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1.
PeerJ ; 12: e17795, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39148678

RESUMO

Background: The imbalance of oral microbiota can contribute to various oral disorders and potentially impact general health. Chronic alcohol consumption beyond a certain threshold has been implicated in influencing both the onset and progression of periodontitis. However, the mechanism by which chronic alcohol consumption affects periodontitis and its association with changes in the oral microbial community remains unclear. Objective: This study used 16S rRNA gene amplicon sequencing to examine the dynamic changes in the oral microbial community of rats with periodontitis influenced by chronic alcohol consumption. Methods: Twenty-four male Wistar rats were randomly allocated to either a periodontitis (P) or periodontitis + alcohol (PA) group. The PA group had unrestricted access to alcohol for 10 weeks, while the P group had access to water only. Four weeks later, both groups developed periodontitis. After 10 weeks, serum levels of alanine aminotransferase and aspartate aminotransferase in the rats' serum were measured. The oral swabs were obtained from rats, and 16S rRNA gene sequencing was conducted. Alveolar bone status was assessed using hematoxylin and eosin staining and micro-computed tomography. Results: Rats in the PA group exhibited more severe periodontal tissue damage compared to those in the periodontitis group. Although oral microbial diversity remained stable, the relative abundance of certain microbial communities differed significantly between the two groups. Actinobacteriota and Desulfobacterota were more prevalent at the phylum level in the PA group. At the genus level, Cutibacterium, Tissierella, Romboutsia, Actinomyces, Lawsonella, Anaerococcus, and Clostridium_sensu_stricto_1 were significantly more abundant in the PA group, while Haemophilus was significantly less abundant. Additionally, functional prediction using Tax4Fun revealed a significant enrichment of carbohydrate metabolism in the PA group. Conclusion: Chronic alcohol consumption exacerbated periodontitis in rats and influenced the composition and functional characteristics of their oral microbiota, as indicated by 16S rRNA gene sequencing results. These microbial alterations may contribute to the exacerbation of periodontitis in rats due to chronic alcohol consumption.


Assuntos
Microbiota , Periodontite , RNA Ribossômico 16S , Ratos Wistar , Animais , Masculino , Periodontite/microbiologia , Microbiota/efeitos dos fármacos , Ratos , RNA Ribossômico 16S/genética , Boca/microbiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Modelos Animais de Doenças
2.
Microb Cell Fact ; 23(1): 232, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169403

RESUMO

Straw pollution and the increasing scarcity of phosphorus resources in many regions of China have had severe impacts on the growing conditions for crop plants. Using microbial methods to enhance straw decomposition rate and phosphorus utilization offers effective solutions to address these problems. In this study, a microbial consortium 6 + 1 (consisting of a straw-degrading bacterium and a phosphate-solubilizing bacterium) was formulated based on their performance in straw degradation and phosphorus solubilization. The degradation rate of straw by 6 + 1 microbial consortium reached 48.3% within 7 days (The degradation ability was 7% higher than that of single bacteria), and the phosphorus dissolution rate of insoluble phosphorus reached 117.54 mg·L- 1 (The phosphorus solubilization ability was 29.81% higher than that of single bacteria). In addition, the activity of lignocellulosic degrading enzyme system was significantly increased, the activities of endoglucanase, ß-glucosidase and xylanase in the microbial consortium were significantly higher than those in the single strain (23.16%, 28.02% and 28.86%, respectively). Then the microbial consortium was processed into microbial agents and tested in rice pots. The results showed that the microbial agent significantly increased the content of organic matter, available phosphorus and available nitrogen in the soil. Ongoing research focuses on the determination of the effects and mechanisms of a functional hybrid system of straw degradation and phosphorus removal. The characteristics of the two strains are as follows: Straw-degrading bacteria can efficiently degrade straw to produce glucose-based carbon sources when only straw is used as a carbon source. Phosphate-solubilizing bacteria can efficiently use glucose as a carbon source, produce organic acids to dissolve insoluble phosphorus and consume glucose at an extremely fast rate. The analysis suggests that the microbial consortium 6 + 1 outperformed individual strains in terms of both performance and application effects. The two strains within the microbial consortium promote each other during their growth processes, resulting in a significantly higher rate of carbon source consumption compared to the individual strains in isolation. This increased demand for carbon sources within the growth system facilitates the degradation of straw by the strains. At the same time, the substantial carbon consumption during the metabolic process generated a large number of organic acids, leading to the solubilization of insoluble phosphorus. It also provides a basis for the construction of this type of microbial consortium.


