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1.
J Voice ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38350807

RESUMO

OBJECTIVE: This study aimed to compare the damage of vocal folds caused by four different surgical instruments: CO2 laser, electrosurgical knife, plasma radiofrequency ablation, and steel knife. STUDY DESIGN: Randomized controlled study. METHODS: The CO2 laser, electrosurgical knife, plasma radiofrequency ablation, steel knife, and other instruments were used to simulate the laryngeal microsurgery on experimental dogs. Both total vocal fold resection and punctate ablation were performed. On the day of surgery and 6 days later, the vocal fold tissue from the surgical site was removed for histological evaluation. The extent of vocal fold damage was assessed using the automatic digital pathological scanning system. RESULTS: We detected varying degrees of damage to the laryngeal tissues. Only the steel knife caused epidermal defects on the vocal fold tissue, while other instruments produced thermal damage of different degrees. Furthermore, the steel knife also showed better and faster healing. The plasma radiofrequency ablation was found to cause more severe thermal burns to vocal folds than other surgical instruments (P < 0.05). Six days postsurgery the inflammatory reaction from the steel knife had basically subsided, with only hyperplasia and tissue repair visible microscopically, showing the best healing degree. On the other hand, the radiofrequency ablation group showed the heaviest inflammatory reaction, indicating relatively poor prognosis (P < 0.05). CONCLUSION: Compared with the CO2 laser, the electrotome and steel knife showed less damage and better healing, while the plasma radiofrequency ablation showed the most obvious thermal burns to laryngeal and vocal tissues during surgery, with relatively poor healing.

2.
BMC Infect Dis ; 24(1): 145, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291356

RESUMO

BACKGROUND: Niemann-Pick Disease type C is a fatal autosomal recessive lipid storage disorder caused by NPC1 or NPC2 gene mutations and characterized by progressive, disabling neurological deterioration and hepatosplenomegaly. Herein, we identified a novel compound heterozygous mutations of the NPC1 gene in a Chinese pedigree. CASE PRESENTATION: This paper describes an 11-year-old boy with aggravated walking instability and slurring of speech who presented as Niemann-Pick Disease type C. He had the maternally inherited c.3452 C > T (p. Ala1151Val) mutation and the paternally inherited c.3557G > A (p. Arg1186His) mutation using next-generation sequencing. The c.3452 C > T (p. Ala1151Val) mutation has not previously been reported. CONCLUSIONS: This study predicted that the c.3452 C > T (p. Ala1151Val) mutation is pathogenic. This data enriches the NPC1 gene variation spectrum and provides a basis for familial genetic counseling and prenatal diagnosis.


Assuntos
Doença de Niemann-Pick Tipo C , Criança , Humanos , Masculino , Proteínas de Transporte/genética , Mutação , Proteína C1 de Niemann-Pick/genética , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/genética , Diagnóstico Pré-Natal
3.
Expert Opin Drug Saf ; 23(3): 297-303, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37608560

RESUMO

BACKGROUND: Migraine has a high prevalence in the population and accounts for 12% of primary headaches. Ubrogepant is used for the treatment of acute migraine, and although some clinical trials have demonstrated the safety of Ubrogepant, its long-term safety in a large sample of the population remains to be investigated. METHODS: We collected data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC) and the empirical Bayes geometric mean (EBGM) to evaluate Ubrogepant-induced adverse events (AEs). RESULTS: We screened out 2,067 reports of Ubrogepant as primary suspected (PS) and 6,190 reports of Ubrogepant-induced AEs as PS. Our results showed that Ubrogepant-induced AEs targeted 4 system organ classes (SOCs), detected 32 Preferred terms (PTs) signals in 9 SOCs, including common Ubrogepant label consistent with Migraine, Nausea, Somnolence, Paraesthesia oral and Dizziness, It also includes the AEs of Hemiparesis, Mental impairment, Dysstasia, Tinnitus, Chest pain, Cold sweat, Neck pain, etc. that have not been demonstrated in previous studies. CONCLUSIONS: Our study identified new AEs that have not been reported, which provides a new guidance to deepen the comprehension of the safety of Ubrogepant.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Transtornos de Enxaqueca , Estados Unidos/epidemiologia , Humanos , Teorema de Bayes , Piridinas/efeitos adversos , Pirróis/efeitos adversos , Transtornos de Enxaqueca/tratamento farmacológico , United States Food and Drug Administration , Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Farmacovigilância
4.
Nano Res ; 16(2): 2968-2979, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36090613

