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1.
J Mech Behav Biomed Mater ; 101: 103418, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31514055

RESUMO

Recent demands in clinical applications drive a large amount of research to plasma sprayed hydroxyapatite (HA) composite coatings. Herein, graphene nanosheet (GNS) reinforced HA coating was fabricated using plasma spray, the effect of heat and hydrothermal treatments (hereafter referred to as thermal treatment) on microstructural evolution and mechanical properties of the composite coating were investigated. Thermally treated GNS/HA coating not only exhibited ~47.1% improvement in HA crystallinity and more denser microstructure, but also displayed increased surface roughness (3 times of that of the as-sprayed sample) due to the fact that GNSs facilitated HA nanoparticle precipitation on the coating surface. Fracture toughness of the as-sprayed HA coating increased by up to ~44.1% at 2.0 wt% GNSs owing to GNS pullout, GNS bridging and arresting of crack propagation by the embedded GNSs. As for thermally treated HA coatings, crack propagation arrested by the sintered regions was found to act as an important toughening mechanism, but thermal treatment introduced more structural defects into the GNSs and led to the reductions in their length and thickness, resulting in negligible enhancement in toughness of the GNS/HA coating.

2.
Nanotechnology ; 31(4): 045704, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31658034

RESUMO

Advances in flexible electronic and optoelectronic devices have caused higher requirements for fabricating high-performance and low cost flexible transparent conductive electrodes (TCEs). Copper nanowires (Cu NWs) possess excellent electrical and optical properties, but the large contact resistance and poor stability limit their practical application in optoelectronic devices. In this work, we report a robust, convenient and environment-friendly method to assemble copper nanowires/reduced graphene oxide (Cu NWs/rGO) TCEs with enhanced conductivity, flexibility and stability at room temperature. The NaBH4 treatment was used to remove the organics and oxides on the surface of Cu NWs, and the graphene oxide (GO) capping layer was also effectively reduced at the same time. The best Cu NWs/rGO composite TCEs show a good optical-electrical performance with a sheet resistance of ∼50 Ω/sq and transmittance of 83% as well as superior mechanical flexibility. The oxidation resistance of Cu NWs in normal environment and even at a relatively high temperature has also been greatly improved. Additionally, the Cu NWs/rGO TCEs based heaters presented high saturation temperature and rapid response time under a low voltage. The high-performance composite Cu NWs TCEs with good stability are expected to be applied in various types of flexible optoelectronic devices.

3.
Cytokine ; 125: 154850, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31557635

RESUMO

BACKGROUND: Endometrial injury can result in thin endometrium and subfertility. Granulocyte macrophage colony stimulating factor (GM-CSF) contributes to tissue repair, but its role in endometrial regeneration has not been investigated. METHODS: To determine the effect of GM-CSF on endometrial regeneration, we established a mouse model of thin endometrium by uterine perfusion with 20 µL 90% ethanol. Thin endometrium in mice was featured by lowered endometrial thickness, decreased expression of Ki67 in glandular cells, and a reduced number of implantation sites. To explore the mechanism of GM-CSF on endometrial regeneration, endometrium was obtained from patients undergoing hysterectomy or hysteroscopy and endometrial biopsy. Effects of GM-CSF on primary cultured human endometrial glandular and stromal cells were examined by the 5-bromo-2'-deoxyuridine (BrdU) proliferation assay and transwell migration assay, followed by exploration of the potential signaling pathway. RESULTS: GM-CSF intraperitoneal (i.p.) injection significantly increased endometrial thickness, expression of Ki67 in endometrial glandular cells, and the number of implantation sites. GM-CSF significantly promoted proliferation of primary human endometrial glandular cells and migration of stromal cells. GM-CSF activated p-Akt and increased expressions of p70S6K and c-Jun, which were blocked by LY294002. CONCLUSION: We found that GM-CSF could improve endometrial regeneration, possibly through activating PI3K/Akt signaling pathway.

