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1.
Biosens Bioelectron ; 171: 112733, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33096430

RESUMO

As promising fluid biomarkers for non-invasive diagnosis, naturally-occurring exosomes in saliva have attracted a wide interest for their potential application in oral diseases especially oral cancers. However, accurate quantification of salivary exosomes is still challenging due to the current difficulties in simultaneous identification and measurement of these nano-sized vesicles. In this study, we developed a novel fluorescent biosensor for one-step sensitive quantification of salivary exosomes based on magnetic and fluorescent bio-probes (MFBPs). Within the MFBPs, self-assembled DNA concatamers loaded with numerous quantum dots (QDs) were ingeniously tethered to aptamers, which were anchored on the surface of magnetic microspheres (MMs). Efficient recognition and capture of an exosome by the aptamer would simultaneously trigger the release of a DNA concatamer as the detection signal carrier, thereby generating a "one exosome-numerous QDs" amplification effect. As the result, this biosensor allowed one-step quantification with less assay time and achieved a high sensitivity with low limit of detection. Moreover, unique fluorescent properties of QDs and the superparamagnetism of MMs offered a strong anti-interference ability, enabling a robust quantification in complex matrices. Furthermore, this biosensor exhibited a good clinical feasibility with favorable accuracy comparable to nanoscale flow cytometry, and a superiority in label-free analysis and convenient operation. This study provides a novel and general strategy for one-step sensitive quantification of exosomes from body fluids, facilitating the development of exosome-based liquid biopsy for disease diagnosis.

2.
Mol Med Rep ; 23(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33200804

RESUMO

Keloids are a skin fibroproliferative condition characterized by the hyperproliferation of fibroblasts and the excessive deposition of extracellular matrix (ECM) components. Previous studies have determined that Caveolin­1 controlled hyperresponsiveness to mechanical stimuli through Runt­related transcription factor 2 (Runx2) activation in keloids. However, the molecular mechanism of Runx2 regulating the pathological progression of keloids has not been elucidated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that most of the differentially expressed genes (DEGs), including Runx2, were significantly enriched in the biological processes 'Positive regulation of cell proliferation', in the cellular components 'Extracellular matrix', in the molecular functions 'Extracellular matrix structural constituents' and in the KEGG 'PI3K­Akt signaling pathway'. The aim of the present study was to investigate the expression levels of the Runx2 in human keloid tissues and primary human keloid fibroblasts (HKFs), and to determine the underlying molecular mechanisms involved in the fibrotic roles of Runx2 in keloid formation. Runx2 expression levels were analyzed in patient keloid tissues and HKFs using western blotting, reverse transcription­quantitative PCR (RT­qPCR) and immunofluorescence microscopy. Primary HKFs were transfected with a small interfering RNA (si) specifically targeting Runx2 (si­Runx2). Subsequently, Cell Counting Kit­8, wound healing and Transwell assays, flow cytometry, RT­qPCR and western blotting were applied to evaluate the proliferation, migration, apoptosis, ECM deposition and PI3K/AKT signaling pathway of HKFs, respectively. In addition, western blotting was also used to determine the expression levels of phosphorylated AKT and PI3K in HKFs. The results revealed that Runx2 expression levels were upregulated in keloid tissues and primary HKFs compared with the normal skin tissues and human normal fibroblasts. Following the transfection with si­Runx2, the proliferative and migratory abilities of HKFs were significantly reduced and the apoptotic rate was increased. The expression levels of type I, type III collagen, fibronectin, and α­smooth muscle actin were downregulated in si­Runx2­transfected cells, which was hypothesized to occur through following the downregulation of the phosphorylation levels of PI3K and AKT. In conclusion, the findings of the present study indicated that Runx2 silencing in HKFs might significantly inhibit the cell proliferation, migration and the expression levels of ECM­related proteins, and promote apoptosis via suppressing the PI3K/AKT signaling pathway. Thus, Runx2 siRNA treatment may reverse the pathological phenotype of keloids through the inhibition of PI3K/AKT signaling in patients.

3.
IEEE Trans Cybern ; PP2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201831

RESUMO

The stability of neural networks with a time-varying delay is studied in this article. First, a relaxed Lyapunov-Krasovskii functional (LKF) is presented, in which the positive-definiteness requirement of the augmented quadratic term and the delay-product-type terms are set free, and two double integral states are augmented into the single integral terms at the same time. Second, a new negative-definiteness determination method is put forward for quadratic functions by utilizing Taylor's formula and the interval-decomposition approach. This method encompasses the previous negative-definiteness determination approaches and has less conservatism. Finally, the proposed LKF and the negative-definiteness determination method are applied to the stability analysis of neural networks with a time-varying delay, whose advantages are shown by two numerical examples.

