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1.
Curr Opin Microbiol ; 72: 102269, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36682279

RESUMO

Harnessing the power of beneficial microbes in the rhizosphere to improve crop performance is a key goal of sustainable agriculture. However, the precise management of rhizosphere microbes for crop growth and health remains challenging because we lack a comprehensive understanding of the plant-rhizomicrobiome relationship. In this review, we discuss the latest research progress on root colonisation by representative beneficial microbes (e.g. Bacillus spp. and Pseudomonas spp.). We also highlight the bidirectional chemical communication between microbes and plant roots for precise functional control of beneficial microbes in the rhizosphere, as well as advances in understanding how beneficial microbes overcome the immune system of plants. Finally, we propose future research objectives that will help us better understand the complex network of plant-microbe interactions.

2.
Mar Pollut Bull ; 187: 114556, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36640496

RESUMO

Filter-feeder bivalves and phytoplankton are interdependent. Their interaction plays important role in estuarine and coastal ecosystem. The correlation between bivalve feeding and phytoplankton is highly species specificity and environment dependent. In the background of miniature and nondiatom trend of phytoplankton in coastal seawaters, how bivalve respond and how the response play roles in the phytoplankton community are poorly known. In the present study, by applying DNA metabarcoding approach based on plastid 23S rDNA, this question was addressed by comparing the phytoplankton composition in the seston and the stomach content of blood clam Tegillarca granosa sampled during the growth period from March to November 2020 in an experimental farm on tidal flat in Xiangshan Bay, East China Sea. The result showed that, a total of seven phyla, 55 genera and 73 species of phytoplankton were identified for all samples. Chlorophyta, Bacillariophyta, and Cyanobacteria were found to be three dominant phyla both in the stomach contents and seston. High diversity of pico-sized phytoplankton, which was easy overlooked by microscopy, was revealed both in seston and stomach contents. This result indicated that the clam was able to feed on the pico-sized algae. At the genus level, the most abundant genera were the pico-sized green alga Ostreococcus (6.12 %-67.88 %) in seston and Picochlorum (4.07 %-35.33 %) in the stomach contents. In addition, microalgae of high nutritional value showed trend of higher proportion in stomach contents than that in seston, especially in July and September when significant growth of T. granosa was observed during this period (the body size increased 155 %). Biodiversity of phytoplankton in the seston was totally higher than that in stomach content, however, the changes among the months showed respective trend. Especially in July when the biodiversity was the lowest in seston, that in the stomach content showed the highest. The results indicated that blood clam farming might influence the phytoplankton composition, including those of pico-sized level, although the particular species in seston were mainly correlating with the dominant environmental factors such as temperature, salinity, pH respectively. These results extend the understanding of roles that bivalve aquaculture may play in the changing of coastal phytoplankton community.

3.
Bioinformatics ; 39(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36525367

RESUMO

SUMMARY: Non-coding RNAs play important roles in transcriptional processes and participate in the regulation of various biological functions, in particular miRNAs and lncRNAs. Despite their importance for several biological functions, the existing signaling pathway databases do not include information on miRNA and lncRNA. Here, we redesigned a novel pathway database named NcPath by integrating and visualizing a total of 178 308 human experimentally validated miRNA-target interactions (MTIs), 32 282 experimentally verified lncRNA-target interactions (LTIs) and 4837 experimentally validated human ceRNA networks across 222 KEGG pathways (including 27 sub-categories). To expand the application potential of the redesigned NcPath database, we identified 556 798 reliable lncRNA-protein-coding genes (PCG) interaction pairs by integrating co-expression relations, ceRNA relations, co-TF-binding interactions, co-histone-modification interactions, cis-regulation relations and lncPro Tool predictions between lncRNAs and PCG. In addition, to determine the pathways in which miRNA/lncRNA targets are involved, we performed a KEGG enrichment analysis using a hypergeometric test. The NcPath database also provides information on MTIs/LTIs/ceRNA networks, PubMed IDs, gene annotations and the experimental verification method used. In summary, the NcPath database will serve as an important and continually updated platform that provides annotation and visualization of the pathways on which non-coding RNAs (miRNA and lncRNA) are involved, and provide support to multimodal non-coding RNAs enrichment analysis. The NcPath database is freely accessible at http://ncpath.pianlab.cn/. AVAILABILITY AND IMPLEMENTATION: NcPath database is freely available at http://ncpath.pianlab.cn/. The code and manual to use NcPath can be found at https://github.com/Marscolono/NcPath/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais
4.
Comput Struct Biotechnol J ; 20: 6543-6551, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467579

