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1.
Ann Clin Lab Sci ; 51(2): 262-266, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33941568

RESUMO

BRAF and NRAS are oncogenes in the RAS/RAF/MEK/MAP-kinase signaling pathway. Coexistent mutations of BRAF and NRAS in a single colorectal cancer patient have always been considered mutually exclusive or at least rare. The clinical outcome of these patients remains undetermined. Herein we report a 53-year-old man harboring an NRAS Q61L mutation in his primary rectal carcinoma, who presented with a concomitant mutation of BRAF V600E in his liver metastasis biopsy 55 months after the primary CRC surgical resection. Our findings suggest that a BRAF and NRAS developed co-mutation may lead to a distinct clinicopathological progression. BRAF-mutated CRCwill not benefit from anti-RAS targeted therapy.

2.
Accid Anal Prev ; 156: 106149, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33933716

RESUMO

Accurate real-time prediction of occupant injury severity in unavoidable collision scenarios is a prerequisite for enhancing road traffic safety with the development of highly automated vehicles. Specifically, a safety prediction model provides a decision reference for the trajectory planning system in the pre-crash phase and the adaptive restraint system in the in-crash phase. The main goal of the current study is to construct a data-driven, vehicle kinematic feature-based model to realize accurate and near real-time prediction of in-vehicle occupant injury severity. A large-scale numerical database was established focusing on occupant kinetics. A first-step deep-learning model was established to predict occupant kinetics and injury severity using a convolutional neural network (CNN). To reduce the computational time for real-time application, the second step was to extract simplified kinematic features from vehicle crash pulses via a feature extraction method, which was inspired by a visualization approach applied to the CNN-based model. The features were incorporated with a low-complexity machine-learning algorithm and achieved satisfactory accuracy (85.4 % on the numerical database, 78.7 % on a 192-case real-world dataset) and decreased computational time (1.2 ± 0.4 ms) on the prediction tasks. This study demonstrated the feasibility of using data-driven and feature-based approaches to achieve accurate injury risk estimation prior to collision. The proposed model is expected to provide a decision reference for integrated safety systems in the next generation of automated vehicles.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33909396

RESUMO

An ultralight and high-strength SiCnw@SiC foam with highly efficient microwave absorption and heat insulation properties was successfully synthesized using the template sacrifice method and chemical vapor deposition process. The microstructure is a novel double network structure, which is formed by the coupling of the morphology-controlled SiCnw and the SiC skeleton. The introduction of SiCnw can not only provide more interface polarization and dielectric loss to the SiC foam, which greatly enhances the microwave absorption capacity of the composite foam, but also can enable it to act as an excellent radiation absorbent, which can effectively reduce the thermal conductivity of the foam, especially at high temperatures. In this study, a minimum reflection loss (RLmin) of -52.49 dB was achieved at 2.82 mm thickness with an effective absorption bandwidth of 5.6 GHz. As the length/diameter ratio of SiCnw decreases, the composite foam exhibits excellent high-temperature thermal insulation and mechanical properties. For the SiCnw@SiC foam, the thermal conductivity is only 0.304 W/mK at 1200 °C and the compressive strength reaches 1.53 MPa. This multifunctional SiCnw@SiC foam is an outstanding material, which has potential applications in microwave absorption and high-temperature heat insulation in harsh environments.

4.
Nat Commun ; 12(1): 2339, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879783

RESUMO

Developing organic photoluminescent materials with high emission efficiencies in the solid state under a water atmosphere is important for practical applications. Herein, we report the formation of both intra- and intermolecular hydrogen bonds in three tautomerizable Schiff-base molecules which comprise active hydrogen atoms that act as proton donors and acceptors, simultaneously hindering emission properties. The intercalation of water molecules into their crystal lattices leads to structural rearrangement and organic hydrate luminogen formation in the crystalline phase, triggering significantly enhanced fluorescence emission. By suppressing hydrogen atom shuttling between two nitrogen atoms in the benzimidazole ring, water molecules act as hydrogen bond donors to alter the electronic transition of the molecular keto form from nπ* to lower-energy ππ* in the excited state, leading to enhancing emission from the keto form. Furthermore, the keto-state emission can be enhanced using deuterium oxide (D2O) owing to isotope effects, providing a new opportunity for detecting and quantifying D2O.