4.
Chemosphere ; 238: 124645, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472352

RESUMO

Bromophenols (BPs) are important organic compounds which have become dominant pollutants during these years. Our present study investigated the potential inhibition behaviour of BPs on the activity of one of the most important phase II drug-metabolizing enzymes (DMEs), UDP-glucuronosyltransferases (UGTs). Recombinant UDP-glucuronosyltransferases (UGTs)-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was utilized as the probe reaction. 100 µM of BPs was utilized as the inhibition screening concentrations, and the complete inhibition profile of UGT isoforms by BPs was obtained. UGT1A7 was the most vulnerable UGT isoform towards BPs. Some structure-activity relationship for the inhibition of UGTs by BPs was found, and this relationship can be furtherly explained by the hydrophobic contacts of BPs with the activity cavity of UGTs using in silico docking method. The inhibition kinetics determination showed that the inhibition kinetic parameter Ki value was calculated to be 2.85, 3.99 and 31.00 µM for the inhibition of UGT1A3, UGT1A7, and UGT2B7 by representative BPs, 2,4,6-TBP. Combined with in vivo exposure concentration of 2,4,6-TBP, in vitro-in vivo extrapolation (IVIVE) was employed to demonstrate the moderate possibility for the inhibition of UGT1A3 and UGT1A7 by 2,4,6-TBP. In conclusion, our study gave the full description towards the inhibition of BPs towards UGT isoforms, which will provide a new perspective for elucidating the toxicity mechanism of bromophenols (BPs).

5.
Food Chem ; 308: 125598, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31648096

RESUMO

An in vitro gastrointestinal digestion model was used to investigate the effects of milk matrix: skimmed milk (Sm), whole milk (Wm) and processing methods: pH adjustment, high pressure homogenization processing (HPHP), thermal treatment (TT) on the antioxidant capacity, phenolics bioaccessibility of coffee. Our findings showed that the antioxidant capacity of all the samples decreased or unchanged after in vitro digestion. The total phenolic bioaccessibility of coffee (C), coffee with whole milk (Cwm), and coffee with skimmed milk (Csm) decreased by 29.2%, 28.5%, 21.1% from the HPHP treatment and by 14.7%, 34.2%, and 33.8% from TT, respectively. pH adjustment had little effect on the total phenolic bioaccessibility of Cwm and Csm but significantly decreased that of C. Wm showed better protective effect on the phenolic bioaccessibility than Sm. These results may contribute to the optimization of formulations and processing methods in coffee beverage production, thereby increasing the health benefits of coffee.

6.
J Colloid Interface Sci ; 559: 206-214, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629274

RESUMO

Controllable synthesis of multimetal nanocrystals with hierarchical structures and tunable compositions are feasible to steeply improve the catalytic properties in fuel cells. Herein, trimetallic PtRhCo petal-assembled alloyed nanoflowers (PtRhCo PAANFs) were fabricated via a one-pot solvothermal method, which showed remarkable enlargement in specific activity and mass activity over PtRh0.25Co nanodentrites (NDs), PtRh1.5Co NDs, PtCo NDs and commercial Pt/C catalysts for ethylene glycol oxidation in 0.5 M KOH solution. The as-developed catalyst exhibited dramatically better CO tolerance and recoverability, coupling with the superior activity and durability for hydrogen evolution reaction (HER) in the alkaline electrolyte. This work demonstrates the significance of Rh in the alloy for improving the stability. This work offers a promising strategy for preparation of advanced trimetallic electrocatalysts for energy conversion applications.

7.
J Nanosci Nanotechnol ; 20(3): 1409-1416, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492301

RESUMO

Ribonuclease H (RNase H) plays key roles in HIV virus replication process and can be used as an important target for anti-AIDS drugs screening. Therefore, we constructed a fluorescent nanosensor based on signal amplification of hybridization chain reaction (HCR) and fluorescence quenching of graphene oxide (GO) nanosheets. The nanosensor provided highly sensitive and selective platform for RNase H activity detection. This method also exhibited a good linear relationship in the range of 0.001-5 U/mL, and the detection limit was 0.0007 U/mL. Our results suggested that the developed system is a promising platform for monitoring the RNase H activity, showing great potential in the biomedical studies and drugs screening.

