Serum sSelectin-L is an early specific indicator of radiation injury.

Objective: It's crucial to identify an easily detectable biomarker that is specific to radiation injury in order to effectively classify injured individuals in the early stage in large-scale nuclear accidents. Methods: C57BL/6J mice were subjected to whole-body and partial-body γ irradiation, as well as whole-body X-ray irradiation to explore the response of serum sSelectin-L to radiation injury. Then, it was compared with its response to lipopolysaccharide-induced acute infection and doxorubicin-induced DNA damage to study the specificity of sSelectin-L response to radiation. Furthermore, it was further evaluated in serum samples from nasopharyngeal carcinoma patients before and after radiotherapy. Simulated rescue experiments using Amifostine or bone marrow transplantation were conducted in mice with acute radiation syndrome to determine the potential for establishing sSelectin-L as a prognostic marker. The levels of sSelectin-L were dynamically measured using the ELISA method. Results: Selectin-L is mainly expressed in hematopoietic tissues and lymphatic tissues. Mouse sSelectin-L showed a dose-dependent decrease from 1 day after irradiation and exhibited a positive correlation with lymphocyte counts. Furthermore, the level of sSelectin-L reflected the degree of radiation injury in partial-body irradiation mice and in nasopharyngeal carcinoma patients. sSelectin-L was closely related to the total dose of γ or X ray. There was no significant change in the sSelectin-L levels in mice intraperitoneal injected with lipopolysaccharide or doxorubicin. The sSelectin-L was decreased slower and recovered faster than lymphocyte count in acute radiation syndrome mice treated with Amifostine or bone marrow transplantation. Conclusions: Our study shows that sSelectin-L has the potential to be an early biomarker to classify injured individuals after radiation accidents, and to be a prognostic indicator of successful rescue of radiation victims.

Interaction of microorganisms with carbonates from the micro to the macro scales during sedimentation: Insights into the early stage of biodegradation.

The assembly process of Organic Matter (OM) from single molecules to polymers and the formation process of Ca-CO3 ion-pairs are explored at the micro-scale, and then the relationship between OM and carbonate based on the results of microbially-induced carbonate precipitation (MICP) laboratory experiments is established at the macro-scale. Molecular dynamics (MD) is used to model the assembly of OM (a) in an aqueous solution, (b) on surfaces of calcite (10 1‾ 4) crystals and (c) on defective calcite (101‾ 4) crystal surfaces. From the MICP experiments, carbonate minerals containing abundant OM were precipitated and were characterized by Scanning Electron Microscopy (SEM), X-Ray Diffractometry (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). The results of the MD show that OM is assembled into polymers in all three simulation systems. Although the Ca-CO3 ion-pairs and OM were briefly combined, the aggregation assembly of OM molecules and the precipitation of carbonate calcium are not related in the long run. The highly specific surface area of the defective calcite shows an increase in the adsorption of OM. The van der Waals forces, which are primarily responsible for controlling the assembly of OM molecules, increase with the degree of aggregation. According to the MICP experiments, OM is enriched on the mineral surfaces, and more OM is found at the steps of defective crystals with their larger surface areas. Through MD and MICP laboratory experiments, this work systematically describes the interaction of OM and carbonate minerals from the micro to the macro scales, and this provides insight into the interaction between OM and carbonates and biogeochemical processes related to the accumulation of OM in sediments.

METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2.

Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether N6-methyladenosine (m6A) specifically modified by methyltransferase-like 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-d-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP). Using dot blotting, immunofluorescence, gain/loss-of-function, and behavioral assays, we found that m6A levels were upregulated in L4-L6 DRG neurons in CINP in a DBP/METTL14-dependent manner, which was also confirmed in human DRGs. Blocking METTL14 reduced m6A methylation and attenuated pain hypersensitivity. Mechanistically, METTL14-mediated m6A modification facilitated the synaptic plasticity of DRG neurons by enhancing the GluN2A subunit of NMDAR, and inhibiting METTL14 blocked this effect. In contrast, overexpression of METTL14 upregulated m6A modifications, enhanced presynaptic NMDAR activity in DRG neurons, and facilitated pain sensation. Our findings reveal a previously unrecognized mechanism of METTL14-mediated m6A modification in DRG neurons to maintain neuropathic pain. Targeting these molecules may provide a new strategy for pain treatment.

