Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 170
Filtrar
1.
ACS Appl Mater Interfaces ; 16(12): 15605-15616, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38477104

RESUMO

Improving the quality of the buried interface is decisive for achieving stable and high-efficiency perovskite solar cells. Herein, we report the interface engineering by using dipolar 2,4-difluoro-3,5-dichloroaniline (DDE) as the adhesive between titanium dioxide (TiO2) and MAPbI3. By manipulation of the anchoring groups of DDE, this molecule not only passivated defects of TiO2 but also optimized the energy level alignment. Furthermore, the perovskite film on the modified TiO2 surface showed improved crystallinity, released residual stress, and reduced trap states. Therefore, these benefits directly contribute to achieving a power conversion efficiency of up to 22.10%. The unencapsulated device retained 90% of initial power conversion efficiencies (PCE) after continuous light illumination for 1000 h and 93% of initial PCE after exposure to air with a relative humidity of 30-40% for over 3000 h. Moreover, the performance of PSCs based on FA0.15MA0.85PbI3 has also increased from 20.48 to 23.51%. Our results demonstrate the effectiveness and universality of dipolar halogen-substituted arylamine (DDE) for enhancing PSC performance.

2.
bioRxiv ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38370825

RESUMO

The precision-recall curve (PRC) and the area under it (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluated 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in >3,000 published studies. We found the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

3.
J Pharm Biomed Anal ; 240: 115937, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38198885

RESUMO

Mirabegron and vibegron, both newly identified beta-3 adrenergic agonists, have significantly improved the quality of life for patients suffering from overactive bladder. In order to comprehensively assess the plasma exposure levels of these agents, the development of a rapid and highly sensitive bioanalytical method becomes imperative. The primary objective of this study was to establish a robust high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the concurrent quantification of mirabegron and vibegron in human plasma. The analytes were extracted from a 100 µL plasma sample through protein precipitation, employing 300 µL of methanol. Subsequently, samples underwent separation and quantification using a Waters XBridge C18 column (2.1 × 100 mm, 3.5 µm), with a mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. The mass analysis was conducted using positive electrospray ionization (ESI+) operated in a multiple reaction monitoring (MRM) mode. The proposed method was meticulously validated in accordance with the guidelines set forth by the U.S. Food and Drug Administration (FDA) for bioanalytical method validation. The regression equations demonstrated exceptional linearity for both mirabegron (r² ≥ 0.994) and vibegron (r² ≥ 0.996) across the concentration range of 0.5 - 200 ng/mL. Furthermore, the assay exhibited accuracy (inter-day relative error ≤ 6.90%) and precision (inter-day coefficient of variation ≤ 8.88%). The average recoveries of the analytes were found to range from 81.94% to 102.02%, with mean matrix effects falling within the range of 89.77% to 110.58%. As a result, this method was deemed highly suitable for the precise determination of the concentrations of both mirabegron and vibegron in the context of therapeutic drug monitoring and bioequivalence studies.


Assuntos
Acetanilidas , Formiatos , Neoplasias , Pirimidinonas , Pirrolidinas , Tiazóis , Bexiga Urinária Hiperativa , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Bexiga Urinária Hiperativa/tratamento farmacológico , 60705 , Qualidade de Vida , Reprodutibilidade dos Testes
4.
Epigenomics ; 16(2): 93-108, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38226561

RESUMO

Purpose: The performance and clinical accuracy of combined SDC2/NDRG4 methylation were evaluated in diagnosing colorectal cancer (CRC) and advanced adenoma. Methods: A total of 2333 participants were enrolled to assess the sensitivity and specificity of biomarkers in diagnosing CRC in a multicenter clinical trial through feces DNA methylation tests. Results: SDC2/NDRG4 methylation showed excellent performance for CRC detection in biomarker research and the real world. Its sensitivity for detecting CRC, early CRC and advanced adenoma were 92.06%, 91.45% and 62.61%, respectively. Its specificity was 94.29%, with a total coincidence rate of 88.28%. When interference samples were included, the specificity was still good (82.61%). Therefore, the SDC2/NDRG4 methylation test showed excellent performance in detecting CRC and advanced adenoma under clinical application.


