Search Results (26,986)

Abstract: This article presents an analysis of the relationship between air pollution and the type of fuel used in households in the Małopolskie Voivodeship from 2010 to 2021. For this article, they are marked as HEU-C (coal), HEU-L (liquid), and HEU-O (other). The analysis area was selected due to the constantly occurring problem of air pollution with PM₁₀ and PM_2.5. Using regression, the relationships between energy consumption in households and specific components of air pollution recorded in the Małopolskie region were established. The developed models were used to determine the potential of individual groups of fuels to generate pollution. The primary finding suggests that the derived regression models offer an appropriate predictive framework. Studies show significant reductions in pollutants like BbF, Cd, Pb, and PM_2.5. Increasing the use of HEU-O fuel is key to cleaner air in the Małopolskie Voivodeship. However, HEU-O may emit more NO_x and NO₂ than HEU-C. The selected thematic emphasis differentiates this article from others examining air quality issues within the Małopolskie Voivodeship. Full article

Biomass material serves as one of the most advantageous carbon sources for the synthesis of carbon dots (CDs) due to its abundant availability, cost-effectiveness, and environmental sustainability. Biomass-derived carbon dots (B-CDs), which are new zero-dimensional carbon nanomaterials, have presented broad application prospects in the medical field and have become a research focus. In recent years, the death rate caused by vascular diseases has been high, and interventional therapy is one of the important means to treat vascular stenosis. As a material with excellent biocompatibility and fluorescence properties, B-CDs have shown great potential in the field of vascular stents, and their unique properties provide new ideas and possibilities for improving the biocompatibility of vascular stents and realizing real-time tracer diagnosis. This paper reviews the preparation methods, modification techniques, and application prospects of B-CDs in the coating of vascular stents. It discusses current challenges and potential solutions while forecasting future development directions, thereby providing innovative insights and pathways for the research and development of a new generation of vascular stents. Full article

In B-cell malignancies, the overexpression of MYC is associated with poor prognosis, but its mechanism underlying resistance to immunochemotherapy remains less clear. In further investigations of this issue, we show here that the pharmacological inhibition of MYC in various lymphoma and multiple myeloma cell lines, as well as patient-derived primary tumor cells, enhances their susceptibility to NK cell-mediated cytotoxicity induced by conventional antibodies targeting CD20 (rituximab) and CD38 (daratumumab), as well as T cell-mediated cytotoxicity induced by the CD19-targeting bispecific T-cell engager blinatumomab. This was associated with upregulation of the target antigen only for rituximab, suggesting additional escape mechanisms. To investigate these mechanisms, we targeted the MYC gene in OCI-LY18 cells using CRISPR-Cas9 gene-editing technology. CRISPR-Cas9-mediated MYC targeting not only upregulated CD20 but also triggered broader apoptotic pathways, upregulating pro-apoptotic PUMA and downregulating anti-apoptotic proteins BCL-2, XIAP, survivin and MCL-1, thereby rendering tumor cells more prone to apoptosis, a key tumor-lysis mechanism employed by T-cells and NK-cells. Moreover, MYC downregulation boosted T-cell activation and cytokine release in response to blinatumomab, revealing a MYC-mediated T-cell suppression mechanism. In conclusion, MYC overexpressing tumor cells mitigated the efficacy of therapeutic antibodies through several non-overlapping mechanisms. Given the challenges associated with direct MYC inhibition due to toxicity, successful modulation of MYC-mediated immune evasion mechanisms may improve the outcome of immunotherapeutic approaches in B-cell malignancies. Full article

Aeromonas hydrophila causes motile Aeromonas septicemia (MAS), a disease with a high mortality rate in tilapia culture. Feed-based vaccines with the incorporation of inactivated whole-cell bacteria into the feed offer promising tools to control MAS. Currently, the incorporation of genome-free bacteria as bacterial vaccine through the implementation of SimCells^® technology into the feed has become a particular interest. Background/Objectives: This study investigates the efficacy of a feed-based vaccine incorporating genome-free A. hydrophila (FBV-GFAH) against MAS infection in red tilapia. Methods: The vaccine was prepared and delivered at 5% fish body weight for three consecutive days in weeks 0 (prime vaccination) and 2 (first booster vaccination), orally. Throughout a five-week experimental period, the immune-related genes (IL-1β, MHC-II, CD4, IgT, and IgM) expression in the hindgut and head kidney of the fish was determined using RT-qPCR assay. Lysozyme (serum) and overall IgM (serum, gut lavage, and skin mucus) productions were also detected. Results: Fish vaccinated with FBV-GFAH showed a significant (p ≤ 0.05) improvement in relative percent survival compared with unvaccinated fish following bacterial challenge. FBV-GFAH induced the expression of immune-related genes in the hindgut and head kidney, especially after booster vaccination. Furthermore, serum lysozyme activity and overall IgM production in serum, skin mucus, and gut lavage were also significantly (p ≤ 0.05) improved in the FBV-GFAH vaccinated fish than the unvaccinated fish. Conclusions: This study showed that FBV-GFAH is a promising feed-based vaccine technology to control MAS in cultured tilapia. Full article