RESUMO

The world's population continues to increase and thus requires more food production to take place in nonarable land, such as saline soil; therefore, it is urgent to find solutions to enhance the salinity tolerance of crops. As the second genome of plants, the rhizosphere microbiome plays critical roles in plant fitness under stress conditions. Many beneficial microbes that help plants cope with salinity stress have been identified, highlighting their roles in mitigating salt stress-induced negative effects on plants. However, a comprehensive review of the microbial species that are able to confer plant salt tolerance and the underlying mechanisms is still lacking. In this review, we compared the representative fungal and bacterial taxa that demonstrate the ability to enhance plant growth in saline soil. We also reviewed the mechanisms by which rhizosphere microbes enhance plant salt stress tolerance, i.e., by re-establishing ion and osmotic homeostasis, preventing damage to plant cells, and resuming plant growth under salt stress. Finally, future research efforts to explore the rhizosphere microbiome for agricultural sustainability are proposed.

5.
Adv Sci (Weinh) ; : e2205215, 2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36529951

RESUMO

Seed-borne pathogens can inhabit the rhizosphere and infect the plant after germination. The rhizosphere microbiome plays critical roles in defending against seed-borne pathogens. However, the assembly of a core rhizosphere microbiome to suppress seed-borne pathogens is unknown. Here, the root-associated microbiome is infested with seed-borne Fusarium in sterile environment, while the root-associated microbiome is not infested when it interacts with the native soil microbiome across maize cultivars, suggesting that a core rhizosphere microbiome assembles to suppress seed-borne Fusarium. Two strategies of progressive dilution and rhizodepositional attraction are applied to identify the core rhizobacteria. A synthetic microbiota (SynM) is constructed using the isolates of the core rhizobacteria and optimized according to superior community stability and Fusarium-suppression capability, which surpasses the single strain and randomly formed microbiota. The optimized SynM (OptSynM) presents a distinctive cooperative pattern in which a key strain harbors the Fusarium suppression function by synthesizing the antagonistic substance fengycin, while other members intensify the functional performance by promoting the growth and the expression of the antagonistic and plant-growth-promoting related genes of the key strain. This study demonstrates innovative approaches to construct stable and minimal microbiota for sustainable agriculture and proposes a unique cooperative pattern to sustain community stability and functionality.

6.
Int J Mol Sci ; 23(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36555150

RESUMO

The pathogenesis of thyroid-associated ophthalmopathy (TAO) is still unclear, and therapeutic drugs have great limitations. As metformin has multiple therapeutic effects in many autoimmune diseases, we explored the effects of metformin on TAO in an in vitro fibroblast model. We used orbital connective tissues and fibroblasts that were obtained from TAO patients and normal controls. The activity of adenosine monophosphate-activated protein kinase (AMPK) and the levels of inflammatory or fibrotic factors were examined by immunofluorescence (IF) and immunohistochemistry (IHC). Quantitative real-time polymerase chain reaction (qPCR), cytokine quantification by enzyme-linked immunosorbent sssay (ELISA), IF, and western blotting (WB) were used to measure the expression of factors related to inflammation, fibrosis, and autophagy. To determine the anti-inflammatory and antifibrotic mechanisms of metformin, we pretreated cells with metformin, 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR, an AMPK activator) or compound C (CC, an AMPK inhibitor) for 24 h and used WB to verify the changes in protein levels in the AMPK/mammalian target of rapamycin (mTOR) pathway. We determined that the low activity of AMPK in the periorbital tissue of TAO patients may be closely related to the occurrence and development of inflammation and fibrosis, and metformin exerts multiple effects by activating AMPK in TAO. Furthermore, we suggest that AMPK may be a potential target of TAO therapy.


