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2.
Neurosci Lett ; 832: 137800, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38697601

RESUMO

Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 µg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.


Assuntos
Lipopolissacarídeos , Microglia , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Receptor 4 Toll-Like/metabolismo , Microglia/metabolismo , Microglia/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Masculino , Inflamação/metabolismo , Inflamação/induzido quimicamente , Camundongos Endogâmicos C57BL
3.
Medicine (Baltimore) ; 103(19): e38051, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728488

RESUMO

This study aimed to explore the potential correlation between atherosclerotic cardiovascular disease (ASCVD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). We enrolled 6540 patients with T2DM who were receiving chronic disease management for hypertension, hyperglycemia, and hyperlipidemia in Chengyang District of Qingdao. Among them, 730 had ASCVD (ASCVD group), which 5810 did not (N-ASCVD group). The results showed significantly higher levels of age, blood glucose, glycosylated hemoglobin (HbA1c), systolic blood pressure, ASCVD family history, female proportion, and DR incidence in the N-ASCVD group. Additionally, the glomerular filtration rate was significantly lower in the ASCVD group. Logistic regression analysis revealed a positive correlation between DR and ASCVD risk. DR was further categorized into 2 subtypes, nonproliferative DR (NPDR) and proliferative DR (PDR), based on e lesion severity. Interestingly, only the PDR was associated with ASCVD. Even after accounting for traditional ASCVD risk factors such as age, sex, and family history, PDR remained associated with ASCVD, with a staggering 718% increase in the risk for patients with PDR. Therefore, there is a strong association between ASCVD and DR in individuals with T2DM, with PDR particularly exhibiting an independent and positive correlation with increased ASCVD risk.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Masculino , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Pessoa de Meia-Idade , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Idoso , Fatores de Risco , China/epidemiologia , Hemoglobinas Glicadas/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Glicemia/análise , Glicemia/metabolismo , Incidência
4.
Environ Pollut ; 352: 124129, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729505

RESUMO

Human-imported pollutants could induce water black, changing microbial community structure and function. Employed 16S rRNA high-throughput sequencing, field-scale investigations and laboratory-scale experiments were successively conducted to reveal mechanistic insights into microbial community assembly and succession of black-odor waters (BOWs). In the field-scale investigation, livestock breeding wastewater (56.7 ± 3.2%) was the most critical microbial source. Moreover, fermentation (27.1 ± 4.4%) was found to be the dominant function. Combined with laboratory experiments, the critical environmental factors, such as total organic carbon (30-100 mg/L), ammonia nitrogen (2.5-9 mg/L), initial dissolved oxygen (2-8 mg/L) and chlorophyll a (0-90 mg/L), impacted the intensity of blackening. The differentiation of ecological niches within the microbial community played a significant role in driving the blackening speed. In laboratory-scale experiments, the microbial ecological niche determined the blackening timing and dominations of the stochastic processes in the microbial assembly process (88 - 51%). The three stages, including the anaerobic degradation stage, blackening stage and slow recovery stage, were proposed to understand the assembly of the microbial communities. These findings enhance our understanding of microorganisms in BOWs and provide valuable insights for detecting and managing heavily organic polluted waters.

5.
Materials (Basel) ; 17(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38612027

RESUMO

In this work, a novel zinc-aluminum-magnesium (Zn-Al-Mg, ZM) coated steel was prepared using the hot-dip method. The microstructure and corrosion resistance of the ZM-coated steel were investigated. Compared to the conventional galvanized steel (GI), the ZM coating demonstrated a distinctive phase structure, consisting of Zn phase, binary eutectic (Zn/MgZn2), and ternary eutectic (Zn/Al/MgZn2). The corrosion resistance of the ZM-coated and GI-coated steels was evaluated by neutral salt spray test (NSST), polarization and electrochemical impedance spectroscopy (EIS). The results indicated that ZM-coated steel provided superior long-term corrosion protection in a NaCl environment compared to GI-coated steel. The scanning vibrating electrode technique (SVET) proved to be an effective method for investigating the evolution of the anodic and cathodic on the local coating surface. GI-coated steel exhibited a potential and current density distribution between the cathodic and anodic sites nearly three orders of magnitude higher than that of ZM-coated steel, suggesting a higher corrosion rate for GI-coated steel.