Colorectal cancer (CRC) is one of the most malignant tumors of the digestive system and second only to breast cancer and lung cancer in terms of global incidence. Early CRCs are challenging to determine given their atypical nature. In contrast, late CRC symptoms are affected by the type, location and range of the lesion and complications. Therefore, CRC patients are generally diagnosed late, present with a high degree of malignancy, and have poor prognosis and 5-year survival rates. The current study therefore evaluated whether SDC2 and NDRG4 methylation could be used for diagnosis CRCs at an early stage and whether it has the potential to detect asymptomatic patients with adenomas. The findings presented herein will certainly help support the early diagnosis of CRC and precancerous lesions in clinical practice.


Assuntos
Adenoma , Neoplasias Colorretais , Humanos , Metilação de DNA , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Biomarcadores Tumorais/genética , Sindecana-2/genética , Sensibilidade e Especificidade , Detecção Precoce de Câncer , Adenoma/diagnóstico , Adenoma/genética , Proteínas Musculares/genética , Proteínas do Tecido Nervoso/genética
6.
J Biol Chem ; 300(2): 105531, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072051

RESUMO

Heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2) is a human ribonucleoprotein that transports RNA to designated locations for translation via its ability to phase separate. Its mutated form, D290V, is implicated in multisystem proteinopathy known to afflict two families, mainly with myopathy and Paget's disease of bone. Here, we investigate this mutant form of hnRNPA2 by determining cryo-EM structures of the recombinant D290V low complexity domain. We find that the mutant form of hnRNPA2 differs from the WT fibrils in four ways. In contrast to the WT fibrils, the PY-nuclear localization signals in the fibril cores of all three mutant polymorphs are less accessible to chaperones. Also, the mutant fibrils are more stable than WT fibrils as judged by phase separation, thermal stability, and energetic calculations. Similar to other pathogenic amyloids, the mutant fibrils are polymorphic. Thus, these structures offer evidence to explain how a D-to-V missense mutation diverts the assembly of reversible, functional amyloid-like fibrils into the assembly of pathogenic amyloid, and may shed light on analogous conversions occurring in other ribonucleoproteins that lead to neurological diseases such as amyotrophic lateral sclerosis and frontotemporal dementia.


Assuntos
Microscopia Crioeletrônica , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B , Modelos Moleculares , Humanos , Domínios Proteicos , Mutação , Concentração de Íons de Hidrogênio , Estabilidade Proteica , Estrutura Terciária de Proteína , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/química , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo
7.
Inorg Chem ; 63(1): 390-399, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38151234

RESUMO

Developing oxide ion conductors with new structural families is important for many energy conversion and storage techniques. Herein, a series of Ca-doped Yb3Ga5O12 garnet-type materials are prepared through a traditional solid-state reaction method, with their oxide ion conduction properties being reported for the first time. The results revealed that Ca substitution for Yb would significantly improve the conductivity of Yb3Ga5O12 from 3.57 × 10-7 S/cm at 900 °C under air to 1.66 × 10-4 S/cm, with an oxide ion transporting number of ∼0.52. The oxygen vacancy defect formation energy (∼0.127 eV) and the local structure around an oxygen vacancy were studied by atomic-level static lattice simulations based on the interatomic potential method. The oxide ion conducting mechanism was studied by the bond-valence-based method, which revealed three-dimensional pathways for oxide ion migration in both the parent and Ca-doped structures. The simulated activation energy of oxide ion migration decreased slightly from ∼0.358 eV in the parent structure to 0.346 eV in the doped one. These discoveries in the Ca-doped Yb3Ga5O12 will stimulate extensive exploitation and fundamental research on garnet-type materials.