Assuntos
Oftalmopatia de Graves , Metformina , Humanos , Oftalmopatia de Graves/patologia , Metformina/farmacologia , Metformina/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Inflamação/tratamento farmacológico , Fibrose
7.
Sci Rep ; 12(1): 22299, 2022 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36566332

RESUMO

This study aimed to evaluate differences in the clinical outcomes of different sacral neuromodulation systems (InterStim and BetterStim) used in the treatment of overactive bladder. Data from a previously established database of sacral neuromodulation in China (the InterStim system) and a 2020 clinical trial of the BetterStim system were screened. Patients with overactive bladder undergoing stage II implanted pulse generator implantation were selected for analysis and divided into InterStim and BetterStim system groups. Voiding diaries and subjective scores obtained preoperatively, after stage I tined-lead implantation (experience period), and after stage II implanted pulse generator implantation were compared between the two groups. This study included 113 patients with overactive bladder (43, InterStim system group; 70, BetterStim system group). Voiding diaries and subjective scores significantly improved in both the InterStim and BetterStim system groups over the treatment period. Specifically, the urination frequency (all P < 0.001), average voiding volume (all P < 0.001), and average urinary leakage (InterStim, P < 0.05; BetterStim, P < 0.01) in both groups significantly improved at different periods during treatment. At the same time, the urgency perception scale (P < 0.001) and OAB-related quality of life score (InterStim, P < 0.05; BetterStim, P < 0.01) also significantly improved. There was no significant difference in urination frequency at baseline between the two groups (P = 0.169). Urination frequency was significantly higher in the BetterStim system group than in the InterStim group during the experience period and at follow-up (P = 0.031, P = 0.006). There was no significant difference in the number of urinary leakages between the different systems at baseline (P = 0.662), although this was higher in the InterStim system group during the experience period (P = 0.016), and the difference disappeared at the last follow-up (P = 0.565). There were significant differences in baseline urgency perception scale (P = 0.001) and OAB-related quality of life score (P < 0.001) between the two groups; however, these differences were not maintained at follow-up (P = 0.81, P = 0.479). Both sacral neuromodulation systems are safe and effective in treating overactive bladder. The InterStim system may be more beneficial for patients with dry overactive bladder. Satisfactory outcomes may be achieved with the BetterStim system in patients with wet overactive bladder. However, further studies are required to confirm this finding.


Assuntos
Terapia por Estimulação Elétrica , Bexiga Urinária Hiperativa , Humanos , Bexiga Urinária Hiperativa/terapia , Qualidade de Vida , Resultado do Tratamento , Micção
8.
Am J Obstet Gynecol ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36403859

RESUMO

BACKGROUND: Serum uric acid (SUA) level is elevated in polycystic ovary syndrome (PCOS), however, the relationship between SUA level and reproductive outcomes in PCOS women remains unclear. OBJECTIVE: To investigate the association between SUA level and the reproductive outcomes in women with PCOS undergoing in-vitro fertilization or intracytoplasmic sperm injection (IVF or ICSI) embryo transfer cycles. STUDY DESIGN: This was a retrospective cohort study performed in a university-affiliated reproductive medicine center. A total of 1903 PCOS women undergoing their first IVF or ICSI embryo transfer cycles between January 2010 and January 2021 were initially included. The trend for rates of reproductive outcomes in PCOS across quartiles of SUA levels were assessed. Logistic regression analysis was performed to obtain the odds ratios (ORs) for IVF outcomes based on the quartiles of SUA with or without adjusting for potential confounding variables. Using generalized additive models (GAM), SUA was further treated as its original continuous property to visualize its nonlinear relationship with IVF outcomes. The live birth rate is the main outcome. RESULTS: After exclusions, a total of 883 PCOS women with their first fresh embryo transfer cycles were included. In quartiles of SUA levels, there was a significant decreasing trend in live birth rate from the lowest quartile (Q1: 61.8%) to the highest (Q4: 45.9%) (Ptrend =0.002). The percentage of low birth weight increased from Q1 (22.3%) to Q4 (31.7%) (Ptrend =0.049). Compared with those in Q1, women in Q4 showed that significant lower probability of live birth and clinical pregnancy and higher risk of low birth weight (all P< 0.05). Both the unadjusted and adjusted GAM models indicated that as the SUA level increased, the probability of clinical pregnancy and the live birth rate exhibited an overall decreasing profile, and the risk of low birth weight showed increasing profile. CONCLUSIONS: An elevated serum uric acid level is associated with decreased the probabilities of live birth and clinical pregnancy, and increased risk of live birth weight in women with PCOS. However, these associations may be confounded by other factors and more well-designed studies are needed to confirm these findings in the future.