8.
Neuroimage Clin ; 24: 102098, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31795054

RESUMO

INTRODUCTION: Disruption to white matter pathways is an important contributor to the pathogenesis of Parkinson's disease. Fixel-based analysis has recently emerged as a useful fiber-specific tool for examining white matter structure. In this longitudinal study, we used Fixel-based analysis to investigate white matter changes occurring over time in patients with Parkinson's disease. METHODS: Fifty patients with idiopathic Parkinson's disease (27 men and 23 women; mean age: 61.8 ± 6.1 years), were enrolled. Diffusion-weighted imaging and clinical examinations were performed at three different time points (baseline, first follow-up [after a mean of 24±2 months], and second follow-up [after a mean of 40 ± 3 months]). Additional 76 healthy control subjects (38 men and 38 women; mean age: 62.3 ± 5.5 years) were examined at baseline. The following fixel-based metrics were obtained: fiber density (FD), fiber bundle cross-section (FC), and a combined measure of both (FDC). Paired comparisons of metrics between three different time points were performed in patients. Linear regression was implemented between longitudinal changes of fixel-based metrics and the corresponding modifications in clinical parameters. A family-wise error corrected p < 0.05 was considered statistically significant. RESULTS AND DISCUSSIONS: Early degeneration in the splenium of corpus callosum was identified as a typical alteration of Parkinson's disease over time. At follow-up, we observed significant FDC reductions compared with baseline in white matter, noticeably in corpus callosum; tapetum; cingulum, posterior thalamic radiation, corona radiata, and sagittal stratum. We also identified significant FC decreases that reflected damage to white matter structures involved in Parkinson's disease -related pathways. Fixel-based metrics were found to relate with a deterioration of 39-item Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale and activity of daily living. A Parkinson's disease -facilitated aging effect was observed in terms of white matter disruption. CONCLUSION: This study provides a thorough fixel-based profile of longitudinal white matter alterations occurring in patients with Parkinson's disease and new evidence of FC as an important role in white matter degeneration in this setting.

9.
Plant Physiol Biochem ; 146: 392-402, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31794899

RESUMO

Tea cultivars with leaf color variation have attracted increasing attention in tea production and research due to their unusual appearances and appealing flavors. However, the molecular mechanism underlying this variation is little known due to the unavailability of genetic transformation and a highly complex genome. Here, a natural tea plant mutant producing pale green branches (pgb) was discovered and characterized. Ultrastructural and biochemical analyses showed that the leaves of the pgb mutant had defective chloroplast structure and significantly lower pigment content than the normal control. Comprehensive expression detection of chloroplast-development-related genes further indicated that a significant downregulation of CsGLKs in the pgb mutant likely caused the chloroplast defect. Transcriptome analyses and polyphenolic compound determination highlighted a tight correlation between photosynthesis and secondary metabolite biosynthesis in tea plant. These results provide useful information illuminating the mechanism of chloroplast development and leaf color variation in tea plant.

10.
BMC Genomics ; 20(1): 911, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783728

RESUMO

BACKGROUND: GRAS gene is an important transcription factor gene family that plays a crucial role in plant growth, development, adaptation to adverse environmental condition. Sweet potato is an important food, vegetable, industrial raw material, and biofuel crop in the world, which plays an essential role in food security in China. However, the function of sweet potato GRAS genes remains unknown. RESULTS: In this study, we identified and characterised 70 GRAS members from Ipomoea trifida, which is the progenitor of sweet potato. The chromosome distribution, phylogenetic tree, exon-intron structure and expression profiles were analysed. The distribution map showed that GRAS genes were randomly located in 15 chromosomes. In combination with phylogenetic analysis and previous reports in Arabidopsis and rice, the GRAS proteins from I. trifida were divided into 11 subfamilies. Gene structure showed that most of the GRAS genes in I. trifida lacked introns. The tissue-specific expression patterns and the patterns under abiotic stresses of ItfGRAS genes were investigated via RNA-seq and further tested by RT-qPCR. Results indicated the potential functions of ItfGRAS during plant development and stress responses. CONCLUSIONS: Our findings will further facilitate the functional study of GRAS gene and molecular breeding of sweet potato.

11.
Cancer Immunol Res ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719059

RESUMO

Loss of target antigens in tumor cells has become one of the major hurdles limiting the efficacy of adoptive cell therapy (ACT)-based immunotherapies. The optimal approach to overcome this challenge includes broadening the immune response from the initially targeted tumor-associated antigen (TAA) to other TAAs expressed in the tumor. To induce a more broadly targeted antitumor response, we utilized our previously developed Re-energized ACT (ReACT), which capitalizes on the synergistic effect of pathogen-based immunotherapy and ACT. In this study, we showed that ReACT induced a sufficient endogenous CD8+ T-cell response beyond the initial target to prevent the outgrowth of antigen loss variants in a B16-F10 melanoma model. Sequentially, selective depletion experiments revealed that Batf3-driven cDC1s were essential for the activation of endogenous tumor-specific CD8+ T cells. In ReACT-treated mice that eradicated tumors, we observed that endogenous CD8+ T cells differentiated into memory cells and facilitated the rejection of local and distal tumors re-challenge. By targeting one TAA with ReACT, we provided broader TAA coverage to counter antigen escape and generate a durable memory response against local relapse and metastasis.