S-Nitrosylation of Septin2 Exacerbates Aortic Aneurysm and Dissection by Coupling the TIAM1-RAC1 Axis in Macrophages.

BACKGROUND: S-Nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in cardiovascular disease. Aortic aneurysm and dissection are high-risk cardiovascular diseases without an effective cure. The aim of this study was to determine the role of SNO of Septin2 in macrophages in aortic aneurysm and dissection. METHODS: Biotin-switch assay combined with liquid chromatography-tandem mass spectrometry was performed to identify the S-nitrosylated proteins in aortic tissue from both patients undergoing surgery for aortic dissection and Apoe-/- mice infused with angiotensin II. Angiotensin II-induced aortic aneurysm model and ß-aminopropionitrile-induced aortic aneurysm and dissection model were used to determine the role of SNO of Septin2 (SNO-Septin2) in aortic aneurysm and dissection development. RNA-sequencing analysis was performed to recapitulate possible changes in the transcriptome profile of SNO-Septin2 in macrophages in aortic aneurysm and dissection. Liquid chromatography-tandem mass spectrometry and coimmunoprecipitation were used to uncover the TIAM1-RAC1 (Ras-related C3 botulinum toxin substrate 1) axis as the downstream target of SNO-Septin2. Both R-Ketorolac and NSC23766 treatments were used to inhibit the TIAM1-RAC1 axis. RESULTS: Septin2 was identified S-nitrosylated at cysteine 111 (Cys111) in both aortic tissue from patients undergoing surgery for aortic dissection and Apoe-/- mice infused with Angiotensin II. SNO-Septin2 was demonstrated driving the development of aortic aneurysm and dissection. By RNA-sequencing, SNO-Septin2 in macrophages was demonstrated to exacerbate vascular inflammation and extracellular matrix degradation in aortic aneurysm. Next, TIAM1 (T lymphoma invasion and metastasis-inducing protein 1) was identified as a SNO-Septin2 target protein. Mechanistically, compared with unmodified Septin2, SNO-Septin2 reduced its interaction with TIAM1 and activated the TIAM1-RAC1 axis and consequent nuclear factor-κB signaling pathway, resulting in stronger inflammation and extracellular matrix degradation mediated by macrophages. Consistently, both R-Ketorolac and NSC23766 treatments protected against aortic aneurysm and dissection by inhibiting the TIAM1-RAC1 axis. CONCLUSIONS: SNO-Septin2 drives aortic aneurysm and dissection through coupling the TIAM1-RAC1 axis in macrophages and activating the nuclear factor-κB signaling pathway-dependent inflammation and extracellular matrix degradation. Pharmacological blockade of RAC1 by R-Ketorolac or NSC23766 may therefore represent a potential treatment against aortic aneurysm and dissection.

Oxytocin neurons mediate stress-induced social memory impairment.

Oxytocin has long been thought to play a substantial role in social behaviors, such as social attachment and parenting behavior. However, how oxytocin neurons respond to social and non-social stimuli is largely unknown, especially in high temporal resolution. Here, we recorded the in vivo real-time responses of oxytocin neurons in the paraventricular nucleus of the hypothalamus (PVN) in freely behaving mice. Our results revealed that oxytocin neurons were activated more significantly by stressors than social stimuli. The activation of oxytocin neurons was precisely correlated with struggling behavior during stress. Furthermore, we found that oxytocin mediated stress-induced social memory impairment. Our results reveal an important role of PVN oxytocin neurons in stress-induced social amnesia.

Oncogene SCARNA12 as a potential diagnostic biomarker for colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, and represents a severe threat to the life and health of individuals. Increasing evidence supports the role of small nucleolar RNAs (snoRNAs) as critical regulatory gene in cancer development. Small Cajal body-specific RNAs (scaRNAs), a subtype of snoRNAs, are named for their subcellular localization within Cajal bodies. SCARNA12, which located at the intronic region of PHB2 in chromosome 12p13.31 with 270 nucleotides (nt) in length. It has been reported function as a diagnostic marker for cervical cancer. However, its biological functions and molecular mechanisms in CRC have yet to be elucidated. In this study, bioinformatics analysis revealed that SCARNA12 was highly expressed in CRC and positively correlated with poor prognosis in CRC patients. Additionally, SCARNA12 showed upregulated expression in CRC cell lines and clinical CRC tissue samples. Moreover, SCARNA12 overexpression in SW620 cells accelerated cell proliferation, suppressed the apoptosis rate, and enhanced tumorigenesis in vivo. The knockdown of SCARNA12 expression in HCT116 and HT29 cells resulted in contrasting effects. The functioning of SCARNA12 is mechanically independent of its host gene PHB2. Notably, the overexpression of SCARNA12 activated PI3K/AKT pathway in SW620 cells, and the malignancy degree of CRC cells was attenuated after treatment with MK2206 (a specific AKT inhibitor). Our findings demonstrated that SCARNA12 plays an oncogenic role in CRC progression and can be used as a potential diagnostic biomarker for CRC.