4.
Sci Signal ; 13(656)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144518

RESUMO

Genetic mutations are a primary driving force behind the adaptive evolution of bacterial pathogens. Multiple clinical isolates of Pseudomonas aeruginosa, an important human pathogen, have naturally evolved one or more missense mutations in bfmS, which encodes the sensor histidine kinase of the BfmRS two-component system (TCS). A mutant BfmS protein containing both the L181P and E376Q substitutions increased the phosphorylation and thus the transcriptional regulatory activity of its cognate downstream response regulator, BfmR. This reduced acute virulence and enhanced biofilm formation, both of which are phenotypic changes associated with a chronic infection state. The increased phosphorylation of BfmR was due, at least in part, to the cross-phosphorylation of BfmR by GtrS, a noncognate sensor kinase. Other spontaneous missense mutations in bfmS, such as A42E/G347D, T242R, and R393H, also caused a similar remodeling of the BfmRS TCS in P. aeruginosa This study highlights the plasticity of TCSs mediated by spontaneous mutations and suggests that mutation-induced activation of BfmRS may contribute to host adaptation by P. aeruginosa during chronic infections.

5.
Clin Rheumatol ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33155157

RESUMO

OBJECTIVE: To explore the association between the creatinine clearance rate (Ccr) and the prognosis of patients, and compared with estimated glomerular filtration rate (eGFR). METHODS: We retrospectively collected information of patients with SLE who were first hospitalized between 1999 and 2009 in Jiangsu Province, China, and followed up in 2010 and 2015. Ccr was calculated and dichotomized into normal group (Ccr ≥ 70) and decreasing group (Ccr < 70). The clinical characteristics of the two groups were compared and Cox proportional-hazards regression models were used to calculate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Among 1990 SLE patients, we observed 437 (22.0%) with decreased Ccr, including 237 cases (11.9%) with mild renal dysfunction, 136 cases (6.8%) with moderate renal dysfunction, and 64 cases (3.2%) with severe renal dysfunction. Compared to normal Ccr, decreasing Ccr had a higher risk for mortality with adjusted HR (95% CI) of 2.21 (1.59-3.06). Dose-response relationships were significantly found between increased mortality of SLE and decreased Ccr (p for trend < 0. 001), as well as eGFR. Positive associations were consistently observed in subgroups, such as systemic lupus disease activity index (SLEDAI) ≥ 15, without comorbidities and abnormal laboratory indexes. Decreasing Ccr was positively associated with mortality from infection and renal failure with HR (95% CI) of 1.80 (1.02-3.19) and 6.84 (3.05-15.36). CONCLUSIONS: A significant association has been observed between decreased Ccr and increased risk for mortality of SLE patients. Early clinical interventions to modulate the Ccr of SLE patients may be beneficial to their survival. Key points • Decreasing creatinine clearance rate (Ccr) was positively associated with an overall mortality of SLE patients, with a dose-response relationship. • Moreover, decreasing Ccr was associated with elevated mortality primarily due to infection and renal failure.