6.
J Am Chem Soc ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38615324

RESUMO

The development of novel soft porous crystals (SPCs) that can be transformed from nonporous to porous crystals is significant because of their promising applications in gas storage and separation. Herein, we systematically investigated for the first time the gas-triggered gate-opening behavior of three-dimensional covalent organic frameworks (3D COFs) with flexible building blocks. FCOF-5, a 3D COF containing C-O single bonds in the backbone, exhibits a unique "S-shaped" isotherm for various gases, such as CO2, C2, and C3 hydrocarbons. According to in situ characterization, FCOF-5 undergoes a pressure-induced closed-to-open structural transition due to the rotation of flexible C-O single bonds in the framework. Furthermore, the gated hysteretic sorption property of FCOF-5 can enable its use as an absorbent for the efficient removal of C3H4 from C3H4/C3H6 mixtures. Therefore, 3D COFs synthesized from flexible building blocks represent a new type of SPC with gate-opening characteristics. This study will strongly inspire us to design other 3D COF-based SPCs for interesting applications in the future.

7.
Food Chem ; 451: 139421, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38663244

RESUMO

Patulin (PAT) is a hazardous mycotoxin frequently occurs in fruit industry. A reusable g-C3N4-SH@KG composite aerogel for PAT removal in a novel "dark adsorption-light regeneration" mode was prepared by thiol(-SH) functionalization and konjac glucomannan (KG) immobilization. The g-C3N4-SH@KG was characterized by SEM, FT-IR, XPS and UV-Vis DRS, and its PAT adsorption and photocatalytic regeneration behaviors and mechanisms were investigated. The g-C3N4-SH@KG exhibited good regeneration performance, maintaining 83% of PAT initial adsorption capacity (0.92 mg/g) after 5 "adsorption-regeneration" cycles. The adsorption process was endothermic and spontaneous. •OH and h+ generated by photocatalysis were the main substances that degraded PAT into two products and regenerated -SH. The g-C3N4-SH@KG could effectively remove PAT without negative impact on juice quality. The study provided a new strategy for the regeneration of thiol-functionalized PAT adsorbents, and a new idea for the application of non-selective photocatalysis in the control of food contaminations.

8.
BMC Cancer ; 24(1): 536, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678211

RESUMO

BACKGROUND: Cervical lymph node metastasis (LNM) is an important prognostic factor for patients with non-small cell lung cancer (NSCLC). We aimed to develop and validate machine learning models that use ultrasound radiomic and descriptive semantic features to diagnose cervical LNM in patients with NSCLC. METHODS: This study included NSCLC patients who underwent neck ultrasound examination followed by cervical lymph node (LN) biopsy between January 2019 and January 2022 from three institutes. Radiomic features were extracted from the ultrasound images at the maximum cross-sectional areas of cervical LNs. Logistic regression (LR) and random forest (RF) models were developed. Model performance was assessed by the area under the curve (AUC) and accuracy, validated internally and externally by fivefold cross-validation and hold-out method, respectively. RESULTS: In total, 313 patients with a median age of 64 years were included, and 276 (88.18%) had cervical LNM. Three descriptive semantic features, including long diameter, shape, and corticomedullary boundary, were selected by multivariate analysis. Out of the 474 identified radiomic features, 9 were determined to fit the LR model, while 15 fit the RF model. The average AUCs of the semantic and radiomics models were 0.876 (range: 0.781-0.961) and 0.883 (range: 0.798-0.966), respectively. However, the average AUC was higher for the semantic-radiomics combined LR model (0.901; range: 0.862-0.927). When the RF algorithm was applied, the average AUCs of the radiomics and semantic-radiomics combined models were improved to 0.908 (range: 0.837-0.966) and 0.922 (range: 0.872-0.982), respectively. The models tested by the hold-out method had similar results, with the semantic-radiomics combined RF model achieving the highest AUC value of 0.901 (95% CI, 0.886-0.968). CONCLUSIONS: The ultrasound radiomic models showed potential for accurately diagnosing cervical LNM in patients with NSCLC when integrated with descriptive semantic features. The RF model outperformed the conventional LR model in diagnosing cervical LNM in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfonodos , Metástase Linfática , Aprendizado de Máquina , Ultrassonografia , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Idoso , Ultrassonografia/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Pescoço/diagnóstico por imagem , Adulto , Estudos Retrospectivos , Radiômica
9.
J Investig Med ; : 10815589241249994, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38632825

