Imaging Diffusion and Stability of Single-Chain Polymeric Nanoparticles in a Multi-Gel Tumor-on-a-Chip Microfluidic Device.

The performance of single-chain polymeric nanoparticles (SCPNs) in biomedical applications highly depends on their conformational stability in cellular environments. Until now, such stability studies are limited to 2D cell culture models, which do not recapitulate the 3D tumor microenvironment well. Here, a microfluidic tumor-on-a-chip model is introduced that recreates the tumor milieu and allows in-depth insights into the diffusion, cellular uptake, and stability of SCPNs. The chip contains Matrigel/collagen-hyaluronic acid as extracellular matrix (ECM) models and is seeded with cancer cell MCF7 spheroids. With this 3D platform, it is assessed how the polymer's microstructure affects the SCPN's behavior when crossing the ECM, and evaluates SCPN internalization in 3D cancer cells. A library of SCPNs varying in microstructure is prepared. All SCPNs show efficient ECM penetration but their cellular uptake/stability behavior depends on the microstructure. Glucose-based nanoparticles display the highest spheroid uptake, followed by charged nanoparticles. Charged nanoparticles possess an open conformation while nanoparticles stabilized by internal hydrogen bonding retain a folded structure inside the tumor spheroids. The 3D microfluidic tumor-on-a-chip platform is an efficient tool to elucidate the interplay between polymer microstructure and SCPN's stability, a key factor for the rational design of nanoparticles for targeted biological applications.

Enhanced Efficiency of Pd(0)-Based Single Chain Polymeric Nanoparticles for in Vitro Prodrug Activation by Modulating the Polymer's Microstructure.

Bioorthogonal catalysis employing transition metal catalysts is a promising strategy for the in situ synthesis of imaging and therapeutic agents in biological environments. The transition metal Pd has been widely used as a bioorthogonal catalyst, but bare Pd poses challenges in water solubility and catalyst stability in cellular environments. In this work, Pd(0) loaded amphiphilic polymeric nanoparticles are applied to shield Pd in the presence of living cells for the in situ generation of a fluorescent dye and anticancer drugs. Pd(0) loaded polymeric nanoparticles prepared by the reduction of the corresponding Pd(II)-polymeric nanoparticles are highly active in the deprotection of pro-rhodamine dye and anticancer prodrugs, giving significant fluorescence enhancement and toxigenic effects, respectively, in HepG2 cells. In addition, we show that the microstructure of the polymeric nanoparticles for scaffolding Pd plays a critical role in tuning the catalytic efficiency, with the use of the ligand triphenylphosphine as a key factor for improving the catalyst stability in biological environments.

Curative Effect of Bracketless and Invisible Orthodontic Treatment for Periodontitis and the Influence on Gingival Crevicular Fluid and Serum IL-6, MMP-8 and TNF-α Levels.