6.
J Speech Lang Hear Res ; : 1-9, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33186510

RESUMO

Objectives This study aimed to evaluate the fidelity and accuracy of a smartphone microphone and recording environment on acoustic measurements of voice. Method A prospective cohort proof-of-concept study. Two sets of prerecorded samples (a) sustained vowels (/a/) and (b) Rainbow Passage sentence were played for recording via the internal iPhone microphone and the Blue Yeti USB microphone in two recording environments: a sound-treated booth and quiet office setting. Recordings were presented using a calibrated mannequin speaker with a fixed signal intensity (69 dBA), at a fixed distance (15 in.). Each set of recordings (iPhone-audio booth, Blue Yeti-audio booth, iPhone-office, and Blue Yeti-office), was time-windowed to ensure the same signal was evaluated for each condition. Acoustic measures of voice including fundamental frequency (F0), jitter, shimmer, harmonic-to-noise ratio (HNR), and cepstral peak prominence (CPP), were generated using a widely used analysis program (Praat Version 6.0.50). The data gathered were compared using a repeated measures analysis-of-variance. Two separate data sets were used. The set of vowel samples included both pathologic (n = 10) and normal (n = 10), male (n = 5) and female (n = 15) speakers. The set of sentence stimuli ranged in perceived voice quality from normal to severely disordered with an equal number of male (n = 12) and female (n = 12) speakers evaluated. Results The vowel analyses indicated that the jitter, shimmer, HNR, and CPP were significantly different based on microphone choice and shimmer, HNR, and CPP were significantly different based on the recording environment. Analysis of sentences revealed a statistically significant impact of recording environment and microphone type on HNR and CPP. While statistically significant, the differences across the experimental conditions for a subset of the acoustic measures (viz., jitter and CPP) have shown differences that fell within their respective normative ranges. Conclusions Both microphone and recording setting resulted in significant differences across several acoustic measurements. However, a subset of the acoustic measures that were statistically significant across the recording conditions showed small overall differences that are unlikely to have clinical significance in interpretation. For these acoustic measures, the present data suggest that, although a sound-treated setting is ideal for voice sample collection, a smartphone microphone can capture acceptable recordings for acoustic signal analysis.

7.
Retina ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33181761

RESUMO

PURPOSE: To investigate the progression of myopic maculopathy (MM) and associated factors in highly myopic Chinese children. METHODS: In this retrospective observational case series, biometric fundus features were morphometrically measured on photographs. Myopic maculopathy was defined as recommended by the Meta-analysis of Pathologic Myopia Study Group. RESULTS: The study included 274 children (mean age:11.7±2.5 years; mean refractive error:-7.66±1.87 diopters) with a mean follow-up of 4.9±1.2 years. MM progression was detected in 52 eyes (18.9%; 95% confidence interval [CI]:14.3%,23.7%). In multivariable analysis, MM progression was associated with a decrease in refractive error (odds ratio [OR]:0.72;95%CI:0.56,0.92;P<0.001) (i.e. higher myopization) and enlargement of parapapillary gamma zone (OR:7.68;95%CI:1.63,36.2;P=0.002). Incident peripapillary diffuse choroidal atrophy noted in 47 of 236 eyes (20.0%; 95%CI, 14.8%-25.2%), was correlated with a decrease in refractive error (OR:0.70;95%CI:0.54,0.92;P=0.009) (i.e., higher myopization) and greater gamma zone enlargement (OR:8.28;95%CI:1.33,51.7;P=0.02). CONCLUSIONS: Myopia in schoolchildren may have a considerable risk of progressing to MM. Enlargement of parapapillary gamma zone was a main independent risk factor.

8.
J Comput Soc Sci ; : 1-18, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33169108

RESUMO

The literature on China's social media foreign propaganda mostly focuses on text-format contents in English, which may miss the real target and the tool for analysis. In this article, we traced 1256 Twitter accounts echoing China government's #USAVirus propaganda before and after Twitter removed state-linked operations on June 12, 2020. The 3567 tweets with #USAVirus we collected, albeit many written in English, 74% of them attached with a lengthy simplified Chinese text-image. Distribution of the post-creation time fits the working-hour in China. Overall, 475 (37.8%) accounts we traced were later suspended after Twitter's disclosure. Our dataset enables us to analyze why and why not Twitter suspends certain accounts. We apply the decision tree, random forest, and logit regression to explain the suspensions. All models suggest that the inclusion of a text-image is the most important predictor. The importance outweighs the number of followers, engagement, and the text content of the tweet. The prevalence of simplified Chinese text-images in the #USAVirus trend and their impact on Twitter account suspensions both evidence the importance of text-image in the study of state-led propaganda. Our result suggests the necessity of extracting and analyzing the content in the attached text-image.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33168191