8.
World J Clin Cases ; 11(33): 8003-8012, 2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38075574

RESUMO

BACKGROUND: The recovery time of hand wounds is long, which can easily result in chronic and refractory wounds, making the wounds unable to be properly repaired. The treatment cycle is long, the cost is high, and it is prone to recurrence and disability. Double layer artificial dermis combined with autologous skin transplantation has been used to repair hypertrophic scars, deep burn wounds, exposed bone and tendon wounds, and post tumor wounds. AIM: To investigate the therapeutic efficacy of autologous skin graft transplantation in conjunction with double-layer artificial dermis in treating finger skin wounds that are chronically refractory and soft tissue defects that expose bone and tendon. METHODS: Sixty-eight chronic refractory patients with finger skin and soft tissue defects accompanied by bone and tendon exposure who were admitted from July 2021 to June 2022 were included in this study. The observation group was treated with double layer artificial dermis combined with autologous skin graft transplantation (n = 49), while the control group was treated with pedicle skin flap transplantation (n = 17). The treatment status of the two groups of patients was compared, including the time between surgeries and hospital stay. The survival rate of skin grafts/flaps and postoperative wound infections were evaluated using the Vancouver Scar Scale (VSS) for scar scoring at 6 mo after surgery, as well as the sensory injury grading method and two-point resolution test to assess the recovery of skin sensation at 6 mo. The satisfaction of the two groups of patients was also compared. RESULTS: Wound healing time in the observation group was significantly longer than that in the control group (P < 0.05, 27.92 ± 3.25 d vs 19.68 ± 6.91 d); there was no significant difference in the survival rate of skin grafts/flaps between the two patient groups (P > 0.05, 95.1 ± 5.0 vs 96.3 ± 5.6). The interval between two surgeries (20.0 ± 4.3 d) and hospital stay (21.0 ± 10.1 d) in the observation group were both significantly shorter than those in the control group (27.5 ± 9.3 d) and (28.4 ± 17.7 d), respectively (P < 0.05). In comparison to postoperative infection (23.5%) and subcutaneous hematoma (11.8%) in the control group, these were considerably lower at (10.2%) and (6.1%) in the observation group. When comparing the two patient groups at six months post-surgery, the excellent and good rate of sensory recovery (91.8%) was significantly higher in the observation group than in the control group (76.5%) (P < 0.05). There was also no statistically significant difference in two point resolution (P > 0.05). The VSS score in the observation group (2.91 ± 1.36) was significantly lower than that in the control group (5.96 ± 1.51), and group satisfaction was significantly higher (P < 0.05, 90.1 ± 6.3 vs 76.3 ± 5.2). CONCLUSION: The combination of artificial dermis and autologous skin grafting for the treatment of hand tendon exposure wounds has a satisfactory therapeutic effect. It is a safe, effective, and easy to operate treatment method, which is worthy of clinical promotion.

9.
Nat Commun ; 14(1): 7503, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980359

RESUMO

Bacteria develop a variety of extracellular fibrous structures crucial for their survival, such as flagella and pili. In this study, we use cryo-EM to identify protein fibrils surrounding lab-cultured Bacillus amyloiquefaciens and discover an unreported fibril species in addition to the flagellar fibrils. These previously unknown fibrils are composed of Vpr, an extracellular serine peptidase. We find that Vpr assembles into fibrils in an enzymatically active form, potentially representing a strategy of enriching Vpr activities around bacterial cells. Vpr fibrils are also observed under other culture conditions and around other Bacillus bacteria, such as Bacillus subtilis, which may suggest a general mechanism across all Bacillus bacterial groups. Taken together, our study reveals fibrils outside the bacterial cell and sheds light on the physiological role of these extracellular fibrils.


Assuntos
Bacillus , Bacillus/metabolismo , Microscopia Crioeletrônica , Serina Endopeptidases/metabolismo , Bacillus subtilis/metabolismo , Serina/metabolismo
10.
Environ Sci Pollut Res Int ; 30(53): 113774-113789, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37851263