12.
Eur J Med Chem ; : 111862, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31735576

RESUMO

Neurodegenerative diseases are a variety of debilitating and fatal disorder in central nervous system (CNS). Besides targeting neuronal activity by influencing neurotransmitters or their corresponding receptors, modulating the underlying processes that lead to cell death, such as oxidative stress and mitochondrial dysfunction, should also be emphasized as an assistant strategy for neurodegeneration therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been closely verified to be related to anti-inflammation and oxidative stress, rationally regulating its belonging pathway and activating Nrf2 is emphasized to be a potential treatment approach. There have existed multiple Nrf2 activators with different mechanisms and diverse structures, but those applied for neuro-disorders are still limited. On the basis of research arrangement and compound summary, we put forward the limitations of existing Nrf2 activators for neurodegenerative diseases and their future developing directions in enhancing the blood-brain barrier permeability to make Nrf2 activators function in CNS and designing Nrf2-based multi-target-directed ligands to affect multiple nodes in pathology of neurodegenerative diseases.

13.
Reproduction ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756167

RESUMO

Sertoli cells are indispensable for normal spermatogenesis and increasing evidence has shown that microRNAs (miRNAs) participate in the regulation of Sertoli cell growth. However, the functions and regulatory mechanisms of miRNAs in Sertoli cells of domestic animals have not been fully investigated. In the present study, we mainly investigated the regulatory roles of miR-499 in immature porcine Sertoli cells. The results showed that miR-499 was mainly located in the basement section of seminiferous tubules of prepubertal porcine testicular tissue. Overexpression of miR-499 promoted cell proliferation and inhibited apoptosis, whereas miR-499 inhibition resulted in the opposite effects. The PTEN gene was directly targeted by miR-499, and the expression of mRNA and protein was also negatively regulated by miR-499 in immature porcine Sertoli cells. siRNA-induced PTEN knockdown resulted in a similar effect as overexpression of miR-499, and abolished the effects of miR-499 inhibition on immature porcine Sertoli cells. Moreover, both miR-499 overexpression and the PTEN knockdown activated the PI3K/AKT signaling pathway, whereas inhibition of the PI3K/AKT signaling pathway caused immature porcine Sertoli cell apoptosis and inhibited cell proliferation. Overall, miR-499 promotes proliferation and inhibits apoptosis in immature porcine Sertoli cells through the PI3K/AKT pathway by targeting the PTEN gene. This study provides novel insights into the effects of miR-499 in spermatogenesis through the regulation of immature Sertoli cell proliferation and apoptosis.

14.
Molecules ; 24(23)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31757047

RESUMO

As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer's disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values < 10 µM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.

15.
Cell Transplant ; : 963689719883842, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665910

RESUMO

Cellular transplantation strategies utilizing intraspinal or intrathecal olfactory ensheathing cells (OECs) have been reported as beneficial for spinal cord injury (SCI). However, there are many disadvantages of these methods, including additional trauma to the spinal cord parenchyma and technical challenges. Therefore, we investigated the feasibility and potential benefits of intravenous transplantation of OECs in a rat hemisection SCI model. OECs derived from olfactory bulb tissue were labeled with quantum dots (QDs), and their biodistribution after intravenous transplantation was tracked using a fluorescence imaging system. Accumulation of the transplanted OECs was observed in the injured spinal cord within 10 min, peaked at seven days after cell transplantation, and decreased gradually thereafter. This time window corresponded to the blood-spinal cord barrier (BSCB) opening time, which was quantitated with the Evans blue leakage assay. Using immunohistochemistry, we examined neuronal growth (GAP-43), remyelination (MBP), and microglia (Iba-1) reactions at the lesion site. Motor function recovery was also measured using a classic open field test (Basso, Beattie and Bresnahan score). Compared with the group injected only with QDs, the rats that received OEC transplantation exhibited a prominent reduction in inflammatory responses, increased neurogenesis and remyelination, and significant improvement in motor function. We suggest that intravenous injection could also be an effective method for delivering OECs and improving functional outcomes after SCI. Moreover, the time course of BSCB disruption provides a clinically relevant therapeutic window for cell-based intervention.

16.
Chem Commun (Camb) ; 55(94): 14210-14213, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31709424

RESUMO

Based on the full understanding of the hydrolysis patterns of duplex-specific nuclease (DSN) against the probe DNAs in DNA/microRNA heteroduplexes, a simple and generic platform for highly specific and sensitive detection of microRNAs was developed by seamlessly integrating DSN-assisted target recycling amplification and strand displacement amplification in tandem.

