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1.
Bioact Mater ; 42: 328-344, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39295733

RESUMEN

Thrombosis, a leading cause of cardiovascular morbidity and mortality, involves the formation of blood clots within blood vessels. Current animal models and in vitro systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions, limiting the research in understanding the mechanisms of thrombosis. Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels. This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies, including the incorporation of key structural, biochemical and mechanical features, the selection of appropriate biomaterials and cell sources, and the challenges and future directions in the field. The advancements in bioprinting techniques, such as multi-material bioprinting and microfluidic integration, have enabled the development of physiologically relevant models of thrombosis. The future of bioprinted models of thrombosis lies in the integration of patient-specific data, real-time monitoring technologies, and advanced microfluidic platforms, paving the way for personalized medicine and targeted interventions. As the field of bioprinting continues to evolve, these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes. The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.

2.
Food Chem ; 463(Pt 1): 141148, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39243611

RESUMEN

This study investigated the effect of liquid nitrogen ball-milled mechanochemical treatment on multiscale structure and physicochemical properties of starches with typically selected A (rice starch, ReS), B (potato starch, PtS) and C (pea starch, PeS) crystal types. The morphology of starch samples changed from integral granules to irregular fragments, and the interaction between the exposure OH bonds led to a serious agglomeration. As the treatment times extended, the crystalline structure of starch samples was gradually destroyed, and the excessive treatment approached amorphization. Moreover, the thermal stability of starch samples showed the downward tendency; and with amorphization increased, the swelling power (SP), solubility (S), water absorption capacity (WAC), oil absorption capacity (OAC) and hydrolysis rate of starch samples gradually increased. The obtained results provided a theoretical foundation for broadening the application range of ball-milled starches with different crystal types.

3.
Ear Nose Throat J ; : 1455613241279718, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248506

RESUMEN

Objectives: It has been proven that patients with unilateral conductive hearing loss (UCHL) may encounter typical problems associated with asymmetric hearing, especially in challenging listening environments. In this study, we aimed to determine how UCHL affects speech recognition under multisource competing environments and the ability of sound source localization, as well as whether assistance with a bone conduction device (BCD) can confer hearing benefits in such listening tasks. Design: Acquired UCHL was simulated using an earplug combined with an earmuff in 10 listeners (mean age: 29.9 ± 4.77 years) with bilateral normal hearing (NH), and a within-subject repeated-measures design was used to compare hearing results among three listening conditions: NH (both ears open, C1), unilateral plug (UP) (simulated UCHL, C2), and UP + BCD (simulated UCHL aided with a BCD, C3). The speech reception threshold (SRT) of summation, squelch, and head shadow (HS) effects and the mean absolute error of sound source localization were used as markers for binaural hearing abilities. Results: BCD assistance (C3) improved the summation and HS effects in all listeners with simulated UCHL, resulting in a lower (i.e., better) SRT than that observed in C2; however, no significant differences in squelch effects were observed between C2 and C3. Notably, most listeners exhibited more accurate sound source localization in C3 than in C2. Further, BCD assistance mainly improved localization accuracy when the noise stimuli were presented at low intensities and on the hearing-impaired (plugged) side, suggesting that the benefits of BCD for sound localization are not based on the reacquisition of binaural processing. Conclusions: The current results have clinical implications for the promotion of BCDs in patients with UCHL, especially those with acquired UCHL who are unable to undergo surgery.