Assuntos
Consórcios Microbianos , Oryza , Fósforo , Solo , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/microbiologia , Fósforo/metabolismo , Solo/química , Bactérias/metabolismo , Bactérias/crescimento & desenvolvimento , Microbiologia do Solo , Lignina/metabolismo , Solubilidade , Nitrogênio/metabolismo
3.
Drug Alcohol Depend ; 262: 111409, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39089187

RESUMO

BACKGROUND: In the U.S., overdose deaths and substance treatment admissions related to methamphetamine are rising. This study aims to measure and compare U.S. temporal trends in methamphetamine-involved psychiatric hospitalizations. METHODS: We conducted a population-based, trend analysis of U.S. psychiatric hospitalizations and calculated quarterly (Q) rates per 100,000 population of substance-involved psychiatric hospitalizations. We assessed U.S. regional quarterly percentage hospitalization rate changes using Joinpoint regression. RESULTS: From Q4 2015-Q4 2019, there were 963,202 psychiatric hospitalizations, 50,223 (5.2 %) involved methamphetamine and 102,877 (10.7 %) involved opioids and/or cocaine without methamphetamine. Methamphetamine-involved psychiatric hospitalization rates increased by 68.0 %, psychiatric hospitalizations rates involving opioid and/or cocaine without methamphetamine decreased by 22 %, while nonsubstance-involved psychiatric hospitalizations rates remained unchanged. The largest significant increases in methamphetamine-involved psychiatric hospitalization rates were among people >61 years old, males, and Midwesterners. Methamphetamine-involved psychiatric hospitalization rates doubled among Black patients. The largest average percent increase among methamphetamine-involved psychiatric hospitalizations was 10.2 % from Q4 2015-Q2 2017 in the Midwest. CONCLUSION AND RELEVANCE: Most psychiatric hospitalizations did not involve substances. Methamphetamine-involved psychiatric hospitalizations greatly increased while opioid-involved psychiatric hospitalizations decreased, but involved more total encounters. Greater access to harm reduction services, contingency management programs, and mental health services is urgently needed.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Hospitalização , Metanfetamina , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Hospitalização/tendências , Hospitalização/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Adulto Jovem , Hospitais Psiquiátricos/tendências , Adolescente , Transtornos Mentais/epidemiologia , Idoso
4.
J Mater Chem B ; 12(35): 8616-8625, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39140256

RESUMO

Similar to clinically applied thermal ablation techniques, the cellular necrosis that occurs during photothermal tumor therapy (PTT) can induce inflammatory response, severely compromising the therapeutic efficacy and clinical translation of the PTT. Inspired by the remarkable ROS-scavenging activity and high photothermal efficiency of molybdenum-based polyoxometalate (POM) and the immunostimulatory effect of cyclic dinucleotides (CDNs), a NIR-responsive and injectable DNA-mediated hybrid hydrogel (CDN-POM) has been developed. The hydrogels have superior photothermal efficiency (43.41%) to POM, impressive anti-inflammatory capability and prolonged intratumoral CDN-releasing behavior, thus enabling synergistic anti-tumor therapeutic outcomes. Meanwhile, local treatment induced by CDN-POM hydrogels displays minimal side effects on normal tissue. Taking advantage of the high phototherapeutic effect, ROS-scavenging activity and sustained CDN release of CDN-POM hydrogels, a novel combined approach that integrates photothermal therapy and immunotherapy of breast tumor is successfully pioneered.