5.
Nano Lett ; 21(8): 3393-3400, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33847115

RESUMO

Correlated translation-orientation tracking of single particles can provide important information for understanding the dynamics of live systems and their interaction with the probes. However, full six-dimensional (6D) motion tracking has yet to be achieved. Here, we developed synchronized 3D translation and 3D rotation tracking of single diamond particles based on nitrogen-vacancy center sensing. We first performed 6D tracking of diamond particles attached to a giant plasma membrane vesicle to demonstrate the method. Quantitative analysis of diamond particles' motion allowed elimination of the geometric effect and revealed the net rotation on the vesicle. 6D tracking was then applied to measure live cell dynamics. Motion characteristics of nanodiamonds on cell membranes under various controlled physiological conditions suggest that the nanodiamonds' rotation is associated with cell metabolic activities. Our technique extends the toolbox of single particle tracking and provides a unique solution to problems where correlated analysis of translation and rotation is critical.

6.
Front Immunol ; 12: 653464, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897700

RESUMO

Workplace exposure to respirable crystalline silica dust (cSiO2) has been etiologically linked to the development of lupus and other human autoimmune diseases. Lupus triggering can be recapitulated in female NZBWF1 mice by four weekly intranasal instillations with 1 mg cSiO2. This elicits inflammatory/autoimmune gene expression and ectopic lymphoid structure (ELS) development in the lung within 1 week, ultimately driving early onset of systemic autoimmunity and glomerulonephritis. Intriguingly, dietary supplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA) found in fish oil, beginning 2 week prior to cSiO2 challenge, prevented inflammation and autoimmune flaring in this novel model. However, it is not yet known how ω-3 PUFA intervention influences established autoimmunity in this murine model of toxicant-triggered lupus. Here we tested the hypothesis that DHA intervention after cSiO2-initiated intrapulmonary autoimmunity will suppress lupus progression in the NZBWF1 mouse. Six-week old NZWBF1 female mice were fed purified isocaloric diet for 2 weeks and then intranasally instilled with 1 mg cSiO2 or saline vehicle weekly for 4 consecutive weeks. One week after the final instillation, which marks onset of ELS formation, mice were fed diets supplemented with 0, 4, or 10 g/kg DHA. One cohort of mice (n = 8/group) was terminated 13 weeks after the last cSiO2 instillation and assessed for autoimmune hallmarks. A second cohort of mice (n = 8/group) remained on experimental diets and was monitored for proteinuria and moribund criteria to ascertain progression of glomerulonephritis and survival, respectively. DHA consumption dose-dependently increased ω-3 PUFA content in the plasma, lung, and kidney at the expense of the ω-6 PUFA arachidonic acid. Dietary intervention with high but not low DHA after cSiO2 treatment suppressed or delayed: (i) recruitment of T cells and B cells to the lung, (ii) development of pulmonary ELS, (iii) elevation of a wide spectrum of plasma autoantibodies associated with lupus and other autoimmune diseases, (iv) initiation and progression of glomerulonephritis, and (v) onset of the moribund state. Taken together, these preclinical findings suggest that DHA supplementation at a human caloric equivalent of 5 g/d was an effective therapeutic regimen for slowing progression of established autoimmunity triggered by the environmental toxicant cSiO2.

7.
Adv Sci (Weinh) ; 8(8): 2002132, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33898167

RESUMO

Self-assembly, as a typical bottom-up strategy for the fabrication of functional materials, has been applied to fabricate chiral materials with subtle chiral nanostructures. The chiral nanostructures exhibit great potential in asymmetric catalysis, chiral sensing, chiral electronics, photonics, and even the realization of several biological functions. According to existing studies, the supramolecular chirality transfer process combined with hierarchical self-assembly plays a vital role in the fabrication of multiscale chiral structures. This progress report focuses on the hierarchical self-assembly of chiral or achiral molecules that aggregate with asymmetric spatial structures such as twisted bands, helices, and superhelices in different environments. Herein, recent studies on the chirality transfer induced self-assembly based on a variety of supramolecular interactions are summarized. In addition, the influence of different environments and the states of systems including solutions, condensed states, gel systems, interfaces on the asymmetric hierarchical self-assembly, and the expression of chirality are explored. Moreover, both the driving forces that facilitate chiral bias and the supramolecular interactions that play an important role in the expression, transfer, and amplification of the chiral sense are correspondingly discussed.