Objective: To observe the therapeutic effects of bracketless and invisible orthodontic treatment on periodontitis, as well as on gingival crevicular fluid and serum interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and tumors. The impact of necrosis factor-alpha (TNF-α) levels fills the current knowledge gap regarding the impact of different orthodontic treatment modalities on biomarker levels in periodontitis patients. Methods: 100 patients with malocclusion secondary to periodontitis were selected as subjects.They were divided into a control group (n=50) and a study group (n=50) according to the random number method. The control group was treated with a straight wire appliances, and the study group was given bracketless and invisible orthodontic treatment. Clinical effects, Periodontal indicators [plaque index (PLI), gingival crevicular bleeding index (SBI), gingival index (GI), periodontal pocket probe depth (PD), clinical attachment loss (CAL)], gingival crevicular fluid and serum IL-6, MMP-8 and TNF-α levels and the incidence of adverse reactions were compared between the two groups. The uniqueness of this method is that it compares the impact of traditional straight-wire orthodontic treatment and invisible orthodontic treatment without brackets on biomarker levels and clinical effects in patients with periodontitis. In order to understand the role of orthodontic treatment methods in Provides useful information for use in periodontitis treatment. Results: The main findings of this study highlight the significant impact of bracketless clear braces in improving periodontal indicators and cytokine levels. Patients treated with bracketless clear braces demonstrate better clinical outcomes in periodontitis treatment compared with traditional straight-wire orthodontic treatment. The response rate of the study group was higher than that of the control group (94.00% vs. 72.00%) (P < .05). After 2 years of treatment, PLT, SBI, GI, PD and CAL were decreased in both groups and the observation group was significantly lower than the control group (P < .05). After 6 months of treatment, the levels of IL-6, MMP-8 and TNF-α in gingival crevicular fluid and serum were decreased in both groups, and the observation group was significantly lower than the control group (P < .05). There was no significant difference in the incidence of adverse reactions between the two groups (P > .05). Conclusion: The treatment of periodontitis without brackets has a significant effect, which can improve the periodontal condition and reduce the levels of IL-6, MMP-8 and TNF-α in gingival crevicular fluid and serum. Bracketless invisible braces have shown potential clinical significance in improving periodontal indicators and cytokine levels in patients with periodontitis, providing support for providing more comfortable and effective orthodontic treatment options, which may help promote patients' Oral health. These findings suggest the positive role of bracketless invisible braces in comprehensive periodontal treatment, which is expected to influence the practice of orthodontics and periodontal treatment and improve patient treatment experience and effects.

Alteration of White Matter Connectivity for MR-Guided Focused Ultrasound in the Treatment of Essential Tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has been implemented as a therapeutic alternative for the treatment of drug-refractory essential tremor (ET). However, its impact on the brain structural network is still unclear. PURPOSE: To investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy. STUDY TYPE: Retrospective. SUBJECTS: Twenty-seven ET patients (61 ± 11 years, 19 males) with MRgFUS thalamotomy and 28 healthy controls (HC) (61 ± 11 years, 20 males) were recruited for comparison. FIELD STRENGTH/SEQUENCE: A 3 T/single shell diffusion tensor imaging by using spin-echo-based echo-planar imaging, three-dimensional T1 weighted imaging by using gradient-echo-based sequence. ASSESSMENT: Patients were undergoing MRgFUS thalamotomy and their clinical data were collected from pre-operation to 6-month post-operation. Network topological metrics, including rich-club organization, small-world, and efficiency properties were calculated. Correlation between the topological metrics and tremor scores in ET groups was also calculated to assess the role of neural remodeling in the brain. STATISTICAL TESTS: Two-sample independent t-tests, chi-squared test, ANOVA, Bonferroni test, and Spearman's correlation. Statistical significance was set at P < 0.05. RESULTS: For ET patients, the strength of rich-club connection and clustering coefficient significantly increased vs. characteristic path length decreased at 6-month post-operation compared with pre-operation. The distribution pattern of rich-club regions was different in ET groups. Specifically, the order of the rich-club regions was changed according to the network degree value after MRgFUS thalamotomy. Moreover, the altered nodal efficiency in the right temporal pole of the superior temporal gyrus (R = 0.434-0.596) and right putamen (R = 0.413-0.436) was positively correlated with different tremor improvement. DATA CONCLUSION: These findings might improve understanding of treatment-induced modulation from a network perspective and may work as an objective marker in the assessment of ET tremor control with MRgFUS thalamotomy. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.

Gray matter alterations in tremor-dominant Parkinson's disease after MRgFUS thalamotomy are correlated with tremor improvement: a pilot study.