9.
Invest Ophthalmol Vis Sci ; 63(12): 27, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409215

RESUMO

Purpose: The purpose of this study was to investigate the molecular mechanism underlying thyroid-associated ophthalmopathy (TAO) clinical subtypes, to do so, we performed transcriptomic analysis to reveal the expression profile of circular RNAs (circRNAs) in TAO subtypes. Methods: High-throughput RNA-sequencing was performed in six pairs of type I and type II orbital connective tissue samples from patients with TAO. The expression levels of circRNAs and mRNAs in type I and type II samples were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in another three pairs of type I and type II TAO connective tissue samples. We used bioinformatics predictions to construct a circRNA-microRNA (miRNA)-mRNA network. A protein-protein interaction (PPI) network was constructed based on differential mRNA expression, and the hub genes were determined by the Cytoscape software plugin. Functional and pathway enrichment analyses were performed to elucidate circRNA function. Lentiviral-mediated overexpression of hsa_circ_0007006 and the relationship between hsa_circ_0007006 with COL1A1 and MMP2 were evaluated by Western blotting (WB). Moreover, the differential pathways were assessed by WB. Results: RNA sequencing results predicted a total of 7489 circRNAs and 15,803 mRNAs, with 94 upregulated and 76 downregulated circRNAs and 488 upregulated and 138 downregulated mRNAs. The qRT-PCR analysis of seven dysregulated circRNAs and two major mRNAs validated the RNA-sequencing data. The competing endogenous RNA (ceRNA) network included 7 circRNAs, 23 miRNAs, and 262 mRNAs. Functional analysis revealed several important pathways. Overexpression of hsa_circ_0007006 led to decreased expression levels of COL1A1 and MMP2. Activation of the relaxin signaling pathway differed between the two subtypes. Conclusion: We showed that circRNAs are differentially expressed between type I and type II TAO. We speculate that the hsa_circ_0007006-COL1A1 and MMP2-relaxin signaling pathways are important regulatory axes in the pathogenesis of this disease type and could be considered promising diagnostic and therapeutic targets in the future.


Assuntos
Oftalmopatia de Graves , MicroRNAs , Relaxina , Humanos , RNA Circular/genética , Metaloproteinase 2 da Matriz , Oftalmopatia de Graves/genética , MicroRNAs/genética , RNA Mensageiro/genética , Tecido Conjuntivo
10.
AMB Express ; 12(1): 133, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36287351

RESUMO

Bacillus is a genus of microorganisms (bacteria) and contains many important commercial species used in industry, agriculture and healthcare. Many different Bacilli are relatively well understood at the single-cell level; however, molecular tools that determine the diversity and ecology of Bacillus community are limited, which limits our understanding of how the Bacillus community works. In the present study, we investigated the potential of the housekeeping gene gyrA as a molecular marker for determining the diversity of Bacillus species. The amplification efficiency for Bacillus species diversity could be greatly improved by primer design. Therefore, we designed a novel primer pair gyrA3 that can detect at least 92 Bacillus species and related species. For B. amyloliquefaciens, B. pumilus, and B. megaterium, we observed that the high variability of the gyrA gene allows for more detailed clustering at the subspecies level that cannot be achieved by the 16S rRNA gene. Since gyrA provides better phylogenetic resolution than 16S rRNA and informs on the diversity of the Bacillus community, we propose that the gyrA gene may have broad application prospects in the study of Bacillus ecology.