4.
World J Gastrointest Surg ; 16(8): 2602-2611, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220072

RESUMEN

BACKGROUND: This study investigated the construction and clinical validation of a predictive model for neuroaggression in patients with gastric cancer. Gastric cancer is one of the most common malignant tumors in the world, and neuroinvasion is the key factor affecting the prognosis of patients. However, there is a lack of systematic analysis on the construction and clinical application of its prediction model. This study adopted a single-center retrospective study method, collected a large amount of clinical data, and applied statistics and machine learning technology to build and verify an effective prediction model for neuroaggression, with a view to providing scientific basis for clinical treatment decisions and improving the treatment effect and survival rate of patients with gastric cancer. AIM: To investigate the value of a model based on clinical data, spectral computed tomography (CT) parameters and image omics characteristics for the preoperative prediction of nerve invasion in patients with gastric cancer. METHODS: A retrospective analysis was performed on 80 gastric cancer patients who underwent preoperative energy spectrum CT at our hospital between January 2022 and August 2023, these patients were divided into a positive group and a negative group according to their pathological results. Clinicopathological data were collected, the energy spectrum parameters of primary gastric cancer lesions were measured, and single factor analysis was performed. A total of 214 image omics features were extracted from two-phase mixed energy images, and the features were screened by single factor analysis and a support vector machine. The variables with statistically significant differences were included in logistic regression analysis to construct a prediction model, and the performance of the model was evaluated using the subject working characteristic curve. RESULTS: There were statistically significant differences in sex, carbohydrate antigen 199 expression, tumor thickness, Lauren classification and Borrmann classification between the two groups (all P < 0.05). Among the energy spectrum parameters, there were statistically significant differences in the single energy values (CT60-CT110 keV) at the arterial stage between the two groups (all P < 0.05) and statistically significant differences in CT values, iodide group values, standardized iodide group values and single energy values except CT80 keV at the portal vein stage between the two groups (all P < 0.05). The support vector machine model with the largest area under the curve was selected by image omics analysis, and its area under the curve, sensitivity, specificity, accuracy, P value and parameters were 0.843, 0.923, 0.714, 0.925, < 0.001, and c:g 2.64:10.56, respectively. Finally, based on the logistic regression algorithm, a clinical model, an energy spectrum CT model, an imaging model, a clinical + energy spectrum model, a clinical + imaging model, an energy spectrum + imaging model, and a clinical + energy spectrum + imaging model were established, among which the clinical + energy spectrum + imaging model had the best efficacy in diagnosing gastric cancer nerve invasion. The area under the curve, optimal threshold, Youden index, sensitivity and specificity were 0.927 (95%CI: 0.850-1.000), 0.879, 0.778, 0.778, and 1.000, respectively. CONCLUSION: The combined model based on clinical features, spectral CT parameters and imaging data has good value for the preoperative prediction of gastric cancer neuroinvasion.

5.
Environ Pollut ; 361: 124792, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39182820

RESUMEN

The use of aspartame as an artificial sweetener is prevalent in a wide range of everyday food products, potentially leading to health complications such as obesity, diabetes mellitus, autism spectrum disorders, and neurodegeneration. Aspartame has also been detected in natural water bodies at a concentration of 0.49 µg/L, yet research on its ecotoxicological effects on aquatic life remains scarce. This study aimed to investigate the potential negative effects of environmentally relevant concentrations of aspartame on the development of various tissues and organs in zebrafish embryos. We used a zebrafish model to treat embryos with aspartame at environmental concentration and those higher than in the environment-up to 1000 times. We observed that after exposure to aspartame body length increased, pigmentation was delayed, and neutrophil production inhibited in zebrafish. Furthermore, transcriptome analysis revealed that early exposure of zebrafish embryos to aspartame affected the transcriptomics of various systems, primarily by downregulating genes related to immune cell production, eye and optic nerve development, nervous system development, and growth hormone-related transcription. Most of the genes associated with ferroptosis were upregulated. This study provides new insights into the ecotoxicological effects of aspartame on aquatic environments.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39208038