8.
J Comp Eff Res ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33906371

RESUMO

Aim: To compare the screw accuracy and clinical outcomes between robot-assisted minimally invasive transforaminal lumbar interbody fusion (RA MIS-TLIF) and open TLIF in the treatment of one-level lumbar degenerative disease. Materials & methods: From May 2018 to December 2019, a consecutive series of patients undergoing robot-assisted minimally invasive one-level lumbar fusion procedures were retrospectively compared with matched controls who underwent one-level open TLIF procedures for clinical and quality-of-life outcomes. Results: A total of 52 patients underwent RA MIS-TLIF procedures (robot-assisted [RA] group) and 52 matched controls received freehand open TLIF procedures (open [OP] group). The RA group had more grade A screws with 96.2% one-time success rate of screw placement (p < 0.05). Besides, the RA group experienced less intraoperative blood loss and shorter length of hospital stay, while the OP group had shorter operative duration and cumulative radiation time (p < 0.001). What is more, the average VAS score for low back pain and ODI score in the RA group were lower than that in the OP group 1 month after operation (p < 0.05). Conclusion: The use of real-time, image-guided robot system may further expand the advantages of MIS-TLIF technique in terms of accuracy and safety.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33908260

RESUMO

Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease. Autoimmune processes have been hypothesised to contribute to disease progression; however, the presence of autoantibodies in the serum has been variable. Given that COPD is a lung disease, we sought to investigate whether autoantibodies in sputum supernatant would better define pulmonary autoimmune processes. Matched sputum and serum samples were obtained from the Airways Disease Endotyping for Personalised Therapeutics (ADEPT) study and at the Guangzhou Institute of Respiratory Health (GIRH). Samples were collected from patients with varying severity of COPD, asymptomatic smokers and healthy control subjects. IgG and IgM autoantibodies were detected in sputum and serum of all subjects in both cohorts using a broad-spectrum autoantigen array. No differences were observed in sputum autoantibodies between COPD and asymptomatic smokers in either cohort. In contrast, 16% of detectable sputum IgG autoantibodies were decreased in COPD subjects compared to healthy controls in the ADEPT cohort. Compared to asymptomatic smokers, approximately 13% of detectable serum IgG and 40% of detectable serum IgM autoantibodies were differentially expressed in GIRH COPD subjects. Of the differentially expressed specificities, anti-nuclear autoantibodies were predominately decreased. A weak correlation between increased serum IgM anti-tissue autoantibodies and a measure of airspace enlargement was observed. The differential expression of specificities varied between the cohorts. In closing, using a comprehensive autoantibody array, we demonstrate that autoantibodies are present in COPD subjects, asymptomatic smokers and healthy controls. Cohorts displayed high levels of heterogeneity, precluding the utilisation of autoantibodies for diagnostic purposes.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33895789

RESUMO

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Highly effective coronavirus disease 2019 (COVID-19) vaccines have brought hope for ending the pandemic. Unprecedented mass vaccination started first among healthcare workers. The aim of this report is to describe key strategies undertaken by a large hospital pharmacy department to meet the challenges of preparing a large quantity of COVID-19 vaccine doses in a short period of time. SUMMARY: MedStar Washington Hospital Center (MWHC) was in the first group of hospitals in Washington, DC, to receive Pfizer-BioNTech vaccine in December 2020. The pharmacy department faced challenges including stringent vaccine storage requirements, a need for specific equipment and workflow, limited funding, and staffing constraints. The pharmacy department's senior leaders defined pharmacy responsibilities, budgeted for equipment, participated in vaccination center design, and instructed pharmacy informatics personnel. The vaccine coordinators were appointed to oversee all vaccination-related operations. An ultra-low temperature freezer was installed 2 weeks before arrival of the first shipment of vaccine. All pharmacy order entry tools and operating procedures were standardized, and staff training and schedules were finalized by December 15. The first dose of the vaccine was administered on December 16 at the vaccination center. Pharmacy staff members dispensed the vaccine doses and monitored patients. By January 6, 2021, MWHC had vaccinated 3,812 employees with their first vaccine dose, with an average of 228 doses administered daily. CONCLUSION: Key strategies such as systemic coordination, early preparation, detailed planning, operating procedure development, and staff education and engagement proved successful in facilitating preparation of thousands of COVID-19 vaccine doses for hospital employees within a short period of time.

11.
J Reprod Dev ; 2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33896883

RESUMO

Upon mammalian fertilization, zygotic genome activation (ZGA) and activation of transposable elements (TEs) occur in early embryos to establish totipotency and support embryogenesis. However, the molecular mechanisms controlling the expression of these genes in mammals remain poorly understood. The 2-cell-like population of mouse embryonic stem cells (mESCs) mimics cleavage-stage embryos with transient Dux activation. In this study, we demonstrated that deficiency of the transcription factor OTX2 stimulates the expression of ZGA genes in mESCs. Further analysis revealed that OTX2 is incorporated at the Dux locus with corepressors for transcriptional inhibition. We also found that OTX2 associates with TEs and silences the subtypes of TEs. Therefore, OTX2 protein plays an important role in ZGA and TE expression in mESCs to orchestrate the transcriptional network.