Activation of G-protein-coupled receptor 183 initiates inflammatory pain via macrophage CCL22 secretion.

Chronic pain is a major public health problem with limited effective therapeutic options. G-protein-coupled receptors play a significant role in pain modulation; however, whether and how G-protein-coupled receptor 183 participates in pain regulation remain unclear. In the present study, we found that G-protein-coupled receptor 183 expression was specifically upregulated in the hind paws of mice in various inflammatory pain models. Activation of G-protein-coupled receptor 183 induced acute pain, whereas inhibition or silencing of this receptor alleviated mechanical allodynia and thermal hyperalgesia in complete Freund's adjuvant (CFA) model. Mechanistically, activating G-protein-coupled receptor 183 triggers pain responses via the upregulation of C-C motif chemokine 22(CCL22) in macrophages while blocking the CCL22 receptor C-C motif chemokine receptor 4 (CCR4) attenuates pain hypersensitivity. Taken together, our findings indicate that the G-protein-coupled receptor 183-CCL22 axis has a critical role in the development and maintenance of inflammatory pain.

Haptoglobin is an early indicator of survival after radiation-induced severe injury and bone marrow transplantation in mice.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is the main treatment for acute radiation sickness, especially after fatal radiation. The determination of HSCT for radiation patients is mainly based on radiation dose, hemogram and bone marrow injury severity. This study aims to explore a better biomarker of acute radiation injury from the perspective of systemic immune response. METHODS: C57BL/6J female mice were exposed to total body irradiation (TBI) and partial body irradiation (PBI). Changes in haptoglobin (Hp) level in plasma were shown at different doses and time points after the exposure and treatment with amifostine or bone marrow transplantation. Student's t-test/two tailed test were used in two groups. To decide the Hp levels as a predictor of the radiation dose in TBI and PBI, multiple linear regression analysis were performed. The ability of biomarkers to identify two groups of different samples was determined by the receiver operating characteristic (ROC) curve. The results were expressed as mean ± standard deviation (SD). Significance was set at P value < 0.05, and P value < 0.01 was set as highly significant. Survival distribution was determined by log-rank test. RESULTS: In this study, we found that Hp was elevated dose-dependently in plasma in the early post-irradiation period and decreased on the second day, which can be used as a molecular indicator for early dose assessment. Moreover, we detected the second increase of Hp on the 3rd and 5th days after the lethal irradiation at 10 Gy, which was eliminated by amifostine, a radiation protection drug, while protected mice from death. Most importantly, bone marrow transplantation (BMT) on the 3rd and 5th day after 10 Gy radiation improved the 30-days survival rate, and effectively accelerated the regression of secondary increased Hp level. CONCLUSIONS: Our study suggests that Hp can be used not only as an early molecule marker of radiation injury, but also as an important indicator of bone marrow transplantation therapy for radiation injury, bringing new scientific discoveries in the diagnosis and treatment of acute radiation injury from the perspective of systemic immunity.

BPIFA2 as a Novel Early Biomarker to Identify Fatal Radiation Injury After Radiation Exposure.