RESUMEN

To investigate the biomechanical mechanisms underlying the pathogenesis and explore the effects of kinesiology taping (KT) on neuromuscular control in HV patients. The study population consisted of 16 young controls (YC group) and 15 patients with hallux valgus (HV group). All subjects underwent a natural velocity gait assessment. Additionally, 11 patients from the HV group received KT intervention over a period of one month, consisting of 15 sessions administered every other day. After the one-month intervention, these patients underwent a gait assessment and were included in the HV-KT group. The electromyography (EMG) and joint motion were evaluated using non-negative matrix factorization (NNMF) to compare the difference in muscle and kinematic synergy among the three groups. The center of plantar pressure (COP) and ground reaction force (GRF) were measured by the force platform. The number of synergies did not differ within the three groups, but the structure of muscle synergies and kinematic synergies differed in the HV group. The KT intervention (HV-KT group) altered the structure of synergies. The correlation between kinematic synergies and muscular synergies was lower in the HV group than in the YC group, whereas the correlation between the two increased after the KT intervention in the HV group. During gait, the HV group tended to activate more muscles around foot joints to maintain body stability. The visual analogue scale (VAS) scores, hallux valgus angle (HVA), and COP were significantly decreased after the intervention ( [Formula: see text]). HV patients exhibited altered kinematic and muscular synergies structures as well as muscle activation. Also, it weakened the balance and athletic ability of HV patients. KT intervention improved neuromuscular control to provide a better gait performance.


Asunto(s)
Cinta Atlética , Electromiografía , Marcha , Hallux Valgus , Músculo Esquelético , Humanos , Hallux Valgus/fisiopatología , Hallux Valgus/rehabilitación , Masculino , Femenino , Músculo Esquelético/fisiopatología , Marcha/fisiología , Fenómenos Biomecánicos , Adulto , Adulto Joven , Resultado del Tratamiento
7.
Food Chem ; 461: 140651, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39154465

RESUMEN

High-throughput and low-cost quantification of the nutrient content in crop grains is crucial for food processing and nutritional research. However, traditional methods are time-consuming and destructive. A high-throughput and low-cost method of quantification of wheat nutrients with VIS-NIR (400-1700 nm) hyperspectral imaging is proposed in this study. Stepwise linear regression (SLR) was used to predict hundreds of nutrients accurately (R2 > 0.6); results improved when the hyperspectral data was processed with the first derivative. Knockout materials were also used to verify their practical application value. Various nutrients' characteristic wavelengths were mainly concentrated in the visible regions of 400-500 nm and 900-1000 nm. Finally, we proposed an improved pix2pix conditional generative network model to visualize the nutrients distribution and showed better results compared with the original. This research highlights the potential of hyperspectral technology in high-throughput and non-destructive determination and visualization of grain nutrients with deep learning.


Asunto(s)
Aprendizaje Profundo , Imágenes Hiperespectrales , Nutrientes , Espectroscopía Infrarroja Corta , Triticum , Triticum/química , Imágenes Hiperespectrales/métodos , Espectroscopía Infrarroja Corta/métodos , Nutrientes/análisis , Grano Comestible/química , Ensayos Analíticos de Alto Rendimiento/métodos , Valor Nutritivo , Semillas/química
9.
Microbiol Spectr ; : e0012224, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150249

