Search Results (28,467)

CAR-T therapy has revolutionized the field of oncology, offering a promising treatment option for cancer patients. However, the significant morbidity associated with therapy-related toxicity presents a major challenge to its widespread use. Despite extensive research into the underlying mechanisms of CAR-T therapy-related toxicity, there are still many unknowns. Furthermore, the lack of adequate in vitro models for assessing immunotoxicity and neurotoxicity further complicates the development of safer cellular therapies. Previously in our laboratory, we developed cancer-stroma spheres (CSS) composed of prostate adenocarcinoma PC3 cells and mesenchymal stem cells (MSC). Herein we present evidence that multicellular CSS could serve as a valuable in vitro model for toxicity studies related to CAR-T therapy. CSS containing CD19-overexpressing PC3M cells exhibited increased secretion of CAR-T cell toxicity-associated IL-8, MCP-1, and IP-10 in the presence of anti-CD19 CAR-T cells, compared to spheres derived from single cell types. Full article

Understanding the correlation between soil chemical properties and tea quality is essential for the comprehensive management of ancient tea gardens. However, the specific links between these factors in ancient tea gardens remain underexplored. This study analyzes the soil chemical properties of four distinct research regions in Nanhua County to explore their effects on key chemical components in ancient tea garden teas, providing a scientific basis for improving the quality of ancient tea garden teas through soil management. Employing high performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS), the chemical components of tea and the chemical properties of the soil were meticulously quantified. Following these measurements, the integrated fertility index (IFI) and the potential ecological risk index (PERI) were evaluated and correlation analysis was conducted. The results revealed that ancient tea garden tea quality is closely linked to soil chemical properties. Soil’s total nitrogen (TN), total sulfur (TS), and available potassium (AK) negatively correlate with tea’s catechin gallate (CG) component and AK also with polyphenols. Most other soil properties show positive correlations with tea components. The research also evaluated soil heavy metals’ IFI and PERI. IFI varied significantly among regions. Hg’s high pollution index indicates ecological risks; Cd in Xiaochun (XC) region poses a moderate risk. PERI suggests moderate risk for XC and Banpo (BP), with other areas classified as low risk. Implementing reasonable fertilization and soil amelioration measures to enhance soil fertility and ensure adequate supply of key nutrients will improve the quality of ancient tea gardens. At the same time, soil management measures should effectively control heavy metal pollution to ensure the quality and safety of tea products. Insights from this study are crucial for optimizing soil management in ancient tea gardens, potentially improving tea quality and sustainability. Full article

Rhizosphere microorganisms are crucial for enhancing plant stress resistance. Current studies have shown that Arbuscular mycorrhizal fungi (AMF) can facilitate vegetation recovery in heavy metal-contaminated soils through interactions with rhizosphere microbiota. However, the mechanisms by which AMF influences rhizosphere microbiota and plant growth under cadmium (Cd) stress remain unclear. In this study, Lolium perenne L. was inoculated with AMF (Rhizophagus irregularis) and grown in soils supplemented with Cd (0 mg kg⁻¹, Cd0; 100 mg kg⁻¹, Cd100). Plant biomass, antioxidant enzyme activities, peroxide content, Cd uptake, and rhizosphere bacterial community composition were evaluated. AMF inoculation reduced Cd influx in aboveground tissues, enhanced nutrient availability in the rhizosphere, and mitigated Cd biotoxicity. Additionally, AMF inoculation improved the scavenging efficiency of reactive oxygen species and alleviated oxidative stress in L. perenne, thereby mitigating biomass reduction. Moreover, AMF treatment increased leaf and root biomass by 342.94% and 41.31%, respectively. Furthermore, under the same Cd concentration, AMF inoculation increased bacterial diversity (as measured by the Shannon index) and reduced bacterial enrichment (as indicated by the ACE index). AMF promoted the enrichment of certain bacterial genera (e.g., Proteobacteria and Actinobacteria) in the Cd100 group. These findings suggest that AMF regulated the composition of the rhizosphere bacterial community and promoted the growth of potentially beneficial microorganisms, thereby enhancing the resistance of L. perenne to Cd stress. Cd contamination in soil severely limits plant growth and threatens ecosystem stability, highlighting the need to understand how AMF and rhizosphere microbes can enhance Cd tolerance in L. perenne. Therefore, inoculating plants with AMF is a promising strategy for enhancing their adaptability to Cd-contaminated soils. Full article

