunogenic epitopes to design multi-epitope vaccines based on B-cell, CD4+, and CD8+ epitopes. Epitopes were selected based on allergenicity, antigenicity, and toxicity parameters. The prioritized epitopes were then combined via peptide linkers and N-terminally fused to various protein adjuvants, including PADRE, beta-defensin 3, 50S ribosomal protein L7/12, RS-09, and the cholera toxin B subunit (CTB). All vaccine constructs were computationally validated for physicochemical properties, antigenicity, allergenicity, safety, solubility, and structural stability. The three-dimensional structure of the selected construct was also predicted. Moreover, molecular docking and molecular dynamics (MD) simulations between the vaccine and the TLR-4 immune receptor demonstrated a strong and stable interaction. The vaccine construct was codon-optimized for high expression in the E. coli and was finally cloned in silico into the pET21a (+) vector. Collectively, these results could represent innovative tools for vaccine formulation against MPXV and be transformative for other infectious diseases. Full article

The effective suppression of inflammation using disease-modifying therapies is essential in the treatment of multiple sclerosis (MS). Anti-CD20 monoclonal antibodies are commonly used long-term as maintenance therapies, largely due to the lack of reliable biomarkers to guide dosing and evaluate treatment response. However, prolonged use increases the risk of infections and other immune-mediated side effects. The unique ability of brain-derived blood extracellular vesicles (EVs) to cross the blood–brain barrier and reflect the central nervous system (CNS) immune status has sparked interest in their potential as biomarkers. This study aimed to assess whether blood-derived L1CAM⁺ EVs could serve as biomarkers of treatment response to rituximab (RTX) in patients with relapsing-remitting MS (RRMS). Serum samples (n = 25) from the baseline (month 0) and after 6 months were analyzed from the RTX arm of the ongoing randomized clinical trial OVERLORD-MS (comparing anti-CD20 therapies in RRMS patients) and were compared with serum samples from healthy controls (n = 15). Baseline cerebrospinal fluid (CSF) samples from the same study cohort were also included. EVs from both serum and CSF samples were characterized, considering morphology, size, and concentration, using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The immunophenotyping of EV surface receptors was performed using flow cytometry with the MACSPlex exosome kit, while label-free quantitative proteomics of EV protein cargo was conducted using a proximity extension assay (PEA). TEM confirmed the presence of EVs with the expected round morphology with a diameter of 50–150 nm. NTA showed significantly higher concentrations of L1CAM⁺ EVs (p < 0.0001) in serum total EVs and EBNA1⁺ EVs (p < 0.01) in serum L1CAM⁺ EVs at baseline (untreated) compared to in healthy controls. After six months of RTX therapy, there was a significant reduction in L1CAM⁺ EV concentration (p < 0.0001) and the downregulation of TNFRSF13B (p = 0.0004; FC = −0.49) in serum total EVs. Additionally, non-significant changes were observed in CD79B and CCL2 levels in serum L1CAM⁺ EVs at baseline compared to in controls and after six months of RTX therapy. In conclusion, L1CAM⁺ EVs in serum showed distinct immunological profiles before and after rituximab treatment, underscoring their potential as dynamic biomarkers for individualized anti-CD20 therapy in MS. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

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