RESUMO

The gases evolution during the low-temperature oxidation of coal is an essential parameter used to assess the state of coal oxidation and to estimate the gaseous pollutants. However, the current semi-quantitative method, which employs gas concentration as the measurement standard, is flawed. This paper presents a quantitative calculation method for gas products during coal oxidation. N2 is used as the tracer gas in the experiment, because nitrogen is an inert gas that will not participate in the reaction, and the amount of matter will not change in the reaction. According to the formula [Formula: see text], the corresponding mass flow rates of each gases component were calculated, and the gas yields during the reaction period were determined by comprehensive calculation. To this end, experiments were conducted on the low-temperature oxidation of coal using a flow reactor. After undergoing quantitative calculations, the main gas products' mass flow rates, yields, and energies, including CO, CO2, CH4, C2H4, C2H6, C2H2, and C3H8 between 30 and 180 °C were obtained. The findings showed that CO2 > CO > CH was generated in all the coal samples. The amount of gases produced in the low-temperature oxidation of coal is proportional to the level of oxygen concentration. When the oxygen concentration ranges from 0 to 21%, the gaseous production of MTH coal ranges from 381.44 g/ton to 8562.80 g/ton. The results of gaseous energy calculations showed that the energy loss for low temperature oxidation of the four coal samples ranged from 4334.14~26,772.73 kJ/ton under air atmosphere. Energy loss is also significantly affected by the oxygen concentration, and the energy loss of MTH coal increases significantly from 520.52 kJ/ton at 0% oxygen concentration to 26,772.73 kJ/ton at 21% oxygen concentration, an increase of about 50 times. Significantly, this method not only reflects the real gas evolution during low-temperature oxidation of coal but also computes the gas emission and energy loss, which is crucial for studying the mechanism of coal spontaneous combustion and assessing gases pollutants.


Assuntos
Poluentes Ambientais , Gases , Gases/análise , Carvão Mineral , Dióxido de Carbono/análise , Temperatura , Oxigênio/análise
11.
Cancer Immunol Res ; 11(12): 1671-1687, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37756564

RESUMO

Tumor-specific neoepitopes are promising targets in cancer immunotherapy. However, the identification of functional tumor-specific neoepitopes remains challenging. In addition to the most common source, single-nucleotide variants (SNV), alternative splicing (AS) represents another rich source of neoepitopes and can be utilized in cancers with low SNVs such as uveal melanoma (UM). UM, the most prevalent adult ocular malignancy, has poor clinical outcomes due to a lack of effective therapies. Recent studies have revealed the promise of harnessing tumor neoepitopes to treat UM. Previous studies have focused on neoepitope targets associated with mutations in splicing factor 3b subunit 1 (SF3B1), a key splicing factor; however, little is known about the neoepitopes that are commonly shared by patients independent of SF3B1 status. To identify the AS-derived neoepitopes regardless of SF3B1 status, we herein used a comprehensive nanopore long-read-sequencing approach to elucidate the landscape of AS and novel isoforms in UM. We also performed high-resolution mass spectrometry to further validate the presence of neoepitope candidates and analyzed their structures using the AlphaFold2 algorithm. We experimentally evaluated the antitumor effects of these neoepitopes and found they induced robust immune responses by stimulating interferon (IFN)γ production and activating T cell-based UM tumor killing. These results provide novel insights into UM-specific neoepitopes independent of SF3B1 and lay the foundation for developing therapies by targeting these actionable neoepitopes.


Assuntos
Melanoma , Neoplasias Uveais , Adulto , Humanos , Processamento Alternativo , Melanoma/genética , Melanoma/patologia , Neoplasias Uveais/genética , Neoplasias Uveais/patologia , Fatores de Processamento de RNA/genética , Fosfoproteínas/genética
12.
Se Pu ; 41(8): 722-729, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37534560