Background: Current dosimeters cannot cope with the two tasks of medical rescue in the early stage of nuclear accident, the accurate determination of radiation exposure and the identification of patients with fatal radiation injury. As radiation can cause alterations in serum components, it is feasible to develop biomarkers for radiation injury from serum. This study aims to investigate whether serum BPIFA2 could be used as a potential biomarker of predicting fatal radiation injury in the early stage after nuclear accident. Methods: A rabbit anti-mouse BPIFA2 polyclonal antibody was prepared to detect the expression of BPIFA2. C57BL/6J female mice were exposed to total body radiation (TBI) at different dose and Partial body radiation (PBI) at lethal dose to detect the dynamic changes of BPIFA2 in serum at different time points after irradiation by Western blot assay. Results: BPIFA2 in mice serum were significantly increased at 1-12 h post-irradiation at .5-10 Gy, and increased again significantly at 3 d after 10 Gy irradiation with associated with mortality closely. It also increased rapidly after PBI and was closely related to injury degree, regardless whether the salivary glands were irradiated. Conclusions: The increase of serum BPIFA2 is a novel early biomarker not only for identifying radiation exposure, but also for fatal radiation injury playing a vital role in rational use of medical resources, and greater efficiency of medical treatment to minimize casualties.

Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury.

Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2-24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.

Immune-Related lncRNA to Construct Novel Signature and Predict the Immune Landscape of Human Hepatocellular Carcinoma.

The signature composed of immune-related long noncoding ribonucleic acids (irlncRNAs) with no requirement of specific expression level seems to be valuable in predicting the survival of patients with hepatocellular carcinoma (HCC). Here, we retrieved raw transcriptome data from The Cancer Genome Atlas (TCGA), identified irlncRNAs by co-expression analysis, and recognized differently expressed irlncRNA (DEirlncRNA) pairs using univariate analysis. In addition, we modified Lasso penalized regression. Then, we compared the areas under curve, counted the Akaike information criterion (AIC) values of 5-year receiver operating characteristic curve, and identified the cut-off point to set up an optimal model for distinguishing the high- or low-disease-risk groups among patients with HCC. We then reevaluated them from the viewpoints of survival, clinic-pathological characteristics, tumor-infiltrating immune cells, chemotherapeutics efficacy, and immunosuppressed biomarkers. 36 DEirlncRNA pairs were identified, 12 of which were included in a Cox regression model. After regrouping the patients by the cut-off point, we could more effectively differentiate between them based on unfavorable survival outcome, aggressive clinic-pathological characteristics, specific tumor immune infiltration status, low chemotherapeutics sensitivity, and highly expressed immunosuppressed biomarkers. The signature established by paring irlncRNA regardless of expression levels showed a promising clinical prediction value.

Identification of prognostic biomarkers and correlations with immune infiltrates among cGAS-STING in hepatocellular carcinoma.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway induces innate immunity by activating the production of inflammatory cytokines and type I interferons. Recently, studies revealed that self-DNA from by-products of chromosome instability and tumors could activate the cGAS-STING pathway, and subsequently promote or inhibit tumor development. However, the prognostic value and correlations with immune infiltrates of the cGAS-STING pathway in hepatocellular carcinoma (HCC) have not been clarified. In the present study, we used the Molecular Signatures Database, Oncomine, UALCAN, Human Protein Atlas, Kaplan-Meier plotter, LinkedOmics, and Tumor Immune Estimation Resource databases. Overexpression of XRCC5, IRF3, TRIM21, STAT6, DDX41, TBK1, XRCC6, TREX1, PRKDC, and TMEM173 was markedly correlated with clinical stages and pathological grades in HCC. Moreover, higher mRNA expression of XRCC5, XRCC6, and PRKDC was significantly related with shorter overall survival. However, higher mRNA expression of IFI16, STAT6, NLRC3, and TMEM173 was associated with favorable overall survival. Our results suggested that the kinase targets of the cGAS-STING pathway included the SRC family of tyrosine kinases (LCK and LYN), phosphoinositide 3-kinase-related protein kinase (PIKK) family kinases (ATM and ATR), and mitogen-activated protein kinase 1 (MAPK1). Furthermore, we identified significant correlations among the expression of cGAS-STING pathway and infiltration of B cells, CD4+T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in HCC. The expression of the cGAS-STING pathway also exhibited strong relationships with diverse immune marker sets in HCC. These findings suggest that cGAS-STING pathway members may be used as prognostic biomarkers and immunotherapeutic targets HCC patients.

Small Nucleolar RNA, C/D Box 16 (SNORD16) Acts as a Potential Prognostic Biomarker in Colon Cancer.