17.
Pharmacol Res ; 151: 104541, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31733326

RESUMO

Oxymatrine is a quinazine alkaloid extracted from Sophora flavescens with various therapeutic effects such as organ- and tissue-protective, anti-inflammatory, anti-cancer, and anti-viral effects. In this review, we summarize the protective effects of oxymatrine on damaged organs and tissues by analyzing both in vivo and in vitro studies. The mechanisms of protective effects of oxymatrine are mainly related to its anti-inflammatory, anti-oxidative stress, anti- or pro-apoptotic, anti-fibrotic, metabolism-regulation, and anti-nociceptive functions. In addition, a variety of signal pathways, cells, and molecules are influenced by oxymatrine, and by these comprehensive actions, maximum therapeutic effects can be achieved. Furthermore, we summarize the protective effects in clinical studies and adverse effects of oxymatrine. It is believed that through more in-depth animal experiments and standardized clinical research, oxymatrine holds a bright future in the process of organ and tissue protection and has a significant therapeutic promise to translate from bench to bedside.

18.
Int J Biol Macromol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31730959

RESUMO

The heterologous nature of SAK, which is a thrombolytic drug, elicits high titers of neutralizing antibodies, which limits its use. Here, we aimed to establish a SAK mutant with equivalent activity to the wild type but reduced antibody reactivity, which would allow for multiple injections. Biosun software was used to predict SAK antigenic epitopes, and several main epitopes were modified by gene deletion and mutation. Ten SAK mutants were constructed, and their thrombolytic activity and immunogenicity were analyzed in vitro. SAK6, with a high expression level (45%), similar thrombolysis activity, and lower antibody reaction, was chosen for in vivo analysis in rhesus monkey. In the nearly 8-month experimental period, the antibody level of the SAK6 group was significantly lower than that of the SAK group. Moreover, only 5% of SAK activity was retained, whereas 75.6% of SAK6 activity was retained after incubating with the respective antiserum. Overall, these results demonstrate that SAK6, established through comprehensive site-directed mutagenesis program, had identical thrombolysis activity to SAK, low immunogenicity, and good safety, demonstrating its great clinical potential for thrombus disease.

19.
J Cardiovasc Pharmacol Ther ; : 1074248419885633, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31698947

RESUMO

AIM: Vascular calcification (VC) is thought to be an independent predictor of cardiovascular morbidity and mortality. Intermedin1-53 (IMD) is a cardiovascular protective peptide and can inhibit vascular medial calcification in rats. In this study, we investigated the effect of IMD on atherosclerotic calcification induced by a high-fat diet plus homocysteine (Hcy) and the potential mechanisms. METHODS: ApoE-/- mice were fed a high-fat diet with Hcy in drinking water to induce atherosclerotic calcification. RESULTS: As compared to the high-fat diet alone, Hcy treatment significantly increased atherosclerotic lesion areas and the number of calcified nodules in aortic roots and was reduced by IMD infusion or 4-phenylbutyric acid (PBA) treatment. In vitro, as compared to calcifying medium alone, Hcy treatment further increased alkaline phosphatase activity, calcium content, and calcium nodule number in human aorta vascular smooth muscle cells (HA-VSMCs), all blocked by IMD or PBA pretreatment. Mechanistically, IMD or PBA significantly alleviated endoplasmic reticulum stress (ERS) activation compared with Hcy treatment. In parallel, IMD or PBA attenuated the messenger RNA levels of osteogenic markers and inflammatory cytokines in aortas and their protein levels in lesions of aortic roots. In vitro, Hcy treatment significantly increased the protein levels of osteoblast-like cell markers in primary rat VSMCs and inflammation markers in mouse peritoneal macrophages, all decreased with IMD or PBA pretreatment. Intermedin1-53 pretreatment also markedly reduced the protein levels of ERS markers in rat VSMCs and mouse peritoneal macrophages. CONCLUSIONS: Intermedin1-53 protects against Hcy-promoted atherosclerotic calcification in ApoE-/- mice by inhibiting ERS.

20.
Biomater Sci ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31728485

RESUMO

Acting as a double-edged sword, the blood-brain barrier (BBB) is essential for maintaining brain homeostasis by restricting the entry of small molecules and most macromolecules from blood. However, it also largely limits the brain delivery of most drugs. Even if a drug can penetrate the BBB, its accumulation in the intracerebral pathological regions is relatively low. Thus, an optimal drug-delivery system (DDS) for the management of brain diseases needs to display BBB permeability, lesion-targeting capability, and acceptable safety. Biomimetic DDSs, developed by directly utilizing or mimicking the biological structures and processes, provide promising approaches for overcoming the barriers to brain drug delivery. The present review summarizes the biological properties and biomedical applications of the biomimetic DDSs including the cell membrane-based DDS, lipoprotein-based DDS, exosome-based DDS, virus-based DDS, protein template-based DDS and peptide template-based DDS for the management of brain diseases.

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