RESUMO

Sophorolipids are secondary metabolites produced during fermentation by nonpathogenic yeasts. These molecules are amphiphilic and consist of a hydrophilic sophora sugar moiety and a hydrophobic hydroxylated fatty acid. Based on their degree of esterification, sophorolipids can be divided into the acid and lactone types. Sophorolipids are highly promising biosurfactants with good antibacterial, antiviral, and other biological activities. Moreover, they are characterized by mildness, low toxicity, and environmental friendliness. However, their composition is quite complex, and effective methods for their quality evaluation are lacking. Since sophorolipids do not absorb ultraviolet (UV) light, common UV detectors are unsuitable for fingerprint establishment. In this study, we first selected a charged aerosol detector (CAD) to establish the ultra-high performance liquid chromatography (UHPLC) fingerprint of sophorolipids. The detector had high sensitivity, good reproducibility, and excellent suitability for the detection of substances with no or weak ultraviolet absorption. We then evaluated the similarities between 17 batches of sophorolipid samples. The samples were extracted by ultrasound for 10 min in 80% ethanol aqueous solution at a liquid-solid ratio of 10∶1 (mL/g) and then separated on a Thermo Fisher Scientific Hypersil Gold chromatographic column (150 mm×2.1 mm, 1.9 µm). Separation was performed using acetonitrile-0.01% (v/v) formic acid aqueous solution as the mobile phase via gradient elution. The flow rate was 0.2 mL/min, and the column temperature was 40 ℃. The CAD was used under the following conditions: power function of 1.0, data rate of 5 Hz, filter constant of 3.6, and evaporation temperature of 45 ℃. The chromatograms and retention times of the sophorolipids were compared, and 16 common peaks with strong responses, good resolutions, and stable retention times were selected as characteristic peaks. Oleic acid was chosen as the reference peak because it achieved good separation and a strong chromatographic response in all batches of samples. UHPLC-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to identify chromatographic peaks in the sophorolipid fingerprints. The results were combined with the retention time rule of the sophorolipids, leading to their identification based on matching with the results of the primary database, the precise relative molecular mass and fragmentation rule of secondary fragments, a self-built database, and the PubChem database. Sixteen compounds were identified, including eight acid sophorolipids, six lactone sophorolipids, and two aliphatic acids. The results of precision, repeatability, and 24 h stability tests indicated that the relative standard deviations (RSDs) of the retention times and peak areas of the 15 characteristic peaks relative to the control peak (oleic acid) were less than 3.0% (n=6). Seventeen batches of sophorolipid samples were analyzed, and the similarity values of all fingerprints were found to be 0.965 or higher. Little differences in chemical composition were observed among the different batches of sophorolipid samples, and the quality of the sophorolipids was relatively consistent. The fingerprint established in this study is stable and reliable; it can be used for the quality evaluation of sophorolipids and lays a solid foundation for future research on production technology and the development and utilization of sophorolipids. The successful application of a universal CAD to the fingerprint establishment of sophorolipids also provides a reliable solution for the fingerprint establishment of substances with no or weak ultraviolet absorption.


Assuntos
Ácidos Oleicos , Cromatografia Líquida de Alta Pressão , Reprodutibilidade dos Testes , Controle de Qualidade
13.
Int J Mol Sci ; 24(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37569533

RESUMO

Cadmium (Cd) is one of the most toxic metals in the environment and exerts deleterious effects on plant growth and production. Duckweed has been reported as a promising candidate for Cd phytoremediation. In this study, the growth, Cd enrichment, and antioxidant enzyme activity of duckweed were investigated. We found that both high-Cd-tolerance duckweed (HCD) and low-Cd-tolerance duckweed (LCD) strains exposed to Cd were hyper-enriched with Cd. To further explore the underlying molecular mechanisms, a genome-wide transcriptome analysis was performed. The results showed that the growth rate, chlorophyll content, and antioxidant enzyme activities of duckweed were significantly affected by Cd stress and differed between the two strains. In the genome-wide transcriptome analysis, the RNA-seq library generated 544,347,670 clean reads, and 1608 and 2045 differentially expressed genes were identified between HCD and LCD, respectively. The antioxidant system was significantly expressed during ribosomal biosynthesis in HCD but not in LCD. Fatty acid metabolism and ethanol production were significantly increased in LCD. Alpha-linolenic acid metabolism likely plays an important role in Cd detoxification in duckweed. These findings contribute to the understanding of Cd tolerance mechanisms in hyperaccumulator plants and lay the foundation for future phytoremediation studies.