Colon cancer (CC) is considered one of the most common and lethal malignancies occurring both in male and female. Its widespread prevalence demonstrates the need for novel diagnostic and prognostic biomarkers for CC. Emerging evidence has shown that small nucleolar RNAs play critical roles in tumor development. In this study, we investigated the expression profile and functions of SNORD16 in CC. Our data showed that SNORD16, rather than its host gene (RPL4), was upregulated in CC cell lines. Compared to matched adjacent normal tissues, CC tissues showed higher SNORD16 expression levels, and no correlation was found between SNORD16 and RPL4. Patients with high SNORD16 expression levels had a worse prognosis, and multivariate analysis showed the high SNORD16 expression was an independent prognostic factor for CC. In vitro gain- and loss-of-function studies revealed that SNORD16 can promote cell growth, proliferation, migration, and invasion of CC cells by inhibiting apoptosis. These results suggested that SNORD16 has an oncogenic role in CC and might be a novel diagnostic and prognostic biomarker for CC.

MiR-1587 Regulates DNA Damage Repair and the Radiosensitivity of CRC Cells via Targeting LIG4.

DNA is subject to a range of endogenous and exogenous insults that can impair DNA replication and lead to DNA double-strand breaks (DSBs). The repair capacity of cancer cells mediates their radiosensitivity, but the roles of miR-1587 during radiation resistance are poorly characterized. In this study, we explored whether miR-1587 regulates the growth and radiosensitivity of colorectal cancer (CRC) cells through its ability to regulate DNA Ligase4 (LIG4). We found that CRC cells in which miR-1587 was overexpressed inhibited cell growth and promoted apoptosis through increasing DSBs and promoting cell cycle arrest. We found that overexpression of miR-1587 significantly inhibited LIG4 messenger RNA and protein expression and further revealed the ability of miR-1587 to directly bind to the LIG4-3'-untranslated region through dual-luciferase reporter assays. More notably, miR-1587 mimics increased the radiosensitivity of CRC cells. Taken together, we show that miR-1587 overexpression enhances the formation of DSBs, arrests CRC cell growth, and enhances the radiosensivity of CRC cells through the direct repression of LIG4 expression. These results reveal novel roles for miR-1587 during DNA damage repair and the radiosensivity of CRC cells. This highlights miR-1587 as a novel therapeutic target for CRC.

Lipidomic Profiling for Serum Biomarkers in Mice Exposed to Ionizing Radiation.

Radiation biodosimeters are required urgently for fast and accurate evaluation of absorbed dose for irradiated individuals. Lipidomics has appeared as a credible technique for identification and quantification of lipid for researching biomarker of diseases. We performed a lipidomic profile on mice serum at time points of 6, 24, and 72 hours after 0, 2, 5.5, 7, and 8 Gy irradiation to select radiation-responsive lipids and conducted Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis to recognize the pathways and network changes. Then, Pearson correlation analysis was performed to evaluate the feasibility of radiation-responsive lipids to estimate radiation dose. Seven radiation-responsive lipids including PC (18:2/18:2), PC (18:0/18:2), Lyso PC 18:1, PC (18:0/20:4), SM (D18:0/24:1), PC (16:0/18:1), and Lyso PC 18:2 were identified in which glycerophospholipid metabolism presented as the most significant pathway, and they all presented good linear correlation with the irradiated dose. This study identified 7 radiation-responsive lipids in mice serum and certificate their feasibility of dose estimation as biodosimeters.

Integrative Analysis for the Roles of lncRNAs in the Immune Responses of Mouse PBMC Exposed to Low-Dose Ionizing Radiation.

It is well accepted that low-dose ionizing radiation (LDIR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Alterations in messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression were to crucially underlie these LDIR responses. However, lncRNAs in LDIR-induced immune responses have been rarely reported, and its functions and molecular mechanisms have not yet been characterized. Here, we used microarray profiling to determine lncRNA in BALB/c mice exposed to single (0.5 Gy×1) and chronic (0.05 Gy×10) low-dose γ-rays radiation (Co60). We observed that a total of 8274 lncRNAs and 7240 mRNAs were altered in single LDIR, while 2077 lncRNAs and 796 mRNAs in chronic LDIR. The biological functions of these upregulated mRNAs in both 2 groups using Gene Ontology functional and pathway enrichment analysis were significantly enriched in immune processes and immune signaling pathways. Subsequently, we screened out the lncRNAs involved in regulating these immune signaling pathways and examined their potential functions by lncRNAs-mRNAs coexpression networks. This is the first study to comprehensively identify lncRNAs in single and chronic LDIR responses and to demonstrate the involvement of different lncRNA expression patterns in LDIR-induced immune signaling pathways. Further systematic research on these lncRNAs will provide new insights into our understanding of LDIR-modulated immune hormesis responses.