Background: Regional differences in gray matter volume (GMV) have been reported to be a reliable marker for diagnosing Parkinson's disease (PD). This study aimed to explore the clinical value of GMV to assess magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment for tremor-dominant PD (TDPD). Methods: Nine TDPD patients with MRgFUS thalamotomy were recruited for structural magnetic resonance image (MRI) scanning and clinical score evaluation. GMV was calculated. To investigate changes after treatment, voxel- and region of interest (ROI)-wise GMV analyses were performed. Then, GMV with significant differences was extracted from patients to investigate its dynamic alterations by one-way repeated-measures analysis of variance (ANOVA). The nonparametric Spearman rank correlation analysis was used to evaluate the relationship between GMV alterations and tremor improvement after thalamotomy. Results: Tremors were significantly relieved after MRgFUS thalamotomy in nine patients (P<0.05). The treated hand tremor scores improved 74.82% on average in patients from pre-operation to 12 months post-operation. Voxel-wise analysis at the cluster level showed a significant decrease in GMV in the left middle occipital gyrus (MOG) [t=11.81, voxel-level P<0.001, cluster-level Pfamily-wise error (FWE) <0.05] and an increase in GMV in the left precentral gyrus (PreCG) (t=7.99, voxel-level P<0.001, cluster-level PFWE <0.05) in TDPD patients from preoperative to 12 months post-operation, which was significantly correlated with tremor scores (rho =0.346-0.439, P<0.05). ROI-wise analysis showed that GMV related to MRgFUS thalamotomy was associated with long-term structural alterations (P<0.05 with Bonferroni correction), including specific basal ganglia and related nuclei and cerebellum subregions. Conclusions: GMV can be used to reflect tremor improvement after MRgFUS thalamotomy and be helpful to better understand the distant effect of MRgFUS thalamotomy and the involvement of GMV in tremor control in TDPD. Trial Registration: ClinicalTrials.gov identifier: NCT04570046.

Amphiphilic polymeric nanoparticles enable homogenous rhodium-catalysed NH insertion reactions in living cells.

Rh-catalysed NH carbene insertion reactions were exported to living cells with help of amphiphilic polymeric nanoparticles. Hereto, hydrophobic dirhodium carboxylate catalysts were efficiently encapsulated in amphiphilic polymeric nanoparticles comprising dodecyl and Jeffamine as side grafts. The developed catalytic nanoparticles promoted NH carbene insertions between α-keto diazocarbenes and 2,3-diaminonaphthalene, followed by intramolecular cyclisation to form fluorescent or biologically active benzoquinoxalines. These reactions were studied in reaction media of varying complexity. The best-performing catalyst was exported to HeLa cells, where fluorescent and cytotoxic benzoquinoxalines were synthesized in situ at low catalyst loading within a short time. Most of the developed bioorthogonal transition metal catalysts reported to date are easily deactivated by the reactive biomolecules in living cells, limiting their applications. The high catalytic efficiency of the Rh-based polymeric nanoparticles reported here opens the door to expanding the repertoire of bioorthogonal reactions and is therefore promising for biomedical applications.

Simultaneously controlling conformational and operational stability of single-chain polymeric nanoparticles in complex media.

Single-chain polymeric nanoparticles (SCPNs) comprising a solvatochromic pyrazoline adduct show conformational and operational stability in complex media and in cellular compartments; the connectivity of the adduct is crucial in modulating interactions with the surrounding media.

Acrylamide Induces Neurotoxicity in SH-SY5Y Cells via NLRP3-mediated Pyroptosis.

Acrylamide (ACR), a soft electrophile, is a typical environmental and food contaminant that presents potential health hazards and, consequently, is attracting increasing attention in the quest for its control. ACR neurotoxicity has been widely reported in experimental animals and attributed to neuroinflammation; however, the mechanisms involved therein require clarification. In this study, we used a neuron cell model to investigate the mechanisms of ACR-induced neuroinflammation and pyroptosis. The results showed that ACR treatment induced lytic cell death morphologically under both the canonical pyroptotic pathway (NOD-like receptor protein 3 (NLRP3)-apoptosis-associated speck-like protein containing CARD (ASC)-cysteinyl aspartate specific proteinase 1 (caspase-1)-gasdermin D (GSDMD)-interleukin-1ß (IL-1ß)/interleukin-18 (IL-18)) and an alternative pyroptotic pathway (cysteinyl aspartate specific proteinase 3 (caspase-3)-gasdermin E (GSDME)-IL-1ß/IL-18) in SH-SY5Y cells. Moreover, the lactate dehydrogenase (LDH) production, cytokines release, and lytic cell death induced by ACR were diminished by caspase-1 and -3 inhibitors. Furthermore, the knockdown of caspase-1 by small interfering RNA attenuated ACR-induced lytic cell death, suggesting that canonical pyroptosis (the NLRP3-caspase 1-GSDMD-IL-1ß signaling axis) played a primary role in the ACR-induced pyroptosis. Of the two pyroptotic-related pathways, the NLRP3 inflammasome cascade was activated first within the 6-h period of ACR exposure, while the activation of the alternative pyroptotic pathway was delayed. Collectively, these results indicate that ACR mainly induces NLRP3-related neuroinflammation and pyroptosis in SH-SY5Y cells, which is, thus, suggestive of an alternative mechanism for ACR-induced neurotoxicity.

