Purpose:Hafnium oxide nanoparticles have been established as effective radiosensitizers, however, tumor cells often develop resistance to single-modality radiotherapy, and the tumor microenvironment (TME) poses additional limitations to treatment efficacy. To address these challenges, we fabricated a doxorubicin and manganese oxide co-loaded hafnium oxide (MD-Hf) nanoplatform for synergistic radio-chemotherapy and evaluated its antitumor performance in cellular and animal models. Results:In MD-Hf nanoplatform, the HfO2 nanocrystal functions as the radiosensitizer and carrier, the Dox works for chemotherapy, while the manganese oxide coating layer are capable of modulating the TME by depleting glutathione (GSH) and converting H2O2 in to ·OH radicals. Moreover, the MnOx coating also allows the nanoplatform possessing TME-responsive Dox release. Upon exposure to X-rays, the MD-Hf exhibited evident toxicity to Panc 02 tumor cells, only 63.9±10.7% cell remain alive after irradiated with 2Gy X-ray, which is much lower than 86.7±6.33% of the group administrated with pure HfO2 NPs. In vivo studies further demonstrated superior therapeutic outcomes with the MD-Hf nanoplatform, as evidenced by markedly reduced tumor size and weight compared to treatment with HfO2 nanoparticles alone. RNA-seq analysis reveals the Dox can potentiate organelle damage, and the MnOx can even activate immune response, which further corroborates the multifunctionality of the integrated nanoplatform. Conclusion:The newly developed doxorubicin and manganese oxide co-loaded HfO2 nanoplatform significantly enhance radio-chemotherapeutic efficacy against pancreatic tumor cells, offering a promising strategy that may guide the future clinical development of HfO2-based radiotherapy.

Diabetes mellitus (DM) is associated with systemic metabolic disturbances across multiple organs. Total-body 18F-fluorodeoxyglucose (F-FDG) PET/CT enables simultaneous quantification of glucose metabolism in numerous organs. This study aimed to characterize multi-organ 18F-FDG uptake patterns in type 2 DM patients compared with healthy controls and to explore associations with clinical variables including brain volume. Compared with controls, DM patients exhibited significantly lower SULmean in brain (− 15.3

PurposeThis study aims to construct an individualized glucose metabolism network using total-body 18F-FDG PET imaging, which provides a comprehensive view of glucose metabolism across various organs, to explore the role of inter-organ interactions in Diabetes Mellitus (DM).MethodsIn this study, we constructed covariance metabolic networks using static total-body PET images, normalized by lean body mass, from 36 patients with DM (DM group) and 36 age- and sex-matched healthy controls (HC group). Differences in network properties between the DM and HC groups were evaluated at both group and individual levels. In addition, correlation analysis was performed to explore the relationship between network properties and baseline clinical data in the DM subjects.ResultsWe observed that the same edges in the first three edges with the largest values were brain-subcutaneous adipose tissue (SAT) and brain-visceral adipose tissue (VAT) at both group and individual levels. There was a positive correlation between the brain-VAT and BMI and there was a negative correlation between the brain-SAT and age. The most perturbed organ was the brain at both group and individual levels, and there was a positive correlation between the strength of abnormality of brain and age.ConclusionThis study successfully used static total-body PET imaging to construct individualized glucose metabolism networks for patients with DM, identifying the brain-VAT and brain-SAT as the most significantly altered edge and the brain as the most affected organ. These findings provide novel insights into the role of the brain-white adipose tissue axis in glucose metabolism in DM.

Cysteine (Cys) is essential for numerous physiological processes and play a vital role in disease diagnostics, underscoring the necessity for effective and sensitive detection techniques for Cys. In this research, we introduce an ultrasensitive colorimetric approach based on oxidase-like Mn3O4 nanozymes. The nanozymes were synthesized through a straightforward wet chemical method and displayed a flower-like globular morphology, showing remarkable oxidase-like catalytic performance with a low Km value of 0.1896 mM and a high Vmax of 2.8 x 10-7 M s-1. By leveraging the outstanding catalytic activities of Mn3O4 nanozymes and optimizing the TMB concentration, we developed a novel and sensitive colorimetric sensor for Cys detection. Experimental results indicated a detection range for Cys between 0.5 and 45 mu M, with a lower limit of detection (LOD) of 0.02636 mu M. This established method for detecting Cys reveals significant promise for the advancement of effective sensing systems.