11.
mSystems ; : e0077822, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36218362

RESUMO

Kin discrimination in nature is an effective way for bacteria to stabilize population cooperation and maintain progeny benefits. However, so far, the research on kin discrimination for Bacillus still has concentrated on "attack and defense" between cells and diffusion-dependent molecular signals of quorum sensing, kin recognition in Bacillus, however, has not been reported. To determine whether flagellar is involve in the kin recognition of Bacillus, we constructed Bacillus velezensis SQR9 assembled with flagellin of its kin and non-kin strains, and performed a swarm boundary assay with SQR9, then analyzed sequence variation of flagellin and other flagellar structural proteins in B. velezensis genus. Our results showed that SQR9 assembled with flagellin of non-kin strains was more likely to form a border phenotype with wild-type strain SQR9 in swarm assay than that of kin strains, and that non-kin strains had greater variation in flagellin than kin strains. In B. velezensis, these variations in flagellin were prevalent and had evolved significantly faster than other flagellar structural proteins. Therefore, we proposed that flagellin is an effective tool partly involved in the kin recognition of B. velezensis strains. IMPORTANCE Kin selection plays an important role in stabilizing population cooperation and maintaining the progeny benefits for bacteria in nature. However, to date, the role of flagellin in kin recognition in Bacillus has not been reported. By using rhizospheric Bacillus velezensis SQR9, we accomplished flagellin region interchange among its related strains, and show that flagellin acts as a mediator to distinguish kin from non-kin in B. velezensis. We demonstrated the polymorphism of flagellin in B. velezensis through alignment analysis of flagellin protein sequences. Therefore, it was proposed that flagellin was likely to be an effective tool for mediating kin recognition in B. velezensis.

12.
Brief Bioinform ; 23(6)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36184256

RESUMO

Fentanyl and its analogues are psychoactive substances and the concern of fentanyl abuse has been existed in decades. Because the structure of fentanyl is easy to be modified, criminals may synthesize new fentanyl analogues to avoid supervision. The drug supervision is based on the structure matching to the database and too few kinds of fentanyl analogues are included in the database, so it is necessary to find out more potential fentanyl analogues and expand the sample space of fentanyl analogues. In this study, we introduced two deep generative models (SeqGAN and MolGPT) to generate potential fentanyl analogues, and a total of 11 041 valid molecules were obtained. The results showed that not only can we generate molecules with similar property distribution of original data, but the generated molecules also contain potential fentanyl analogues that are not pretty similar to any of original data. Ten molecules based on the rules of fentanyl analogues were selected for NMR, MS and IR validation. The results indicated that these molecules are all unreported fentanyl analogues. Furthermore, this study is the first to apply the deep learning to the generation of fentanyl analogues, greatly expands the exploring space of fentanyl analogues and provides help for the supervision of fentanyl.


Assuntos
Aprendizado Profundo , Fentanila , Fentanila/química , Analgésicos Opioides/química , Espectroscopia de Ressonância Magnética , Gerenciamento de Dados
13.
BJU Int ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36084065