Evaluation of postcontrast images of intracranial tumors at 7T and 3T MRI: An intra-individual comparison study.

AIM: This study aimed to evaluate the diagnostic value of ultrahigh-field magnetic resonance imaging (MRI) for brain tumors in clinical practice. METHODS: Thirty patients with brain tumors underwent 7- and 3-T MRI. The performance and diagnostic confidence of 7- and 3-T MRI in the visualization of tumor details such as internal structure and feeding artery were evaluated by radiologists. Contrast-enhanced region performance and tumor detail diagnostic confidence score (DCS) were calculated and compared between 7 and 3T using Wilcoxon rank sum test. RESULTS: In 19 with obvious enhancement and 11 cases without obvious enhancement, 7- and 3-T MRI showed similar performance. The tumors' internal structure and feeding artery were more clearly depicted by 7-T MRI (62.2% and 54.4%, respectively) than by 3-T MRI (2.2% and 6.7%, respectively). Furthermore, the mean DCSs of both internal structure and feeding artery were higher at 7T than at 3T (internal structure: 16.29 ± 9.67 vs. -5.79 ± 4.12, p = 0.028; feeding artery: 21.96 ± 6.93 vs. 4.46 ± 7.07, p = 0.028). The DCS was more significantly improved in the senior radiologist group. CONCLUSION: Better visualization of brain tumor details and higher tumor detail diagnostic confidence can be obtained with 7-T MRI.

Spectrally PAINTing a Single Chain Polymeric Nanoparticle at Super-Resolution.

Folding a polymer chain into a well-defined single-chain polymeric nanoparticle (SCPN) is a fascinating approach to obtaining structured and functional nanoparticles. Like all polymeric materials, SCPNs are heterogeneous in their nature due to the polydispersity of their synthesis: the stochastic synthesis of polymer backbone length and stochastic functionalization with hydrophobic and hydrophilic pendant groups make structural diversity inevitable. Therefore, in a single batch of SCPNs, nanoparticles with different physicochemical properties are present, posing a great challenge to their characterization at a single-particle level. The development of techniques that can elucidate differences between SCPNs at a single-particle level is imperative to capture their potential applications in different fields such as catalysis and drug delivery. Here, a Nile Red based spectral point accumulation for imaging in nanoscale topography (NR-sPAINT) super-resolution fluorescence technique was implemented for the study of SCPNs at a single-particle level. This innovative method allowed us to (i) map the small-molecule binding rates on individual SCPNs and (ii) map the polarity of individual SCPNs for the first time. The SCPN designs used here have the same polymeric backbone but differ in the number of hydrophobic groups. The experimental results show notable interparticle differences in the binding rates within the same polymer design. Moreover, a marked polarity shift between the different designs is observed. Interestingly, interparticle polarity heterogeneity was unveiled, as well as an intraparticle diversity, information which has thus far remained hidden by ensemble techniques. The results indicate that the addition of hydrophobic pendant groups is vital to determine binding properties and induces single-particle polarity diversity. Overall, NR-sPAINT represents a powerful approach to quantifying the single-particle polarity of SCPNs and paves the way to relate the structural heterogeneity to functionality at the single-particle level. This provides an important step toward the aim of rationally designing SCPNs for the desired application.