RESUMEN

Background emergence of multidrug-resistant (MDR) bacterial strains is a public health concern that threatens global and regional security. Efflux pump-overexpressing MDR strains from clinical isolates are the best subjects for studying the mechanisms of MDR caused by bacterial efflux pumps. A Klebsiella pneumoniae strain overexpressing the OqxB-only efflux pump was screened from a clinical strain library to explore reverse OqxB-mediated bacterial resistance strategies. We identified non-repetitive clinical isolated K. pneumoniae strains using a matrix-assisted laser desorption/ionization time-of-flight (TOF) mass spectrometry clinical TOF-II (Clin-TOF-II) and susceptibility test screening against levofloxacin and ciprofloxacin. And the polymorphism analysis was conducted using pulsed-field gel electrophoresis. Efflux pump function of resistant strains is obtained by combined drug sensitivity test of phenylalanine-arginine beta-naphthylamide (PaßN, an efflux pump inhibitor) and detection with ethidium bromide as an indicator. The quantitative reverse transcription PCR was performed to assess whether the oqxB gene was overexpressed in K. pneumoniae isolates. Additional analyses assessed whether the oqxB gene was overexpressed in K. pneumoniae isolates and gene knockout and complementation strains were constructed. The binding mode of PaßN with OqxB was determined using molecular docking modeling. Among the clinical quinolone-resistant K. pneumoniae strains, one mediates resistance almost exclusively through the overexpression of the resistance-nodulation-division efflux pump, OqxB. Crystal structure of OqxB has been reported recently by N. Bharatham, P. Bhowmik, M. Aoki, U. Okada et al. (Nat Commun 12:5400, 2021, https://doi.org/10.1038/s41467-021-25679-0). The discovery of this strain will contribute to a better understanding of the role of the OqxB transporter in K. pneumoniae and builds on the foundation for addressing the threat posed by quinolone resistance.IMPORTANCEThe emergence of antimicrobial resistance is a growing and significant health concern, particularly in the context of K. pneumoniae infections. The upregulation of efflux pump systems is a key factor that contributes to this resistance. Our results indicated that the K. pneumoniae strain GN 172867 exhibited a higher oqxB gene expression compared to the reference strain ATCC 43816. Deletion of oqxB led a decrease in the minimum inhibitory concentration of levofloxacin. Complementation with oqxB rescued antibiotic resistance in the oqxB mutant strain. We demonstrated that the overexpression of the OqxB efflux pump plays an important role in quinolone resistance. The discovery of strain GN 172867 will contribute to a better understanding of the role of the OqxB transporter in K. pneumoniae and promotes further study of antimicrobial resistance.

10.
Biosens Bioelectron ; 264: 116693, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39167887

RESUMEN

The microbial fuel cell (MFC) is a device that simultaneously achieves electricity generation and sewage degradation. In this study, a novel cathode catalyst metal-organic frameworks (MOFs) have been fabricated by two-step hydrothermal and dual-solution method (CuCo-MOF@ZIF-8). The synthesized trimetal MOFs exhibited a 3D badminton-like structure morphology and porosity. The results of the characterizations showed that CuCo-MOF@ZIF-8 possesses greater surface area porosity and novel functional groups. The Trimetal MOF-on-MOF mode not only demonstrated the stability of the structure but also enhanced its mechanism. Molecular mechanism analysis revealed changes in the organic ligand and metal binding site due to the transformation of Cu2+ to Cu+, Co2+ to Co3+, and Zn-N to Zn-O organic connection. Furthermore, differences between the two fabrication methods were compared. The solid-state single preparation (CuCo-MOF@ZIF-8-1), was synthesized using the two-step hydrothermal method; the liquid mixed preparation material (CuCo-MOF@ZIF-8-2), was synthesized using the dual-solution method; they exhibited completely different chemical structures and morphologies during material testing and characterization. The maximum output power density of CuCo-MOF@ZIF-8-2-MFC was 246.38 mW/m2, about 2.49 times of ZIF-8 (98.72 mW/m2). The output voltage of CuCo-MOF@ZIF-8-1-MFC was measured at 357 mV over 10 d, while that of CuCo-MOF@ZIF-8-2-MFC reached 365 mV over 12 d.


Asunto(s)
Fuentes de Energía Bioeléctrica , Cobre , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Cobre/química , Catálisis , Electrodos , Técnicas Electroquímicas/métodos , Zeolitas/química , Técnicas Biosensibles/métodos
11.
Front Vet Sci ; 11: 1436426, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161459

RESUMEN

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs.