12.
J Clin Lab Anal ; : e23776, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792998

RESUMO

BACKGROUND: Nowadays, hand, foot, and mouth disease (HFMD) has a significant negative impact on children's health, especially in the Asia-Pacific region. Loop-mediated isothermal amplification assay (LAMP) is a highly efficient and convenient novel tool. However, its diagnostic accuracy for HFMD is still not clear. Therefore, we conducted a meta-analysis in order to evaluate the potential of LAMP assay for the diagnosis of HFMD, in which the reference standard was polymerase chain reaction (PCR). METHODS: A protocol was predetermined (CRD42020212882) in PROSPERO. We retrieved seven databases including PubMed for relevant studies published before October 2020. Articles were included if they compared the diagnostic efficiency of LAMP with PCR for HFMD through detecting clinical samples which was more than 15. Statistical analysis was performed by STATA 15.1 software. Risk of bias and applicability were assessed using Quality Assessment of Diagnostic Accuracy Studies. No funding was used for the study. RESULTS: A total of 18 retrospective studies including 2495 samples from China were finally included. Reference standards of them included RT-PCR and non-RT-PCR. The merged sensitivity and specificity with 95% confidence interval (95% CI) were 1.00 (0.97-1.00) and 0.97 (0.88-0.99), respectively. The pooled PLR, NLR, and DOR with 95% CI were 11.17 (5.91-21.11), 0.05 (0.03-0.09), and 538.12 (183.17-1580.83), respectively. The AUC of SROC was 1.00 (95% CI: 0.99-1.00). CONCLUSION: In conclusion, our research revealed high sensitivity and specificity of LAMP in diagnosing HFMD. However, more high-quality research is required to prove this conclusion.

13.
Genome Biol ; 22(1): 111, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863366

RESUMO

BACKGROUND: Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance. RESULTS: In reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5-100× more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels. CONCLUSION: These new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33872152

RESUMO

As a decentralized training approach, horizontal federated learning (HFL) enables distributed clients to collaboratively learn a machine learning model while keeping personal/private information on local devices. Despite the enhanced performance and efficiency of HFL over local training, clues for inspecting the behaviors of the participating clients and the federated model are usually lacking due to the privacy-preserving nature of HFL. Consequently, the users can only conduct a shallow-level analysis of potential abnormal behaviors and have limited means to assess the contributions of individual clients and implement the necessary intervention. Visualization techniques have been introduced to facilitate the HFL process inspection, usually by providing model metrics and evaluation results as a dashboard representation. Although the existing visualization methods allow a simple examination of the HFL model performance, they cannot support the intensive exploration of the HFL process. In this study, strictly following the HFL privacy-preserving protocol, we design an exploratory visual analytics system for the HFL process termed HFLens, which supports comparative visual interpretation at the overview, communication round, and client instance levels. Specifically, the proposed system facilitates the investigation of the overall process involving all clients, the correlation analysis of clients' information in one or different communication round(s), the identification of potential anomalies, and the contribution assessment of each HFL client. Two case studies confirm the efficacy of our system. Experts' feedback suggests that our approach indeed helps in understanding and diagnosing the HFL process better.

15.
Angew Chem Int Ed Engl ; 60(20): 11247-11251, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33655581

RESUMO

Bioinspired smart materials with synergistic allochroic luminescence and complex deformation are expected to play an important role in many areas of science and technology. However, it is still challenging to fabricate such soft actuators with high programmability that can be manipulated in situ with high spatial resolution. Herein, we have incorporated terminally functionalized aggregation-induced emission active tetraphenylethene derivative and photochromic spiropyran moieties into the networks of liquid crystal elastomers through covalent bonding to obtain the synergistic photochromic luminescence and programmable soft actuators. Bio-mimic functions and light-induced auxetic metamaterial-like devices were shown to be feasible based on the combination of assembly and origami-programming strategy. These bioinspired devices with synergistic photochromic luminescence and complex photodeformation abilities provide an elegant strategy to design multi-functional liquid crystal actuators.