Assuntos
Hidrogéis , Imunoterapia , Raios Infravermelhos , Hidrogéis/química , Imunoterapia/métodos , Animais , Camundongos , Humanos , Molibdênio/química , Molibdênio/farmacologia , Feminino , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Terapia Fototérmica , Fototerapia/métodos , Proliferação de Células/efeitos dos fármacos , Tamanho da Partícula , Injeções , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia
5.
Nat Commun ; 15(1): 7562, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39215012

RESUMO

DNA polymerase ζ (Pol ζ) plays an essential role in replicating damaged DNA templates but contributes to mutagenesis due to its low fidelity. Therefore, ensuring tight control of Pol ζ's activity is critical for continuous and accurate DNA replication, yet the specific mechanisms remain unclear. This study reveals a regulation mechanism of Pol ζ activity in human cells. Under normal conditions, an autoinhibition mechanism keeps the catalytic subunit, REV3L, inactive. Upon encountering replication stress, however, ATR-mediated phosphorylation of REV3L's S279 cluster activates REV3L and triggers its degradation via a caspase-mediated pathway. This regulation confines the activity of Pol ζ, balancing its essential role against its mutations causing potential during replication stress. Overall, our findings elucidate a control scheme that fine tunes the low-fidelity polymerase activity of Pol ζ under challenging replication scenarios.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Replicação do DNA , DNA Polimerase Dirigida por DNA , Humanos , DNA Polimerase Dirigida por DNA/metabolismo , DNA Polimerase Dirigida por DNA/genética , Fosforilação , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Dano ao DNA , Células HEK293 , Estresse Fisiológico
6.
Sensors (Basel) ; 24(16)2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39204922

RESUMO

Accurately detecting atmospheric carbon dioxide is a vital part of responding to the global greenhouse effect. Conventional off-axis integral cavity detection systems are computationally intensive and susceptible to environmental factors. This study deploys an Extreme Learning Machine model incorporating a cascaded integrator comb (CIC) filter into the off-axis integrating cavity. It is shown that appropriate parameters can effectively improve the performance of the instrument in terms of lower detection limit, accuracy, and root mean square deviation. The proposed method is incorporated successfully into a monitoring station situated near an industrial area for detecting atmospheric carbon dioxide (CO2) concentration daily.

8.
Mol Cancer Ther ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172730

RESUMO

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced disease in which patients ultimately fail standard of care androgen-deprivation therapies and exhibit poor survival rates. The prostate-specific membrane antigen (PSMA) has been validated as a mCRPC tumor antigen with over-expression in tumors and low expression in healthy tissues. Using our proprietary technology for incorporating synthetic amino acids (SAAs) into proteins at selected sites, we have developed ARX517, an antibody drug conjugate (ADC) which is composed of a humanized anti-PSMA antibody site-specifically conjugated to a tubulin inhibitor at a drug-to-antibody ratio of 2. After binding PSMA, ARX517 is internalized and catabolized, leading to cytotoxic payload delivery and apoptosis. To minimize premature payload release and maximize delivery to tumor cells, ARX517 employs a non-cleavable PEG linker and stable oxime conjugation enabled via SAA protein incorporation to ensure its overall stability. In vitro studies demonstrate that ARX517 selectively induces cytotoxicity of PSMA-expressing tumor cell lines. ARX517 exhibited a long terminal half-life and high serum exposure in mice, and dose-dependent anti-tumor activity in both enzalutamide-sensitive and -resistant CDX and PDX prostate cancer models. Repeat dose toxicokinetic studies in non-human primates demonstrated ARX517 was tolerated at exposures well above therapeutic exposures in mouse pharmacology studies, indicating a wide therapeutic index. In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on the encouraging preclinical data, ARX517 is currently being evaluated in a Phase 1 clinical trial ([NCT04662580]).