13.
Artículo en Inglés | MEDLINE | ID: mdl-39102330

RESUMEN

Extensive research indicates that microRNAs (miRNAs) play a crucial role in the analysis of complex human diseases. Recently, numerous methods utilizing graph neural networks have been developed to investigate the complex relationships between miRNAs and diseases. However, these methods often face challenges in terms of overall effectiveness and are sensitive to node positioning. To address these issues, the researchers introduce DARSFormer, an advanced deep learning model that integrates dynamic attention mechanisms with a spectral graph Transformer effectively. In the DARSFormer model, a miRNA-disease heterogeneous network is constructed initially. This network undergoes spectral decomposition into eigenvalues and eigenvectors, with the eigenvalue scalars being mapped into a vector space subsequently. An orthogonal graph neural network is employed to refine the parameter matrix. The enhanced features are then input into a graph Transformer, which utilizes a dynamic attention mechanism to amalgamate features by aggregating the enhanced neighbor features of miRNA and disease nodes. A projection layer is subsequently utilized to derive the association scores between miRNAs and diseases. The performance of DARSFormer in predicting miRNA-disease associations is exemplary. It achieves an AUC of 94.18% in a five-fold cross-validation on the HMDD v2.0 database. Similarly, on HMDD v3.2, it records an AUC of 95.27%. Case studies involving colorectal, esophageal, and prostate tumors confirm 27, 28, and 26 of the top 30 associated miRNAs against the dbDEMC and miR2Disease databases, respectively. The code and data for DARSFormer are accessible at https://github.com/baibaibaialone/DARSFormer.

14.
Front Neurosci ; 18: 1439443, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39148522

RESUMEN

Background and objectives: The advent of new clinical subtyping systems for Parkinson's disease (PD) has led to the classification of patients into distinct groups: mild motor predominant (PD-MMP), intermediate (PD-IM), and diffuse malignant (PD-DM). Our goal was to evaluate the efficacy of diffusion tensor imaging (DTI) in the early diagnosis, assessment of clinical progression, and prediction of prognosis of these PD subtypes. Additionally, we attempted to understand the pathological mechanisms behind white matter damage using single-photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) analyses. Methods: We classified 135 de novo PD patients based on new clinical criteria and followed them up after 1 year, along with 45 healthy controls (HCs). We utilized tract-based spatial statistics to assess the microstructural changes of white matter at baseline and employed multiple linear regression to examine the associations between DTI metrics and clinical data at baseline and after follow-up. Results: Compared to HCs, patients with the PD-DM subtype demonstrated reduced fractional anisotropy (FA), increased axial diffusivity (AD), and elevated radial diffusivity (RD) at baseline. The FA and RD values correlated with the severity of motor symptoms, with RD also linked to cognitive performance. Changes in FA over time were found to be in sync with changes in motor scores and global composite outcome measures. Furthermore, baseline AD values and their rate of change were related to alterations in semantic verbal fluency. We also discovered the relationship between FA values and the levels of α-synuclein and ß-amyloid. Reduced dopamine transporter uptake in the left putamen correlated with RD values in superficial white matter, motor symptoms, and autonomic dysfunction at baseline as well as cognitive impairments after 1 year. Conclusions: The PD-DM subtype is characterized by severe clinical symptoms and a faster progression when compared to the other subtypes. DTI, a well-established technique, facilitates the early identification of white matter damage, elucidates the pathophysiological mechanisms of disease progression, and predicts cognitively related outcomes. The results of SPECT and CSF analyses can be used to explain the specific pattern of white matter damage in patients with the PD-DM subtype.

15.
Clin Transl Med ; 14(8): e1786, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39113235

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune-inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single-cell level. METHODS: We performed single-cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co-culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single-cell analyses. RESULTS: LSCC with COPD showed increased proportions of tumour-associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-programmed cell death-1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. CONCLUSIONS: Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. HIGHLIGHT: Our results demonstrated higher proportions of tumour-associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-PD-L1 signalling pathway, facilitating immune evasion.