RESUMO

Myocardial ischemia-reperfusion (MIR) represents critical challenge for the treatment of acute myocardial infarction diseases. Presently, identifying the molecular basis revealing MIR progression is scientifically essential and may provide effective therapeutic strategies. Phosphoglycerate mutase 1 (PGAM1) is a key aerobic glycolysis enzyme, and exhibits critical role in mediating several biological events, such as energy production and inflammation. However, whether PGAM1 can affect MIR is unknown. Here we showed that PGAM1 levels were increased in murine ischemic hearts. Mice with cardiac knockout of PGAM1 were resistant to MIR-induced heart injury, evidenced by the markedly reduced infarct volume, improved cardiac function and histological alterations in cardiac sections. In addition, inflammatory response, apoptosis and fibrosis in hearts of mice with MIR operation were significantly alleviated by the cardiac deletion of PGAM1. Mechanistically, the activation of nuclear transcription factor κB (NF-κB), p38, c-Jun NH2-terminal kinase (JNK) and transforming growth factor ß (TGF-ß) signaling pathways were effectively abrogated in MI-operated mice with specific knockout of PGAM1 in hearts. The potential of PGAM1 suppression to inhibit inflammatory response, apoptosis and fibrosis were verified in the isolated cardiomyocytes and fibroblasts treated with oxygen-glucose deprivation reperfusion (OGDR) and TGF-ß, respectively. Importantly, PGAM1 directly interacted with TGF-ß to subsequently mediate inflammation, apoptosis and collagen accumulation, thereby achieving its anti-MIR action. Collectively, these findings demonstrated that PGAM1 was a positive regulator of myocardial infarction remodeling due to its promotional modulation of TGF-ß signaling, indicating that PGAM1 may be a promising therapeutic target for MIR treatment.

10.
Life Sci ; : 118758, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33188835

RESUMO

AIMS: Insulin-like growth factor (IGF) signaling has been documented in several human malignancies and is thought to contribute to cellular differentiation and migration, as well as malignant progression. A major binding molecule of IGF, IGF-binding protein 3 (IGFBP-3), regulates multiple IGF effects. Here, we focused on the effect of IGFBP-3 in the motility of osteosarcoma cells and examined signaling regulation. MATERIALS AND METHODS: Using a human osteosarcoma tissue array, immunohistochemical staining determined levels of IGFBP-3 expression in osteosarcoma tissue and in normal tissue. The wound healing migration assay, Transwell migration assay, luciferase reporter assay, immunofluorescence staining, Western blot and real-time quantitative PCR were performed to examine whether IGFBP-3 facilitates VCAM-1-dependent migration of osteosarcoma cells. KEY FINDINGS: In this study, we found significantly higher IGFBP-3 levels in osteosarcoma tissue compared with normal healthy tissue. IGFBP-3 treatment of two human osteosarcoma cell lines promoted cell migration and upregulated levels of VCAM-1 expression via PI3K/Akt and AP-1 signaling. SIGNIFICANCE: IGFBP-3 appears to be a novel therapeutic target in metastatic osteosarcoma.

11.
PLoS One ; 15(11): e0241362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33157550

RESUMO

Buprenorphine is a µ-opioid receptor (MOR) partial agonist used to manage pain and addiction. QTC prolongation that crosses the 10 msec threshold of regulatory concern was observed at a supratherapeutic dose in two thorough QT studies for the transdermal buprenorphine product BUTRANS®. Because QTC prolongation can be associated with Torsades de Pointes (TdP), a rare but potentially fatal ventricular arrhythmia, these results have led to further investigation of the electrophysiological effects of buprenorphine. Drug-induced QTC prolongation and TdP are most commonly caused by acute inhibition of hERG current (IhERG) that contribute to the repolarizing phase of the ventricular action potentials (APs). Concomitant inhibition of inward late Na+ (INaL) and/or L-type Ca2+ (ICaL) current can offer some protection against proarrhythmia. Therefore, we characterized the effects of buprenorphine and its major metabolite norbuprenorphine on cardiac hERG, Ca2+, and Na+ ion channels, as well as cardiac APs. For comparison, methadone, a MOR agonist associated with QTC prolongation and high TdP risk, and naltrexone and naloxone, two opioid receptor antagonists, were also studied. Whole cell recordings were performed at 37°C on cells stably expressing hERG, CaV1.2, and NaV1.5 proteins. Microelectrode array (MEA) recordings were made on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The results showed that buprenorphine, norbuprenorphine, naltrexone, and naloxone had no effect on IhERG, ICaL, INaL, and peak Na+ current (INaP) at clinically relevant concentrations. In contrast, methadone inhibited IhERG, ICaL, and INaL. Experiments on iPSC-CMs showed a lack of effect for buprenorphine, norbuprenorphine, naltrexone, and naloxone, and delayed repolarization for methadone at clinically relevant concentrations. The mechanism of QTC prolongation is opioid moiety-specific. This remains undefined for buprenorphine, while for methadone it involves direct hERG channel block. There is no evidence that buprenorphine use is associated with TdP. Whether this lack of TdP risk can be generalized to other drugs with QTC prolongation not mediated by acute hERG channel block warrants further study.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33044149