Assuntos
Araceae , Transcriptoma , Cádmio/toxicidade , Cádmio/metabolismo , Antioxidantes/metabolismo , Perfilação da Expressão Gênica , Araceae/genética , Araceae/metabolismo
14.
ACS Appl Mater Interfaces ; 15(31): 38154-38162, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37505507

RESUMO

The power conversion efficiency (PCE) and stability of n-i-p perovskite solar cells (PSCs) are significantly affected by inherent defects of SnO2 and perovskite layers. In this work, we incorporate 2-bromo-3-thiophenic acid (BrThCOOH) as a multifunctional passivant to simultaneously passivate the defects of SnO2 surface and perovskite layer. BrThCOOH permeates evenly into the MAPbI3 and coordinates with Pb2+ and iodine vacancies (VI+) to reduce surface defect density and inhibit the decomposition of MAPbI3. Carboxylic acid effectively passives the oxygen vacancy on the surface of SnO2 through coordination bonds, reducing the probability of electron capture by SnO2 surface defects, thus contributing to electron transport in device. The interaction of BrThCOOH with MAPbI3 and SnO2 surfaces leads to an upward shift in energy levels, reducing energy loss during charge migration. The optimal MAPbI3 device with BrThCOOH-modified SnO2 (T-SnO2) reveals an improved PCE of 21.12%, much higher than that of the control one (19.12%). The hydrophobicity of BrThCOOH-modified MAPbI3 is also improved, which is beneficial to the durability of the device. After 100 h of storage in the environment, the generated PSCs maintain their initial PCE of 75%, demonstrating excellent long-term stability without any encapsulation.

15.
Medicine (Baltimore) ; 102(7): e32903, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36800609

RESUMO

To explore the effect of individualized comfortable nursing on prognosis of vacuum sealing drainage (VSD) in patients with orthopedic trauma. 110 patients with orthopedic trauma VSD were randomly divided into the control group and the observation group, with 55 patients in each group receiving routine care and comfortable care. The wound healing time, visual analog scale, quality of life score, the level of inflammatory factors, the incidence of complications, and patient satisfaction were compared between the 2 groups. The average time of wound healing in the observation group was significantly lower than that in the control group (P < .01). The satisfaction rate in the observation group was significantly higher than that in the control group (P = .029). Meanwhile, the results showed that visual analog scale and quality of life scores in the observation group was significantly improved than that of the control group after receiving intervention (P < .05). After receiving intervention, the levels of TNF-α and IL-6 of patients in both groups were decreased, and the levels of TNF-α and IL-6 in the observation group were significantly decreased than those in the control group. Moreover, the incidence rate of adverse reaction in the observation group was significantly lower than that in the control group (P < .01). Comfortable nursing can reduce the wound healing time, the postoperative pain level, the incidence of complications, and improve patient satisfaction, which is of great significance for the prognosis of VSD in patients with orthopedic trauma.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Humanos , Tratamento de Ferimentos com Pressão Negativa/métodos , Fator de Necrose Tumoral alfa , Interleucina-6 , Qualidade de Vida , Drenagem , Prognóstico
16.
PLoS Pathog ; 19(1): e1011110, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36689471

RESUMO

Pseudomonas aeruginosa is an opportunistic pathogen that predominantly causes nosocomial and community-acquired lung infections. As a member of ESKAPE pathogens, carbapenem-resistant P. aeruginosa (CRPA) compromises the limited therapeutic options, raising an urgent demand for the development of lead compounds against previously-unrecognized drug targets. Biotin is an important cofactor, of which the de novo synthesis is an attractive antimicrobial target in certain recalcitrant infections. Here we report genetic and biochemical definition of P. aeruginosa BioH (PA0502) that functions as a gatekeeper enzyme allowing the product pimeloyl-ACP to exit from fatty acid synthesis cycle and to enter the late stage of biotin synthesis pathway. In relative to Escherichia coli, P. aeruginosa physiologically requires 3-fold higher level of cytosolic biotin, which can be attributed to the occurrence of multiple biotinylated enzymes. The BioH protein enables the in vitro reconstitution of biotin synthesis. The repertoire of biotin abundance is assigned to different mouse tissues and/or organ contents, and the plasma biotin level of mouse is around 6-fold higher than that of human. Removal of bioH renders P. aeruginosa biotin auxotrophic and impairs its intra-phagosome persistence. Based on a model of CD-1 mice mimicking the human environment, lung challenge combined with systemic infection suggested that BioH is necessary for the full virulence of P. aeruginosa. As expected, the biotin synthesis inhibitor MAC13772 is capable of dampening the viability of CRPA. Notably, MAC13772 interferes the production of pyocyanin, an important virulence factor of P. aeruginosa. Our data expands our understanding of P. aeruginosa biotin synthesis relevant to bacterial infectivity. In particular, this study represents the first example of an extracellular pathogen P. aeruginosa that exploits biotin cofactor as a fitness determinant, raising the possibility of biotin synthesis as an anti-CRPA target.


