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1.
Gigascience ; 132024 Jan 02.
Article in English | MEDLINE | ID: mdl-38832466

ABSTRACT

BACKGROUND: Due to human error, sample swapping in large cohort studies with heterogeneous data types (e.g., mix of Oxford Nanopore Technologies, Pacific Bioscience, Illumina data, etc.) remains a common issue plaguing large-scale studies. At present, all sample swapping detection methods require costly and unnecessary (e.g., if data are only used for genome assembly) alignment, positional sorting, and indexing of the data in order to compare similarly. As studies include more samples and new sequencing data types, robust quality control tools will become increasingly important. FINDINGS: The similarity between samples can be determined using indexed k-mer sequence variants. To increase statistical power, we use coverage information on variant sites, calculating similarity using a likelihood ratio-based test. Per sample error rate, and coverage bias (i.e., missing sites) can also be estimated with this information, which can be used to determine if a spatially indexed principal component analysis (PCA)-based prescreening method can be used, which can greatly speed up analysis by preventing exhaustive all-to-all comparisons. CONCLUSIONS: Because this tool processes raw data, is faster than alignment, and can be used on very low-coverage data, it can save an immense degree of computational resources in standard quality control (QC) pipelines. It is robust enough to be used on different sequencing data types, important in studies that leverage the strengths of different sequencing technologies. In addition to its primary use case of sample swap detection, this method also provides information useful in QC, such as error rate and coverage bias, as well as population-level PCA ancestry analysis visualization.


Subject(s)
High-Throughput Nucleotide Sequencing , Sequence Analysis, DNA , Humans , High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, DNA/methods , Software , Principal Component Analysis , Computational Biology/methods , Algorithms
2.
Article in English | MEDLINE | ID: mdl-38836956

ABSTRACT

PURPOSE: After robotic-assisted total knee arthroplasty (RA-TKA) surgery, some patients still experience joint discomfort. We aimed to establish an effective machine learning model that integrates radiomic features extracted from computed tomography (CT) scans and relevant clinical information to predict patient satisfaction three months postoperatively following RA-TKA. MATERIALS AND METHODS: After careful selection, data from 142 patients were randomly divided into a training set (n = 99) and a test set (n = 43), approximately in a 7:3 ratio. A total of 1329 radiomic features were extracted from the regions of interest delineated in CT scans. The features were standardized using normalization algorithms, and the least absolute shrinkage and selection operator regression model was employed to select radiomic features with ICC > 0.75 and P < 0.05, generating the Rad-score as feature markers. Univariate and multivariate logistic regression was then used to screen clinical information (age, body mass index, operation time, gender, surgical side, comorbidities, preoperative KSS score, preoperative range of motion (ROM), preoperative and postoperative HKA angle, preoperative and postoperative VAS score) as potential predictive factors. The satisfaction scale ≥ 20 indicates patient satisfaction. Finally, three prediction models were established, focusing on radiomic features, clinical features, and their fusion. Model performance was evaluated using Receiver Operating Characteristic curves and decision curve analysis. RESULTS: In the training set, the area under the curve (AUC) of the clinical model was 0.793 (95% CI 0.681-0.906), the radiomic model was 0.854 (95% CI 0.743-0.964), and the combined radiomic-clinical model was 0.899 (95% CI 0.804-0.995). In the test set, the AUC of the clinical model was 0.908 (95% CI 0.814-1.000), the radiomic model was 0.709 (95% CI 0.541-0.878), and the combined radiomic-clinical model was 0.928 (95% CI 0.842-1.000). The AUC of the radiomic-clinical model was significantly higher than the other two models. The decision curve analysis indicated its clinical application value. CONCLUSION: We developed a radiomic-based nomogram model using CT imaging to predict the satisfaction of RA-TKA patients at 3 months postoperatively. This model integrated clinical and radiomic features and demonstrated good predictive performance and excellent clinical application potential.

3.
Nat Methods ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730258

ABSTRACT

Despite advances in long-read sequencing technologies, constructing a near telomere-to-telomere assembly is still computationally demanding. Here we present hifiasm (UL), an efficient de novo assembly algorithm combining multiple sequencing technologies to scale up population-wide near telomere-to-telomere assemblies. Applied to 22 human and two plant genomes, our algorithm produces better diploid assemblies at a cost of an order of magnitude lower than existing methods, and it also works with polyploid genomes.