The interaction between ionizing radiation and materials composed of high Z-number elements could be applied to enhance radiotherapy. In this work, we fabricated an ionizing radiation-sensitive nanoplatform by grafting chlorin e6 (Ce6) onto the surface of ultrasmall gold nanoparticles (Au NPs), aiming to enhance the radiation effects induced by different radiation sources. Poly-(ethylene glycol) (PEG) was applied as the shape-controlling agent during the synthesis of Au nanoparticles. The as-prepared Au NPs show excellent monodispersity, with an average hydrodynamic diameter of around 5 nm. U87 and HeLa cell lines were utilized to evaluate the biological properties of the as-prepared Ce6-Au NPs. The Cell Counting Kit-8 (CCK-8) results reveal that the Ce6-Au NPs conjugate can significantly affect the growth of U87 cells under X-ray and 68Ga exposure, which is not seen for the pure Au NPs, Ce6, and physically mixed Ce6 and Au NPs. Moreover, the Ce6-Au NPs conjugate show evident cell prefoliation inhibition of U87 and HeLa cells under both X-ray and 18F-radiolabeled fluorodeoxyglucose (18F-FDG) exposure. These results indicate that interaction exists between Ce6 and Au NPs under radiation exposure. The mRNA sequencing results show that the tumor killing performance induced by Ce6-Au NPs may be due to regulation of the tumor microenvironment (TME) and immune-relevant signaling pathway. Our research proves that the rational combination of Au NPs and Ce6 can make better use of ionizing radiation energy and thus improve the therapeutic outcome of radiotherapy.

The intricate interplay between organs can give rise to a multitude of physiological conditions. Disruptions such as inflammation or tissue damage can precipitate the development of chronic diseases such as tumors or diabetes mellitus (DM). While both lung cancer and DM are the consequences of disruptions in homeostasis, the relationship between them is intricate. This study sought to investigate the potential influence of DM on lung cancer by employing total-body dynamic PET imaging. The present study proposes a framework for metabolic network analysis using total-body dynamic PET imaging of 20 lung cancer patients with DM (DM group) and 20 lung cancer patients without DM (Non-DM group), with the residuals of a third-order polynomial fit serving as an indicator of Pearson correlation. The framework successfully captured the deviation of the DM group from the Non-DM group at both the edge and organ levels. At the edge level, there was a significant difference in the lesion- left ventricle (LV) between the DM and Non-DM groups (P < 0.05). Furthermore, we discovered a positive correlation between the absolute value of Z-score (ZCC) of lesion - LV and the duration of DM (R = 0.680, P < 0.001). At the organ level, there was a significant difference in the kidney, brain, and abdominal fat between the DM and Non-DM groups (P < 0.05). This study demonstrated the feasibility of constructing metabolic networks to uncover complex alterations in lung cancer patients with DM. The findings contribute to understanding the systemic effects of DM on lung cancer metabolism and highlight the importance of personalized metabolic network analysis to comprehend the implications of concurrent diseases.

Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.

An increasing number of novel biomaterials have been applied in wound healing therapy. Creating beneficial environments and containing various bioactive molecules, hydrogel- and extracellular vesicle (EV)-based therapies have respectively emerged as effective approaches for wound healing. Moreover, the synergistic combination of these two components demonstrates more favorable outcomes in both chronic and acute wound healing. This review provides a comprehensive discussion and summary of the combined application of EVs and hydrogels to address the intricate scenario of wounds. The wound healing process and related biological mechanisms are outlined in the first section. Subsequently, the utilization of EV-loaded hydrogels during the wound healing process is evaluated and discussed. The moist environment created by hydrogels is conducive to wound tissue regeneration. Additionally, the continuous and controlled release of EVs from various origins could be achieved by hydrogel encapsulation. Finally, recent in vitro and in vivo studies reported on hydrogel dressings loaded with EVs are summarized and challenges and opportunities for the future clinical application of this therapeutic approach are outlined.