Assessing the impact of MR-guided focused ultrasound thalamotomy on brain activity and connectivity in patients with essential tremor.

OBJECTIVE: Although magnetic resonance-guided focused ultrasound (MRgFUS) at the ventral intermediate (VIM) thalamic nucleus is a novel and effective treatment for medication-refractory essential tremor (ET), it is unclear how the ablation lesion affects functional activity. The current study sought to evaluate the functional impact of MRgFUS thalamotomy in patients with ET, as well as to investigate the relationship between neuronal activity changes and tremor control. METHODS: This study included 30 patients with ET who underwent MRgFUS thalamotomy with a 6-month follow-up involving MRI and clinical tremor rating. Additional sex- and age-matched healthy people were recruited for the healthy control group. The fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity were used to identify functional alteration regions of interest (ROIs). To investigate changes after treatment, ROI- and seed-based functional connectivity (FC) analyses were performed. RESULTS: Patients with ET had significantly increased fALFF in the right postcentral gyrus (PoCG; ROI 1), regional homogeneity in the left PoCG (ROI 2), and regional homogeneity in the right PoCG (ROI 3, cluster-level p value family-wise error [pFWE] < 0.05), which were recovered and normalized at 6 months after MRgFUS thalamotomy. FCs between ROI 2 and the right supramarginal gyrus, ROI 2 and the right superior parietal gyrus, and ROI 3 and the left precentral gyrus were also found to be increased after treatment (cluster-level pFWE < 0.05). Furthermore, changes in fALFF, regional homogeneity, and FC values were significantly correlated with tremor relief (p < 0.05). Preoperative FC strengths were found to be inversely related to the postoperative tremor control ratio (p < 0.05). CONCLUSIONS: In patients with ET, the VIM lesion of MRgFUS thalamotomy resulted in symptom-related regional functional recovery associated with sensorimotor and attention networks. Preoperative FC strengths may reflect the postoperative tremor control ratio, implying that this metric could be a useful neuroimaging biomarker for predicting symptom relief in patients with ET following thalamotomy.

En Route to Stabilized Compact Conformations of Single-Chain Polymeric Nanoparticles in Complex Media.

Precise control over the folding pathways of polypeptides using a combination of noncovalent and covalent interactions has evolved into a wide range of functional proteins with a perfectly defined 3D conformation. Inspired hereby, we develop a series of amphiphilic copolymers designed to form compact, stable, and structured single-chain polymeric nanoparticles (SCPNs) of defined size, even in competitive conditions. The SCPNs are formed through a combination of noncovalent interactions (hydrophobic and hydrogen-bonding interactions) and covalent intramolecular cross-linking using a light-induced [2 + 2] cycloaddition. By comparing different self-assembly pathways of the nanoparticles, we show that, like for proteins in nature, the order of events matters. When covalent cross-links are formed prior to the folding via hydrophobic and supramolecular interactions, larger particles with less structured interiors are formed. In contrast, when the copolymers first fold via hydrophobic and hydrogen-bonding interactions into compact conformations, followed by covalent cross-links, good control over the size of the SCPNs and microstructure of the hydrophobic interior is achieved. Such a structured SCPN can stabilize the solvatochromic dye benzene-1,3,5-tricarboxamide-Nile Red via molecular recognition for short periods of time in complex media, while showing slow exchange dynamics with the surrounding complex media at longer time scales. The SCPNs show good biocompatibility with cells and can carry cargo into the lysosomal compartments of the cells. Our study highlights the importance of control over the folding pathway in the design of stable SCPNs, which is an important step forward in their application as noncovalent drug or catalyst carriers in biological settings.

[Design of a device for preventing pollution and air pollution in the pipeline joint of the ventilator].