RESUMO

Metal-organic frameworks (MOFs) have attracted widespread interest due to their unique and unprecedented advantages in microstructures and properties. Besides, surface-enhanced Raman scattering (SERS) technology has also rapidly developed into a powerful fingerprint spectroscopic technique that can provide rapid, non-invasive, non-destructive, and ultra-sensitive detection, even down to single molecular level. Consequently, a considerable amount of researchers combined MOFs with the SERS technique to further improve the sensing performance and broaden the applications of SERS substrates. Herein, representative synthesis strategies of MOFs to fabricate SERS-active substrates are summarized and their applications in ultra-sensitive biomedical trace detection are also reviewed. Besides, relative barriers, advantages, disadvantages, future trends, and prospects are particularly discussed to give guidance to relevant researchers.

5.
Opt Express ; 31(26): 43698-43711, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38178460

RESUMO

We propose a neuromorphic convolution system using a photonic integrated distributed feedback laser with a saturable absorber (DFB-SA) as a photonic spiking neuron. The experiments reveal that the DFB-SA laser can encode different stimulus intensities at different frequencies, similar to biological neurons. Based on this property, optical inputs are encoded into rectangular pulses of varying intensities and injected into the DFB-SA laser, enabling the convolution results to be represented by the firing rate of the photonic spiking neuron. Both experimental and numerical results show that the binary convolution is successfully achieved based on the rate-encoding properties of a single DFB-SA laser neuron. Furthermore, we numerically predict 4-channel quadratic convolution and accomplish MNIST handwritten digit classification using a spiking DFB-SA laser neuron model with rate coding. This work provides a novel approach for convolution computation, indicating the potential of integrating DFB-SA laser into future photonics spiking neural networks.

6.
Appl Microbiol Biotechnol ; 106(23): 7779-7791, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36350403

RESUMO

Ganoderma sinense, with more than 2000 years of medicinal history, is a fungus of the basidiomycetes that is rich in polysaccharides and terpenoids. However, the biosynthesis of terpenes, especially sesquiterpenes, has been little studied. The functional identification of sesquiterpene synthases from G. sinense is of great significance to the study of fungal terpenoid biosynthesis and regulation. Our research group has completed the functional characterization of 21 sesquiterpene synthase genes from G. sinense. It was found that gleenol, biosynthesis of which is catalyzed by the sesquiterpene synthase GsSTS26 and GsSTS27, has the functions of killing termites, antihelminth, and plant growth regulation. In the unmodified E. coli Rosetta (DE3) strain, the content of gleenol produced by sesquiterpene synthase from G. sinense is low, which makes it difficult to meet the demand of industrial production and the market. Therefore, it is of great significance to obtain high-yielding strains by means of synthetic biology. In this study, we constructed eight recombinant strains by using tandem gene expression and promoter engineering, and the content of gleenol was increased by up to 23-fold. In this study, we realized the de novo synthesis of gleenol in E. coli and provided a basis for the biosynthesis of terpenoids in basidiomycetes. KEY POINTS: • Eight recombinant expression systems were constructed by using tandem genes and promoter engineering. • The recombinant strain promoted the efficient production of gleenol in E. coli Rosetta (DE3). • The recombinant strain achieved de novo production of gleenol in E. coli.


Assuntos
Alquil e Aril Transferases , Sesquiterpenos , Escherichia coli/genética , Escherichia coli/metabolismo , Sesquiterpenos/metabolismo , Terpenos/metabolismo , Alquil e Aril Transferases/metabolismo
7.
J Breath Res ; 17(1)2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36347037

RESUMO

The spread of coronavirus disease 2019 (COVID-19) results in an increasing incidence and mortality. The typical diagnosis technique for severe acute respiratory syndrome coronavirus 2 infection is reverse transcription polymerase chain reaction, which is relatively expensive, time-consuming, professional, and suffered from false-negative results. A reliable, non-invasive diagnosis method is in urgent need for the rapid screening of COVID-19 patients and controlling the epidemic. Here we constructed an intelligent system based on the volatile organic compound (VOC) biomarkers in human breath combined with machine learning models. The VOC profiles of 122 breath samples (65 of COVID-19 infections and 57 of controls) were identified with a portable gas chromatograph-mass spectrometer. Among them, eight VOCs exhibited significant differences (p< 0.001) between the COVID-19 and the control groups. The cross-validation algorithm optimized support vector machine (SVM) model was employed for the prediction of COVID-19 infection. The proposed SVM model performed a powerful capability in discriminating COVID-19 patients from healthy controls, with an accuracy of 97.3%, a sensitivity of 100%, a specificity of 94.1%, and a precision of 95.2%, and anF1 score of 97.6%. The SVM model was also compared with other common machine models, including artificial neural network,k-nearest neighbor, and logistic regression, and demonstrated obvious superiority in the prediction of COVID-19 infection. Furthermore, user-friendly software was developed based on the optimized SVM model. The developed intelligent platform based on breath analysis provides a new strategy for the point-of-care screening of COVID and shows great potential in clinical application.