Background/Objectives: Porcine Circovirus 2 (PCV2) infection poses significant health and economic challenges to the global swine industry. The disease in pigs leads to lymphoid depletion, resulting in immunosuppression and increased susceptibility to co-infections with other bacterial and viral pathogens. This study evaluated the efficacy of two novel recombinant Newcastle disease virus (NDV) strain R2B vectored vaccines that express the cap gene of PCV2 alone and along with the transmembrane and cytoplasmic tail (TMCT) domains of the NDV F gene. The efficacy of the vaccine candidates was studied in mouse and pig models. Methods: Six-week-old BALB/c mice were divided into five groups and immunized intramuscularly three times at 14-day intervals with various vaccine candidates, namely rNDV-R2B-PCVcap-TMCT, rNDV-R2B-PCVcap, and CircoFLEX commercial vaccine, along with controls. Following immunization and PCV2d virus challenge, multiple assays assessed the immune responses in animal trials. In the pig animal trial, pigs were divided into four groups: a control group (PBS), NDV-vectored PCVcap-TMCT group, NDV-vectored-PCVcap group, and CircoFLEX vaccine group. Pigs were immunized intramuscularly twice at 28-day intervals. Blood samples were collected at regular intervals over 70 days to evaluate the humoral and cell-mediated immune responses. Results: Both mice and pigs’ trials indicated that the NDV-vectored PCV2 cap-TMCT vaccine candidate elicited superior immune responses. In mice, the rNDV-R2B-PCVcap-TMCT group showed enhanced humoral and cellular immunity, increased PCV2-specific antibody levels, higher CD4+/CD8+ ratio, elevated IFN-γ and TNF-α levels, decreased IL-10 levels, reduced viral loads, and minimal histopathological changes. In pigs, the NDV-vectored PCVcap-TMCT group demonstrated better antibody responses, cytokine profiles (IFN-γ and IL-10), and higher levels of PCV2-specific neutralizing antibodies against the PCV2a, PCV2b and PCV2d genotypes when compared to other groups. Conclusions: These findings suggest NDV-vectored PCVcap-TMCT vaccine candidate, expressing the cap gene of PCV2 along with the TMCT domain, offers a promising alternative for protecting against PCV2 infection, potentially addressing the challenges posed by emerging PCV2 strains in the swine industry. Full article

Slow pyrolysis was carried out in biosolids under three different temperatures (400, 500 and 600 °C) and two different carrier gases (CO₂ and N₂) on a fluidized bed reactor. The total concentration, chemical fractionation, and plant availability of the heavy metals in biochar were assessed by standard methods. The total concentration of Fe, Zn, Cu, Mn, Cr, Ni and Pb increased with the conversion of biosolids to biochar and with increasing pyrolysis temperature. The community’s Bureau of Reference (BCR) sequential extraction identified the migration of metals from toxic and bioavailable to potentially stable available or non-available forms at higher pyrolysis temperatures. Diethylenetriamine penta-acetic acid (DTPA)-extractable metals (Cu, Zn, Cd, Cu, Fe and Pb) were significantly lower in biochar compared to biosolids. By replacing N₂ with CO₂, the total metal concentration of heavy metals was significantly different for Mn, Ni, Cd, Pb and As. There were larger amounts of metals in the residual and oxidizable fractions compared to when N₂ was used as a carrier gas. Consequently, the biochar produced at higher temperatures (500 and 600 °C) in the N₂ environment exhibited lower potential ecological risks than in CO₂ environments (69.94 and 52.16, respectively, compared to values from 75.95 to 151.38 for biochars prepared in N₂). Overall, the results suggest that the higher temperature biochar can support obtaining environmentally safe biochar and can be effective in attenuating the ecological risks of biosolids. Full article

Semi-supervised learning has gained significant attention in the field of remote sensing due to its ability to effectively leverage both a limited number of labeled samples and a large quantity of unlabeled data. An effective semi-supervised learning approach utilizes unlabeled samples to enforce prediction consistency under minor perturbations, thus reducing the model’s sensitivity to noise and suppressing false positives in change-detection tasks. This principle underlies consistency regularization-based methods. However, while these methods enhance noise robustness, they also risk overlooking subtle but meaningful changes, leading to information loss and missed detections. To address this issue, we introduce a simple yet efficient method called Sample Inflation Interpolation (SII). This method leverages labeled sample pairs to mitigate the information loss caused by consistency regularization. Specifically, we propose a novel data augmentation strategy that generates additional change samples by combining existing supervised change samples with calculated proportions of change areas. This approach increases both the quantity and diversity of change samples in the training set, effectively compensating for potential information loss and reducing missed detections. Furthermore, to prevent overfitting, small perturbations are applied to the generated sample pairs and their labels. Experiments conducted on two public change detection (CD) datasets validate the effectiveness of our proposed method. Remarkably, even with only 5% of labeled training data, our method achieves performance levels that closely approach those of fully supervised learning models. Full article