RESUMO

Liver and lung tissue damage caused by sepsis is still one of the causes of death. B-lymphocyte-induced maturation protein-1 (Blimp-1) has a protective role in inflammation-related disease. However, whether Blimp-1 can regulate cell pyroptosis and affect disease progression in sepsis is still unclear. Animal and cell models were established by the cecal ligation and puncture method and lipopolysaccharides (LPS)-induced RAW 264.7 cells, respectively, and the role of Blimp-1 in regulation inflammatory response and pyroptosis was verified. The changes of inflammation and pyroptosis in liver and lung tissues of septic mice were determined by the addition of TAK-242 (TLR4 inhibitor). Cell pyroptosis and the level of inflammation was detected after Blimp-1 knockdown and TAK-242 treatment in the cell model. The expression of Blimp-1 was continuously increased in a septic mice model. After treatment with TAK-242, the expression of Blimp-1, pyroptosis and inflammatory levels were reduced in mice. In the LPS-induced cell model, cell injury by knockout Blimp-1 was increased, and cell activity was restored after TAK-242 intervention. Overexpression of Blimp-1 relieved LPS-induced cellular inflammatory damage and pyroptosis. Our study had shown that Blimp-1 could improve septic damage by regulating the level of cellular inflammation and pyroptosis in sepsis.

10.
Front Microbiol ; 15: 1346252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38486702

RESUMO

The fungus Rhizopus arrhizus (=R. oryzae) is commonly saprotrophic, exhibiting a nature of decomposing organic matter. Additionally, it serves as a crucial starter in food fermentation and can act as a pathogen causing mucormycosis in humans and animals. In this study, two distinct endofungal bacteria (EFBs), associated with individual strains of R. arrhizus, were identified using live/dead staining, fluorescence in situ hybridization, transmission electron microscopy, and 16S rDNA sequencing. The roles of these bacteria were elucidated through antibiotic treatment, pure cultivation, and comparative genomics. The bacterial endosymbionts, Pandoraea sputorum EFB03792 and Mycetohabitans endofungorum EFB03829, were purified from the host fungal strains R. arrhizus XY03792 and XY03829, respectively. Notably, this study marks the first report of Pandoraea as an EFB genus. Compared to its free-living counterparts, P. sputorum EFB03792 exhibited 28 specific virulence factor-related genes, six specific CE10 family genes, and 74 genes associated with type III secretion system (T3SS), emphasizing its pivotal role in invasion and colonization. Furthermore, this study introduces R. arrhizus as a new host for EFB M. endofungorum, with EFB contributing to host sporulation. Despite a visibly reduced genome, M. endofungorum EFB03829 displayed a substantial number of virulence factor-related genes, CE10 family genes, T3SS genes, mobile elements, and significant gene rearrangement. While EFBs have been previously identified in R. arrhizus, their toxin-producing potential in food fermentation has not been explored until this study. The discovery of these two new EFBs highlights their potential for toxin production within R. arrhizus, laying the groundwork for identifying suitable R. arrhizus strains for fermentation processes.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38466060