RESUMO

AIM: To evaluate the efficacy and safety of intravesical electrical stimulation (IVES) performed with a novel device in patients with underactive bladder (UAB). PATIENTS AND METHODS: This was a multicentre, prospective, single-blind, randomized controlled clinical trial of patients with UAB in China. Eligible patients were randomly assigned in a 1:1 ratio to receive conventional IVES (n = 38) or IVES with an open circuit (n = 38). The primary efficacy measure was change from baseline in post-void residual urine volume (PVR) after 4 weeks of treatment. Secondary efficacy measures included changes in maximum urinary flow rate (Qmax ), bladder voiding efficiency (BVE), number of 24-h clean intermittent catheterization (CIC) procedures, and Patient Perception of Bladder Condition-Scale (PPBC-S) and American Urological Association Symptom Index Quality of Life (AUA-SI-QoL) scores from baseline after 4 weeks of treatment. Adverse events (AEs) were monitored throughout the trial. RESULTS: In the full analysis set (FAS), the mean (sd) PVR changes in the trial and control groups at 4 weeks were -97.1 (107.5) mL and -10.5 (86.7) mL, respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -102.9 (100.0) mL vs 0.7 (82.5) mL (P < 0.01). In the FAS and PPS, Qmax improved significantly at 4 weeks (P = 0.04 and P = 0.03). In the FAS and PPS, BVE was significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas no significant differences in the number of 24-h CIC procedures, PPBC-S score or AUA-SI-QoL score were observed between the groups. Six possible therapy-related AEs occurred in six patients (four in the trial group and two in the control group; P = 0.67), all of which were urinary tract infections. No severe AEs were reported. CONCLUSIONS: The results of this clinical study strongly demonstrate that UAB patients benefit from this novel IVES device. More research is needed to validate the clinical utility of this device.

14.
Mikrochim Acta ; 189(8): 293, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35881205

RESUMO

CuO nanorods bearing Au nanoparticles (Au/CuO nanocomposites) were prepared by a solution-phase synthesis and exhibited efficient hydroquinone (HQ)-oxidase activity with good specificity. The Au/CuO nanocomposites effectively catalyzed the oxidation of colorless HQ to brown benzoquinone with an absorbance maximum at 376 nm but did not catalyze the conversions of catechol or resorcinol. Kinetic studies indicated that the Au/CuO nanocomposites exhibited a strong affinity for HQ, with a Michaelis-Menten constant of Km = 0.33 mM. Owing to the high catalytic activity and specificity, a strong color was observed at low concentrations of HQ. Quantitative measurement of HQ was performed via colorimetric analysis, which yielded a detection limit of 3 µM with a linear range of 5-200 µM. This colorimetric sensor was successfully applied to an HQ assay of real water samples with satisfactory results.


Assuntos
Nanopartículas Metálicas , Nanocompostos , Colorimetria/métodos , Cobre , Ouro , Hidroquinonas , Cinética
15.
Proc Natl Acad Sci U S A ; 119(29): e2201747119, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858353

RESUMO

Bacteria have evolved multiple signal transduction systems that permit an adaptation to changing environmental conditions. Chemoreceptor-based signaling cascades are very abundant in bacteria and are among the most complex signaling systems. Currently, our knowledge on the molecular features that determine signal recognition at chemoreceptors is limited. Chemoreceptor McpA of Bacillus velezensis SQR9 has been shown to mediate chemotaxis to a broad range of different ligands. Here we show that its ligand binding domain binds directly 13 chemoattractants. We provide support that organic acids and amino acids bind to the membrane-distal and membrane-proximal module of the dCache domain, respectively, whereas binding of sugars/sugar alcohols occurred at both modules. Structural biology studies combined with site-directed mutagenesis experiments have permitted to identify 10 amino acid residues that play key roles in the recognition of multiple ligands. Residues in membrane-distal and membrane-proximal regions were central for sensing organic acids and amimo acids, respectively, whereas all residues participated in sugars/sugar alcohol sensing. Most characterized chemoreceptors possess a narrow and well-defined ligand spectrum. We propose here a sensing mechanism involving both dCache modules that allows the integration of very diverse signals by a single chemoreceptor.