The effects of different forms of multi-strain probiotics on weaning piglets are limitedly addressed. Thus, this study investigated the effects of live or inanimate multi-strain probiotics comprising Lactobacillus plantarum, Streptococcus thermophilus, and Bacillus subtilis on growth performance, intestinal morphology, fecal microbiota, short-chain fatty acids, and intestinal gene expression of weaning piglets. A total of 160 weaning piglets (4 weeks old) were randomly allocated into four treatments (CON: basal diet; AB: basal diet with 110 ppm and 66 ppm colistin in the weaning and nursery phases, respectively; LP: basal diet with 2.0 × 10⁹ CFU/kg live probiotics; and IP: basal diet with 2.0 × 10⁹ CFU/kg inanimate probiotics). Piglets fed with LP had significantly lower FCR compared to those of the CON and IP groups in week 4 to week 8 (p < 0.05). Moreover, the LP group had significantly higher villus height (VH) compared with AB at week 6, lower crypt depth (CD) compared with IP, and higher VH/CD ratio compared to other treatments at week 10 (p < 0.05), which indicate healthier intestinal morphology. Probiotic treatments (LP and IP) increased Bifidobacterium population compared to CON at week 6 and lowered Enterobacteriaceae at week 6 and week 10 (p < 0.05). Regarding gene expressions of intestinal integrity, LP showed significantly higher TFF3 expression compared with CON and AB at week 6 and compared with other treatments in jejunum at week 10 (p < 0.05). IP treatment had significantly higher MUC2 expression compared to other treatments at week 6 and week 10 (p < 0.05). Overall, live multi-strain probiotics improved growth efficiency by enhancing gut integrity and microbiome balance, making them a potential antibiotic alternative to ameliorate weaning stress and promote productive performance in weaning piglets. Full article

Urban air pollution, especially from heavy metal (HM) contamination, poses significant risks to human health and environmental sustainability. This study investigates the spatial and temporal distribution of HM contamination in Thessaloniki, Greece, using Syntrichia moss as a bioindicator to inform urban environmental management strategies. Moss samples were collected from 16 locations representing diverse urban activity zones (motorway, industrial, city center, airport) in March, May, and July 2024. The concentrations of 12 HMs (Al, Sb, As, Ba, Cd, Cr, Co, Cu, Pb, Ni, V, and Zn) were analyzed using ICP-MS, and the contamination factors were calculated relative to controlled moss samples. The results revealed significant spatial variation, with elevated levels of As, Cd, Cr, Pb, and Zn, particularly in high-traffic and industrial zones, exceeding the background levels by up to severe and extreme contamination categories. Temporal trends showed decreases in Al, Ba, and Ni from March to July 2024, while Cr and Cu increased, suggesting seasonally varying sources. Multivariate analyses further distinguished the contamination patterns, implicating traffic and industrial activities as key contributors. Syntrichia effectively captures HM contamination variability, demonstrating its value as a cost-effective bioindicator. These findings provide critical data that can guide urban planners in developing targeted pollution mitigation strategies, ensuring compliance with the European Green Deal’s Zero Pollution Action Plan. Full article

Chagas disease (CD), a disease affecting millions globally, remains shrouded in scientific uncertainty, particularly regarding the role of the intestinal microbiota in disease progression. This study investigates the effects of antibiotic-induced microbiota depletion on parasite burden, immune responses, and clinical outcomes in BALB/c mice infected with either the Trypanosoma cruzi Colombiana or CL Brener strains. Mice were treated with a broad-spectrum antibiotic cocktail before infection, and parasite burden was quantified via qPCR at 30 and 100 days post-infection (dpi). Immune responses were analyzed using flow cytometry and ELISA, while histopathology was conducted on cardiac and intestinal tissues. Antibiotic treatment uncovered strain-specific correlations, with Colombiana infections affecting Bifidobacterium populations and CL Brener infections linked to Lactobacillus. Microbiota depletion initially reduced parasite burden in the heart and intestine, but an increase was observed in the chronic phase, except in the CL Brener-infected gut, where an early burden spike was followed by a decline. Antibiotic-induced bacterial shifts, such as reductions in Bacteroides and Bifidobacterium, promoted a more pro-inflammatory immune profile. These findings highlight the importance of microbiota and strain-specific factors in CD and suggest further research into microbiota manipulation as a potential therapeutic strategy. Full article