Assuntos
COVID-19 , Compostos Orgânicos Voláteis , Humanos , Testes Respiratórios/métodos , Compostos Orgânicos Voláteis/análise , Máquina de Vetores de Suporte , Biomarcadores/análise
8.
Gland Surg ; 11(9): 1538-1545, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36221278

RESUMO

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, but locally aggressive breast disease. Steroids are widely used as a breast-conserving option, however, the response rate of steroids varies in reported studies, as well as its different reported usage. This prospective observational cohort study aimed to report the outcomes of methylprednisolone for IGM treatment. Methods: From Aug 2019 to Dec 2021, the clinicopathological information of 156 IGM patients who sought treatment at West China Hospital was prospectively collected. A total of 88 patients treated with methylprednisolone were included in the study. The clinical features, treatment response, and follow-up data were analyzed. Results: The median age at diagnosis was 32 years, and 90.9% of patients were multipara. The predominant symptom at presentation was painful breast mass, with a median size of 4.7 cm. For steroid usage, an initial 20 mg methylprednisolone daily was given until disease stable. The median duration of 20 mg methylprednisolone treatment was 45 (range, 14-376) days. The median duration of whole steroid therapy was 105 (range, 28-381) days. A total of 80.7% of patients (71/88) responded well to steroid treatment. In 63 patients, steroid treatment was successfully withdrawn, and treatment was completed. With an average of 283 days follow-up (range, 0-770 days), relapse was observed in 21 (33.33%) patients. Compared with patients with residual disease as shown by physical examination (PE), those with complete clinical remission (CCR) at the end of treatment had longer relapse-free intervals. Conclusions: Steroids are the preferable breast-conserving option for IGM. Treatment with 20 mg methylprednisolone for an average of 1.5 months is usually required, and full steroid treatment might last for 3 months.

9.
Mater Today Bio ; 16: 100426, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36133795

RESUMO

Restoring skin integrity after wound infection remains a tougher health challenge due to the uncontrolled antibiotic-resistant pathogens caused by antibiotic abuse. Herein, an injectable hydrogel with dual antibacterial and anti-inflammatory activities composed of gold nanoclusters (GNCs) and carbomer (CBM) is developed for wound dressing to overcome multidrug-resistant infection. Firstly, both experimental investigations and molecular dynamics simulation validate the protonation state of 6-mercaptohexanoic acid (MHA) ligands play an important role in its antibacterial action of GNCs. The self-organizing GNCs-CBM composite hydrogel is then spontaneously cross-linked by the dimeric hydrogen bonds (H-bonds) between the MHA ligands and the acrylic acid groups of CBM. Benefitting from the dimeric H-bonds, the hydrogel becomes thickening enough as an ideal wound dressing and the GNCs exist in the hydrogel with a high protonation level that contributes to the enhanced bactericidal function. In all, by combining bactericidal and immunomodulatory actions, the GNCs-CBM hydrogel demonstrated excellent synergy in accelerating wound healing in animal infection models. Hence, the dimeric H-bonds strengthening strategy makes the GNCs-CBM hydrogel hold great potential as a safe and effective dressing for treating infected wounds.

10.
Acta Otolaryngol ; 142(7-8): 590-609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36018303

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon in most areas of the world but poses a significant public health burden in endemic regions. OBJECTIVES: We provide an overview of the most recent global epidemiology of nasopharyngeal cancer (NPC). METHODS: We estimated the burden of NPC in 204 countries and territories by age, sex, and Socio-Demographic Index (SDI) from 1990 to 2019. RESULTS: At the GBD regional level, the most severe age-standardized incidence in 2019 occurred in East Asia. From 1990 to 2019, the East Asia and High-income Asia Pacific had the greatest increase in percentage in age-standardized incidence. Central Asia and the Caribbean had the greatest increase in percentage in age-standardized disability-adjusted life-years (DALY) and death rates. At the national level, Cabo Verde, Romania, and the Cyprus reported the largest percentage increases in the age-standardized incidence. Cabo Verde, Romania, and Jamaica reported the largest increases in the age-standardized DALY and death rates. CONCLUSIONS: The global age-standardized incidence of NPC increased globally between 1990 and 2019, especially in the East Asia.