9.
J Adv Res ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39214416

RESUMO

INTRODUCTION: Bacterial living states and the distribution of microbial colony signaling molecules are widely studied using mass spectrometry imaging (MSI). However, current approaches often treat 3D colonies as flat 2D disks, inadvertently omitting valuable details. The challenge of achieving 3D MSI in biofilms persists due to the unique properties of microbial samples. OBJECTIVES: The study aimed to develop a new biofilm sample preparation method that can realize high-resolution 3D MSI of bacterial colonies to reveal the spatial organization of bacterial colonies. METHODS: This article introduces the moisture-assisted cryo-section (MACS) method, enabling embedding-free sectioning parallel to the growth plane. The MACS method secures intact sections by controlling ambient humidity and slice thickness, preventing molecular delocalization. RESULTS: Combined with matrix-assisted laser desorption ionization mass spectrometry (MALDI)-MSI, the MACS method provides high-resolution insights into endogenic and exogenous molecule distributions in Pseudomonas aeruginosa (P. aeruginosa) biofilms, including isomeric pairs. Moreover, analyzed colonies are revived into 3D models, vividly depicting molecular distribution from inner to outer layers. Additionally, we investigated metabolite spatiotemporal dynamics in multiple colonies, observing changes over time and distinct patterns in single versus merged colonies. These findings shed light on the repel-merge process for multi-colony formation. Furthermore, our study monitored chemical responses inside biofilms after antibiotic treatment, showing increased antibiotic levels in the outer biofilm layer over time while maintaining low levels in the inner region. Moreover, the MACS method demonstrated its universality and applicability to other bacterial strains. CONCLUSION: These results unveil complex cell activities within biofilm colonies, offering insights into microbe communities. The MACS method is universally applicable to loosely packed microorganism colonies, overcoming the limitations of previously reported MSI methods. It has great potential for studying bacterial-infected cancer tissues and artificial organs, making it a valuable tool in microbiological research.

10.
Int J Biol Macromol ; 277(Pt 2): 134198, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39084419

RESUMO

Ovarian cancer, a malignant tumor that poses a significant threat to women's health, has seen a rise in incidence, prompting the urgent need for more effective treatment. This study primarily aimed to explore the potential of bovine collagen peptides in inhibiting ovarian cancer. The investigation in this study began with the identification of 268 peptide sequences through LC-MS/MS, followed by a screening process using molecular docking techniques to identify potential peptides capable of binding to EGFR. Subsequently, a series of experiments were performed, demonstrating the inhibitory effects of the peptide GPAGADGDRGEAGPAGPAGPAGPR on the proliferation of ovarian cancer cells. Transcriptomic analysis further revealed that this peptide can regulate cholesterol metabolism in ovarian cancer cells. Finally, a combination of time-resolved fluorescence resonance energy transfer, isothermal titration calorimetry, molecular docking, and molecular dynamics simulations were utilized to validate the ability of this peptide to bind to the epidermal growth factor receptor (EGFR) and impede the binding of epidermal growth factor (EGF) and EGFR.


Assuntos
Colágeno , Receptores ErbB , Simulação de Acoplamento Molecular , Neoplasias Ovarianas , Peptídeos , Animais , Bovinos , Feminino , Humanos , Sequência de Aminoácidos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , Receptores ErbB/química , Simulação de Dinâmica Molecular , Neoplasias Ovarianas/tratamento farmacológico , Peptídeos/química , Peptídeos/farmacologia , Ligação Proteica , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia
11.
J Chromatogr A ; 1731: 465179, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39047447

RESUMO

Conjugated microporous polymers (CMPs) have unique characteristics and have been used in a range of fascinating applications in separation sciences. In this study, a CMP, designated as CMP-1, was synthesized via the Sonogashira-Hagihara coupling reaction using 1,3,5-triphenylbenzene and 1,4-dibromobenzene as building blocks. CMP-1 features a large surface area, abundant micropore structures, and excellent stability, making it a promising solid-phase extraction adsorbent for the efficient enrichment of neonicotinoid insecticides (NEOs). Under the optimized conditions, CMP-1 was combined with high-performance liquid chromatography and diode array detection to enable the detection of NEOs with a wide linear range (0.5-200 µg·L-1), a low detection limit (0.26-0.58 µg·L-1), and acceptable precision. The developed method was applied to determine spiked NEOs in three types of environmental water samples, with recoveries of 73.7%-112.0% and relative standard deviations of 0.6%-9.4%.