The early diagnosis of tumorigenesis is crucial for clinical treatment, but the resolution and sensitivity of conventional short-wavelength biomarkers are not ideal because of the complicated interference in living tissue. Herein, a nicotinamide adenine dinucleotide (NAD⁺)-responsive probe with deep-red emissive ratiometric fluorescence was synthetized as a promising target for energy metabolism patterns during tumorigenesis. Interestingly, the solvents H₃PO₄ and 2,2′-dithiodibenzoic acid enhanced the red emission (640 and 680 nm) of o-phenylenediamine-based carbon dots (CDs), leading to the formation of a nanoscale graphite-like skeleton covered with -P=O, -CONH-, -COOH and -NH₂ on their surfaces. Meanwhile, this method exhibited high sensitivity to the discriminating target NAD⁺, with a detection limit of 63 μM due to the inner filter effect and fluorescence resonance energy transfer process between NAD⁺ and CDs, which is superior to the reported capillary electrophoresis and liquid chromatographic detection methods (the reported detection limit was about 0.2 mM) in complex biological samples and even cancer cells. Encouragingly, NAD⁺ significantly promoted nucleus-targeting fluorescence and cell migration compared to GSH and pH stimulation, which were gradually eliminated in human hepatocellular carcinoma (HepG2) cells after 2-deoxy-d-Glucose inhibited the glycolytic phenotype. The proposed method holds great potential for the temporal and spatial resolution of NAD⁺-dependent tumor diagnosis in complex living systems. Full article

CD47 is expressed on cell surfaces and acts as a “don’t eat me” signal by interacting with signal-regulatory protein-α on the macrophage surface. Some cancer cells express CD47 protein and can evade macrophage phagocytosis. Herein, we evaluated the feasibility of targeting CD47 for osteosarcoma by analyzing its expression patterns, clinicopathological correlations, and immunotherapeutic potential. We performed a retrospective analysis on 24 biopsy samples from patients with osteosarcoma to investigate correlations between CD47 protein positivity and clinicopathological characteristics. CD47 protein expression was detected in 20.8% of the biopsy samples. CD47 positivity correlated with metastasis at diagnosis. Patients with CD47-positive tumors were older than those with CD47-negative tumors. However, CD47 protein expression was not associated with sex, tumor size, or histologic response to preoperative chemotherapy. In vitro, CD47 antibody (B6H12) did not affect osteosarcoma cell viability or apoptosis. In a wound-healing assay, CD47 inhibited the migration of osteosarcoma cells. Differentiated macrophages exhibited higher phagocytic activity against osteosarcoma cells when pretreated with B6H12 compared with the isotype control. Our preliminary data suggest a possible interaction between CD47 protein and macrophage phagocytosis in osteosarcoma metastasis. A better understanding of the role of CD47 is necessary to develop an innovative immunotherapeutic approach against osteosarcoma. Full article

Inflammatory bowel disease (IBD) is a complex and chronic condition that requires the use of various pharmacological agents for its management. Despite advancements in IBD research, the multifaceted mechanisms involved continue to pose significant challenges for strategic prevention. Therefore, it is crucial to prioritize safe and effective treatment strategies using the currently available pharmacological agents. Given that patients with IBD often require multiple medications due to combination therapy or other underlying conditions, a comprehensive understanding of drug interactions is essential for optimizing treatment regimens. In this review, we examined the pharmacological treatment options recommended in the current IBD management guidelines and provided a comprehensive analysis of the known pharmacokinetic interactions associated with these medications. In particular, this review includes recent research results for the impact of anti-drug antibodies (ADAs) on the concentrations of biological agents used in IBD treatment. By leveraging detailed interaction data and employing personalized dosing strategies, healthcare providers can improve therapeutic outcomes and minimize adverse effects, ultimately improving the quality of care for patients with IBD. Full article