Assuntos
Carga Global da Doença , Neoplasias Nasofaríngeas , Saúde Global , Humanos , Incidência , Carcinoma Nasofaríngeo/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco
11.
ACS Sens ; 7(5): 1581-1592, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35536008

RESUMO

Gas sensor-embedded smartphones would offer the opportunity of on-site tracking of gas molecules for various applications, for example, harmful air pollutant alarms or noninvasive assessment of health status. Nevertheless, high power consumption and difficulty in replacing malfunctioned sensors as well as limited space in the smartphone to host the sensor restrain the relevant advancements. In this article, we create a smartphone case-based sensing platform by integrating the functional units into a smartphone case, which performs a low detection limit of 117 ppb to acetone and high specificity. Particularly, dimming glass-regulated light fidelity (Li-Fi) communication is successfully developed, allowing the sensing platform to operate with relatively low power consumption (around 217 mW). Experimental proof on harmful gas sensing and potential clinic application is implemented with the sensing platform, demonstrating satisfactory sensing performance and acceptable health risk pre-warning accuracy (87%). Thus, the developed smartphone case-based sensing platform would be a good candidate for realizing harmful gas alarms and noninvasive assessment of health status.


Assuntos
Acetona , Smartphone
12.
Sci Rep ; 12(1): 6625, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459923

RESUMO

Alzheimer's disease (AD) is the most common cause of progressive dementia. In the present study, we showed hippocampal tissue transcriptome analysis in APPswe/PSEN1dE9 (APP/PS1, AD model) mice treated with fasudil (ADF) and compared with AD mice treated with saline (ADNS) and wild type mice (WT). The competing endogenous RNA (ceRNA) network was constructed and validated the differential expression of mRNA, lncRNA, miRNA, and circRNA. Our study showed differentially expressed mRNAs (DEMs) between WT and ADNS, while enriched in cell growth and death and nervous system pathways. DEMs between ADNS-ADF were enriched in the nervous system, glycosaminoglycan biosynthesis-keratan sulfate (KS) and Quorum sensing pathways. We validated four genes with RT-PCR, whereas enrichment of Acyl-CoA Synthetase Long Chain Family Member 4 (Acsl4, ENSMUST00000112903) in Quorum sensing pathways, and BTG anti-proliferation factor 1 (Btg1, ENSMUST00000038377) in RNA degradation pathways were conducted. Expression of these two genes were higher in ADNS, but were significantly reduced in ADF. Histone H4 transcription factor (Hinfp, ENSMUST00000216508) orchestrate G1/S transition of mitotic cell cycle and co-expressed with mmu-miR-26a-2-3p-mediated ceRNA and mmu-miR-3065-5p-mediated ceRNA; Wnt family member 4 (Wnt4, ENSMUST00000045747) was enriched in mTOR, Hippo and Wnt signaling pathway. Expression of these two genes were significantly lower in ADNS, and fasudil treatment reverse it. The present studies demonstrated four genes: Acsl4, Btg1, Hinfp, Wnt4 could be potential biomarkers of AD and the targets of fasudil treatment. These results will pave a novel direction for future clinic studies for AD and fasudil treatment.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina , Doença de Alzheimer , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Longo não Codificante/genética , Transcriptoma
13.
ACS Omega ; 7(8): 7229-7239, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35252713

RESUMO

Enzymes boost protein engineering, directed evolution, and the biochemical industry and are also the cornerstone of metabolic engineering. Basidiomycetes are known to produce a large variety of terpenoids with unique structures. However, basidiomycetous terpene synthases remain largely untapped. Therefore, we provide a modeling method to obtain specific terpene synthases. Aided by bioinformatics analysis, three γ-cadinene enzymes from Ganoderma lucidum and Ganoderma sinensis were accurately predicted and identified experimentally. Based on the highly conserved amino motifs of the characterized γ-cadinene enzymes, the enzyme was reassembled as model 1. Using this model as a template, 67 homologous sequences of the γ-cadinene enzyme were screened from the National Center for Biotechnology Information (NCBI). According to the 67 sequences, the same gene structure, and similar conserved motifs to model 1, the γ-cadinene enzyme model was further improved by the same construction method and renamed as model 2. The results of bioinformatics analysis show that the conservative regions of models 1 and 2 are highly similar. In addition, five of these sequences were verified, 100% of which were γ-cadinene enzymes. The accuracy of the prediction ability of the γ-cadinene enzyme model was proven. In the same way, we also reanalyzed the identified Δ6-protoilludene enzymes in fungi and (-)-α-bisabolol enzymes in plants, all of which have their own unique conserved motifs. Our research method is expected to be used to study other terpenoid synthases with a similar or the same function in basidiomycetes, ascomycetes, bacteria, and plants and to provide rich enzyme resources.