RESUMO

A novel, Gram-stain-positive, aerobic, non-spore-forming, non-motile and irregular rod-shaped bacterium designated Q22T was isolated from the rhizosphere soil of mangrove plant, Kandelia candel collected in Zhangzhou, Fujian province, China. Strain Q22T was able to grow at 10-40 °C (optimum 30 °C), pH 5.5-9.0 (optimum 7.0-8.0) and with 0-5.0% (w/v) NaCl (optimum 1.0 %). The genomic DNA G+C content was 71.9%. The average nucleotide identity, and in silico DNA-DNA hybridization values between strain Q22T and the reference strains were 79.7-88.9% and 22.6-37.4%, respectively. The predominant isoprenoid quinone was MK-12 and the major fatty acids were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The major polar lipids of strain Q22T were diphosphatidylglycerol, phosphatidylglycerol, one glycolipid and three unidentified lipids. The strain Q22T contained 2,4-diaminobutyric acid, alanine acid, glutamic acid and glycine in the peptidoglycans. The phylogenetic analysis and genotypic features, along with the phenotypic and chemotaxonomic characteristics, indicate that strain Q22T represents a novel species of the genus Agromyces, for which the name Agromyces kandeliae sp. nov. is proposed. The type strain is Q22T (=MCCC 1K03340T= KCTC 39961T).

13.
Am J Case Rep ; 21: e924889, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044949

RESUMO

BACKGROUND Bipolar dislocation of the clavicle is a rare disease that is often associated with some high-energy injuries. It refers to concomitant dislocation of the ipsilateral acromioclavicular joint and sternoclavicular joint. Because of its rarity, the diagnosis of bipolar dislocation of the clavicle is often difficult. Additionally, few reports are available on its treatment. Here, we describe a case of bipolar dislocation of the clavicle in which a secondary operation was needed because of a missed diagnosis. However, after surgery for bipolar dislocation of the clavicle, the clavicle shaft had a fracture that required reoperation. CASE REPORT A 58-year-old woman presented at our hospital with left shoulder pain. The patient had a history of sternoclavicular joint (SCJ) reconstruction and had a plate for left SCJ dislocation inserted 1 month ago at another hospital. Plain radiography images revealed that the left acromioclavicular joint (ACJ) was dislocated. We performed ACJ reconstruction with a hook plate. However, 4 weeks after the operation, the patient fell and visited to our hospital with left shoulder pain again. Plain radiography images revealed a left clavicle shaft fracture. We removed the plates from both ends of the clavicle and performed an open reduction and internal fixation using the long clavicular plate for clavicle shaft fracture. CONCLUSIONS Bipolar dislocation of the clavicle is frequently missed at the first diagnostic imaging examination; therefore, careful attention is required when SCJ or ACJ dislocation is observed. This case suggested that clavicle shaft fracture can occur after reconstruction of the SCJ and ACJ for bipolar dislocation of the clavicle. We conducted a literature review of this related case, highlighting the treatment of such cases.

14.
Mol Cancer Ther ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999045

RESUMO

Immunotherapy using OX40 agonist antibodies shows great preclinical efficacy in mouse tumor models. But in a clinical setting, OX40 agonist antibody alone or in combination with checkpoint blockade exhibit only modest efficacy due to lack of sufficient activation. We hypothesize that the limited antitumor activity in patients may due to insufficient clustering of OX40 antibody in the tumor. To test this hypothesis, we generated a tetravalent PD-L1/OX40 BsAb by fusing two PD-L1 VHH fragments to the C-terminus of a non-blocking agonistic anti-OX40 antibody. The resulting BsAb has intact function of each parental Ab, including efficiently blocking PD1/PD-L1 interaction and inducing OX40 activation. In addition, this BsAb showed significantly enhanced potency in activation of OX40-expressing T cells when PD-L1-expressing tumor cells or DCs were present, through PD-L1-mediated crosslinking of OX40. Moreover, the BsAb exhibited superior antitumor activities over the parental monospecific antibodies alone or in combination in multiple in vivo tumor models. These results demonstrated a great potential for further clinical development of the potent immunostimulatory PD-L1/OX40 bispecific antibody.