Asunto(s)
Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Análisis de Expresión Génica de una Sola Célula , Humanos , Antígenos de Diferenciación de Linfocitos B/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Evasión Inmune/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Análisis de Expresión Génica de una Sola Célula/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
16.
Antimicrob Agents Chemother ; : e0034424, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39194261

RESUMEN

Limited treatment options and multidrug-resistant (MDR) Klebsiella pneumoniae present a significant therapeutic challenge, underscoring the need for novel approaches. Drug repurposing is a promising tool for augmenting the activity of many antibiotics. This study aimed to identify novel synergistic drug combinations against K. pneumoniae based on drug repurposing. We used the clinically isolated GN 172867 MDR strain of K. pneumoniae to determine the reversal resistance activity of zidovudine (AZT). The combined effects of AZT and various antibiotics, including nitrofurantoin (NIT) and omadacycline (OMC), were examined using the checkerboard method, growth curves, and crystal violet assays to assess biofilms. An in vitro combination activity testing was carried out in 12 isolates of K. pneumoniae. In vivo murine urinary tract and lung infection models were used to evaluate the therapeutic effects of AZT + NIT and AZT + OMC, respectively. The fractional inhibitory concentration index and growth curve demonstrated that AZT synergized with NIT or OMC against K. pneumoniae strains. In addition, AZT + NIT inhibited biofilm formation and cleared mature biofilms. In vivo, compared with untreated GN 172867-infected mice, AZT + NIT and AZT + OMC treatment decreased colony counts in multiple tissues (P < 0.05) and pathological scores in the bladder and kidneys (P < 0.05) and increased the survival rate by 60% (P < 0.05). This study evaluated the combination of AZT and antibiotics to treat drug-resistant K. pneumoniae infections and found novel drug combinations for the treatment of acute urinary tract infections. These findings suggest that AZT may exert significant anti-resistance activity.

17.
Genome Biol ; 25(1): 234, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210441

RESUMEN

BACKGROUND: UV-B, an important environmental factor, has been shown to affect the yield and quality of rice (Oryza sativa) worldwide. However, the molecular mechanisms underlying the response to UV-B stress remain elusive in rice. RESULTS: We perform comprehensive metabolic profiling of leaves from 160 diverse rice accessions under UV-B and normal light conditions using a widely targeted metabolomics approach. Our results reveal substantial differences in metabolite accumulation between the two major rice subspecies indica and japonica, especially after UV-B treatment, implying the possible role and mechanism of metabolome changes in subspecies differentiation and the stress response. We next conduct a transcriptome analysis from four representative rice varieties under UV-B stress, revealing genes from amino acid and flavonoid pathways involved in the UV-B response. We further perform a metabolite-based genome-wide association study (mGWAS), which reveals 3307 distinct loci under UV-B stress. Identification and functional validation of candidate genes show that OsMYB44 regulates tryptamine accumulation to mediate UV-B tolerance, while OsUVR8 interacts with OsMYB110 to promote flavonoid accumulation and UV-B tolerance in a coordinated manner. Additionally, haplotype analysis suggests that natural variation of OsUVR8groupA contributes to UV-B resistance in rice. CONCLUSIONS: Our study reveals the complex biochemical and genetic foundations that govern the metabolite dynamics underlying the response, tolerance, and adaptive strategies of rice to UV-B stress. These findings provide new insights into the biochemical and genetic basis of the metabolome underlying the crop response, tolerance, and adaptation to UV-B stress.


Asunto(s)
Oryza , Rayos Ultravioleta , Oryza/genética , Oryza/metabolismo , Oryza/efectos de la radiación , Metaboloma , Regulación de la Expresión Génica de las Plantas , Estudio de Asociación del Genoma Completo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico , Flavonoides/metabolismo , Metabolómica , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Transcriptoma
18.
Artículo en Inglés | MEDLINE | ID: mdl-39217212

