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Polycyclic aromatic hydrocarbons (PAHs) have been classified as the earliest discovered class of environmental carcinogens, seriously endangering human health and ecological safety, and the hydroxylpolycyclic aromatic hydrocarbons (OH-PAHs) in human urine are considered as the main biomarkers to evaluate the exposure levels of PAHs in human body. Therefore, it is necessary to develop an accurate and sensitive method for the determination of urinary OH-PAHs. Herein, we proposed electromembrane extraction (EME) as a simple, effective and ecofriendly sample pretreatment technique for selective extraction, purification and enrichment of four typical OH-PAHs (2-naphthol, 2- and 3-phenanthrol, 2-hydroxyfluorene) in human urine for the first time. Under the optimum conditions, an analytical method of EME coupled with HPLC was established, which provided wide linear ranges for four OH-PAHs from 1 to 500 ng mL-1 with low LODs of 0.05-0.3 ng mL-1. The average recoveries of four OH-PAHs at three spiked levels in human urine were 81.6-102.5% with RSDs all below 9.4%. The present method has been successfully applied for the sensitive determination of trace four OH-PAHs in urine samples from non-smokers and smokers with a maximum concentration of 2.24 and 3.56 ng mL-1, respectively, which showed a great potential for the analysis of trace OH-PAHs in biological samples.

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Paper-based cultural relics often undergo acidification and deterioration during long-term preservation. Accurate detection of paper acidity is of great significance to assess aging status and extend the preservation lifetime of paper-based cultural relics. Rapid identification of the acidification degree and acid distribution across multiple regions of paper is essential. Inspired by fluorescent sensing technology, pH-sensitive cadmium telluride (CdTe) quantum dots (QDs) and rhodamine B (RB) fluorescent probes are synthesized and incorporated onto the nanofibers of a bacterial cellulose (BC) membrane to enable visual acidity detection of paper. Due to the complementary pH detection range of CdTe QDs and RB probes, the composite BC membrane exhibits a clear pH response across an acidic to neutral range (pH 3.0-7.5). Notably, the contrasting fluorescent colors of the two probes within the BC membrane allow for easy visualization of paper pH and acidity distribution with the naked eyes. A distinct color transition from red to green was observed on the fluorescent BC membrane when it is applied to a model paper with a gradient pH distribution. The feasibility of this method was verified by using the flat-headed pH electrode method. Additionally, common metal ions in most paper fillers, inks, pigments, as well as some sugars and amino acids showed minimal interference with the pH response of the composite BC membrane, highlighting its potential and broad applicability for visual acidity detection in paper-based cultural relics.

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BACKGROUND: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. METHODS: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. RESULTS: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). CONCLUSIONS: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ.

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The United Nations proposed the Sustainable Development Goals with the aim to make human settlements in cities resilient and sustainable. The excessive discharge of urban waste including sludge and garden waste can pollute groundwater and lead to the emission of greenhouse gases (e.g., CH4). The proper recycling of urban waste is essential for responsible consumption and production, reducing environmental pollution and addressing climate change issues. This study aimed to prepare biochar with high adsorption amounts of iodine using urban sludge and peach wood from garden waste. The study was conducted to examine the variations in the mass ratio between urban sludge and peach wood (2/1, 1/1, and 1/2) as well as pyrolysis temperatures (300 °C, 500 °C, and 700 °C) on the carbon yield and adsorption capacities of biochar. Scanning electron microscopy, Brunauer-Emmett-Teller analysis, Fourier transform infrared spectrometry, powder X-ray diffraction, and elemental analysis were used to characterize the biochar produced at different pyrolysis temperatures and mass ratios. The results indicate that the carbon yield of biochar was found to be the highest (>60%) at a pyrolysis temperature of 300 °C across different pyrolysis temperatures. The absorbed amounts of iodine in the aqueous solution ranged from 86 to 223 mg g-1 at a mass ratio of 1:1 between urban sludge and peach wood, which were comparably higher than those observed in other mass ratios. This study advances water treatment by offering a cost-effective method by using biochar derived from the processing of urban sludge and garden waste.