15.
Int J Nanomedicine ; 15: 7315-7327, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061383

RESUMO

Objective: To investigate the antifibrotic effect of the combination of a PPARγ agonist-loaded nanoparticle-microbubble complex with ultrasound (US) exposure on renal interstitial fibrosis (RIF). Materials and Methods: Polylactide-co-glycolide (PLGA) nanoparticles were used to load PPARγ agonist (rosiglitazone, RSG) and prepare PLGA-RSG nanoparticles (PLNPs-RSG); then, a novel complex between PLNPs-RSG and SonoVue microbubbles (MBs) (PLNPs-RSG-MBs) was prepared. The size distribution, zeta potentials, RSG-loading capacity and entrapment efficiency were measured, and the release of RSG was assessed using a UV-vis spectrophotometer. The in vitro cytotoxicity and in vivo systemic toxicity assays were performed. The cellular uptake assessment was performed using a confocal laser scanning microscope (CLSM). The in vivo biodistribution assessment was performed using fluorescence imaging with a near-infrared (NIR) imaging system. Furthermore, this complex was administered to a unilateral ureteral obstruction (UUO) rat model with the assistance of US exposure to investigate the antifibrotic effect. Results: This PLNPs-RSG-MBs complex had a size of 2199.5± 988.1 nm and a drug-loading efficiency of 28.5%. In vitro cytotoxicity and in vivo systemic toxicity assays indicated that the PLNPs-RSG-MBs complex displayed excellent biocompatibility. In addition, the complex showed high cellular uptake efficiency in vitro and kidney-targeting ability in vivo. In a UUO rat model, the combination of the PLNPs-RSG-MBs complex with US exposure significantly reduced collagen deposition and successfully attenuated renal fibrosis. Conclusion: The combination of the PLNPs-RSG-MBs complex with US exposure may be a promising approach for the treatment of RIF.

16.
Transl Psychiatry ; 10(1): 350, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067412

RESUMO

Mounting evidence suggests that gut microbiota can play an important role in pathophysiology of depression, but its specific molecular mechanisms are still unclear. This study was conducted to explore the associations between changes in neurotransmitters and short-chain fatty acids (SCFAs) and altered gut microbiota in depressed mice. Here, the chronic restraint stress (CRS) model of depression was built. The classical behavioral tests were conducted to assess the depressive-like behaviors of mice. The 16S rRNA gene sequence extracted from fecal samples was used to assess the gut microbial composition. Liquid and gas chromatography mass spectroscopy were used to identify neurotransmitters in hypothalamus and SCFAs in fecal samples, respectively. Finally, 29 differential bacteria taxa between depressed mice and control mice were identified, and the most differentially abundant bacteria taxa were genus Allobaculum and family Ruminococcaceae between the two groups. The acetic acid, propionic acid, pentanoic acid, norepinephrine, 5-HIAA and 5-HT were significantly decreased in depressed mice compared to control mice. Genus Allobaculum was found to be significantly positively correlated with acetic acid and 5-HT. Taken together, these results provided novel microbial and metabolic frameworks for understanding the role of microbiota-gut-brain axis in depression, and suggested new insights to pave the way for novel therapeutic methods.

17.
Water Res ; 187: 116454, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33011570

RESUMO

Expansion in the size is an indispensable stage in the granular sludge life cycle, but little attention has been payed to the enlargement mechanism of granular sludge. Here, we propose a novel anammox granule enlargement mechanism by the self-assembly of heterogenous granules. Two different colors of anammox granules, dark-red granules (DR-Granules) and bright-red granules (BR-Granules) were found in an expanded granular sludge bed reactor. These two heterogenous granules were not isolated but were assembled into granules with a larger DR-Granule in the center and many smaller BR-Granules aggregated on the surface, increasing the overall granular size. Their physiochemical characteristics in terms of EPS, adherence, rheological properties, and microbial compositions, were identified and compared to elucidate the interaction between the different colors of granules. The BR-Granules created 92% more extracellular polymeric substances than the DR-Granules. This material blocked the passage of gas and substrate, leading to BR-Granules smaller size and a yield stress approximately 48% lower than that of the DR-Granules. Nevertheless, the BR-Granules had compact extracellular protein secondary structures and a high adherence rate to the surface of the DR-Granules, upon which they formed a compact adhered layer. These unique features enabled them to directionally adhere to DR-Granules in the core, that is, two heterogenous colors of granules self-assembled into large anammox granules. The enlargement mechanism was further supported by the abundance of K-strategy Ca. Kuenenia in the DR-Granules (inner layer) being higher than in the BR-Granules (outer layer; 2.9 ± 0.4% vs. 0.4 ± 0.1%; p = 0.0003) and by visualized confirmation that the larger BR-Granules wrapped around smaller DR-Granules inside. This demonstrates that heterogenous anammox granules actively self-assemble into large granules, which is an important step in the lifecycle of anammox granules.