Background: We have previously reported engineered macrophages (MacTriggers) that can accelerate the release of tumor necrosis factor-α in response to M2 polarization. MacTriggers are characterized by two original characteristics of macrophages: (1) migration to tumors; and (2) polarization to the M2 phenotype in tumors. Intravenously administered MacTriggers efficiently accumulated in the tumors and induced tumor-specific inflammation. This study reports a novel methodology for enhancing the anti-tumor effects of immune checkpoint inhibitors (ICIs). Results: In this study, we newly found that the intravenously administered MacTriggers in BALB/c mouse models upregulated the expression levels of immune checkpoint proteins, such as programmed cell death (PD)-1 in CD8⁺ T cells and PD-ligand 1 (PD-L1) in cancer cells and macrophages. Consequently, in two ICI-resistant tumor-inoculated mouse models, the combined administration of MacTrigger and anti-PD-1 antibody (aPD-1) synergistically inhibited tumor growth, whereas monotherapy with aPD-1 did not exhibit anti-tumor effects. This synergistic effect was mainly from aPD-1 enhancing the tumor-attacking ability of CD8⁺ T cells, which could infiltrate into the tumors following MacTrigger treatment. Importantly, no side effects were observed in normal tissues, particularly in the liver and spleen, indicating that the MacTriggers did not enhance the aPD-1 reactivity in normal tissues. This specificity was from the MacTriggers not polarizing to the M2 phenotype in normal tissues, thereby avoiding inflammation and increased PD-1/PD-L1 expression. MacTriggers could enhance aPD-1 reactivity only in tumors following tumor-specific inflammation induction. Conclusions: Our findings suggest that the MacTrigger and aPD-1 combination therapy is a novel approach for potentially overcoming the current low ICI response rates while avoiding side effects. Full article

To assess the human impact on the water of Dayat Roumi Lake and to develop effective management strategies to protect and restore this vital ecosystem in the region, seasonal sampling was carried out at six stations distributed around the lake. During these sampling campaigns, 24 parameters were measured, including 20 trace elements. Results showed that measured levels of trace elements increased in the following order: Cd < Be < Tl < Co < Sb < Mo < Cu < Zn < Ni < V < Rb < Mn < As < Cr < Pb < Li < Ba < Se < Pd < Sr in the lake water and that these recorded values were lower than those recommended by the Moroccan standard and the World Health Organization, except for Pb and Se. Correlation analysis revealed two principal water-contamination sources: natural geological origins and anthropogenic inputs. In addition, the Water Quality Index WQI showed that the lake’s water quality is poor, and its use can be dangerous for human and animal health. Health risk assessment associated with prolonged exposure to trace elements in lake water revealed that the Hazard quotient HQ and Hazard index HI of certain elements, such as Tl, Sb, V, As, Cr, Pb, Li, and Se, are higher than 1 in adult and children, indicating a significant risk for people living near the lake. Children are particularly vulnerable, with higher levels of HQ and HI, and selenium poses a substantial risk to their health through ingestion and skin absorption. In both adults and children, the total risk of cancer due to metals is classified as follows: CI (Cr) > CI (Ni) > CI (As) > CI (Pb) > CI (Cd). The Cr presents the highest carcinogenic risk—by ingestion or dermal route—in both groups. The total risk for these five metals exceeds 1 × 10⁻⁴, indicating a danger for residents who drink or swim in the lake. Full article

The interaction between gut-residing microorganisms plays a critical role in the pathogenesis of Crohn’s disease (CD), where microbiome dysregulation can alter immune responses, leading to unresolved local inflammation. The aim of this study is to analyze the immunomodulatory properties of a recently developed probiotic + amylase blend in the SAMP1/YitFc (SAMP) mouse model of CD-like ileitis. Four groups of SAMP mice were gavaged for 56 days with the following treatments: 1) probiotic strains + amylase (0.25 mg/100 µL PBS); 2) only probiotics; 3) only amylase; PBS-treated controls. Ilea were collected for GeoMx Digital Spatial Profiler (DSP) analysis and histological evaluation. Histology assessment for inflammation indicated a significantly reduced level of ileitis in mice administered the probiotics + amylase blend. DSP analysis showed decreased abundance of neutrophils and increased abundance of dendritic cells, regulatory T cells, and macrophages, with a significant enrichment of five intracellular pathways related to apoptosis, in probiotics + amylase-treated mice. Increased apoptosis occurrence was confirmed by (TdT)- deoxyuridine triphosphate (dUTP)-biotin nick end labeling assay. Our data demonstrate a beneficial role of the probiotic and amylase blend, highlighting an increased apoptosis of innate immunity-associated cell subsets, thus promoting the resolution of inflammation. Hence, we suggest that the developed probiotic enzyme blend may be a therapeutic tool to manage CD and therefore is a candidate formulation to be tested in clinical trials. Full article