Long noncoding RNA lnc-RI regulates DNA damage repair and radiation sensitivity of CRC cells through NHEJ pathway.

A percentage of colorectal cancer (CRC) patients display low sensitivity to radiotherapy, which affects its therapeutic effect. Cancer cells DNA double-strand breaks (DSBs) repair capacity is crucial for radiosensitivity, but the roles of long noncoding RNAs (lncRNAs) in this process are largely uncharacterized. This study aims to explore whether lnc-RI regulates CRC cell growth and radiosensitivity by regulating the nonhomologous end-joining (NHEJ) repair pathway. CRC cells in which lnc-RI has been silenced showed lower cell growth and higher apoptosis rates due to increased DSBs and cell cycle arrest. We found that miR-4727-5p targets both lnc-RI and LIG4 mRNA and inhibit their expression. CRC cells showed increased radiosensitivity when lnc-RI was silenced. These results reveal novel roles for lnc-RI in both DNA damage repair and radiosensitivity regulation in CRC cells. Our study revealed that lnc-RI regulates LIG4 expression through lnc-RI/miR-4727-5p/LIG4 axis and regulates NHEJ repair efficiency to participate in DNA damage repair. The level of lnc-RI was negatively correlated with the radiosensitivity of CRC cells, indicates that lnc-RI may be a potential target for CRC therapy. We also present the first report of the function of miR-4727-5p.

Proteomic Profiling for Serum Biomarkers in Mice Exposed to Ionizing Radiation.

In response to large-scale radiological incidents, rapid, accurate, and early triage biodosimeters are urgently required. In this study, we investigated candidate radiation-responsive biomarkers using proteomics approaches in mouse models. A total of 452 dysregulated proteins were identified in the serum samples of mice exposed to 0, 2, 5.5, 7, and 8 Gy at 6, 24, and 72 hours postirradiation. Ninety-eight proteins, including 46 at 6 hours, 36 at 24 hours, and 36 at 72 hours, were identified as radiation-responsive proteins (RRPs). Gene Ontology analysis showed the RRPs were involved in proteolysis, extracellular space, hydrolase activity, and carbohydrate binding. Kyoto Encyclopedia of Genes and Genome enrichment showed the RRPs were regulated in "the pentose phosphate pathway," "the proteasome," and "AGE-RAGE signaling in diabetic complications." There were 3 proteins changed and overlapped at all the 3 time points, 8 proteins changed at 6 and 24 hours, 4 proteins changed at 24 and 72hours, and 2 proteins changed at both 6 and 72 hours. Of these proteins, ORM2, HP, SAA1, SAA2, MBL2, COL1A1, and APCS were identified as candidate biomarkers for biodosimeter-based diagnosis through Pearson correlation analysis.

Single-Component Bismuth Nanoparticles as a Theranostic Agent for Multimodal Imaging-Guided Glioma Therapy.

Single-component nanomaterials such as bismuth (Bi) based on nanoparticles (NPs) intrinsically having both diagnostic and therapeutic capabilities are widely needed in biomedical fields. However, their design and fabrication still face enormous challenges. Here, a kind of pure Bi NPs with ultrahigh X-ray attenuation coeffcient was developed and evaluated as a simple but powerful theranostic nanomaterals and potent light-to-heat conversion efficiency for photoacuostic imaging (PAI)/photothermal therapy (PTT) in this study. The prepared pure Bi NPs showed excellent photothermal performance and the temperature of NPs solution (1 mg/mL) increased to 70 °C under near-infrared light irradiation within 4 min. The pure Bi NPs showed obvious enhancement effect both in X-ray computed tomography (CT) and PA imaging modalities in vivo. In addition, the glioma growth was efficiently suppressed by the pure Bi NPs after 808 nm laser irradiation, while maintained the biosafety and low toxicity. Thus, it is notable that this type of Bi nanomaterial has great potential in multi-imaging guided cancer treatment.