4.
J Proteomics ; 302: 105195, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38734407

ABSTRACT

Different populations exhibit varying pathophysiological responses to plateau environments. Therefore, it is crucial to identify molecular markers in body fluids with high specificity and sensitivity to aid in determination. Proteomics offers a fresh perspective for investigating protein changes linked to diseases. We utilize urine as a specific biomarker for early chronic mountain sickness (CMS) detection, as it is a simple-to-collect biological fluid. We collected urine samples from three groups: plains health, plateau health and CMS. Using DIA's proteomic approach, we found differentially expressed proteins between these groups, which will be used as a basis for future studies to identify protein markers. Compared with the healthy plain population, 660 altering proteins were identified in plateau health, which performed the resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Compared to the healthy plateau population, the CMS group had 140 different proteins identified, out of which 8 were potential biomarkers for CMS. Our study has suggested that CMS may be closely related to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity. SIGNIFICANCE: Our team has compiled a comprehensive dataset of urine proteomics for AMS disease. We successfully identified differentially expressed proteins between healthy and AMS groups using the DIA proteomic approach. We discovered that 660 proteins were altered in plateau health compared to the healthy plain population, resulting in a heightened resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Additionally, we pinpointed 140 different proteins in the AMS group compared to the healthy plateau population, with 8 showing potential as biomarkers for AMS. Our findings suggest that the onset of AMS may be closely linked to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity.

6.
Small ; : e2312124, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38751072

ABSTRACT

Rechargeable metal batteries have received widespread attention due to their high energy density by using pure metal as the anode. However, there are still many fundamental problems that need to be solved before approaching practical applications. The critical ones are low charge/discharge current due to slow ion transport, short cycle lifetime due to poor anode/cathode stability, and unsatisfied battery safety. To tackle these problems, various strategies have been suggested. Among them, electrolyte additive is one of the most widely used strategies. Most of the additives currently studied are soluble, but their reliability is questionable, and they can easily affect the electrochemical process, causing unwanted battery performance decline. On the contrary, insoluble additives with excellent chemical stability, high mechanical strength, and dimensional tunability have attracted considerable research exploration recently. However, there is no timely review on insoluble additives in metal batteries yet. This review summarizes various functions of insoluble additives: ion transport modulation, metal anode protection, cathode amelioration, as well as battery safety enhancement. Future research directions and challenges for insoluble solid additives are also proposed. It is expected this review will stimulate inspiration and arouse extensive studies on further improvement in the overall performance of metal batteries.

7.
Heliyon ; 10(9): e30433, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38737233

ABSTRACT

Salidroside (SAL), belonging to a kind of the main active ingredient of Rhodiola rosea, is extensively utilized for anti-hypoxia and prevention of altitude sickness in the plateau region of China. However, the research on the systemic changes induced by SAL at intracellular protein level is still limited, especially at protein phosphorylation level. These limitations hinder a comprehensive understanding of the regulatory mechanisms of SAL. This study aimed to investigate the potential molecular mechanism of SAL in ameliorating the acute myocardial hypoxia induced by cobalt chloride using integrated proteomics and phosphoproteomics. We successfully identified 165 differentially expressed proteins and 266 differentially expressed phosphosites in H9c2 cells following SAL treatment under hypoxic conditions. Bioinformatics analysis and biological experiment validation revealed that SAL significantly antagonized CoCl2-mediated cell cycle arrest by downregulating CCND1 expression and upregulating AURKA, AURKAB, CCND3 and PLK1 expression. Additionally, SAL can stabilize the cytoskeleton through upregulating the Kinesin Family (KIF) members expression. Our study systematically revealed that SAL had the ability to protect myocardial cells against CoCl2-induced hypoxia through multiple biological pathways, including enhancing the spindle stability, maintaining the cell cycle, relieving DNA damage, and antagonizing cell apoptosis. This study supplies a comprehension perspective on the alterations at protein and protein phosphorylation levels induced by SAL treatment, thereby expanded our knowledge of the anti-hypoxic mechanisms of SAL. Moreover, this study provides a valuable resource for further investigating the effects of SAL.

8.
Org Lett ; 26(19): 4122-4126, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38695413

ABSTRACT

Glycoluril-expanded pillararenes composed of glycoluril and dialkoxybenzene units, namely, pillarurilarenes (PURA), were synthesized through a fragment coupling macrocyclization strategy. Partial replacement of dialkoxybenzene with glycoluril endows PURA with polarized equatorial methine protons for derivatization or CH-anion binding. Crystal structures of pillar[2]uril[4]arene and pillar[1]uril[4]arene containing two glycoluril units and one glycoluril unit, respectively, indicated the inward orientation of the glycoluril unit, as also suggested by 1H nuclear magnetic resonance and density functional theory calculation. This work lays a good foundation for expanding pillararenes using non-aromatic rings.