18.
Adv Mater ; : e2005222, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079417

RESUMO

Bacteria hiding in host phagocytes are difficult to kill, which can cause phagocyte disorders resulting in local and systemic tissue damage. Effective accumulation of activatable photosensitizers (PSs) in phagocytes to realize selective imaging and on-demand photodynamic ablation of bacteria is of great scientific and practical interests for precise bacteria diagnosis and treatment. Herein, HClO-activatable theranostic nanoprobes, DTF-FFP NPs, for image-guided bacterial ablation in phagocytes are introduced. DTF-FFP NPs are prepared by nanoprecipitation of an HClO-responsive near-infrared molecule FFP and an efficient PS DTF with aggregation-induced emission characteristic using an amphiphilic polymer Pluronic F127 as the encapsulation matrix. As an energy acceptor, FFP can quench both fluorescence and production of reactive oxygen species (ROS) of DTF, thus eliminating the phototoxicity of DTF-FFP NPs in normal cells and tissues. Once delivered to the infection sites, DTF-FFP NPs light up with red fluorescence and efficiently generate ROS owing to the degradation of FFP by the stimulated release of HClO in phagocytes. The selective activation of fluorescence and photosensitization is successfully confirmed by both in vitro and in vivo results, demonstrating the effectiveness and theranostic potential of DTF-FFP NPs in precise bacterial therapy.

19.
Braz J Med Biol Res ; 53(11): e9266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053114

RESUMO

The etiology of polycystic ovary syndrome (PCOS) is complex and the pathogenesis is not fully understood. Some studies have shown that dysregulation of ovarian granulosa cells may be related to abnormal follicles and excessive androgen in women with PCOS. Our team has also confirmed the high expression status of H19 in PCOS patients in the early stage. However, the relationship between H19 and miR-19b in the development of PCOS is still unknown. Therefore, we used bioinformatics to predict the binding sites of human H19 and miR-19b, and of miR-19b and CTGF genes. After the silencing and overexpression of H19, real-time polymerase chain reaction (PCR) was used to detect the expressions of H19, miR-19b, and CTGF. Western blotting was used to detect CTGF protein. Proliferation of KGN cells after H19 silencing was detected by CCK8. Flow cytometry was used to detect the apoptosis of KGN cells after H19 silencing. After the overexpression of H19, it was found that the expression of miR-19b gene decreased and the expression of CTGF increased, whereas silencing of H19 did the opposite. In addition, H19 could promote cell proliferation and decrease cell apoptosis. Finally, luciferase reporter assays showed that the 3'-end sequences of lncRNA H19 and CTGF contained the binding site of miR-19b. In conclusion, our study indicated that lncRNA H19 acted as a ceRNA to bind to miR-19b via a "sponge" to regulate the effect of CTGF on KGN cells, which may play a vital role in PCOS.

20.
Ann Hum Biol ; : 1-26, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33050724

RESUMO

Background: Cognitive decline can develop into mild cognitive impairment, a high-risk factor in the progression of Alzheimer's disease. The antioxidant micronutrient selenium may have some effect on preventing cognitive decline, but the association between whole blood selenium concentration and cognitive function remains controversial.Aim: To investigate the association between whole blood selenium concentration and cognitive function score in elderly Americans.Subjects and methods: Data was obtained from the national health and nutrition survey between 2011 and 2014. A general linear model was used to adjust for possible risk factors to analyse the association between blood selenium concentration and cognitive function.Results: 2068 participants were included in our study, and the average blood selenium concentration was high at 195.08µg/L. The risk of lower cognitive scores was higher in people with lower blood selenium concentration (p < 0.05). The lower cognition may also be associated with one or more of the following characteristics: older, male, had a low poverty-income ratio, low education level, and consumed less alcohol. Related conditions such as stroke, diabetes and high blood pressure may also affect cognitive scores.Conclusions: Higher blood selenium is associated with higher cognitive scores in elderly Americans.

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