Assuntos
Biotina , Infecções por Pseudomonas , Animais , Humanos , Camundongos , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Vias Biossintéticas , Biotina/química , Biotina/metabolismo , Pseudomonas aeruginosa/metabolismo
17.
Sci Total Environ ; 865: 161305, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36592903

RESUMO

Two anaerobic reactors with and without Ca2+ were operated at 35 °C to investigate the effects of different H2/CO2 ratios on products and microbial communities. Through the investigation of various parameters, it was shown that the change of pH triggered by the variations of H2/CO2 is the decisive factor affecting the product selection in anaerobic fermentation system. During the biosynthesis of ATP for cell growth and reproduction, protons (H+) were pumped from extracellular to intracellular by proton pump, which caused an increase of intrinsic pH of fermentative system. When the pH below 9.5, the methanogenic pathway was more prevalent. While the pH above 10.0 was conducive to the homoacetogenesis. Microbial community analysis showed that with the changes of H2/CO2 ratio, a turnover had occurred. When the ratio of H2/CO2 was 4, the main methanogen was Methanobacterium with the dominant interspecies electron transfer bacteria (IETB) of Thermovirga and DMER64. The turnover of microbial community occurred when the H2/CO2 ratio was 4.5 and 4.25. The dominant acetogenic microorganisms were norank_o_Clostridia_UCG-014 (homoacetogen) and Natronincola (obligately alkaliphilic acetogen). When the H2/CO2 ratio returned to 4, the dominant methanogens were hydrotropic Methanobacterium and Methanobrevibacter with four interspecies electron transfer bacteria including DMER64, Thermovirga, Dechlorobacter and Achromobacter.


Assuntos
Reatores Biológicos , Microbiota , Fermentação , Reatores Biológicos/microbiologia , Dióxido de Carbono/metabolismo , Anaerobiose , Biocombustíveis , Bactérias/metabolismo , Prótons , Metano/metabolismo , Hidrogênio/metabolismo
18.
Medicine (Baltimore) ; 102(4): e32777, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705360

RESUMO

The effect and safety of endovascular treatment of basilar tip aneurysms associated with moyamoya disease are unknown. This study was to investigate the safety and effect of endovascular treatment of basilar tip aneurysms associated with moyamoya disease. Patients with moyamoya disease concurrent with basilar tip aneurysms were retrospectively enrolled and treated with endovascular embolization. The clinical and angiographic data were analyzed. Thirty patients with a basilar tip aneurysm were enrolled, including 8 (26.67%) male and 22 (73.33%) female patients aged 38 to 72 years (mean 54.4 ± 8.15). Endovascular treatment was successfully performed in 29 (96.67%) patients but failed in 1 (3.33%). Immediately after embolization, aneurysm occlusion degree was Raymond-Roy grade I in 26 (89.66%), grade II in 2 (6.90%), and grade III in 1 (3.45%). Intraprocedural complications occurred in 2 (10%) patients, including aneurysm rupture in 1 (3.33%), leading to death of the patient, and stent thrombosis in 2 (6.67%) which was successfully treated with thrombolysis. At discharge, good clinical outcome (modified Rankin Scale 0-2) was achieved in 29 (96.67%) and death in 1 (3.03%). Follow-up was performed 6 to 26 months (median 15) in 27 (93.1%) patients. Aneurysm occlusion degree was Raymond-Roy grade I in 21 (77.78%) patients, grade II in 4 (14.81%), and grade III in 2 (7.41%), not significantly (P = .67) different from those immediately after embolization. Aneurysm recurrence was found in 4 patients (14.81%). The clinical outcome was modified Rankin Scale 0 to 2 in all 27 patients, not significantly different from that at discharge. Endovascular embolization can be performed safely and effectively for basilar tip aneurysms associated with moyamoya disease even though more advanced embolization techniques are necessary.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Doença de Moyamoya , Humanos , Masculino , Feminino , Resultado do Tratamento , Estudos Retrospectivos , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/complicações , Doença de Moyamoya/complicações , Doença de Moyamoya/terapia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Angiografia Cerebral/métodos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Stents
19.
Allergy ; 78(4): 1088-1103, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36153808