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With the development of PD-1/PD-L1 immune checkpoint inhibitor therapy, the ability to monitor PD-L1 expression in the tumor microenvironment is important for guiding therapy. This study was performed to develop a novel radiotracer with optimal pharmacokinetic properties to reflect PD-L1 expression in vivo via single-photon emission computed tomography (SPECT) imaging. [99mTc]Tc-HYNIC-WL12-tricine/M (M = TPPTS, PDA, ISONIC, 4-PSA) complexes with high radiochemical purity (>97%) and suitable molar activity (from 100.5 GBq/µmol to 300 GBq/µmol) were prepared through a kit preparation process. All 99mTc-labeled HYNIC-WL12 radiotracers displayed good in vitro stability for 4 h. The affinity and specificity of the four radiotracers for PD-L1 were demonstrated both in vitro and in vivo. The results of biodistribution studies displayed that the pharmacokinetics of the 99mTc-HYNIC-conjugated radiotracers were significantly influenced by the coligands of the radiotracers. Among them, [99mTc]Tc-HYNIC-WL12-tricine/ISONIC exhibited the optimal pharmacokinetic properties (t1/2α = 8.55 min, t1/2ß = 54.05 min), including the fastest clearance in nontarget tissues, highest tumor-to-background contrast (e.g., tumor-to-muscle ratio, tumor-to-blood ratio: 40.42 ± 1.59, 14.72 ± 2.77 at 4 h p.i., respectively), and the lowest estimated radiation absorbed dose, highlighting its potential as a clinical SPECT imaging probe for tumor PD-L1 detection.

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Lead (Pb) and arsenic (As) are commonly occurring heavy metals in the environment and produce detrimental impacts on the central nervous system. Although they have both been indicated to exhibit neurotoxic properties, it is not known if they have joint effects, and their mechanisms of action are likewise unknown. In this study, zebrafish were exposed to different concentrations of Pb (40 µg/L, 4 mg/L), As (32 µg/L, 3.2 mg/L) and their combinations (40 µg/L + 32 µg/L, 4 mg/L + 3.2 mg/L) for 30 days. The histopathological analyses showed significant brain damage characterized by glial scar formation and ventricular enlargement in all exposed groups. In addition, either Pb or As staining inhibited the swimming speed of zebrafish, which was enhanced by their high concentrations in a mixture. To elucidate the underlying mechanisms, we examined changes in acetylcholinesterase (AChE) activity, neurotransmitter (dopamine, 5-hydroxytryptamine) levels, HPI axis-related hormone (cortisol and epinephrine) contents and neurodevelopment-related gene expression in zebrafish brain. The observations suggest that combined exposure to Pb and As can cause abnormalities in swimming behavior and ultimately exacerbate neurotoxicity in zebrafish by interfering with the cholinergic system, dopamine and 5-hydroxytryptamine signaling, HPI axis function as well as neuronal development. This study provides an important theoretical basis for the mixed exposure of heavy metals and their toxicity to aquatic organisms.

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The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

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Chronic renal failure (CRF) resulting in vascular calcification, which does damage to blood vessels and endothelium, is an independent risk factor for stroke. It has been reported that cilostazol has a protective effect on the focal cerebral ischemic infarct. However, its impact on vascular injury in CRF combined stroke and its molecular protection mechanism have not been investigated. In this study, we carried out the effect of cilostazol on CRF combined stroke rats, and the results confirmed that it improved the neurobehavior, renal function as well as pathologic changes in both the kidney and brain. In addition, the inflammation and oxidative stress factors in the kidney and brain were suppressed. Moreover, the rates of brain edema and infarction were decreased. The injured brain-blood barrier (BBB) was recovered with less Evans blue extravasation and more expressions of zonula occludens-1(ZO-1) and occludin. More cerebral blood flow (CBF) in the ipsilateral hemisphere and more expression of CD31 and vascular endothelial growth factor (VEGF) in brain and kidney were found in the cilostazol group. Furthermore, cell apoptosis and cell autophagy became less, on the contrary, proteins of vascular endothelial growth factor receptor 2 (VEGFR2) after the cilostazol treatment were increased. More importantly, this protective effect is related to the pathway of Janus Kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and the hypoxia inducible factor-1α (HIF-1α). In conclusion, our results confirmed that cilostazol exerted a protective effect on the brain and kidney function, specifically in vascular injury, oxidative stress, cell apoptosis, cell autophagy, and inflammation response in CRF combined with stroke rats which were related to the upregulation of JAK/STAT3/mTOR signal pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00217-w.