RESUMO

Objective: To explore the effect of interdisciplinary collaboration in emergency nursing using the strengths-weaknesses-opportunities-threats (SWOT) model on patients with acute myocardial infarction (AMI). Methods: Eighty AMI patients undergoing rescue treatment at Affiliated Hospital of Inner Mongolia Medical University from October 2020 to June 2022 were selected and randomly divided into the SWOT group and the control group. The patients in the control group received routine emergency nursing intervention, while those in the SWOT group were given interdisciplinary collaboration using the SWOT model. The emergency-related time, cardiac function indicators, incidence of adverse events, quality of life, and nursing satisfaction were compared between the two groups. Results: The waiting time, triage assessment time, electrocardiogram examination time, emergency treatment time, PCI duration and ICU stay time in SWOT group were significantly shorter than those in control group. The left ventricular end-systolic diameter (LVESd), left ventricular end-diastolic diameter (LVEDd), and left ventricular ejection fraction (LVEF) in the SWOT group were all superior to those in the control group. The SWOT group had a significantly lower incidence rate of adverse events than the control group. The quality of life scores of SWOT group were higher than those of control group. The nursing satisfaction in the SWOT group was higher than that in the control group. Conclusion: Interdisciplinary collaboration using the SWOT model for AMI patients can effectively shorten the rescue time, ameliorate cardiac function indicators, reduce the risk of adverse events, improve patients' quality of life, and enhance nursing satisfaction.

12.
Eur J Ophthalmol ; : 11206721241240511, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488462

RESUMO

INTRODUCTION: Heimler syndrome (HS) is a rare disorder that includes sensorineural hearing loss (SNHL), nail abnormalities, and enamel hypoplasia. Patients with this syndrome can also exhibit ocular manifestations. At present, only a few cases of HS have been reported, existing knowledge of this syndrome is limited, and many cases have been misdiagnosed or even missed. This is the first report of Heimler syndrome with blurred vision as the first complaint, which was diagnosed by genetic analysis in the ophthalmology department. CASE DESCRIPTION: An 8-year-old girl complained of bilateral visual blur and night blindness from birth. Ophthalmic examinations revealed bilateral retinitis pigmentosa with cystoid macular edema, visual impairment with hyperopia and astigmatism. Hearing test revealed bilateral severe sensorineural hearing loss. Dental examinations revealed enamel hypoplasia. In addition, whole-exome sequencing (WES) identified two pathogenic variants in PEX1: the previously reported missense variant c.2966T > C (p.I989 T), and the novel frameshift variant c.1671_1672del (p.G558Sfs*33). CONCLUSION: Heimler syndrome is caused by compound heterozygous PEX1 pathogenic variants, c.2966T > C (p.I989 T) and c.1671_1672del (p.G558Sfs*33), which contributed to the diversity of clinical and genetic profiles in this patient. The main clinical manifestations include bilateral retinitis pigmentosa with cystoid macular edema, sensorineural hearing loss, and enamel hypoplasia. Systemic examinations are suggested for patients suspected of having pigmentary retinal dystrophy, especially combined with hearing-related impairments. Genetic testing can help us to make a definitive diagnosis.

13.
Int J Biol Macromol ; 265(Pt 1): 130951, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503373

RESUMO

Hsian-tsao polysaccharide (HP) with preferable bioactivities was used to produce starchy gel foods. This study elucidated how interactions of HP (0-0.6 %, w/v) with gelatinized corn starch (CS, 6 %, w/v) reduced in vitro digestibility of CS. The CS digestibility (82.85 %, without HP) was reduced to 68.85 % (co-heated) and 74.75 % (non-co-heated) when 0.6 % HP was added, demonstrating that HP reduced the CS digestibility to a larger extent under co-heating by both HP-CS interactions and inhibiting digestive enzyme activities by HP which was dominated under non-co-heating. Moreover, when co-heated, HP bonded to the amylose of CS via physical forces with a composite index of 21.95 % (0.4 % HP), impeded CS swelling and promoted CS aggregation with the average particle size increased to 42.95 µm (0.6 % HP). Also, the HP-CS complexes formed strong association network structures that increased their apparent viscosity and digestive fluid viscosity. Additionally, HP enhanced the short-range ordered structure and crystal structure of CS. These results evidenced that HP-CS interactions significantly reduced the CS digestibility by forming physical barriers, viscosity effects, and ordered structures, to hinder the enzymes from accessing starch matrices. This laid a foundation for applying HP to starchy foods with a low predicted glycemic index.