Ventilators are currently the most commonly used auxiliary mechanical ventilation equipment in clinical practice, and play an important role in the treatment of hypoxemia. Ventilator-associated pneumonia (VAP) is a special type of pulmonary parenchymal inflammation of nosocomial infection in patients with mechanical ventilation, which leads the increase of mortality and affects the prognosis of patients. The non-standard management of ventilator pipeline joints and the aerosol formed by bacterial condensate splashed from ventilator pipeline pollute the air, resulting in cross infection, which are the important reasons for VAP. The existing ventilator pipeline joint cap can achieve the effect of preventing pollution, but the clinical application compliance is not high. Based on the above factors, teachers, students and medical staff of the School of Public Health and Management, Guangxi University of Chinese Medicine and other units have designed a device for preventing pollution and air pollution of the ventilator pipeline joint, and obtained the national utility model patent of China (ZL 2020 2 1361981.X). The device is composed of a model lung, a mask body, a suspension part and a beam mouth part, etc. The use method is simple, and can be applied to the pollution avoidance of invasive ventilator and non-invasive ventilator pipeline joints, to reduce the occurrence of VAP in patients and the occupational exposure of medical staff.

The Mechanism of Acrylamide-Induced Neurotoxicity: Current Status and Future Perspectives.

Acrylamide (ACR), a potential neurotoxin, is produced by the Maillard reaction between reducing sugars and free amino acids during food processing. Over the past decade, the neurotoxicity of ACR has caused increasing concern, prompting many related studies. This review summarized the relevant literature published in recent years and discussed the exposure to occupational, environmental, and daily ACR contamination in food. Moreover, ACR metabolism and the potential mechanism of ACR-induced neurotoxicity were discussed, with particular focus on the axonal degeneration of the nervous system, nerve cell apoptosis, oxidative stress, inflammatory response, and gut-brain axis homeostasis. Additionally, the limitations of existing knowledge, as well as new perspectives, were examined, specifically regarding the connection between the neurotoxicity caused by ACR and neurodegenerative diseases, NOD-like receptor protein 3 (NLRP3) inflammasome-related neuroinflammation, and microbiota-gut-brain axis signaling. This review might provide systematic information for developing an alternative pathway approach to assess ACR risk.

Yes-associated protein 1 exerts its tumor-promoting effects and increases cisplatin resistance in tongue squamous cell carcinoma cells by dysregulating Hippo signal pathway.

Tongue squamous cell carcinoma (TSCC) has been well-known for its high metastasis and poor prognosis, but the molecular mechanisms of TSCC pathogenesis and chemoresistance are still largely unknown. Thus, the present study aimed to identify the involvement of a classic Hippo/Yes-associated protein 1 (YAP1) pathway in regulating TSCC progression and cisplatin (DDP) resistance. DDP-resistant TSCC cell lines were established by gradual exposure to DDP. Through western blot analysis, the protein expression of Hippo/YAP1 axis in TSCC tissues and cell lines was detected separately. Then, YAP1 was inhibited or overexpressed in TSCC cells. Cell viability and drug resistance were evaluated by cell counting kit-8 method, colony formation assay and Trypan blue staining assay. Cell migration ability was measured by Transwell assay. The Hippo pathway was dysregulated, and YAP1 was upregulated and dephosphorylated in the TSCC tissues or DDP-resistant cell lines, compared with normal tissues or DDP-sensitive cells. YAP1 knockdown inhibited cell proliferation, colony formation ability and migration, whereas overexpression of YAP1 exacerbated these malignant characteristics. YAP1 knockdown increased DDP-sensitivity by reducing the RAD51-mediated DNA damage repair behavior under DDP intervention in the DDP-resistant TSCC cells. Conversely, YAP1 overexpression significantly increased DDP-resistance by enhancing the RAD51-mediated DNA damage repair behavior under DDP intervention in the DDP-sensitive TSCC cells. In a word, upregulation and dephosphorylation of YAP1 caused dysregulation of the tumor-inhibiting Hippo pathway, resulting in the aggressiveness and DDP resistance in TSCC.

The involvement of oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation in acrylamide-induced neurotoxicity in C57/BL6 mice.