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Microplastics (MPs) commonly coexist with heavy metals in the soil environment. MPs can influence the activity of heavy metals, and the specific mechanisms need to be further explored. Here, different contents of polystyrene (PS) MPs were added to soil to explore their effects on the adsorption and desorption characteristics of copper (Cu2+) in soil. The adsorption process was mainly chemical adsorption and belonged to a spontaneous, endothermic reaction. The hydrophobicity of MPs slowed down the adsorption and desorption rates. The main adsorption mechanisms included complexation by oxygen-containing functional groups, ion exchange (accounting for 33.97-36.04 % of the total adsorption amounts), and electrostatic interactions. MPs lacked oxygen-containing functional groups and were predominantly engaged in ion exchange and electrostatic interactions. MPs diluted, blocked the soil, and covered the active sites of soil, which reduced adsorption (3.56-16.18 %) and increased desorption (0.90-2.07 %) of Cu2+ in soil samples, thus increasing the activity and mobility of Cu2+. These findings provide new insights into the effects of MPs on the fate and risk of heavy metals in soil. ENVIRONMENTAL IMPLICATION: The existing literature concerning the effects of microplastics on the adsorption of heavy metals in soil is insufficient. Our investigation unveiled that the main adsorption mechanisms of different soil samples included complexation by oxygen-containing functional groups, ion exchange (accounting for 33.97-36.04 % of the total adsorption amounts), and electrostatic interactions. MPs lacked oxygen-containing functional groups and were predominantly engaged in ion exchange and electrostatic interactions. MPs diluted, blocked the soil, and covered the active sites of soil, which reduced adsorption (3.56-16.18 %) and increased desorption (0.90-2.07 %) of Cu2+ in soil samples, thus increasing the activity and mobility of Cu2+.

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The present investigation aims to design and development of hybrid zinc oxide (ZnO) and manganese dioxide (MnO2) nanoparticles (NPs) doped-biopolymer matrix-based cost-effective technique for the synthesis of biocompatible Kaolinite/Chitosan (Ka/CS) nanocomposites (NCs) could be used as agents for wound healing due to their efficiency and low toxicity. The crystallite size, phase purity and surface morphology of the synthesised NCs were investigated systemic analytical methods. The results revealed that the metal oxide nanocomposites presented that in rod-crystalline in shape and additionally exhibits that 20-30 nm in size. In vitro antibacterial analyses demonstrates that NCs have significantly improved bactericidal inhibition efficiency when compared to the bare hybrid NPs and polymeric components. The in vitro biocompatibility observation demonstrates that prepared hybrid-NPs encapsulated NCs have enhanced cell survival rate (>90 %), which was established by MTT assay and Live/Dead fluorescence assay methods at different incubation time. The DPPH assay was used to investigate the synergistic effects of prepared dressing materials increased antioxidant activity. Preliminary research indicates that these nanocomposites, ZnO/MnO2 incorporated and decorated with Ka/CS NCs, could be a significant promoter and potential candidate for use as a robust wound healing agent in post-operative nursing care.

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Paper-based cultural relics experience irreversible aging and deterioration during long-term preservation. The most common process of paper degradation is the acid-catalyzed hydrolysis of cellulose. Nowadays, deacidification has been considered as a practical way to protect acidified literature; however, two important criteria of minimal intervention and reversibility should be considered. Inspired by the superior properties of bacterial cellulose (BC) and its structural similarity to paper, herein, the mineralized BC membranes are applied to deacidification and conservation of paper-based materials for the first time. Based on the enzyme-induced mineralization process, the homogeneous and high-loaded calcifications of hydroxyapatite (HAP) and calcium carbonate (CaCO3) nanoparticles onto the nanofibers of BC networks have been achieved, respectively. The size, morphology, structure of minerals, as well as the alkalinity and alkali reserve of BC membranes are well controlled by regulating enzyme concentration and mineralization time. Compared with HAP/CaCO3-immersed method, HAP/CaCO3-BC membranes show more efficient and sustained deacidification performance on paper. The weak alkalinity of mineralized BC membranes avoids the negative effect of alkali on paper, and the high alkali reserve implies a good sustained-release effect of alkali to neutralize the future generated acid. The multiscale nanochannels of the BC membrane provide ion exchange and acid/alkali neutralization channels between paper and the BC membrane, and the final pH of protected paper can be well stabilized in a certain range. Most importantly, this BC-deacidified method is reversible since the BC membrane can be removed without causing any damage to paper and the original structure and fiber morphology of paper are well preserved. In addition, the mineralized BC membrane provides excellent flame-retardant performance on paper thanks to its unique organic-inorganic composite structure. All of these advantages of the mineralized BC membrane indicate its potential use as an effective protection material for the reversible deacidification and preventive conservation of paper-based cultural relics.

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High-performance flexible piezoresistive sensors are becoming increasingly essential in various novel applications such as health monitoring, soft robotics, and human-computer interaction. The evolution of the interfacial contact morphology determines the sensing properties of piezoresistive devices. The introduction of microstructures enriches the interfacial contact morphology and effectively boosts the sensitivity; however, the limited compressibility of conventional microstructures leads to rapid saturation of the sensitivity in the low-pressure range, which hinders their application. Herein, we present a flexible piezoresistive sensor featuring a two-stage micropyramid array structure, which effectively enhances the sensitivity while widening the sensing range. Owing to the synergistic enhancement effect resulting from the sequential contact of micropyramids of various heights, the devices demonstrate remarkable performance, including boosting sensitivity (30.8 kPa-1) over a wide sensing range (up to 200 kPa), a fast response/recovery time (75/50 ms), and an ultralong durability of 15,000 loading-unloading cycles. As a proof of concept, the sensor is applied to detect human physiological and motion signals, further demonstrating a real-time spatial pressure distribution sensing system and a game control system, showing great potential for applications in health monitoring and human-computer interaction.