RESUMEN

PURPOSE: Obesity is commonly linked to both adenotonsillar hypertrophy (ATH) and allergic disorders, in which the roles of adipokines are not fully illuminated. This study aims to investigate the levels of leptin and adiponectin and their associations with allergic sensitization in pediatric ATH. METHODS: Serum levels of specific immunoglobulin E (IgE), leptin and adiponectin were quantified in 35 controls and 111 ATH children, in which 54 were non-atopic and 57 were atopic. Spearman's correlation analysis and polynomial linear trend test were conducted. The odds ratios and 95% confidence intervals were calculated by binary logistic regression after multivariable adjustment. RESULTS: The serum level of leptin and leptin/adiponectin (L/A) ratio was significantly increased in children with ATH. An increase in leptin level and L/A ratio and a decrease in adiponectin level were observed in atopic children compared with non-atopic children. Among ATH children, the level of adiponectin was negatively while L/A ratio was positively correlated with specific IgE. After multivariable adjustment, leptin was significantly associated with increased risk of atopy to D. pteronyssinus and D. farina, and adiponectin was significantly associated with decreased risk of atopy to willow and mugwort. Leptin was associated with higher odds while adiponectin was associated with lower odds of overall atopy. Besides, significant multiplicative interactions of obesity with leptin and adiponectin on atopy were observed respectively. CONCLUSION: Leptin and adiponectin were both associated with allergic sensitization and function differently in pediatric ATH. Mechanistic studies are needed to elucidate the involvement of adipokines in allergic sensitization of pediatric ATH.

19.
J Environ Manage ; 367: 121994, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39083939

RESUMEN

With the increasing production and demand of plastic products in life, inescapable bisphenol A (BPA) exposure results in a threat to the health of organisms. Selenium (Se) is an essential trace element for living organisms. The insufficient Se intake can cause multi-tissue organ damage. In the process of production and life, the exposure of BPA is usually accompanied by Se deficiency. In this study, the models of chicken with BPA exposure and/or Se deficiency was duplicated, the status of nitrification stress, apoptosis, necroptosis, and changes in TNF-α/FADD signaling pathways in chicken spleen were examined. At the same time, nitrification stress inhibitor and TNF-α inhibitor were introduced into MSB-1 cell model tests in vitro, indicating that BPA exposure and Se deficiency up-regulated TNF-α/FADD signaling pathway through nitrification stress, inducing necroptosis and apoptosis, and heat shock protein was also involved in this process. This study provides a new control idea for healthy poultry breeding based on Se, and also provides a new reference for toxicity control of environmental pollutants.


Asunto(s)
Pollos , Nitrificación , Fenoles , Bazo , Factor de Necrosis Tumoral alfa , Animales , Factor de Necrosis Tumoral alfa/metabolismo , Bazo/efectos de los fármacos , Bazo/metabolismo , Fenoles/toxicidad , Selenio/deficiencia , Compuestos de Bencidrilo/toxicidad , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
20.
Adv Mater ; 36(36): e2403979, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39044708

RESUMEN

The manipulation of cell surface receptors' activity will open a new frontier for drug development and disease treatment. However, limited by the desensitization of drugs, effective physical intervention strategy remains challenging. Here, the controllable internalization of transient receptor potential vanilloid 1 (TRPV1) on neural cells by local piezoelectric field is reported. Single-cell-level local electric field is construct by synthesizing piezoelectric BiOIO3 nanosheets (BIONSs). Upon a mild ultrasound of 0.08 W cm-2, an electric field of 15.29 µV is generated on the surface of BIONSs, further inducing TRPV1 internalization in 5 min. The as-downregulated TRPV1 expression results in the reduction of Ca2+ signal in a spinal neuron and the inhibition of the activity of wide range dynamic neurons, therefore effectively preventing the transmission of cancer-induced bone pain (CIBP). This strategy not only charts a new course for CIBP alleviation, but also introduces a promising nanotechnology for regulating cell surface receptors, showing significant potential in neuropathological and receptor-related diseases.


Asunto(s)
Dolor en Cáncer , Canales Catiónicos TRPV , Animales , Canales Catiónicos TRPV/metabolismo , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/metabolismo , Ratones , Analgesia/métodos , Neoplasias Óseas/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Humanos , Línea Celular Tumoral , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/patología , Nanoestructuras/química
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