RESUMO

BACKGROUND: One of the most common cockroach types in urban areas, the American cockroach (Periplaneta americana), has been reported to impose an increased risk of allergies and asthma. Limited groups of allergens (Per a 1-13) have been identified in this species due to the lack of genome-related information. METHODS: To expand the allergen profile of P. americana, genomic, transcriptomic, and proteomic approaches were applied. With the support of a high-quality genome assembled using nanopore, Illumina, and Hi-C sequencing techniques, potential allergens were identified based on protein homology. Then, using enzyme-linked immunosorbent assay, selected allergens were tested in Thai patients allergic to P. americana. RESULTS: A chromosomal-level genome of P. americana (3.06 Gb) has been assembled with 94.6% BUSCO completeness, and its contiguity has been significantly improved (N50 = 151 Mb). A comprehensive allergen profile has been characterized, with seven novel groups of allergens, including enolase (Per a 14), cytochrome C (Per a 15), cofilin (Per a 16), alpha-tubulin (Per a 17), cyclophilin (Per a 18), porin3 (Per a 19), and peroxiredoxin-6 (Per a 20), showing IgE sensitivity in enzyme-linked immunosorbent assay. A new isoallergen of tropomyosin (Per a 7.02) and multiple potential isoallergens of Per a 5 were revealed using bioinformatics and proteomic approaches. Additionally, comparative analysis of P. americana with the closely related Blattodea species revealed the possibility of cross-reaction. CONCLUSION: The high-quality genome and proteome of P. americana are beneficial in studying cockroach allergens at the molecular level. Seven novel allergen groups and one isoallergen in Per a 7 were identified.


Assuntos
Baratas , Hipersensibilidade , Periplaneta , Animais , Humanos , Proteômica , Alérgenos/genética , Hipersensibilidade/genética
20.
J Environ Manage ; 329: 116972, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36528938

RESUMO

Partial nitrification is an effective process for treating high-strength ammonium landfill leachate with low C/N ratio, for the cooperation with denitrification can save almost 40% carbon addition in biological nitrogen removal. However, high ammonia loading often causes the instability of partial nitrification process. Less carbon addition can promote the stability of partial nitrification and increase the nitrite accumulation ratio (NAR). Nevertheless, the microbial mechanisms within remain further elusive. In this study, two laboratory-scale sequencing batch reactors were constructed and operated for 125 days, which were fed with ammonia synthetic wastewater with C/N of 0.6 (CN system) and C/N of 0.0 as the control (N system). CN system performed more stably and had the highest NAR of 100%. Extracellular polymeric substances (EPS) generated from carbon source provided spatial and nutrient niches to tighten the cooperation of functional microorganisms, thus, enhanced the stability and efficiency of partial nitrification. Thauera was the dominant denitrifier in CN system. Nitrosomonas was one of the most important autotrophic ammonia oxidizing bacteria, while Paracoccus and Flavobacterium were the main heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria in CN system. The enrichment of HN-AD bacteria outcompeted nitrite oxidizing bacteria (NOB), therefore leaded to higher nitrite accumulation in CN system. The findings of this study may be conducive to increasing the understanding of the microbial collaboration mechanisms of partial nitrification, thereby provides theoretical support for the improvement of biological nitrogen removal technology.


Assuntos
Compostos de Amônio , Poluentes Químicos da Água , Nitrificação , Amônia , Nitritos , Reatores Biológicos/microbiologia , Bactérias , Nitrogênio , Carbono , Desnitrificação , Esgotos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...