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The issue of micro-plastics is becoming more and more important due to their ubiquity and the harm they cause to the human body. Therefore, evaluating the biological–physical interaction of micro-plastics with health cells has become the focus of many research efforts. This study focuses on the movement mode and low concentration detection development for micro-plastics in surface plasmon resonance (SPR). Firstly, 20-micrometer micro-plastics were prepared by grinding and filtering, and the movement mode was explored; then, the characteristics were investigated by SPR. Chromatographic analysis showed that the surface charge of micro-plastics dominated the elution time, and estrogen receptors (ERs) played a supporting role. A difference of micro-plastics in SPR sensorgram was observed, inferring the micro-plastics’ movement in rolling mode on the ERs. Characteristics analysis indicated that the low particle number of micro-plastics on SPR showed a linear relationship with the response unit (RU). When ERs were immobilized on the biosensor, the force of the binding of micro-plastics to ERs under an ultra-low background was equivalent to the dissociation rate constant shown as follows: PS (0.05 nM) > PVC (0.09 nM) > PE (0.14 nM). The ELISA-like magnetic beads experiment verified the specificity between ERs and micro-plastics. Therefore, by using the SPR technique, a biological-derived over-occupation of PS was found via higher binding force with ERs and longer retention time. In the future, there will be considerable potential for micro-plastics issues, such as identification in natural samples, biomarking, real-time detection in specific environments/regions and human health subject.

The use of immune checkpoint inhibitors (ICIs) is a potential immunotherapy strategy to prevent immune escape in cancer cells. However, low immune infiltration and low antigen presentation in the tumor microenvironment (TME) have led to ineffective ICI immunotherapy in clinical studies. Although intratumoral injection of Toll-like receptor 9 (TLR9) agonists was shown to improve the efficacy of ICIs by increasing the number of tumor-infiltrating lymphocytes (TILs), it has limited effects on metastatic or deep-seated tumors. To overcome this challenge, we developed CpG7909 (a TLR9 agonist) lipoplex using a cationic lipid formulation, which exhibited preferential accumulation in tumors and spleen following systemic administration, Combination immunotherapy with an anti-PD1 antibody and CpG7909 lipoplex significantly promoted the infiltration of CD8 + T cells (> twofold) into the TME of the CT26 tumor animal model and effectively inhibited both deep-seated colorectal and metastatic lung tumors. Furthermore, the complete response (CR) rate of mice receiving concurrent therapy increased from 0 to 75% compared with that of those receiving anti-PD1 monotherapy. To our knowledge, this study is among the first to evaluate the combination of CpG7909 lipoplexes with anti-PD1 antibodies in the context of cancer immunotherapy. The findings suggest that this approach may convert the TME from an immunologically “cold” to “hot” state, thereby enhancing tumor suppression and potentially improving the response rate to ICIs.

Background Caffeic acid phenethyl ester (CAPE) is the main bioactive component of poplar type propolis. We previously reported that treatment with caffeic acid phenethyl ester (CAPE) suppressed the cell proliferation, tumor growth, as well as migration and invasion of prostate cancer (PCa) cells via inhibition of signaling pathways of AKT, c-Myc, Wnt and EGFR. We also demonstrated that combined treatment of CAPE and docetaxel altered the genes involved in glycolysis and tricarboxylic acid (TCA) cycle. We therefore suspect that CAPE treatment may interfere glucose metabolism in PCa cells. Methods Seahorse Bioenergetics platform was applied to analyzed the extra cellular acidification rate (ECAR) and oxygen consumption rate (OCR) of PCa cells under CAPE treatment. UPLC-MSMS with Multiple Reaction Monitoring (MRM), PCR, and western blot were used to analyze the effects of CAPE on metabolites, genes, and proteins involved in glycolysis, TCA cycle and pentose phosphate pathway in PCa cells. Flow cytometry and ELISA were used to determine the level of reactive oxygen species in PCa cells being treated with CAPE. Results Seahorse Bioenergetics analysis revealed that ECAR, glycolysis, OCR, and ATP production were elevated in C4-2B cells under CAPE treatment. Protein levels of glucose-6-phosphate dehydrogenase (G6PD), phosphogluconate dehydrogenase (PGD), glutaminase (GLS), phospho-AMPK Thr172 as well as abundance of pyruvate, lactate, ribulose-5-phosphate, and sedoheptulose-7-phosphate were increased in CAPE-treated C4-2B cells. ROS level decreased 48 h after treatment with CAPE. Co-treatment of AMPK inhibitor with CAPE exhibited additive growth inhibition on PCa cells. Conclusions Our study indicated that PCa cells attempted to overcome the CAPE-induced stress by upregulation of glycolysis and G6PD but failed to impede the growth inhibition caused by CAPE. Concurrent treatment of CAPE and inhibitors targeting glycolysis may be effective therapy for advanced PCa.