The tumor suppressor protein B-cell translocation gene 2 (BTG2) is downexpressed in lung adenocarcinoma (LUAD); however, its role in LUAD survival remains unknown. This investigation is aimed at exploring the activity of BTG2 in LUAD. We analyzed BTG2 expression in LUAD datasets of the TCGA database and examined that BTG2 was markedly downregulated in comparison with adjacent normal tissues. The prognostic analysis suggested that higher expression of BTG2 protein correlates with prolonged survival in patients. Vectors expressing BTG2 were stably transduced into lung adenocarcinoma A549 cells. The overexpression of BTG2 in A549 cells causes cellular G1 phase arrest but did not affect cell proliferation, accompanied by increased activation of NF-κB. Our data indicate that BTG2 overexpression may trigger an autoregulatory prosurvival NF-κB pathway, which is resistant to environmental intervention owing to an increased level of BTG2.

An optimized support vector machine model was used to construct a lung cancer diagnosis model based on serological indicators, and a molecular regulation model of Wogonin, a component of Scutellaria baicalensis , was established. Serological indexes of patients were collected, the grid search method was used to identify the optimal penalty coefficient C and parameter g of the support vector machine model, and the benign and malignant auxiliary diagnosis model of isolated pulmonary nodules based on serological indicators was established. The regulatory network and key targets of Wogonin in lung cancer were analyzed by network pharmacology, and key targets were detected by western blot. The relationship between serological susceptibility genes and key targets of Wogonin was established, and the signaling pathway of Wogonin regulating lung cancer was constructed. After support vector machine parameter optimization ( C = 90.597, g = 32), the accuracy of the model was 90.8333%, with nine false positives and two false negative cases. Ontology functional analysis of 67 common genes between Wogonin targets and lung cancer–related genes showed that the targets were associated with biological processes involved in peptidye-serine modification and regulation of protein kinase B signaling; cell components in the membrane raft and chromosomal region; and molecular function in protein serine/threonine kinase activity and heme binding. Kyoto Encyclopedia of Genes and Genomes analysis showed that the regulation pathways involved the PI3K-Akt signaling pathway, ERBB signaling pathway, and EGFR tyrosine kinase inhibitor resistance. In vitro analyses using lung cancer cells showed that Wogonin led to significantly increased levels of cleaved caspase-3 and Bad and significantly decreased Bcl-2 expression in a concentration-dependent manner. ErbB4 expression also significantly decreased in lung cancer cells after treatment with Wogonin. A regulatory network of Wogonin regulating lung cancer cell apoptosis was constructed, including the participation of serological susceptibility genes. There is a certain regulatory effect between the serological indexes that can be used in the diagnosis of lung cancer and the key targets of Chinese herbal medicine treatment of lung cancer, which provides a new idea for the diagnosis, treatment and prognosis of clinical lung cancer.

Ethnopharmacological relevance: Scutellaria baicalensis georgi is one of the most widely studied TCMs; its effects in ALI have been studied in a large number of experiments, and the efficacy of volatile oil from TCM remains to be studied. Aim: The volatile component of Scutellaria baicalensis georgi was selected to act on the key target of acute lung injury and was preliminarily studied for its specific molecular mechanism. Methods: The volatile active substances of Scutellaria baicalensis georgi were extracted by GC–MS, and the active ingredients related with the occurrence and development of acute lung injury were searched and matched by the TCMSP database. The pharmacologic data and analysis platform of TCM were used to retrieve and screen for the volatile active components and the possible therapeutic targets of Scutellaria baicalensis georgi. In addition, acute lung injury was searched in the disease target database to identify the corresponding disease target proteins, thereby establishing a protein–protein interaction network. Finally, the effects of wogonin on the apoptotic and inflammatory factors in the acute lung injury cell model were analyzed experimentally. Results: We identified 100 candidate targets and successfully constructed a complex target network. The targets identified by the above gene enrichment analysis played important roles in the autoimmune disease cell cycle apoptosis and related signaling pathways. The KEGG pathway analysis showed that most of the target genes were involved in the inflammatory response regulation of the TRP, PI3K-Akt, and IL-17 signaling pathways. The participation of wogonin in the specific regulatory pathways of PI3K-Akt signaling and IL-17 signaling was verified through experiments. In the lung-injured cell model, the results showed that wogonin inhibited the apoptosis of injured lung cells by inhibiting the expression of BAD gene and the activation of cleaved caspase-3 gene while increasing Bcl-2 expression. In addition, wogonin inhibited the expression of the abovementioned inflammatory factors and further inhibited the inflammatory response in the lung injury cells. Conclusion: The results of pharmacological network analysis can predict and explain the regulation mechanism of multi-target and multi-pathway of TCM components. This study identified the potential target and important pathway of wogonin in regulating acute lung injury. At the same time, the accuracy of network pharmacological prediction is also preliminarily verified by molecular biology experiment.