Assuntos
Medicamentos de Ervas Chinesas , Amido , Zea mays , Amido/química , Zea mays/química , Polissacarídeos/química , Amilose/química
14.
Sci Total Environ ; 926: 172059, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38556012

RESUMO

Anemia in pregnancy (AIP) is associated with multiple severe maternal and perinatal adverse outcomes. However, there is a lack of evidence on the association between environmental factors and AIP. Aim to explore the association between ambient temperature and the risk of AIP, and identify susceptible exposure windows, we conducted a matched case-control study from 2013 to 2016 in Xi'an, China, which included 710 women with AIP and 1420 women without AIP. The conditional logistic regression model was used to evaluate the association between ambient temperature and AIP at different gestational weeks and gestational months. The association between extreme temperature and AIP was evaluated using the distributed lag nonlinear model (DLNM). We conducted stratified analyses of age, parity, and season of conception, and estimated the interaction between ambient temperature and air pollutants on AIP. Ambient temperature was significantly positively associated with the risk of AIP, and the susceptible exposure windows were 2-25 gestational weeks and 1-6 gestational months, respectively. The strongest effect was observed in the week 8 and month 2, for each 1 °C increase in weekly and monthly mean temperature, the odds ratio (OR) for AIP was 1.038 (95 % confidence interval (CI): 1.022, 1.055) and 1.040 (95 % CI: 1.020, 1.060), respectively. Extreme heat may increase the risk of AIP. Stratified analyses showed that there was no significant difference among different age, parity, and season of conception groups. No significant interaction effect of ambient temperature with air pollution on AIP was found. In summary, high ambient temperature may increase the risk of AIP, and the first and second trimesters may be susceptible exposure windows. Understanding the effect of temperature on pregnant women will be beneficial to reduce the occurrence of AIP.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Anemia , Humanos , Feminino , Gravidez , Estudos de Casos e Controles , Temperatura , Poluentes Atmosféricos/análise , China/epidemiologia , Anemia/epidemiologia , Exposição Materna , Material Particulado/análise
15.
BMC Gastroenterol ; 24(1): 113, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491354

RESUMO

PURPOSE: This retrospective study aimed to investigate the changes in peripheral blood lymphocyte subsets before and after immunotherapy in patients with advanced gastric cancer and their relationship n with the therapeutic efficacy and clinical prognosis. METHODS: Peripheral blood lymphocyte subsets, including CD4 + T cells, CD8 + T cells, CD4+/CD8 + ratio, NK cells, Treg cells, and B cells, were collected from 195 patients with advanced gastric cancer who were admitted to the First Hospital of Shanxi Medical University with immunotherapy from January 2020 to October 2021, at the time of diagnosis of advanced gastric cancer, before immunotherapy and after 3 cycles of immunotherapy. T-tests were used to examine the factors influencing the patients' peripheral blood lymphocyte subsets and the changes after immunotherapy. To examine the relationship between lymphocyte subsets and treatment outcomes, ROC curves were plotted using a logistic regression. Kaplan-Meier curve was drawn, and the Log Rank test was carried out to compare the differences in PFS between the different groups. Cox proportional hazards regression model was used to analyze the factors affecting PFS after calibration of other variables. RESULTS: The proportion of peripheral blood lymphocyte subsets in patients with advanced gastric cancer was affected by age and PD-L1 level. Compared to the baseline, the treatment effective group had higher proportions of CD4 + T cells, a higher CD4+/CD8 + ratio, NK cells and Treg cells, and lower proportions of CD8 + T cells and B cells in the peripheral blood after three cycles of immunotherapy. In the treatment-naive group, there were no significant differences in the lymphocyte subsets. With cut-off values of 30.60% and 18.00%, baseline CD4 + T cell and NK cell ratios were independent predictors of immunotherapy efficacy and PFS. Treg cell ratio, gender, PD-L1 levels, and MMR status all predicted PFS independently. CONCLUSION: The proportion of peripheral blood lymphocyte subsets was modified in patients who responded to PD-1 inhibitors. Different lymphocyte subpopulation levels can be used as biomarkers to predict immunotherapy efficacy and clinical prognosis in patients with advanced gastric cancer.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Antígeno B7-H1 , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Prognóstico , Subpopulações de Linfócitos
16.
Int J Biol Macromol ; 263(Pt 1): 130688, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458294