17.
Front Cell Infect Microbiol ; 11: 609160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732659

RESUMO

There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent dangerous coronaviruses are MERS-CoV, SARS-CoV, and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. In this study, we analyzed transcriptome of MERS-CoV, SARS-CoV, and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression with upregulation of TET genes. Upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation may lead to increased genome instability and enhanced expression of genes with readthrough from retrotransposons. Therefore, people with higher basal level of retrotransposon such as cancer patients and aged people may have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA. Thus, we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. In summary, we propose our hypothesis that coronavirus invades human cells and interacts with retrotransposon, eliciting more severe symptoms in patients with underlying diseases. In the treatment of patients with coronavirus infection, it may be necessary to pay more attention to the potential harm contributed by retrotransposon dysregulation.


Assuntos
Infecções por Coronavirus/virologia , Coronavirus/genética , Genoma Viral/genética , Retroelementos/genética , Transcriptoma , Linhagem Celular Tumoral , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Vírus da SARS/genética , /genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-33727162

RESUMO

Cirrhosis is the terminal stage of progressive liver fibrosis, affecting 1%-2% of the global population and accounting for 1.3 million deaths annually.1,2 Median survival for persons with compensated cirrhosis is approximately 12 years, compared with only 2 years for those with hepatic decompensation. Accurate prediction of hepatic decompensation is an unmet need to enable identification of patients with cirrhosis who could benefit from close monitoring and timely medical interventions. Besides, risk stratification of patients with cirrhosis could help inform patient selection for trials evaluating therapies to prevent hepatic decompensation. Although various clinical scores, such as the albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4) indices (ALBI-FIB4 score) have been proposed to predict long-term risk of hepatic decompensation,3 external validation has often shown suboptimal prognostic capability and revealed room for improvement.4.

19.
Mol Oral Microbiol ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721398

RESUMO

Antimicrobial peptides are naturally occurring protein molecules with antibacterial, antiviral and/or antifungal activity. Some antimicrobial peptides kill microorganisms through direct binding with negatively charged microbial surfaces. This action disrupts the cytoplasmic membrane and leads to the leakage of the cytoplasm. In addition, they are involved in the innate immune response. Antimicrobial peptides play an important role in oral health, as natural antimicrobial peptides are the first line of host defence in response to microbial infection. The level of natural antimicrobial peptides increases during severe disease conditions and play a role in promoting the healing of oral tissues. However, they are insufficient for eliminating pathogenic micro-organisms. The variability of the oral environment can markedly reduce the effect of natural antimicrobial peptides. Thus, researchers are developing synthetic antimicrobial peptides with promising stability and biocompatibility. Synthetic antimicrobial peptides are a potential alternative to traditional antimicrobial therapy. Pertinent to oral diseases, the deregulation of antimicrobial peptides is involved in the pathogenesis of dental caries, periodontal disease, mucosal disease and oral cancer, where they can kill pathogenic microorganisms, promote tissue healing, serve as biomarkers and inhibit tumor cells. This narrative review provides an overview of the multifaceted roles of antimicrobial peptides in oral diseases.

20.
J Toxicol Environ Health A ; 84(12): 503-517, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-33682625

RESUMO

The Southwestern United States has a legacy of industrial mining due to the presence of rich mineral ore deposits. The relationship between environmental inhaled particulate matter (PM) exposures and neurological outcomes within an autoimmune context is understudied. The aim of this study was to compare two regionally-relevant dusts from high-priority abandoned mine-sites, Claim 28 PM, from Blue Gap Tachee, AZ and St. Anthony mine PM, from the Pueblo of Laguna, NM and to expose autoimmune-prone mice (NZBWF1/J). Mice were randomly assigned to one of three groups (n = 8/group): DM (dispersion media, control), Claim 28 PM, or St. Anthony PM, subjected to oropharyngeal aspiration of (100 µg/50 µl), once per week for a total of 4 consecutive doses. A battery of immunological and neurological endpoints was assessed at 24 weeks of age including: bronchoalveolar lavage cell counts, lung gene expression, brain immunohistochemistry, behavioral tasks and serum autoimmune biomarkers. Bronchoalveolar lavage results demonstrated a significant increase in number of polymorphonuclear neutrophils following Claim 28 and St. Anthony mine PM aspiration. Lung mRNA expression showed significant upregulation in CCL-2 and IL-1ß following St. Anthony mine PM aspiration. In addition, neuroinflammation was present in both Claim 28 and St. Anthony mine-site derived PM exposure groups. Behavioral tasks resulted in significant deficits as determined by Y-maze new arm frequency following Claim 28 aspiration. Neutrophil elastase was significantly upregulated in the St. Anthony mine exposure group. Interestingly, there were no significant changes in serum autoantigens suggesting systemic inflammatory effects may be mediated through other molecular mechanisms following low-dose PM exposures.

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