9.
Int J Part Ther ; 11: 100001, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38757076

ABSTRACT

Purpose: To describe the commissioning of real-time gated proton therapy (RGPT) and the establishment of an appropriate clinical workflow for the treatment of patients. Materials and Methods: Hitachi PROBEAT provides pencil beam scanning proton therapy with an advanced onboard imaging system including real-time fluoroscopy. RGPT utilizes a matching score to provide instantaneous system performance feedback and quality control for patient safety. The CIRS Dynamic System combined with a Thorax Phantom or plastic water was utilized to mimic target motion. The OCTAVIUS was utilized to measure end-to-end dosimetric accuracy for a moving target across a range of simulated situations. Using this dosimetric data, the gating threshold was carefully evaluated and selected based on the intended treatment sites and planning techniques. An image-guidance workflow was developed and applied to patient treatment. Results: Dosimetric data demonstrated that proton plan delivery uncertainty could be within 2 mm for a moving target. The dose delivery to a moving target could pass 3%/3 mm gamma analysis following the commissioning process and application of the clinical workflow detailed in this manuscript. A clinical workflow was established and successfully applied to patient treatment utilizing RGPT. Prostate cancer patients with implanted platinum fiducial markers were treated with RGPT. Their target motion and gating signal data were available for intrafraction motion analysis. Conclusion: Real-time gated proton therapy with the Hitachi System has been fully investigated and commissioned for clinical application. RGPT can provide advanced and reliable real-time image guidance to enhance patient safety and inform important treatment planning parameters, such as planning target volume margins and uncertainty parameters for robust plan optimization. RGPT improved the treatment of patients with prostate cancer in situations where intrafraction motion is more than defined tolerance.

10.
IET Syst Biol ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760669

ABSTRACT

Trap formation is the key indicator of carnivorous lifestyle transition of nematode-trapping fungi (NTF). Here, the DNA methylation profile was explored during trap induction of Arthrobotrys oligospora, a typical NTF that captures nematodes by developing adhesive networks. Whole-genome bisulfite sequencing identified 871 methylation sites and 1979 differentially methylated regions (DMRs). This first-of-its-kind investigation unveiled the widespread presence of methylation systems in NTF, and suggested potential regulation of ribosomal RNAs through DNA methylation. Functional analysis indicated DNA methylation's involvement in complex gene regulations during trap induction, impacting multiple biological processes like response to stimulus, transporter activity, cell reproduction and molecular function regulator. These findings provide a glimpse into the important roles of DNA methylation in trap induction and offer new insights for understanding the molecular mechanisms driving carnivorous lifestyle transition of NTF.

11.
Chem Phys Lipids ; : 105405, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38795837

ABSTRACT

At present, consumers increasingly favored the natural food preservatives with fewer side-effects on health. The green tea catechins and black tea theaflavins attracted considerable interest, and their antibacterial effects were extensively reported in the literature. Epicatechin (EC), a green tea catechin without a gallate moiety, showed no bactericidal activity, whereas the theaflavin (TF), also lacking a gallate moiety, exhibited potent bactericidal activity, and the antibacterial effects of green tea catechins and black tea theaflavins were closely correlated with their abilities to disrupt the bacterial cell membrane. In our present study, the mechanisms of membrane interaction modes and behaviors of TF and EC were explored by molecular dynamics simulations. It was demonstrated that TF exhibited markedly stronger affinity for the POPG bilayer compared to EC. Additionally, the hydrophobic interactions of tropolone/catechol rings with the acyl chain part could significantly contribute to the penetration of TF into the POPG bilayer. It was also found that the resorcinol/pyran rings were the key functional groups in TF for forming hydrogen bonds with the POPG bilayer. We believed that the findings from our current study could offer useful insights to better understand the stronger antibacterial effects of TF compared to EC.