Assuntos
Bacillus , Proteínas de Bactérias , Quimiotaxia , Proteínas Quimiotáticas Aceptoras de Metil , Bacillus/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Ligantes , Proteínas Quimiotáticas Aceptoras de Metil/química , Proteínas Quimiotáticas Aceptoras de Metil/metabolismo , Ligação Proteica , Domínios Proteicos , Açúcares/química
16.
Front Endocrinol (Lausanne) ; 13: 891922, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663306

RESUMO

Graves' ophthalmopathy (GO) is a common orbital disease that threatens visual function and appearance. Orbital fibroblasts (OFs) are considered key target and effector cells in GO. In addition, hyaluronan (HA) production, inflammation, and orbital fibrosis are intimately linked to the pathogenesis of GO. In this study, we explored the therapeutic effects of dihydroartemisinin (DHA), an antimalarial drug, on GO-derived, primary OFs. CCK8 and EdU assays were applied to evaluate the antiproliferative effect of DHA on OFs. Wound healing assays were conducted to assess OF migration capacity, while qRT-PCR, western blotting, ELISA, and immunofluorescence were used to determine the expression of fibrosis-related and pro-inflammatory markers in these cells. Moreover, RNA sequencing was conducted to identify differentially expressed genes (DEGs) in DHA-treated OFs, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was performed to explore potential mechanisms mediating the antifibrotic effect of DHA on GO-derived OFs. Results showed that DHA dose-dependently inhibited OF proliferation and downregulated, at the mRNA and protein levels, TGF-ß1-induced expression of fibrosis markers, including alpha smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF). Furthermore, DHA inhibited TGF-ß1 induced phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3), which suggested that DHA exerted antifibrotic effects via suppression of the ERK and STAT3 signaling pathways. In addition, DHA suppressed the expression of pro-inflammatory cytokines and chemokines, including IL-6, IL-8, CXCL-1, MCP-1, and ICAM-1, and attenuated HA production induced by IL-1ß in GO-derived OFs. In conclusion, our study provides first-time evidence that DHA may significantly alleviate pathogenic manifestations of GO by inhibiting proliferation, fibrosis- and inflammation-related gene expression, and HA production in OFs. These data suggest that DHA may be a promising candidate drug for treatment of GO.


Assuntos
Oftalmopatia de Graves , Fator de Crescimento Transformador beta1 , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Artemisininas , Células Cultivadas , Fibroblastos/metabolismo , Fibrose , Oftalmopatia de Graves/metabolismo , Humanos , Ácido Hialurônico , Inflamação/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia
17.
Front Med (Lausanne) ; 9: 746064, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646944

RESUMO

Purpose: The purpose of this study was to evaluate the efficacy and safety of low power micro radiofrequency (RF) therapy (µRFthera®) through urethra in the treatment of overactive bladders (OAB) through a prospective, single-blind, placebo-controlled, multi-center clinical protocol. Materials and Methods: One hundred and fourteen patients with refractory OAB were randomized at 2:1 ratio, treatment to control undergoing same procedures except only the micro-RF treatment group at turned "on" setting in energy. Bladder diaries recorded during the screening period (3 days before enrollment) and during follow-up period on week 1, 3, and 7, respectively. The patients in control could choose receiving an energized treatment during extension stage. Results: The treatment efficacy was 76.1%. There was 49.80% rate improvement compared to control (95%CL 32.48%, 67.13%). The crude rate ration (RR) was 2.89, 95% CI (1.67-5.01) with p < 0.001 in uni-variate analysis, while the RR became 2.94, 95% CI (1.67-5.16) with p < 0.001 after adjusted potential confounding factors in multi-variate analysis. Statistically significant improvements have been demonstrated in the frequency of urination, urgency, nocturia, and quality of life (QoL) scores. Conclusions: Micro RF therapy is safe and effective for the treatment of OAB. The main treatment-related complications were catheterization related complications. Clinical Trial Registration: Zhejiang Device Registration Certificate No. 202090909, www.chictr.org.cn, Clinical Trial Accession Number: ChiCTR2100050096.