Popular photoluminescent (PL) nanomaterials, such as carbon dots, have attracted substantial attention from scientists due to their photophysical properties, biocompatibility, low cost, and diverse applicability. Carbon dots have been used in sensors, cell imaging, and cancer therapy. Leek seeds with anticancer, antimicrobial, and antioxidant functions serve as traditional Chinese medicine. However, leek seeds have not been studied as a precursor of carbon dots. In this study, leek seeds underwent a supercritical fluid extraction process. Leek seed extract was obtained and then carbonized using a dry heating method, followed by hydrolysis to form carbon dot micelles (CD-micelles). CD-micelles exhibited analyte-induced PL quenching against Co²⁺ through the static quenching mechanism, with the formation of self-assembled Co²⁺-CD-micelle sphere particles. In addition, CD-micelles extracted metal ion through liquid–liquid extraction, with removal efficiencies of >90% for Pb²⁺, Al³⁺, Fe³⁺, Cr³⁺, Pd²⁺, and Au³⁺. Moreover, CD-micelles exhibited ABTS•⁺ radical scavenging ability and cytotoxicity for cisplatin-resistant lung cancer cells. CD-micelles killed cisplatin-resistant small-cell lung cancer cells in a dose-dependent manner with a cancer cell survival rate down to 12.8 ± 4.2%, with a similar treatment function to that of cisplatin. Consequently, CD-micelles functionalized as novel antioxidants show great potential as anticancer nanodrugs in cancer treatment. Full article

The natural compounds PSK and PSP have antitumor and immunostimulant properties. These pharmacological benefits have been documented in vitro and in vivo, although there is no information in silico which describes the action mechanisms at the molecular level. In this study, the inverse docking method was used to identify the interactions of PSK and PSP with two local databases: BPAT with 66 antitumor proteins, and BPSIC with 138 surfaces and intracellular proteins. This led to the identification interactions and similarities of PSK and the AB680 inhibitor in the active site of CD73. It was also found that PSK binds to CD59, interacting with the amino acids APS22 and PHE23, which coincide with the rlLYd4 internalization inhibitor. With the isoform of the K-RAS protein, PSK bonded to the TYR32 amino acid at switch 1, while with BAK it bonded to the region of the α1 helix, while PSP bonded to the activation site and the C-terminal and N-terminal ends of that helix. In Bcl-2, PSK interacted at the binding site of the Venetoclax inhibitor, showing similarities with the amino acids ASP111, VAL133, LEU137, MET115, PHE112, and TYR108, while PSP had similarities with THR132, VAL133, LEU137, GLN118, MET115, APS111, PHE112, and PHE104. Full article

Head and neck squamous cell carcinoma (HNSCC) is highly enriched with tumor-infiltrating myeloid cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). However, effective therapeutic agents targeting tumor-associated myeloid cells in HNSCC are currently lacking. Here, we employed a unique co-culture system to investigate how HNSCC cells affect tumor-associated myeloid cells. We found that the presence of cancer cells significantly enhances myeloid cell proliferation and promotes TAM differentiation. To identify potential therapeutic agents, we screened a custom library of 70 kinase inhibitors to assess their effects on distinct subsets of tumor-associated myeloid cells. We discovered specific inhibitors that differentially suppressed the populations of TAMs, monocytic MDSCs (M-MDSCs), or polymorphonuclear MDSCs (PMN-MDSCs), suggesting that inhibiting different targets could reduce distinct subsets of tumor-associated myeloid cells. Conversely, some inhibitors were found to increase the population of CD11b⁺Ly6G⁻Ly6C⁻ myeloid cells. Among the promising inhibitors tested, vatalanib, a VEGF-R inhibitor, demonstrated significant in vivo efficacy at inhibiting tumor growth and reducing tumor-associated myeloid cells, thereby underscoring its potential as a therapeutic agent. Our findings highlight specific kinase inhibitors with differential modulatory effects on HNSCC-associated myeloid subsets and caution the application of some as anti-cancer drugs. This experimental system may provide a robust platform for identifying new agents targeting tumor-associated myeloid cells in HNSCC and beyond, and for elucidating mechanistic insights into tumor-myeloid cell interaction. Full article