Acrylamide (ACR) is a typical environmental contaminant, presenting potential health hazards that have been attracting increasing attention. Its neurotoxicity is known to cause significant damage to health. However, the mechanisms of ACR-induced neurotoxicity require further clarification. This study uses a mouse model to explore how ACR-induced oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation mutually contribute to neurotoxicity. A distinct increase in the cellular reactive oxygen species (ROS) levels, malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG) content and a significant decrease in the glutathione (GSH) content after ACR exposure were indicative of oxidative stress. Moreover, ACR caused neurological defects associated with gait abnormality and neuronal loss while suppressing the acetylcholine (ACh) and dopamine (DA) levels and increasing the protein expression of α-synuclein (α-syn), further inhibiting cholinergic and dopaminergic neuronal function. Additionally, ACR treatment caused an inflammatory response via nuclear factor-kappa B (NF-κB) activation and increased the protein expression of NOD-like receptor protein-3 (NLRP3), consequently activating the NLRP3 inflammasome constituents, including cysteinyl aspartate specific proteinase 1 (Caspase-1), apoptosis-associated speck-like protein containing CARD (ASC), N domain gasdermin D (N-GSDMD), interleukin-1ß (IL-1ß), and IL-18. The results revealed the underlying molecular mechanism of ACR-induced neurotoxicity via oxidative stress, neurotransmission impairment, and neuroinflammation-related signal cascade. This information will further improve the development of an alternative pathway strategy for investigating the risk posed by ACR. The hypothetical mechanism of ACR-induced neurotoxicity in vivo.

Acrylamide induces intrinsic apoptosis and inhibits protective autophagy via the ROS mediated mitochondrial dysfunction pathway in U87-MG cells.

Acrylamide (ACR) is a potential neurotoxin commonly found in the environment, as well as in food repeatedly exposed heat processing, but the mechanism underpinning ACR-induced neurotoxicity remains unclear. This study investigated the potential association and underlying signal transduction of oxidative stress, apoptosis, and autophagy associated with ACR-triggered neurotoxicity. Therefore, U87-MG cells were treated with varying ACR concentrations, while the cell activity reduction depended on the specific dosage and time parameters. Biochemical analyses showed that ACR significantly increased the reactive oxygen species (ROS), malondialdehyde (MDA), and Ca2+ levels while decreasing the glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm), finally leading to a higher cell apoptotic rate. Moreover, ACR induced U87-MG cell apoptosis and autophagy via ROS-triggered expression in the mitochondrial apoptosis pathway, NF-κB activation, and autophagosome accumulation. In addition, the autophagosome accumulation induced by ACR could probably be ascribed to blocked autophagic flux, inhibiting the autophagosomes from combining with lysosomes, while the inhibition of autophagy caused by ACR further promoted the initiation of apoptosis. In conclusion, the results indicated that the apoptotic and autophagic pathways responded to ACR-induced neurotoxicity. However, inhibited protective autophagy further promoted apoptotic progression. New insights may be derived from these cellular responses that can help develop diverse pathway strategies for assessing the risk posed by ACR.HIGHLIGHTSACR induced mitochondrial- and caspase-dependent apoptosis in U87-MG cells.ACR regulated the autophagic markers and blocked autophagic flux in U87-MG cells.ACR inhibited protective autophagy and promoted apoptotic initiation in U87-MG cells.

Elucidating the Stability of Single-Chain Polymeric Nanoparticles in Biological Media and Living Cells.

The controlled folding of synthetic polymer chains into single-chain polymeric nanoparticles (SCPNs) of defined size and shape in water is a viable way to create compartmentalized, nanometer-sized structures for a range of biological applications. Understanding the relationship between the polymer's microstructure and the stability of folded structures is crucial to achieving desired applications. Here, we introduce the solvatochromic dye Nile red into SCPNs and apply a combination of spectroscopic and microscopic techniques to relate polymer microstructure to nanoparticle stability in complex biological media and cellular environments. Our experimental data show that the polymer's microstructure has little effect on the stability of SCPNs in biological media and cytoplasm of living cells, but only SCPNs comprising supramolecular benzene-1,3,5-tricarboxamide (BTA) motifs showed good stability in lysosomes. The results indicate that the polymer's microstructure is vital to ensure nanoparticle stability in highly competitive environments: both hydrophobic collapse and a structured interior are required. Our study provides an accessible way of probing the stability of SCPNs in cellular environments and paves the way for designing highly stable SCPNs for efficient bio-orthogonal catalysis and sensing applications.