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AIM: The aim of this study was to determine the usefulness of magnetic resonance imaging (MRI) characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in the spinal cord. MATERIALS AND METHODS: Fifty-eight patients with spinal cord gliomas were enrolled in this study. The H3 K27 gene status was identified by Sanger sequencing or immunohistochemistry test of resection tumor specimens. The MR imaging characteristics were evaluated and compared between H3 K27M-mutant and wildtype gliomas using the χ2 test and the Mann-Whitney U test. RESULTS: Of 58 recruited patients, 23 (39.7%) were diagnosed with H3 K27M-mutant glioma. The H3 K27M-mutant gliomas were found to more likely occur in men compared with wildtype gliomas (87.0% vs. 42.9%, p = 0.001). On T2-weighted MR images, the signal-to-noise ratio (SNR) of H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (103.9 ± 72.0 vs. 168.9 ± 86.8, p < 0.001). Of 35 wildtype tumors, 60% showed well-defined margin but this feature was not found in all mutant tumors (p < 0.001). The SNR of tumors on contrast-enhanced T1-weighted images of the H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (187.7 ± 160.4 vs. 295.1 ± 207.8, p = 0.006). Receiver operating-characteristic analysis revealed that area under curve (AUC) of combination of 1/SNR on T2-weighted images, 1/SNR on contrast-enhanced T1-weighted images, ill-defined margin, and sex reached 0.937 (95% CI, 0.873-1.000) in discriminating H3 K27M-mutant gliomas. CONCLUSIONS: The MR imaging characteristics are valuable in discriminating H3 K27M-mutant from wildtype gliomas in the spinal cord and the combination of these imaging features with sex had a high strength in this discrimination.

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To develop radiolabeled FGFR2-targeting probes for visualizing fibroblast growth factor receptor (FGFR) expression levels in the tumor microenvironment, four novel 99mTc-labeled FGFR2-targeting peptides ([99mTc]Tc-FGFR2-1, [99mTc]Tc-FGFR2-2, [99mTc]Tc-FGFR2-3, and [99mTc]Tc-FGFR2-4) with different amino acid linkers between the targeted peptide moiety and the 99mTc chelating group were designed and synthesized. The in vitro cellular inhibition, internalization, and efflux results demonstrated that the four 99mTc complexes exhibited FGFR2-specific binding and prolonged cellular retention in DU145 human prostate cancer cells, which indicated that modification from the glycine side (N-terminal) of CH02 was feasible. Among them, [99mTc]Tc-FGFR2-1 exhibited the highest in vitro cellular uptake and in vivo tumor uptake at 30 min postinjection, and tumor uptake could be significantly inhibited by the competitor CH02 (53% inhibited, p < 0.05), suggesting the tumor-specific targeting ability of [99mTc]Tc-FGFR2-1. The DU145-xenografted tumor lesions were clearly visualized by single photon emission computed tomography (SPECT)/CT at 30 min postinjection of [99mTc]Tc-FGFR2-1, highlighting its potential as a SPECT imaging probe for tumor FGFR2 detection.

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The prevalence of Anaplastic Lymphoma Kinase gene (ALK) fusion is about 5% among patients with lung adenocarcinoma, underscoring the importance of pinpointing distinct fusion variants for optimizing treatment approaches. This is the first reported case of a 74-year-old female with stage IV lung adenocarcinoma, featuring a novel Kinesin Family Member 13A (KIF13A)-ALK fusion, identified via next-generation sequencing (NGS) and confirmed with fluorescence in situ hybridization (FISH). Initially undergoing chemotherapy and then crizotinib, she achieved a partial response (PR) before progressing with multiple bone metastases. However, subsequent treatment with alectinib as a third-line option yielded positive results. A stable disease state persisted for an impressive 31 months of progression-free survival (PFS), accompanied by minimal toxicity symptoms. Up until now, a remarkable near 4-year span of overall survival (OS) has been consistently observed and monitored. This report of a KIF13A-ALK fusion case benefit significantly from alectinib with extensive follow-up. The case diversifies the array of ALK fusion partners and holds clinical relevance in refining therapeutic choices for KIF13A-ALK fusion-associated lung cancer.