Mycoplasma bovis (M. bovis) is capable of causing pneumonia, arthritis, mastitis, and various other ailments in cattle of all age groups, posing a significant threat to the healthy progression of the worldwide cattle industry. The invasion of non-phagocytic host cells serves as a pivotal mechanism enabling M. bovis to evade the immune system and penetrate mucosal barriers, thereby promoting its spread. To investigate the differences in M. bovis invasion into four types of non-phagocytic cells (Madin–Darby bovine kidney (MDBK) cells, embryonic bovine lung (EBL) cells, bovine embryo tracheal (EBTr) cells and bovine turbinate (BT) cells) and further elucidate its invasion mechanism, this study first optimized the experimental methods for M. bovis invasion into cells. Utilizing laser scanning confocal microscopy, transmission electron microscopy, and high-content live-cell imaging systems, the invasion process of M. bovis into four types of non-phagocytic cells was observed. The invasion rates of three different strains of M. bovis (PG45, 07801, 08M) were quantified through the plate counting method. In order to clarify the specific pathway of M. bovis invasion into cells, chlorpromazine (CPZ), amiloride (AMI), and methyl-β-cyclodextrin (M-β-CD) were used to inhibit CLR-mediated clathrin-dependent endocytosis (CDE) pathway, macropinocytosis, and lipid raft pathway, respectively. Subsequently, the invasion rates of PG45 into these four types of cells were measured. Using siRNA technology, the expression of clathrin (CLR) in EBL cells was knocked down to further verify the role of CLR in the invasion process of M. bovis. The results showed that the optimal conditions for M. bovis to invade non-phagocytic cells were a multiplicity of infection (MOI) of 1000 and an optimal invasion time of 4 h. All three strains of M. bovis have the ability to invade the four types of non-phagocytic cells, yet their invasion abilities vary significantly. Observations from transmission electron microscopy further confirmed that at 120 min post-infection, PG45 had successfully invaded EBL cells and was present within endocytic vesicles. It is noteworthy that almost all PG45 successfully escaped from the endocytic vesicles after 240 min of infection had passed. Through chemical inhibition experiments and CLR protein knockdown experiments, it was found that when the CDE and lipid raft pathways were blocked or CLR protein expression was reduced, the invasion rates of PG45, 07801, and 08M in MDBK, EBL, EBTr, and BT cells were significantly decreased (p < 0.05). The above results indicate that M. bovis can invade all types of non-phagocytic cells through endocytic pathways involving CDE (clathrin-dependent endocytosis) or lipid raft-mediated endocytosis, and possesses the ability to escape from phagosomes. Full article

Multicolor emission and dynamic color tuning with large spectral range are challenging to realize but critically important in many areas of technology and daily life, such as general lighting, display, multicolor detection and multi-band communication. Herein, we report an excitation-power-dependent color-tuning emission from an individual Sn-doped CdS nanowire with a large spectral range and continuous color tuning. Its photoluminescence (PL) spectrum shows a broad trap-state emission band out of Sn dopants, which is superposed by whispering-gallery (WG) microcavity due to the nanostructure size and its structure, besides the CdS band-edge emission. By simply changing the excitation power from 0.25 to 1.36 mW, we demonstrate that the typical Sn-doped CdS nanowire with the weight ratio of 10:1 of CdS and SnO₂, the emission color can change from red to orange to yellow to green. In view of the stable properties and large spectral range, the Sn-doped CdS nanowires are very promising potential candidates in nanoscale optoelectronic devices. Full article

Diabetic retinopathy is a complex, microvascular disease that impacts millions of working adults each year. High blood glucose levels from Diabetes Mellitus lead to the accumulation of advanced glycation end-products (AGEs), which promote inflammation and the breakdown of the inner blood retinal barrier (iBRB), resulting in vision loss. This study used an in vitro model of hyperglycemia to examine how endothelial cells (ECs) and Müller glia (MG) collectively regulate molecular transport. Changes in cell morphology, the expression of junctional proteins, and the reactive oxygen species (ROS) of ECs and MG were examined when exposed to a hyperglycemic medium containing AGEs. Trans-endothelial resistance (TEER) assays were used to measure the changes in cell barrier resistance in response to hyperglycemic and inflammatory conditions, with and without an anti-VEGF compound. Both of the cell types responded to hyperglycemic conditions with significant changes in the cell area and morphology, the ROS, and the expression of the junctional proteins ZO-1, CX-43, and CD40, as well as the receptor for AGEs. The resistivities of the individual and dual ECs and MG barriers decreased within the hyperglycemia model but were restored to that of basal, normoglycemic levels when treated with anti-VEGF. This study illustrated significant phenotypic responses to an in vitro model of hyperglycemia, as well as significant changes in the expression of the key proteins used for cell–cell communication. The results highlight important, synergistic relationships between the ECs and MG and how they contribute to changes in barrier function in combination with conventional treatments. Full article