Background Effects of air pollution on neurotoxicity and behavioral alterations have been reported. The objective of this study was to investigate the pathophysiology caused by particulate matter (PM) in the brain. We examined the effects of traffic-related particulate matter with an aerodynamic diameter of < 1 μm (PM 1 ), high-efficiency particulate air (HEPA)-filtered air, and clean air on the brain structure, behavioral changes, brainwaves, and bioreactivity of the brain (cortex, cerebellum, and hippocampus), olfactory bulb, and serum after 3 and 6 months of whole-body exposure in 6-month-old Sprague Dawley rats. Results The rats were exposed to 16.3 ± 8.2 (4.7~ 68.8) μg/m 3 of PM 1 during the study period. An MRI analysis showed that whole-brain and hippocampal volumes increased with 3 and 6 months of PM 1 exposure. A short-term memory deficiency occurred with 3 months of exposure to PM 1 as determined by a novel object recognition (NOR) task, but there were no significant changes in motor functions. There were no changes in frequency bands or multiscale entropy of brainwaves. Exposure to 3 months of PM 1 increased 8-isoporstance in the cortex, cerebellum, and hippocampus as well as hippocampal inflammation (interleukin (IL)-6), but not in the olfactory bulb. Systemic CCL11 (at 3 and 6 months) and IL-4 (at 6 months) increased after PM 1 exposure. Light chain 3 (LC3) expression increased in the hippocampus after 6 months of exposure. Spongiosis and neuronal shrinkage were observed in the cortex, cerebellum, and hippocampus (neuronal shrinkage) after exposure to air pollution. Additionally, microabscesses were observed in the cortex after 6 months of PM 1 exposure. Conclusions Our study first observed cerebral edema and brain impairment in adult rats after chronic exposure to traffic-related air pollution.

Platelet‐activating factor (PAF) is a potent phospholipid mediator with therapeutic potential in neuroregeneration, but its therapeutic application is hindered by rapid degradation and systemic proinflammatory effects. Here, we present an engineered extracellular vesicle (EV)‐based delivery strategy that stabilizes and targets PAF to sites of hippocampal injury, restoring neuronal structure and cognitive function. EVs derived from EP4 antagonist‐primed mesenchymal stem cells (GWEVs) exhibit enhanced secretion and selective enrichment of bioactive lipids, particularly PAF, which promotes neuroregeneration, attenuates gliosis and rescues spatial memory. Mechanistic studies reveal that PAF's therapeutic activity depends not on classical PTAFR engagement but on neuronal metabolism via PAF‐acetylhydrolase (PAFAH), particularly the PAFAH1B1 subunit. The hydrolysis‐resistant analogue MPAF fails to confer benefit, underscoring the requirement for enzymatic processing. To address translational needs, we developed a bioorthogonal click‐labelling platform that enables real‐time SPECT imaging of EV biodistribution while preserving function. GWEVs preferentially accumulate in injured hippocampi, confirming targeted delivery. This study defines a previously unrecognized lipid metabolism‐dependent repair mechanism and demonstrates the feasibility of leveraging EVs for CNS‐targeted delivery of labile lipid therapeutics. These findings offer a platform for advancing regenerative strategies in neurodegenerative diseases and traumatic brain injury. Encapsulation within GWEVs stabilizes platelet‐activating factor (PAF), prevents peripheral inflammation and enables targeted delivery across the blood–brain barrier. In the brain, GWEVs localize to injury sites and deliver PAF to neurons, where PAFAH1B1‐dependent cytoskeletal remodelling promotes repair, supporting GWEVs as a therapeutic platform for neural regeneration.

Background Prostate cancer (PCa) patients with elevated level of androgen receptor (AR) correlate with higher metastatic incidence. Protein expression of AR and its target gene prostate‐specific antigen (PSA) are elevated in metastatic prostate tumors as compared to organ‐confined tumors. Androgen treatment or elevation of AR promotes metastasis of PCa in cell culture and murine model. However, under androgen depleted condition, AR suppressed cell mobility and invasiveness of PCa cells. Androgen deprivation therapy in PCa patients is associated with higher risk of cancer metastasis. We therefore investigated the dual roles of AR and miRNAs on PCa metastasis. Methods The PC‐3AR (PC‐3 cells re‐expressing AR) and LNCaP cells were used as PCa cell model. Transwell migration and invasion assay, wound‐healing assay, zebrafish xenotransplantation assay, and zebrafish vascular exit assay were used to investigate the role of AR and androgen on PCa metastasis. Micro‐Western Array, co‐immunoprecipitation and Immunofluorescence were applied to dissect the molecular mechanism lying underneath. The miRNA array, miRNA inhibitors or plasmid, and chromatin immunoprecipitation assay were used to study the role of miRNAs on PCa metastasis. Results In the absence of androgen, AR repressed the migration and invasion of PCa cells. When androgen was present, AR stimulated the migration and invasion of PCa cells both in vitro and in zebrafish xenotransplantation model. Androgen increased phospho‐AR Ser81 and yes‐associated protein 1 (YAP), decreased phospho‐YAP Ser217, and altered epithelial‐mesenchymal transition (EMT) proteins in PCa cells. Co‐IP assay demonstrated that androgen augmented the interaction between YAP and AR in nucleus. Knockdown of YAP or treatment with YAP inhibitor abolished the androgen‐induced migration and invasion of PCa cells, while overexpression of YAP showed opposite effects. The miRNA array revealed that androgen decreased hsa‐miR‐5001‐5p but increased hsa‐miR‐203a and hsa‐miR‐210‐3p in PC‐3AR cells but not PC‐3 cells. Treatment with inhibitors targeting hsa‐miR‐203a/hsa‐miR‐210‐3p, or overexpression of hsa‐miR‐5001‐5p decreased YAP expression as well as suppressed the androgen‐induced migration and invasion of PCa cells. Chromatin immunoprecipitation (ChIP) assay demonstrated that AR binds with promoter region of has‐miR‐210‐3p in the presence of androgen. Conclusions Our observations indicated that miRNAs 203a/210‐3p/5001‐5p regulate the androgen/AR/YAP‐induced PCa metastasis. Our finding provided new knowledge for understanding how androgen determines the dual roles of AR on prostate cancer metastasis. We made new discovery that androgen promotes metastasis of AR‐positive PCa via regulation of hsa‐miR‐203a, hsa‐miR‐210‐3p, hsa‐miR‐5001‐5p, and YAP. The finding of the pathway AR/androgen/miRNAs/YAP offered an opportunity for developing novel drugs to delay or to suppress the PCa metastasis.