RESUMO

This study reports the rational engineering of the S1' substrate-binding pocket of a thermally-stable keratinase from Pseudomonas aeruginosa 4-3 (4-3Ker) to improve substrate specificity to typical keratinase (K/C > 0.5) and catalytic activity without compromising thermal stability for efficient keratin degradation. Of 10 chosen mutation hotspots in the S1' substrate-binding pocket, the top three mutations M128R, A138V, and V142I showing the best catalytic activity and substrate specificity were identified. Their double and triple combinatorial mutants synergistically overcame limitations of single mutants, fabricating an excellent M128R/A138V/V142I triple mutant which displayed a 1.21-fold increase in keratin catalytic activity, 1.10-fold enhancement in keratin/casein activity ratio, and a 3.13 °C increase in half-inactivation temperature compared to 4-3Ker. Molecular dynamics simulations revealed enhanced flexibility of critical amino acid residues at the substrate access tunnel, improved global protein rigidity, and heightened hydrophobicity within the active site likely underpinned the increased catalytic activity and substrate specificity. Additionally, the triple mutant improved the feather degradation rate by 32.86 % over the wild-type, far exceeding commercial keratinase in substrate specificity and thermal stability. This study exemplified engineering a typical keratinase with enhanced substrate specificity, catalytic activity, and thermal stability from thermally-stable 4-3Ker, providing a more robust tool for feather degradation.


Assuntos
Queratinas , Peptídeo Hidrolases , Queratinas/metabolismo , Especificidade por Substrato , Peptídeo Hidrolases/metabolismo , Temperatura , Concentração de Íons de Hidrogênio
17.
Int J Biol Macromol ; 266(Pt 1): 131144, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38556234

RESUMO

The increasing emergence and dissemination of bacterial pathogens in largemouth bass culture accelerate the desire for new treatment measures. Antimicrobial peptides as the host's antimicrobial source dominate the preferred molecules for discovering antibacterial agents. Here, the potential of Hepcidin-1 from largemouth bass (Micropterus salmoides) (MsHep-1) against bacterial infection is demonstrated. MsHep-1 not only improved the survival rate in infection experiments involving Nocardia seriolae (12 %) and Aeromonas hydrophila (18 %) but also coped with iron overload conditions in vivo. Moreover, the antibacterial activity of MsHep-1 in vitro was identified against both gram-negative and gram-positive bacteria. Mechanistic studies show MsHep-1 leads to bacterial death by changing the bacterial membrane potential and disrupting the bacterial membrane structure. These findings demonstrate that MsHep-1 may play an important role in the host response to bacterial infection. It provides promising strategies in the application of immunosuppression prevention and control in fish. AMPs may be a promising and available reservoir for treating the current bacterial diseases.


Assuntos
Infecções Bacterianas , Bass , Doenças dos Peixes , Hepcidinas , Animais , Hepcidinas/metabolismo , Bass/microbiologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/tratamento farmacológico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Antibacterianos/farmacologia , Aeromonas hydrophila/efeitos dos fármacos , Aeromonas hydrophila/patogenicidade
18.
Biochem Genet ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386213

RESUMO

Discovering more novel antimicrobial compounds has become a keen research problem. In this study, YA215 genome was sequenced by the Illumina HiSeq + PacBio sequencing platform. Genome assembly was performed by Unicycler software and the gene clusters responsible for secondary metabolite biosynthesis were predicted by antiSMASH. The genome comprised 3976514 bp and had a 46.56% G + C content. 3809 coding DNA sequences, 27 rRNAs, 86 tRNAs genes, and 79 sRNA were predicted. Strain YA215 was re-identified as Bacillus velezensis based on ANI and OrthoANI analysis. In the COG database, 23 functional groups from 3090 annotations were predicted. In the GO database, 2654 annotations were predicted. 2486 KEGG annotations linked 41 metabolic pathways. Glycosyl transferases, polysaccharide lyases, auxiliary activities, glycoside hydrolases, carbohydrate esterases, and carbohydrate-binding modules were predicted among the 127 annotations in the CAZy database. AntiSMASH analysis predicted that B. velezensis YA215 boasted 13 gene clusters involved in synthesis of antimicrobial secondary metabolites including surfactin, fengycin, macrolactin H, bacillaene, difficidin, bacillibactin, bacilysin, and plantazolicin. Three of the gene clusters (gene cluster 5, gene cluster 9, and gene cluster 10) have the potential to synthesize unknown compounds. The research underscore the considerable potential of secondary metabolites, identified in the genomic composition of B. velezensis YA215, as versatile antibacterial agents with a broad spectrum of activity against pathogenic bacteria.