In this study, the CuS/BiVO4-X (where X represents the mass percentage of CuS associated with CuS/BiVO4; X = 2%, 5% and 7%) p–n heterostructures were fabricated using a two-step hydrothermal method.

In this study, the CuS/BiVO4-X (where X represents the mass percentage of CuS associated with CuS/BiVO4; X = 2%, 5% and 7%) p-n heterostructures were fabricated using a two-step hydrothermal method. The structural and morphological features were ascertained in great detail using several physical characterization processes. According to the results of the photoelectrochemical (PEC) experimental processes, the PEC properties of CuS/BiVO4-5% were much more obvious as compared to those of pure BiVO4, CuS and CuS/BiVO4-X. Moreover, the photoluminescence (PL) and UV-vis diffuse reflection spectra (DRS) affirmed that the CuS/BiVO4-5% demonstrates an excellent capacity for absorbing visible light and low electron recombination rate as compared with the other composites. Accordingly, PEC sensors with CuS/BiVO4-5% were fabricated for the detection of dopamine (DA) and bisphenol A (BPA) with outstanding selectivity and stability. For DA, it implied a broad linear range from 0.01-10 μM and 10-120 μM, and for BPA, the broad linear range was 0.01-90 μM. Thus, the PEC sensor has significant potential application when it comes to DA and BPA detection.

纳米氧化钛尺寸极小,具有表面活性高、光催化活性强等优良特性,目前已作为药物助剂、药物载体、植入材料用于医学影像、肿瘤治疗、外科矫形等.近年来相关研究表明,医用纳米氧化钛通过注射、口服、植入等方式直接进入人体,可能产生不良的生物学效应.本文以生物医用纳米材料-纳米氧化钛为例,对其理化特性、进入生物体途径、在生物体内的分布等进行介绍,并综述了纳米氧化钛的细胞毒性、遗传毒性和光毒性及相关可能的作用机制,最后总结了纳米材料毒性影响因素及降低其生物毒性可能的方法.

OBJECTIVE:This research was to establish a mitochondrial-related Drp1 gene and a lung cancer-related Erbb4 gene to participate in the regulatory network of lung cancer cell apoptosis, and to provide theoretical support for mitochondria to participate in tumor regulation. METHOD:The GO and KEGG methods were used to construct the regulatory networks of lung cancer related Drp1 and Erbb4 proteins that involved in the apoptosis of tumor cells, and to combine with the Bayesian network theory to screen out the largest possible action path acting on this network; The information about Drp1 in Oncomine database was collected, and the data in current database were analyzed twice. The role of Drp1 in lung cancer was meta-analyzed. RESULT:A regulatory network of Drp1 and Erbb4 involved in the apoptosis of tumor cells was successfully constructed; the optimal pathway was optimized using Bayesian theory; a total of 446 different types of research results were collected in the Oncomine database, of which there were 18 studies with statistical differences in Drp1 expression, 13 studies with increased Drp1's expression, and 5 studies with decreased expression. Compared with the control group, Drp1 was expressed in lung cancer tissues highly (P < 0.05). CONCLUSION:Establishment and optimization of mitochondrial-related Drp1 and tumor-related Erbb4 genes involved in the regulation of apoptosis of cancer cells. It was proposed that Drp1 was expressed in lung cancer tissues highly through in-depth excavation of tumor-associated gene information in the Oncomine gene chip database.