Assuntos
Inseticidas , Limite de Detecção , Neonicotinoides , Polímeros , Extração em Fase Sólida , Poluentes Químicos da Água , Extração em Fase Sólida/métodos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/química , Inseticidas/análise , Inseticidas/isolamento & purificação , Inseticidas/química , Cromatografia Líquida de Alta Pressão/métodos , Neonicotinoides/análise , Neonicotinoides/isolamento & purificação , Neonicotinoides/química , Polímeros/química , Porosidade , Adsorção
12.
Eur J Med Chem ; 276: 116633, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968785

RESUMO

Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)-bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains.


Assuntos
Antivirais , Soroalbumina Bovina , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Animais , Humanos , Influenza Humana/tratamento farmacológico , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Estrutura Molecular , Cães , Bovinos , Testes de Sensibilidade Microbiana , Neuraminidase/antagonistas & inibidores , Neuraminidase/metabolismo , Internalização do Vírus/efeitos dos fármacos , Células Madin Darby de Rim Canino/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Glicosídeos
13.
Water Res ; 261: 122056, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38996733

RESUMO

The emission of methane (CH4) from streams and rivers contributes significantly to its global inventory. The production of CH4 is traditionally considered as a strictly anaerobic process. Recent investigations observed a "CH4 paradox" in oxic waters, suggesting the occurrence of oxic methane production (OMP). Human activities promoted dissolved organic carbon (DOC) in streams and rivers, providing significant substrates for CH4 production. However, the underlying DOC molecular markers of CH4 production in river systems are not well known. The identification of these markers will help to reveal the mechanism of methanogenesis. Here, Fourier transform ion cyclotron mass spectrometry and other high-quality DOC characterization, ecosystem metabolism, and in-situ net CH4 production rate were employed to investigate molecular markers attributing to riverine dissolved CH4 production across different land uses. We show that endogenous CH4 production supports CH4 oversaturation and positively correlates with DOC concentrations and gross primary production. Furthermore, sulfur (S)-containing molecules, particularly S-aliphatics and S-peptides, and fatty acid-like compounds (e.g., acetate homologs) are characterized as markers of water-column aerobic and anaerobic CH4 production. Watershed characterization, including riverine discharge, allochthonous DOC input, turnover, as well as autochthonous DOC, affects the CH4 production. Our study helps to understand riverine aerobic or anaerobic CH4 production relating to DOC molecular characteristics across different land uses.


Assuntos
Carbono , Metano , Rios , Rios/química , Biomarcadores , Solubilidade
14.
Arthritis Rheumatol ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982844

RESUMO

OBJECTIVE: There are few existing studies that investigate the risk of systemic lupus erythematosus (SLE) associated with long-term exposure to air pollutants. This study aimed to explore associations between long-term exposure to air pollutants and incident SLE and further evaluate interactions and joint effects of genetic risk and air pollutants. METHODS: A total of 459,815 participants were included from UK Biobank. The concentrations of air pollutants (fine particulate matter with diameter ≤2.5 µm [PM2.5], particulate matter diameter ≤10 µm [PM10], nitrogen dioxide [NO2], and nitrogen oxides [NOx]) were estimated by land-use regression model. We applied Cox proportional hazards model to explore linkages of air pollutants and incident SLE. The polygenic risk score (PRS) was used for further assessing the interactions and joint effects of genetic risk and air pollutants. RESULTS: A total of 399 patients with SLE were identified during a median follow-up of 11.77 years. There were positive associations between air pollutant exposure and incident SLE, as the adjusted hazard ratios were 1.18 (95% confidence interval [95% CI] 1.06-1.32), 1.23 (1.10-1.39), 1.27 (1.14-1.41), and 1.13 (1.03-1.23) for each interquartile range increase in PM2.5, PM10, NO2, and NOx, respectively. Moreover, participants with high genetic risk and high air pollution exposure had the highest risk of incident SLE compared with those with low genetic risk and low air pollution exposure (adjusted hazard ratio: PM2.5, 4.16 [95% CI 2.67-6.49]; PM10, 5.31 [95% CI 3.30,-8.55]; NO2, 5.61 [95% CI 3.45-9.13]; and NOx, 4.80 [95% CI 3.00-7.66]). There was a significant multiplicative interaction between NO2 and PRS. CONCLUSION: Long-term exposure to air pollutants (PM2.5, PM10, NO2, and NOx) may increase the risk of developing SLE.