18.
Comput Biol Med ; 145: 105519, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35585734

RESUMO

In recent years, with the rapid development of machine learning, automatic emotion recognition based on electroencephalogram (EEG) signals has received increasing attention. However, owing to the great variance of EEG signals sampled from different subjects, EEG-based emotion recognition experiences the individual difference problem across subjects, which significantly hinders recognition performance. In this study, we presented a method for EEG-based emotion recognition using a combination of a multi-scale residual network (MSRN) and meta-transfer learning (MTL) strategy. The MSRN was used to represent connectivity features of EEG signals in a multi-scale manner, which utilized different receptive fields of convolution neural networks to capture the interactions of different brain regions. The MTL strategy fully used the merits of meta-learning and transfer learning to significantly reduce the gap in individual differences between various subjects. The proposed method can not only further explore the relationship between connectivity features and emotional states but also alleviate the problem of individual differences across subjects. The average cross-subject accuracies of the proposed method were 71.29% and 71.92% for the valence and arousal tasks on the DEAP dataset, respectively. It achieved an accuracy of 87.05% for the binary classification task on the SEED dataset. The results show that the framework has a positive effect on the cross-subject EEG emotion recognition task.


Assuntos
Nível de Alerta , Eletroencefalografia , Emoções , Humanos , Aprendizado de Máquina , Redes Neurais de Computação
19.
Eur Urol Focus ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35525837

RESUMO

BACKGROUND: A novel sacral neuromodulation system (SacralStim) which has an electrode with six contact points was recently designed. OBJECTIVE: To evaluate the effectiveness and safety of the SacralStim system for treating patients with refractory overactive bladder (OAB). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, randomized, single-blind clinical trial. Patients with refractory OAB were enrolled from January 2018 to May 2020. INTERVENTION: Participants were randomly allocated to the treatment group (SNM on) or the control group (SNM off) for a single-blind period of 12 ± 2 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the percentage of patients with a reduction in the average number of voids/24 h of at least 50% at the 12-wk follow-up visit. Other follow-up evaluations, including voiding diary outcomes, questionnaires on Overactive Bladder Symptom Score (OABSS), quality of life (QoL), device satisfaction, and causes of adverse events (AEs), were performed over the first 48 wk after implantation. RESULTS AND LIMITATIONS: The therapeutic success rate at 12 wk was 56.76% in the treatment group and 11.11% in the control group (p < 0.001). There were significant differences in voiding diary variables between the two groups, including changes in the average number of voids/24 h, micturition volume/void, and improvement in the urge incontinence ratio. No severe AEs occurred. A limitation is the sham stimulation used as a control in the study. A head-to-head study is required to make a direct comparison of devices with six and four contact points. CONCLUSIONS: This clinical trial provides strong evidence that patients with refractory OAB benefit from the novel SacralStim system. More research is required for direct comparison of the SacralStim system with traditional four-contact-point devices. PATIENT SUMMARY: This study confirms the effectiveness and safety of a novel SacralStim system that stimulates the sacral nerve for treatment of overactive bladder. The system has an electrode with six contact points and can provide more programming options after implantation.

20.
Technol Health Care ; 30(5): 1107-1116, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35599518

RESUMO

BACKGROUND: Automatic identification of proper image frames at the end-diastolic (ED) and end-systolic (ES) frames during the review of invasive coronary angiograms (ICA) is important to assess blood flow during a cardiac cycle, reconstruct the 3D arterial anatomy from bi-planar views, and generate the complementary fusion map with myocardial images. The current identification method primarily relies on visual interpretation, making it not only time-consuming but also less reproducible. OBJECITVE: In this paper, we propose a new method to automatically identify angiographic image frames associated with the ED and ES cardiac phases. METHOD: A detection algorithm is first used to detect the key points (i.e. landmarks) of coronary arteries, and then an optical flow method is employed to track the trajectories of the selected key points. The ED and ES frames are identified based on all these trajectories. Our method was tested with 62 ICA videos from two separate medical centers. RESULTS: Comparing consensus interpretations by two human expert readers, excellent agreement was achieved by the proposed algorithm: the agreement rates within a one-frame range were 92.99% and 92.73% for the automatic identification of the ED and ES image frames, respectively. CONCLUSION: The proposed automated method showed great potential for being an integral part of automated ICA image analysis.


Assuntos
Coração , Processamento de Imagem Assistida por Computador , Algoritmos , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Diástole , Coração/fisiologia , Humanos , Processamento de Imagem Assistida por Computador/métodos
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