12.
Pathol Res Pract ; 259: 155367, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38797130

ABSTRACT

Central nervous system tumor with BCOR internal tandem duplication (CNS tumor with BCOR-ITD) constitutes a molecularly distinct entity, characterized by internal tandem duplication within exon 15 of the BCOR transcriptional co-repressor gene (BCOR-ITD). The current study aimed to elucidate the clinical, pathological, and molecular attributes of CNS tumors with BCOR-ITD and explore their putative cellular origin. This study cohort comprised four pediatric cases, aged 23 months to 13 years at initial presentation. Magnetic resonance imaging revealed large, well-circumscribed intra-CNS masses localized heterogeneously throughout the CNS. Microscopically, tumors were composed of spindle to ovoid cells, exhibiting perivascular pseudorosettes and palisading necrosis, but lacking microvascular proliferation. Immunohistochemical staining showed diffuse tumor cell expression of BCOR, CD56, CD99, vimentin, and the stem cell markers PAX6, SOX2, CD133 and Nestin, alongside focal positivity for Olig-2, S100, SOX10, Syn and NeuN. Molecularly, all cases harbored BCOR-ITDs ranging from 87 to 119 base pairs in length, including one case with two distinct ITDs. Notably, the ITDs were interrupted by unique 1-3 bp insertions in all cases. In summary, CNS tumors with BCOR-ITD exhibit characteristic clinical, pathological, and molecular features detectable through BCOR immunohistochemistry and confirmatory molecular analyses. Their expression of stem cell markers raises the possibility of an origin from neuroepithelial stem cells rather than representing true embryonal neoplasms.

13.
Foods ; 13(10)2024 May 13.
Article in English | MEDLINE | ID: mdl-38790808

ABSTRACT

α-Dicarbonyl compounds (α-DCs) are commonly present in various foods. We conducted the investigation into concentration changes of α-DCs including 3-deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) in fresh fruits and decapped commercial juices during storage at room temperature and 4 °C, as well as in homemade juices during storage at 4 °C. The studies indicate the presence of α-DCs in all samples. The initial contents of 3-DG in the commercial juices (6.74 to 65.61 µg/mL) are higher than those in the homemade ones (1.97 to 4.65 µg/mL) as well as fruits (1.58 to 3.33 µg/g). The initial concentrations of GO and MGO are normally less than 1 µg/mL in all samples. During storage, the α-DC levels in the fruits exhibit an initial increase followed by a subsequent decrease, whereas, in all juices, they tend to accumulate continuously over time. As expected, 4 °C storage reduces the increase rates of the α-DC concentrations in most samples. From the viewpoint of the α-DC contents, fruits and homemade juices should always be the first choice for daily intake of nutrients and commercial juices ought to be mostly avoided.

14.
Analyst ; 149(11): 3073-3077, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38752735

ABSTRACT

We prepared novel green, eco-friendly carbon dots as a dual-channel probe for highly sensitive and selective detection of tartrazine (Trz) and palladium(II) (Pd(II)) involving, respectively, FRET and electron transfer mechanisms. Furthermore, the successful utilization of the carbon dots for detecting Trz and Pd(II) in actual samples implies its potential application prospects in analysis.

15.
Clin Biomech (Bristol, Avon) ; 115: 106257, 2024 May.
Article in English | MEDLINE | ID: mdl-38714108

ABSTRACT

BACKGROUND: The majority of the ankle osteoarthritis cases are posttraumatic and affect younger patients with a longer projected life span. Hence, joint-preserving surgery, such as supramalleolar osteotomy becomes popular among young patients, especially those with asymmetric arthritis due to alignment deformities. However, there is a lack of biomechanical studies on postoperative evaluation of stress at ankle joints. We aimed to construct a verifiable finite element model of the human hindfoot, and to explore the effect of different osteotomy parameters on the treatment of varus ankle arthritis. METHODS: The bones of the hindfoot are reconstructed using normal CT tomography data from healthy volunteers, while the cartilages and ligaments are determined from the literature. The finite element calculation results are compared with the weight-bearing CT (WBCT) data to validate the model. By setting different model parameters, such as the osteotomy height (L) and the osteotomy distraction distance (h), the effects of different surgical parameters on the contact stress of the ankle joint surface are compared. FINDINGS: The alignment and the deformation of hindfoot bones as determined by the finite element analysis aligns closely with the data obtained from WBCT. The maximum contact stress of the ankle joint surface calculated by this model increases with the increase of the varus angle. The maximum contact stresses as a function of the L and h of the ankle joint surface are determined. INTERPRETATION: The relationship between surgical parameters and stress at the ankle joint in our study could further help guiding the planning of the supramalleolar osteotomy according to the varus/valgus alignment of the patients.