19.
J Sci Food Agric ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345737

RESUMO

BACKGROUND: Silkworm (Bombyx moil L.) Pupa protein (SPP) is a high-quality insect protein and is considered a sustainable alternative source for traditional animal food protein. However, the utilization of SPP is limited because of its low solubility and emulsifying ability. In the present study, the synergistic effect of hydration and pulsed ultrasound on the physicochemical properties of SPP and SPP-stabilized Pickering emulsions was evaluated. RESULTS: Pulsed ultrasound changed the particle size of SPP and its conformation. As the pulsed ultrasound increased from 0 s to 5 s, the α-helix and SS contents of SPP decreased, whereas the ß-sheet and SH contents increased, which in turn improved its solubility and amphiphilicity. As a result, the SPP treated by a combination of 12 h of hydration and 3 s of ultrasound exhibited a contact angle of 74.95°, hydrophobicity of 904.83, EAI of 6.66 m2 g-1 and ESI of 190.69 min. Compared with the combination of 1 h of hydration and 5 s of ultrasound, the combination of 12 h of hydration and 3 s of ultrasound exerted more soluble and hydrophobic SPP, whereas the EAI and ESI of the samples were higher. Notably, the ultrasound-treated SPP can form a stable gel-like emulsion (oil fraction ranging from 70% to 80%). CONCLUSION: The combination of hydration and ultrasound can effectively improve the physicochemical characteristics of SPP as well as its emulsion stability. Sufficient hydration is a cost-effective method for facilitating the modification of proteins by ultrasound treatment. © 2024 Society of Chemical Industry.

20.
Biochem Biophys Res Commun ; 704: 149702, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38422898

RESUMO

BACKGROUND: As a chronic inflammatory disease, diabetes mellitus (DM) contributes to the development of atherosclerosis (AS). However, how the NLRP3 inflammasome participates in diabetes-related AS remains unclear. Therefore, this study aimed to elucidate the mechanism through which NLRP3 uses high glucose (HG) levels to promote AS. METHODS: Serum and coronary artery tissues were collected from coronary artery disease (CAD) patients with and without DM, respectively. The expression of NLRP3 was detected, and the effects of this inflammasome on diabetes-associated AS were evaluated using streptozotocin (STZ)-induced diabetic apoE-/- mice injected with Adenovirus-mediated NLRP3 interference (Ad-NLRP3i). To elucidate the potential mechanism involved, ox-LDL-irritated human aortic smooth muscle cells were divided into the control, high-glucose, Si-NC, and Si-NLRP3 groups to observe the changes induced by downregulating NLRP3 expression. For up-regulating NLRP3, control and plasmid contained NLRP3 were used. TNF-α, IL-1ß, IL-6, IL-18, phosphorylated and total p38, JNK, p65, and IκBα expression levels were detected following the downregulation or upregulation of NLRP3 expression. RESULTS: Patients with comorbid CAD and DM showed higher serum levels and expression of NLRP3 in the coronary artery than those with only CAD. Moreover, mice in the Ad-NLRP3i group showed markedly smaller and more stable atherosclerotic lesions compared to those in other DM groups. These mice had decreased inflammatory cytokine production and improved glucose tolerance, which demonstrated the substantial effects of NLRP3 in the progression of diabetes-associated AS. Furthermore, using the siRNA or plasmid to downregulate or upregulate NLRP3 expression in vitro altered cytokines and the MAPK/NF-κB pathway. CONCLUSIONS: NLRP3 expression was significantly increased under hyperglycemia. Additionally, it accelerated AS by promoting inflammation via the IL/MAPK/NF-κB pathway.


Assuntos
Aterosclerose , Diabetes Mellitus Experimental , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Camundongos Knockout para ApoE , Inflamação/metabolismo , Aterosclerose/complicações , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Glucose
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