In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using 1H-NMR, 13C-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 µM to AGS, 4.4 µM to HT-29 cells and 5.8 µM to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 µM to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma.

Epidemiological and toxicological evidence indicates that fine particulate matter (PM 2.5 , particulate matter < 2.5 µm in aerodynamic diameter) causes cardiopulmonary toxicity; however, its neurotoxic effects remain unclear. The objective of this study was to investigate the role of the neurofilament light (NEFL) serum polypeptide in neurotoxicity. 6-month-old male Sprague Dawley (SD) rats were exposed to traffic-related PM1 (< 1 µm in aerodynamic diameter; 16.3 µg m −3 ) and gaseous pollutants (via high-efficiency particulate air, HEPA) for 3 and 6 months through a whole-body exposure system. According to our observations, the levels of interleukin (IL)-4, IL-10, and tumor necrosis factor (TNF)-α in the serum of the rats significantly increased ( p < 0.05) after 3 months of exposure to PM 1 , whereas that of NEFL polypeptide significantly increased ( p < 0.05) after 3 and 6 months of exposure. Additionally, increases in the IL-2, IL-6, IL-10, IL-17a, TNF-α, and interferon (IFN)-γ levels after 3 and/or 6 months of exposure to this pollutant ( p < 0.05) were observed in the cerebrospinal fluid (CSF). In terms of their respective levels, the IL-6 correlated well with the CSF IL-2 and IL-10; the TNF-α correlated well with the CSF IL-6, IL-17a, TNF-α, and IFN-γ; and the NEFL polypeptide correlated well with the CSF IL-2, IL-4, IL-6, IL-10, IL-17a, TNF-α, and IFN-γ. In summary, systemic neuroinflammatory and immune responses in rats occurred after chronic exposure to PM1. Hence, NEFL polypeptide in serum may be a suitable biomarker for neurotoxicity caused by chronic exposure to this pollutant.

In this report, 19 boron-containing depsipeptides were synthesized via microwave-assisted Passerini three-component reaction (P-3CR) in an aqueous environment. The linker-free DAHMI fluorescent tagging approach was used on selected boron-containing compounds to study the relationship between their structures and their level of cellular uptake of HEK293 cells. The biological data retrieved from the DAHMI experiments indicated that while the structures of tested compounds may be highly similar, their bio-distribution profile could be vastly distinctive. The reported optimized one-pot synthetic strategy along the linker-free in vitro testing protocol could provide an efficient platform to accelerate the development of boron-containing drugs.

The increased global incidence of hemophilia, along with its concomitant consequences arising from prolonged hemorrhage after an injury and a heightened vulnerability to internal bleeding in joints or the brain, brings to the forefront the development of innovative therapeutic strategies to alleviate this hereditary genetic disorder. Current treatments for hemophilia primarily depend on plasma concentrates; however, their widespread use is constrained by the reliance on blood donations and the associated risk of infections. Alternative protein-based therapeutics, such as recombinant coagulation factors, bypassing agents, and non-factor-based drugs, have been approved and utilized for the prophylaxis and treatment of hemophilia with promising outcomes; yet, their shortcomings consist of the necessity for repeated administration and the likelihood of inhibitor formation. With the emergence of the cutting-edge gene editing (CRISPR/Cas9) and gene delivery (viral and non-viral vectors) techniques, the recent progression in gene therapy, stem cell transplantation, and prenatal interventions via in utero stem cell therapy inspires optimism for individuals afflicted with hemophilia and their families, even though these innovative techniques remain in the preclinical stage with a lot of technical and ethical issues needing to be resolved. This review article provides a comprehensive overview of hemophilia management, from traditional therapies to advanced prenatal stem cell treatments, highlighting the evolution and future directions in addressing this genetic bleeding disorder.