Subject(s)
Ankle Joint , Finite Element Analysis , Osteotomy , Humans , Osteotomy/methods , Ankle Joint/surgery , Ankle Joint/physiopathology , Ankle Joint/diagnostic imaging , Stress, Mechanical , Computer Simulation , Models, Biological , Tomography, X-Ray Computed/methods , Weight-Bearing , Adult , Male , Foot/surgery , Foot/physiopathology , Foot/diagnostic imaging , Osteoarthritis/surgery , Osteoarthritis/physiopathology , Osteoarthritis/diagnostic imaging
16.
J Colloid Interface Sci ; 670: 28-40, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38754329

ABSTRACT

Inversion symmetry broken 3R phase transition metal dichalcogenides (TMDs) show fascinating prospects in spintronics, valleytronics, and nonlinear optics. However, the controlled synthesis of 3R phase TMDs is still a great challenge. In this work, two-dimensional 3R-NbSe2 single crystals up to 0.2 mm were synthesized for the first time through chemical vapor deposition method by designing a space-confined system. The crystal size and morphology can be controlled by the location of the stacked substrates and the amount of the Nb2O5 precursor. Scanning transmission electron microscopy and Raman measurements reveal the NbSe2 exhibits a pure 3R stacking mode with relatively weak interlayer van der Waals interactions. Importantly, 3R-NbSe2 shows obvious second harmonic generation signal which intensity intensified as thickness increases. Density functional theory calculations and optical absorption demonstrate the coexistence of metallic and semiconducting optical properties of 3R-NbSe2. We designed a NbSe2/WS2/NbSe2 photodetector utilizing the metallicity of 3R-NbSe2, which shows good performance especially an ultrafast response (6-7 µs, 0.5 ms - 7.9 s for Au electrodes in literature). The proposed strategy and findings are of great significance for the growth of many other 3R-TMDs and applications of nonlinear optical and ultrafast devices.

17.
Biomater Adv ; 161: 213888, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38759305

ABSTRACT

Short carbon fiber (SCF) reinforced polymer composites are expected to possess outstanding biotribological and mechanical properties in certain direction, while the non-oriented SCF weakens its reinforcing effect in the matrix. In this work, high-oriented SCF was achieved during nozzle extrusion, and then SCF reinforced polyether-ether-ketone (PEEK) composites were fabricated by fused deposition modeling (FDM). The concrete orientation process of SCF was theoretically simulated, and significant shear stress difference was generated at both ends of SCF. As a result, the SCF was distributed in the matrix in a hierarchical structure, containing surface layer I, II and core layer. Moreover, the SCF was oriented highly along the printing direction and demonstrated a more competitive orientation distribution compared to other studies. The SCF/PEEK composites showed a considerable improvement in wear resistance by 44 % due to self-lubricating and load-bearing capability of SCF. Besides, it demonstrated enhancements in Brinell hardness, compressive and impact strength by 48.52 %, 16.42 % and 53.64 %, respectively. In addition, SCF/PEEK composites also showed good cytocompatibility. The findings gained herein are useful for developing the high-oriented SCF reinforced polymer composites with superior biotribological and mechanical properties for artificial joints.


Subject(s)
Benzophenones , Carbon Fiber , Ketones , Materials Testing , Polyethylene Glycols , Polymers , Printing, Three-Dimensional , Carbon Fiber/chemistry , Polymers/chemistry , Polyethylene Glycols/chemistry , Ketones/chemistry , Materials Testing/methods , Biocompatible Materials/chemistry , Joint Prosthesis , Humans
18.
Sensors (Basel) ; 24(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38732921

ABSTRACT

In the context of construction and demolition waste exacerbating environmental pollution, the lack of recycling technology has hindered the green development of the industry. Previous studies have explored robot-based automated recycling methods, but their efficiency is limited by movement speed and detection range, so there is an urgent need to integrate drones into the recycling field to improve construction waste management efficiency. Preliminary investigations have shown that previous construction waste recognition techniques are ineffective when applied to UAVs and also lack a method to accurately convert waste locations in images to actual coordinates. Therefore, this study proposes a new method for autonomously labeling the location of construction waste using UAVs. Using images captured by UAVs, we compiled an image dataset and proposed a high-precision, long-range construction waste recognition algorithm. In addition, we proposed a method to convert the pixel positions of targets to actual positions. Finally, the study verified the effectiveness of the proposed method through experiments. Experimental results demonstrated that the approach proposed in this study enhanced the discernibility of computer vision algorithms towards small targets and high-frequency details within images. In a construction waste localization task using drones, involving high-resolution image recognition, the accuracy and recall were significantly improved by about 2% at speeds of up to 28 fps. The results of this study can guarantee the efficient application of drones to construction sites.