Mitragynine is an “atypic opioid” analgesic with an alternative mechanism of action and a favorable side-effect profile. Our aim was to optimize the alkaloid extraction procedure from kratom leaves and to determine and isolate the most relevant compounds capable of penetrating the central nervous system. The PAMPA-BBB study revealed that mitragynine and its coalkaloids, speciociliatine, speciogynine, and paynantheine, possess excellent in vitro BBB permeability. An optimized sequence of CPC, flash chromatography, and preparative HPLC methods was used to isolate the four identified BBB+ alkaloids. To improve the bioavailability of the isolated alkaloids, their cyclodextrin (CD) complexation behavior was investigated via affinity capillary electrophoresis using almost 40 CD derivatives. The apparent alkaloid–CD complex stability constants were determined and compared, and the most relevant CDs phase-solubility studies were also performed. Both the neutral and negatively charged derivatives were able to form complexes with all four kratom alkaloids. It was found that cavity size, substituent type, and degree of substitution also influenced complex formation. The negatively charged Sugammadex, Subetadex, and the sufoalkylated-beta-CD analogs were able to form the most stable complexes, exceeding 1000 M⁻¹. These results serve as a good basis for further solubility and stability enhancement studies of kratom alkaloids. Full article

Background: Pancreatic cancer is among the malignancies with the poorest prognosis, largely due to its aggressive nature and resistance to conventional therapies. Case Summary: This report describes the case of a 69-year-old male patient with stage IV primary lung adenocarcinoma presenting with high levels of programmed death-ligand 1 (PD-L1). Simultaneously, abdominal computed tomography (CT) showed a dilated pancreatic duct at the level of the pancreatic head and a hypodense lesion in the uncinate process involving the superior mesenteric artery. Fine-needle aspiration (FNA) of the pancreatic lesions was negative. After three cycles of chemoimmunotherapy, positron emission tomography–computed tomography (PET-CT) showed complete remission of the lung nodules, lymphadenopathy, and pleural thickening, as well as a decrease in the size of the pancreatic lesion. After another six months, a PET-CT scan showed a focal increased uptake in the pancreatic mass in the same location, indicating disease progression. A core biopsy of the pancreatic tumor showed atypical spindle cell morphology with positive staining for vimentin, characteristic of mesenchymal differentiation with no apparent epithelial features. Comprehensive molecular profiling through Caris Molecular Intelligence^® revealed four genes with actionable mutations in the pancreatic tissue, including KRAS (p.G12D) and TP53 (p.R175H). These molecular findings suggested the diagnoses of sarcomatoid carcinoma and conventional pancreatic ductal adenocarcinoma with epithelial–mesenchymal transition. Primary mesenchymal tumors and neuroendocrine neoplasms were excluded because immunohistochemistry was negative for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA), desmin, CD34, signal transducer and activator of transcription 6 (STAT6), S100, HMB45, CD117, discovered on GIST-1 (DOG1), CD56, progesterone, and synaptophysin. However, despite multiple rounds of systemic chemotherapy, immunotherapy, and radiation, his pancreatic disease rapidly deteriorated and metastasized to the liver and bone. Conclusions: Despite multiple lines of treatment, the patient’s condition worsened and he succumbed to his pancreatic malignancy. This study highlights the clinical characteristics, diagnosis, and treatment of rare pancreatic cancer, emphasizing the importance of molecular testing and histopathological biomarkers in personalizing treatment. It also provides insights into promising therapeutic approaches for similar cases with an unusual presentation. Full article