15.
Int J Biol Macromol ; 275(Pt 1): 133564, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38955298

RESUMO

Influenza viruses contribute significantly to the global health burden, necessitating the development of strategies against transmission as well as effective antiviral treatments. The present study reports a biomimetic strategy inspired by the natural antiviral properties of mucins. A bovine serum albumin (BSA) conjugate decorated with the multivalent neuraminidase inhibitor Zanamivir (ZA-BSA) was synthesized using copper-free click chemistry. This synthetic pseudo-mucin exhibited potent neuraminidase inhibitory activity against several influenza strains. Virus capture and growth inhibition assays demonstrated its effective absorption of virion particles and ability to prevent viral infection in nanomolar concentrations. Investigation of the underlying antiviral mechanism of ZA-BSA revealed a dual mode of action, involving disruption of the initial stages of host-cell binding and fusion by inducing viral aggregation, followed by blocking the release of newly assembled virions by targeting neuraminidase activity. Notably, the conjugate also exhibited potent inhibitory activity against Oseltamivir-resistant neuraminidase variant comparable to the monomeric Zanamivir. These findings highlight the application of multivalent drug presentation on protein scaffold to mimic mucin adsorption of viruses, together with counteracting drug resistance. This innovative approach has potential for the creation of antiviral agents against influenza and other viral infections.


Assuntos
Antivirais , Mucinas , Neuraminidase , Vírion , Zanamivir , Neuraminidase/antagonistas & inibidores , Neuraminidase/metabolismo , Zanamivir/farmacologia , Zanamivir/química , Antivirais/farmacologia , Antivirais/química , Mucinas/metabolismo , Mucinas/química , Humanos , Vírion/efeitos dos fármacos , Animais , Soroalbumina Bovina/química , Cães , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Células Madin Darby de Rim Canino , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/enzimologia
16.
Adv Healthc Mater ; : e2402139, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39039984

RESUMO

Appropriate regulation of immunomodulatory responses, particularly acute inflammation involving macrophages, is crucial for the desired functionality of implants. Decellularized amnion membrane (DAM) is produced by removing cellular components and antigenicity, expected to reduce immunogenicity and the risk of inflammation. Despite the potential of DAM as biomaterial implants, few studies have investigated its specific effects on immunomodulation. Here, it is demonstrated that DAM can regulate macrophage-driven inflammatory response and potential mechanisms are investigated. In vitro results show that DAM significantly inhibits M1 polarization in LPS-induced macrophages by inhibiting Toll-like receptors (TLR) signaling pathway and TNF signaling pathway and promotes macrophage M2 polarization. Physical signals from the 3D micro-structure and the active protein, DCN, binding to key targets may play roles in the process. In the subcutaneous implant model in rats, DAM inhibits the persistence of inflammation and fibrous capsule formation, while promoting M2 macrophage polarization, thereby facilitating tissue regeneration. This study provides insights into DAM's effect and potential mechanisms on the balance of M1/M2 macrophage polarization in vitro and vivo, emphasizing the immunomodulation of ECM-based materials as promising implants.