14.
J Hazard Mater ; 424(Pt C): 127686, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34775316

RESUMO

Probing water-soluble organic compounds via Surface-enhanced Raman scattering (SERS) technique could be helpful to prevent harmful impacts of polluted water. A key limitation of restraining SERS technique in probing these pollutants is the difficulty to control the spacing distance of plasmonic nanoparticles within 10 nm so that SERS effect can be efficiently induced. Herein, a strategy of mass-producing Ag-based SERS active material with tunable spacing distance is reported. In brevity, metal-organic framework (MOF) engineered corn-like Ag@Carbon is synthesized by simply thermal treating Ag-MOF. The thermal treatment in-situ turns Ag+ into Ag nanoparticles (NPs), resulting in Ag NPs well-dispersed on the surface of the carbonized MOF and forming ordered SERS hotspots. Due to the spatial distance of Ag+ directly depends on the molecular diameter of MOF organic ligands, spacing distance of Ag NP is fixed at around 7 nm. Theoretical analysis and experimental study confirm that the uniformly distributed Ag NPs lead to desirable SERS activity. Further study evidences the presented corn-like Ag@Carbon could be a good candidate for tacking organic compounds with satisfactory sensitivity, specificity and low detection limit (10-8 M). Conclusively, these impressive results indicate a bright future of adopting the proposed strategy to design future SERS active materials.


Assuntos
Nanopartículas Metálicas , Estruturas Metalorgânicas , Carbono , Prata , Análise Espectral Raman , Zea mays
15.
Eur J Cancer Prev ; 31(1): 54-63, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34871199

RESUMO

Inflammatory bowel disease (IBD) has been found to be correlated to increased risk of both gastrointestinal and extraintestinal malignancies. It still remains conflicting whether IBD has influence on risk of breast cancer, requesting further investigations. A systematic literature research before June 2020 was conducted in PubMed and Web of Science databases. Observational studies reporting incident breast cancer after IBD diagnosis and providing measures of association were included in the meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the associations between IBD and risk of breast cancer. Our analysis included 16 cohort studies and the overall pooled OR in patients with IBD was 0.94 (95% CI, 0.82-1.06). In further subgroup analysis, no significant association with breast cancer risk among patients with Crohn's disease (OR, 0.91; 95% CI, 0.70-1.12) and ulcerative colitis (OR, 0.99; 95% CI, 0.90-1.08). For geographic differences, the summary OR of populations in Asia (OR, 1.01; 95% CI, 0.73-1.30) was only numerically larger than that in European populations (OR, 0.90; 95% CI, 0.75-1.06). Our findings indicated that IBD had no significant influence on breast cancer risk regardless of different IBD types and geographical areas.


Assuntos
Neoplasias da Mama , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Doença Crônica , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Doença de Crohn/complicações , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Fatores de Risco
16.
Front Aging Neurosci ; 13: 755164, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721000