We reported the gold/silver core-shell nanoparticles (Au_core@Ag_shell NPs) functionalized with β-cyclodextrin (β-CD) as versatile nano-agents demonstrated for human urine-based biosensing of cysteamine and catalytic conversion from nitrobenzene (NB) to aniline. First, the hybrid bimetallic nanoparticles, i.e., β-CD-Au_core@Ag_shell NPs, constituted a colorimetric sensing platform based on localized surface plasmons, enabling cysteamine (Cyst) to be detected in a remarkably rapid manner, i.e., within 2 min, which was greatly shortened in comparison with that of our previous report. This was due largely to use of β-CD being effectively replaceable by Cyst. The detection of Cyst was demonstrated using human urine specimens in the linear range of 25–750 nM with a limit of detection of 1.83 nM. Excellent specificity in detecting Cyst was also demonstrated against potential interfering molecules. Meanwhile, the β-CD-Au_core@Ag_shell NPs were demonstrated as nanocatalysts for converting NB to aniline with efficiency enhanced by more than three-fold over the pure gold nanoparticles previously reported, due to the dual functions of the structural core-shell. The demonstrated versatile features of the hybrid nanoparticles can find applications in human urine-based biosensors for Cyst detection, and in the screening of Cyst-containing drugs, while detoxicating NB for ecological protection in aqueous media. Full article

Bacteria respond to metal pollution through sensors that control the uptake and the detoxification machineries. Specificity in metal recognition is therefore a prerequisite for triggering the appropriate response, particularly when facing a mixture of metals. In response to Cu⁺, the purple bacterium Rubrivivax gelatinosus induces the efflux Cu⁺-ATPase CopA by the Cu⁺ regulator CopR. However, genetic analyses have suggested the presence of additional regulators. Here, we show that CadR, the Cd²⁺ sensor, is involved in Cd²⁺ and Cu⁺ tolerance and demonstrate that CopR and CadR share common target genes. Interestingly, expression of the Cu⁺ detoxification and efflux (CopI/CopA) system was induced by Cd²⁺ and downregulated in the double mutant copRcadR⁻. This double mutant was more sensitive to low Cu⁺ concentration than the single copR⁻ mutant, and accumulation of coproporphyrin III pointed to a significantly decreased expression of CopA. Furthermore, analyses of Cd²⁺ toxicity in the cadR⁻ mutant suggested that although CopR is Cu⁺ selective, CopR is involved in Cd²⁺ response since the addition of Cu⁺ alleviates Cd²⁺ toxicity. Based on our current knowledge of metal transport across the inner membrane, Cd²⁺ and Cu⁺ do not share common efflux routes nor do they share common regulators. Nevertheless, the crosstalk between Cd²⁺ and Cu⁺ tolerance systems is demonstrated in the present study. The modulation of Cu⁺ detoxification by a Cd²⁺ regulator in vivo places emphasis on the relaxed selectivity, under elevated metal concentration, in MerR regulators. Full article

Informal e-waste recycling can cause serious heavy metal(loid) pollution to nearby bodies of water, thereby increasing the risk of heavy metal exposure to local residents. This study investigates metal(loid) pollution levels in the Lianjiang River, which flows through Guiyu, an e-waste recycling town in Shantou, Guangdong. In 2009 and 2020, water samples from the Lianjiang River were taken, and the levels of 12 metal(loid)s (V, Cr, Mn, Sr, Ni, Cu, Zn, As, Se, Cd, Ba, and Pb) were measured by ICP-MS. In total, 380 valid questionnaires from Guiyu kindergarten children were selected to assess child health. Exposure health risks for children were calculated using two forms of exposure (dermal and inhalation) and statistical methods (multiple linear regression and Bayesian kernel machine regression—BKMR). The concentrations of Mn, Ni, Pb, and Cd in 2009 were significantly higher than those in 2020. The concentration of heavy metal(loid)s had been decreasing in 2020. The non-carcinogenic risk levels of the 12 metal(loid)s in both exposure routes were at an acceptable risk level. The average carcinogenic risk levels for As, Cr, Ni, Pb, and Cd exceeded the ILCRi <10–6 acceptable range. According to MLR, it was found that daily oral intake doses of Pb [β(95% CI): −0.949 (−1.596, −0.863), p < 0.001 and Se [β(95% CI): −0.911 (−1.888, −0.092), p = 0.031] were negatively associated with body mass index. A BKMR model was developed, through which the synergistic effects of co-exposure to 12 heavy metal(loid)s on growth and development indicators in children were analyzed. Concentrations of heavy metal(loid)s in rivers near e-waste recycling sites have been decreasing for 10 years. It was found that the growth and development of children are affected by the intake of heavy metal(loid)s in water. The reduction in heavy metal(loid) contamination in e-waste recycling areas needs to be continued, and concern about its impact on children’s health must remain. Full article