19.
Clin Exp Med ; 24(1): 95, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717497

ABSTRACT

The prognostication of survival trajectories in multiple myeloma (MM) patients presents a substantial clinical challenge. Leveraging transcriptomic and clinical profiles from an expansive cohort of 2,088 MM patients, sourced from the Gene Expression Omnibus and The Cancer Genome Atlas repositories, we applied a sophisticated nested lasso regression technique to construct a prognostic model predicated on 28 gene pairings intrinsic to cell death pathways, thereby deriving a quantifiable risk stratification metric. Employing a threshold of 0.15, we dichotomized the MM samples into discrete high-risk and low-risk categories. Notably, the delineated high-risk cohort exhibited a statistically significant diminution in survival duration, a finding which consistently replicated across both training and external validation datasets. The prognostic acumen of our cell death signature was further corroborated by TIME ROC analyses, with the model demonstrating robust performance, evidenced by AUC metrics consistently surpassing the 0.6 benchmark across the evaluated arrays. Further analytical rigor was applied through multivariate COX regression analyses, which ratified the cell death risk model as an independent prognostic determinant. In an innovative stratagem, we amalgamated this risk stratification with the established International Staging System (ISS), culminating in the genesis of a novel, refined ISS categorization. This tripartite classification system was subjected to comparative analysis against extant prognostic models, whereupon it manifested superior predictive precision, as reflected by an elevated C-index. In summation, our endeavors have yielded a clinically viable gene pairing model predicated on cellular mortality, which, when synthesized with the ISS, engenders an augmented prognostic tool that exhibits pronounced predictive prowess in the context of multiple myeloma.


Subject(s)
Cell Death , Multiple Myeloma , Multiple Myeloma/pathology , Multiple Myeloma/genetics , Multiple Myeloma/mortality , Humans , Prognosis , Male , Female , Risk Assessment , Gene Expression Profiling , Middle Aged , Neoplasm Staging , Aged , Survival Analysis
20.
PLoS One ; 19(5): e0300883, 2024.
Article in English | MEDLINE | ID: mdl-38758927

ABSTRACT

Development of novel biodosimetry assays and medical countermeasures is needed to obtain a level of radiation preparedness in the event of malicious or accidental mass exposures to ionizing radiation (IR). For biodosimetry, metabolic profiling with mass spectrometry (MS) platforms has identified several small molecules in easily accessible biofluids that are promising for dose reconstruction. As our microbiome has profound effects on biofluid metabolite composition, it is of interest how variation in the host microbiome may affect metabolomics based biodosimetry. Here, we 'knocked out' the microbiome of male and female C57BL/6 mice (Abx mice) using antibiotics and then irradiated (0, 3, or 8 Gy) them to determine the role of the host microbiome on biofluid radiation signatures (1 and 3 d urine, 3 d serum). Biofluid metabolite levels were compared to a sham and irradiated group of mice with a normal microbiome (Abx-con mice). To compare post-irradiation effects in urine, we calculated the Spearman's correlation coefficients of metabolite levels with radiation dose. For selected metabolites of interest, we performed more detailed analyses using linear mixed effect models to determine the effects of radiation dose, time, and microbiome depletion. Serum metabolite levels were compared using an ANOVA. Several metabolites were affected after antibiotic administration in the tryptophan and amino acid pathways, sterol hormone, xenobiotic and bile acid pathways (urine) and lipid metabolism (serum), with a post-irradiation attenuative effect observed for Abx mice. In urine, dose×time interactions were supported for a defined radiation metabolite panel (carnitine, hexosamine-valine-isoleucine [Hex-V-I], creatine, citric acid, and Nε,Nε,Nε-trimethyllysine [TML]) and dose for N1-acetylspermidine, which also provided excellent (AUROC ≥ 0.90) to good (AUROC ≥ 0.80) sensitivity and specificity according to the area under the receiver operator characteristic curve (AUROC) analysis. In serum, a panel consisting of carnitine, citric acid, lysophosphatidylcholine (LysoPC) (14:0), LysoPC (20:3), and LysoPC (22:5) also gave excellent to good sensitivity and specificity for identifying post-irradiated individuals at 3 d. Although the microbiome affected the basal levels and/or post-irradiation levels of these metabolites, their utility in dose reconstruction irrespective of microbiome status is encouraging for the use of metabolomics as a novel biodosimetry assay.


Subject(s)
Mice, Inbred C57BL , Animals , Mice , Female , Male , Radiation Exposure , Microbiota/radiation effects , Metabolomics/methods , Metabolome/radiation effects , Radiation, Ionizing
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