17.
Quant Imaging Med Surg ; 14(7): 4436-4449, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39022267

RESUMO

Background: Hepatocellular carcinoma (HCC) is often associated with the overexpression of multiple proteins and genes. For instance, patients with HCC and a high expression of the glypican-3 (GPC3) gene have a poor prognosis, and noninvasive assessment of GPC3 expression before surgery is helpful for clinical decision-making. Therefore, our primary aim in this study was to develop and validate multisequence magnetic resonance imaging (MRI) radiomics nomograms for predicting the expression of GPC3 in individuals diagnosed with HCC. Methods: We conducted a retrospective analysis of 143 patients with HCC, including 123 cases from our hospital and 20 cases from The Cancer Genome Atlas (TCGA) or The Cancer Imaging Archive (TCIA) public databases. We used preoperative multisequence MRI images of the patients for the radiomics analysis. We extracted and screened the imaging histologic features using fivefold cross-validation, Pearson correlation coefficient, and the least absolute shrinkage and selection operator (LASSO) analysis method. We used logistic regression (LR) to construct a radiomics model, developed nomograms based on the radiomics scores and clinical parameters, and evaluated the predictive performance of the nomograms using receiver operating characteristic (ROC) curves, calibration curves, and decision curves. Results: Our multivariate analysis results revealed that tumor morphology (P=0.015) and microvascular (P=0.007) infiltration could serve as independent predictors of GPC3 expression in patients with HCC. The nomograms integrating multisequence radiomics radiomics score, tumor morphology, and microvascular invasion had an area under the curve (AUC) value of 0.989. This approach was superior to both the radiomics model (AUC 0.979) and the clinical model (AUC 0.793). The sensitivity, specificity, and accuracy of 0.944, 0.800, and 0.913 for the test set, respectively, and the model's calibration curve demonstrated good consistency (Brier score =0.029). The decision curve analysis (DCA) indicated that the nomogram had a higher net clinical benefit for predicting the expression of GPC3. External validation of the model's prediction yielded an AUC value of 0.826. Conclusions: Our study findings highlight the close association of multisequence MRI imaging and radiomic features with GPC3 expression. Incorporating clinical parameters into nomograms can offer valuable preoperative insights into tailoring personalized treatment plans for patients diagnosed with HCC.

18.
Microbiome ; 12(1): 120, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956705

RESUMO

BACKGROUND: Functional redundancy (FR) is widely present, but there is no consensus on its formation process and influencing factors. Taxonomically distinct microorganisms possessing genes for the same function in a community lead to within-community FR, and distinct assemblies of microorganisms in different communities playing the same functional roles are termed between-community FR. We proposed two formulas to respectively quantify the degree of functional redundancy within and between communities and analyzed the FR degrees of carbohydrate degradation functions in global environment samples using the genetic information of glycoside hydrolases (GHs) encoded by prokaryotes. RESULTS: Our results revealed that GHs are each encoded by multiple taxonomically distinct prokaryotes within a community, and the enzyme-encoding prokaryotes are further distinct between almost any community pairs. The within- and between-FR degrees are primarily affected by the alpha and beta community diversities, respectively, and are also affected by environmental factors (e.g., pH, temperature, and salinity). The FR degree of the prokaryotic community is determined by deterministic factors. CONCLUSIONS: We conclude that the functional redundancy of GHs is a stabilized community characteristic. This study helps to determine the FR formation process and influencing factors and provides new insights into the relationships between prokaryotic community biodiversity and ecosystem functions. Video Abstract.


Assuntos
Bactérias , Biodiversidade , Glicosídeo Hidrolases , Polissacarídeos , Glicosídeo Hidrolases/metabolismo , Glicosídeo Hidrolases/genética , Polissacarídeos/metabolismo , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Ecossistema , Microbiota , Células Procarióticas/metabolismo , Células Procarióticas/classificação , Filogenia , Concentração de Íons de Hidrogênio
19.
Front Med (Lausanne) ; 11: 1409477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38831994