The Jialu River in China has been seriously polluted by the direct discharge of industrial and domestic wastewater. The predominant contaminants of the Jialu River and its adjacent groundwater were recently investigated. However, the potential genotoxic impact of polluted water on human health remains to be clarified. Here, we used human–hamster hybrid (AL) cells, which are sensitive for detecting environmental mutagens. We found that the cytotoxicity and mutagenicity of the groundwater in the Jialu River basin were influenced by the infiltration of the Jialu River. Hydrological periods significantly affected the cytotoxicity, but not the mutagenic potential, of surface and groundwater. Further, the mutagenic potential of groundwater samples located <1km from the Jialu River (SM-2 water samples) was detected earlier than that of groundwater samples located approximately 20km from the Jialu River (SN water samples). Because of high cytotoxicity, the mutagenic potential of water samples from the Jialu River (SM-1 water samples) was not significantly enhanced compared with that of untreated controls. To further assess the mutagenic dispersion potential, an artificial neural network model was adopted. The results showed that the highest mutagenic potential of groundwater was observed approximately 10km from the Jialu River. Although further investigation of mutagenic spatial dispersion is required, our data are significant for advancing our understanding of the origin, dispersion, and biological effects of water samples from polluted areas.

Flow cytometric investigation of the toxic effects of nanoparticles on bacteria is highly challenging and not sensitive due to the interference of aggregated nanoparticles: aggregated nanoparticles and bacteria are similar in size. In this study, an optimized dual fluorescence flow cytometric analysis was developed using PI-Lac::GFP (propidium iodide stained Escherichia coli (lac::GFP)) to monitor the toxicity of silver nanoparticles (AgNPs). As compared with single fluorescence analysis, the dual fluorescence analysis enabled more accurate evaluation of the toxic effects of AgNPs. We used this dual fluorescence analysis to investigate how AgNPs toxicity was affected by two typical environmental factors, divalent metal ions and surfactants. Our data revealed that Cu(2+) and SDS significantly enhanced the toxicity of AgNPs in a dose-dependent manner. SDS enhanced the toxicity of both AgNPs and Ag(+) ions, whereas Cu(2+) increased the toxicity of AgNPs but not dissolved Ag(+) ions. Our results suggest that this dual fluorescence analysis can be used to evaluate the toxicity of AgNPs accurately and sensitively.

Ultrafine carbon nanodots can be obtained through simple combustion of small molecules with stable blue luminescence bands.

With the expanding use of engineered nanoparticles (NPs), development of a high-throughput, sensitive method for evaluating NP safety is important. In this study, we developed cell-based biosensors to efficiently and conveniently monitor NP toxicity. The biosensor cells were obtained by transiently transfecting human cells with biosensor plasmids containing a mCherry gene regulated by an inducible promoter [an activator protein 1 (AP-1) promoter, an interleukin 8 (IL8) promoter, or a B cell translocation gene 2 (BTG2) promoter], with an enhanced green-fluorescent protein gene driven by the cytomegalovirus promoter as the internal control. After optimizing flow cytometric analysis, these dual-fluorescence cell-based biosensors were capable of accurately and rapidly detecting NP toxicity. We found that the responses of AP-1, BTG2, and IL8 biosensors in assessing the toxicity of silver nanoparticles (Ag NPs) showed good dose-related increases after exposure to Ag NPs and were consistent with data acquired by conventional assays, such as western blot, real-time polymerase chain reaction, and immunofluorescence. Further investigation of the effects of environmental factors on Ag NP toxicity revealed that aging in water, co-exposure with fulvic acid, and irradiation with ultraviolet A light could affect Ag NP-induced biosensor responses. These results indicated that these novel dual-fluorescence biosensors can be applied to accurately and sensitively monitor NP toxicity.