N,Cl-Codoped Carbon Dots from Impatiens balsamina L. Stems and a Deep Eutectic Solvent and Their Applications for Gram-Positive Bacteria Identification, Antibacterial Activity, Cell Imaging, and ClO- Sensing.

In this study, we first synthesized metal-free N,Cl-doped carbon dots (N,Cl-CDs) using Impatiens balsamina L. stems as green precursors in a deep eutectic solvent (DES). The obtained N,Cl-CDs were characterized through transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, fluorescence (FL) spectroscopy, and ultraviolet (UV) spectroscopy. In addition to the common features of carbon dots (CDs), such as high light stability, small size, low toxicity, good aqueous solubility, and favorable biocompatibility, these N,Cl-CDs exhibited excellent recognition and selectivity for Gram-positive bacteria by doping with N and Cl elements using DES. The N,Cl-CDs with positive charge cannot only differentiate Gram-positive bacteria by selective fluorescence imaging but also have antibacterial effects on Gram-positive bacteria. Through potential, ROS, and morphological analyses of bacteria before and after treatment with N,Cl-CDs, the antibacterial mechanisms of bacteriostasis, Enterococcus faecium, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Salmonella were explored. In addition, N,Cl-CDs demonstrated low cytotoxicity and good cell imaging ability in cancer and normal cells. Moreover, they can be used as a fluorescence sensor for the detection of ClO- with a detection range from 100 nM to 40 µM and a limit of detection (LOD) of 30 nM. In summary, the prepared N,Cl-CDs could be applied as environmentally friendly Gram-positive bacterial identification and antibacterial agents. Additionally, their cell imaging and ClO- detection abilities were outstanding.

Highly Crystalline Covalent Organic Frameworks Act as a Dual-Functional Fluorescent-Sensing Platform for Myricetin and Water, and Adsorbents for Myricetin.

Selective detection of active ingredients in complex samples has always been a crucial challenge because there are many disturbing compounds, especially structural analogues that interfere with the detection. In this work, a fluorescent covalent organic framework (named COF-TD), which can be used for the selective fluorescence detection and enrichment of myricetin from complex samples, was reported for the first time. The highly crystalline COF-TD with bright blue fluorescence was formed through a solution polymerization method by the condensation reaction between 4,4',4″-(1,3,5-triazine-2,4,6-triyl)trianiline and 2,5-dihydroxy-1,4-benzenedicarboxaldehyde. Due to spatial size selectivity, multisites hydrogen bonding, and π-π interaction, myricetin can quench the fluorescence of COF-TD with an inner filter effect (IFE) and static quenching mechanisms as well as can be enriched on COF-TD. Myricetin can observably eliminate the interference of other compounds and selectively quench the fluorescence of COF-TD with a limit of detection (LOD) of 0.30 µg·mL-1. The high adsorption ability of COF-TD (Q = 124.6 mg·g-1) to myricetin was also obtained. Finally, a sensing platform based on COF-TD for myricetin was successfully developed and applied for the detection of myricetin from vine teas. In addition, COF-TD also showed good water sensing ability and could be used effectively to detect water content in organic solvent (1-18% water in acetone, 0.5-5% water in acetonitrile, 1-4.5% water in ethyl acetate, v/v). To the best of our knowledge, this is the first report where COF-TD was used to detect water in a relatively wide concentration range. In all, this work provided dual-functional fluorescent COFs with the properties of an adsorbent, opening up new methodologies for the simple, selective, and enrichment detection method for myricetin.