RESUMO

Purpose: This study aims to explore the value of clinical features, CT imaging signs, and radiomics features in differentiating between adults and children with Mycoplasma pneumonia and seeking quantitative radiomic representations of CT imaging signs. Materials and methods: In a retrospective analysis of 981 cases of mycoplasmal pneumonia patients from November 2021 to December 2023, 590 internal data (adults:450, children: 140) randomly divided into a training set and a validation set with an 8:2 ratio and 391 external test data (adults:121; children:270) were included. Using univariate analysis, CT imaging signs and clinical features with significant differences (p < 0.05) were selected. After segmenting the lesion area on the CT image as the region of interest, 1,904 radiomic features were extracted. Then, Pearson correlation analysis (PCC) and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomic features. Based on the selected features, multivariable logistic regression analysis was used to establish the clinical model, CT image model, radiomic model, and combined model. The predictive performance of each model was evaluated using ROC curves, AUC, sensitivity, specificity, accuracy, and precision. The AUC between each model was compared using the Delong test. Importantly, the radiomics features and quantitative and qualitative CT image features were analyzed using Pearson correlation analysis and analysis of variance, respectively. Results: For the individual model, the radiomics model, which was built using 45 selected features, achieved the highest AUCs in the training set, validation set, and external test set, which were 0.995 (0.992, 0.998), 0.952 (0.921, 0.978), and 0.969 (0.953, 0.982), respectively. In all models, the combined model achieved the highest AUCs, which were 0.996 (0.993, 0.998), 0.972 (0.942, 0.995), and 0.986 (0.976, 0.993) in the training set, validation set, and test set, respectively. In addition, we selected 11 radiomics features and CT image features with a correlation coefficient r greater than 0.35. Conclusion: The combined model has good diagnostic performance for differentiating between adults and children with mycoplasmal pneumonia, and different CT imaging signs are quantitatively represented by radiomics.

20.
Quant Imaging Med Surg ; 14(6): 3951-3958, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38846305

RESUMO

Background: With the increase of pancreatic tumor patients in recent years, there is an urgent need to find a way to treat pancreatic tumors. Surgery is one of the best methods for the treatment of pancreatic tumors, the success of which depends on the evaluation of peripancreatic vessels before surgery. Computed tomography (CT), as a non-invasive, fast, and economical auxiliary examination method, is undoubtedly one of the best means of clinical auxiliary examination. In this study, we investigated the impact of single-energy spectral CT imaging on the image quality of peripancreatic blood vessels and the clinical value of low-keV imaging in enhancing the image quality of peripancreatic arteriovenous vessels. Methods: We prospectively enrolled 103 patients who underwent abdominal vascular-enhanced CT examinations at the Affiliated Hospital of Hebei University between December 2022 and May 2023 and who were all scanned with the dual-energy feature on the United Imaging ATLAS scanner. The images were reconstructed at 70 keV, mixed energy, and optimized single energy in the post-processing station of United Imaging Healthcare Technology Co., Ltd. The CT value and contrast-to-noise ratio (CNR) of the superior mesenteric artery (SMA), gastroduodenal artery (GDA), inferior pancreaticoduodenal artery (IPDA), and superior mesenteric vein (SMV) were compared across energy levels, and then the image quality was subjectively evaluated. One-way analysis of variance and rank-sum tests were utilized for the statistical analysis. Results: The CT values of SMA, GDA, IPDA, and SMV in the optimal single energy group were 358.37±70.24, 323.36±88.23, 300.76±76.27, and 257.74±20.56 Hounsfield unit (HU), respectively, which were superior to those in the mixed energy (241.66±47.69, 235.17±53.71, 207.36±45.17, and 187.39±23.21 HU) and 70 keV groups (260.89±54.27, 252.41±58.87, 223.17±43.65, and 203.18±18.17 HU) (P<0.05). The diagnostic efficacy was greater in the optimal single energy group than in the other 2 groups (4.63±0.50, 3.91±0.57, and 4.23±0.83) (P<0.05). Conclusions: The optimal single energy for showing peripancreatic blood vessels is 62±7 keV when utilizing single-energy spectral CT imaging.

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