RESUMO

Background: Fasudil, a Rho kinase inhibitor, exerts therapeutic effects in a mouse model of Alzheimer's disease (AD), a chronic neurodegenerative disease with progressive loss of memory. However, the mechanisms remain unclear. In addition, the gut microbiota and its metabolites have been implicated in AD. Methods: We examined the effect of fasudil on learning and memory using the Morris water-maze (MWM) test in APPswe/PSEN1dE9 transgenic (APP/PS1) mice (8 months old) treated (i.p.) with fasudil (25 mg/kg/day; ADF) or saline (ADNS) and in age- and gender-matched wild-type (WT) mice. Fecal metagenomics and metabolites were performed to identify novel biomarkers of AD and elucidate the mechanisms of fasudil induced beneficial effects in AD mice. Results: The MWM test showed significant improvement of spatial memory in APP/PS1 mice treated with fasudil as compared to ADNS. The metagenomic analysis revealed the abundance of the dominant phyla in all the three groups, including Bacteroidetes (23.7-44%) and Firmicutes (6.4-26.6%), and the increased relative abundance ratio of Firmicutes/Bacteroidetes in ADNS (59.1%) compared to WT (31.7%). In contrast, the Firmicutes/Bacteroidetes ratio was decreased to the WT level in ADF (32.8%). Lefse analysis of metagenomics identified s_Prevotella_sp_CAG873 as an ADF potential biomarker, while s_Helicobacter_typhlonius and s_Helicobacter_sp_MIT_03-1616 as ADNS potential biomarkers. Metabolite analysis revealed the increment of various metabolites, including glutamate, hypoxanthine, thymine, hexanoyl-CoA, and leukotriene, which were relative to ADNS or ADF microbiota potential biomarkers and mainly involved in the metabolism of nucleotide, lipids and sugars, and the inflammatory pathway. Conclusions: Memory deficit in APP/PS1 mice was correlated with the gut microbiome and metabolite status. Fasudil reversed the abnormal gut microbiota and subsequently regulated the related metabolisms to normal in the AD mice. It is believed that fasudil can be a novel strategy for the treatment of AD via remodeling of the gut microbiota and metabolites. The novel results also provide valuable references for the use of gut microbiota and metabolites as diagnostic biomarkers and/or therapeutic targets in clinical studies of AD.

17.
AMB Express ; 11(1): 150, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779947

RESUMO

Basidiomycetes, also known as club fungi, consist of a specific group of fungi. Basidiomycetes produce a large number of secondary metabolites, of which sesquiterpenoids, diterpenoids and triterpenoids are the primary components. However, these terpenoids tend to be present in low amounts, which makes it difficult to meet application requirements. Terpenoid biosynthesis improves the quantity of these secondary metabolites. However, current understanding of the biosynthetic mechanism of terpenoids in basidiomycetes is insufficient. Therefore, this article reviews the latest research on the biosynthesis of terpenoids in basidiomycetes and summarizes the CYP450 involved in the biosynthesis of terpenoids in basidiomycetes. We also propose opportunities and challenges for chassis microbial heterologous production of terpenoids in basidiomycetes and provide a reference basis for the better development of basidiomycete engineering.

18.
Org Biomol Chem ; 19(42): 9138-9147, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34622268

RESUMO

Tetracyclic norditerpene dilactones are an important class of terpenoids that have been isolated from both terrestrial and marine sources, typically from Podocarpus plants and from filamentous fungi. This class of molecules shares a common 6/6/6/5 tetracyclic ring skeleton, which possesses a densely oxygenated carbon framework and contiguous stereocenters. What's more challenging for synthetic chemists are the consecutive sp2-hybridized carbon centers, which exacerbates the strain/rigidity of the whole molecule. In addition, many of these molecules display promising biological activities, such as antitumor, insecticidal, anti-feedant, allelopathic, and antibiotic activities. The unique structures and interesting biological profiles of norditerpene dilactones have attracted considerable attention from synthetic chemists. Herein we summarize the synthetic efforts with respect to tetranorditerpene dilactones.


Assuntos
Diterpenos
20.
J Hazard Mater ; 398: 122973, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32492618

RESUMO

Food wastes are significant reservoir of antibiotic-resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) available for exchange with clinical pathogens. However, food wastes-related changes of antibiotic resistance in long-period decomposition have been overlooked. Here, we evaluated the comprehensive ARG profile and its association with microbial communities, explained how this might vary with household garbage decomposition. Average of 128, 150 and 91 ARGs were detected in meat, vegetable and fruit wastes, respectively, with multidrug and tetracycline as the predominant ARG types. ARG abundance significantly increased at initial stage of waste fermentation and then decreased. High abundance of Eubacterium-coprostanoligenes, Sporanaerobacter, Peptoniphilus, Peptostreptococcus might be explained for the high relative abundance of ARGs in meat, while high abundance of Advenella, Prevotella, Solobacterium was attributed to the high diversity of ARGs in vegetables. Significant correlations were observed among volatile organic compounds, mobile genetic elements and ARGs, implying that they might contribute to transfer and transport of ARGs. Network analysis revealed that aph(2')-Id-01, acrA-05, tetO-1 were potential ARG indicators, while Hathewaya, Paraclostridium and Prevotellaceae were possible hosts of ARGs. Our work might unveil underlining mechanism of the effects of food wastes decomposition on development and spread of ARGs in environment and also clues to ARG mitigation.


Assuntos
Antibacterianos , Genes Bacterianos , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Bactérias/genética , Resistência Microbiana a Medicamentos/genética
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