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1.
Brief Bioinform ; 24(6)2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37889117

RESUMEN

Artificial intelligence (AI) approaches in cancer analysis typically utilize a 'one-size-fits-all' methodology characterizing average patient responses. This manner neglects the diverse conditions in the pancancer and cancer subtypes of individual patients, resulting in suboptimal outcomes in diagnosis and treatment. To overcome this limitation, we shift from a blanket application of statistics to a focus on the explicit recognition of patient-specific abnormalities. Our objective is to use multiomics data to empower clinicians with personalized molecular descriptions that allow for customized diagnosis and interventions. Here, we propose a highly trustworthy multiomics learning (HTML) framework that employs multiomics self-adaptive dynamic learning to process each sample with data-dependent architectures and computational flows, ensuring personalized and trustworthy patient-centering of cancer diagnosis and prognosis. Extensive testing on a 33-type pancancer dataset and 12 cancer subtype datasets underscored the superior performance of HTML compared with static-architecture-based methods. Our findings also highlighting the potential of HTML in elucidating complex biological pathogenesis and paving the way for improved patient-specific care in cancer treatment.


Asunto(s)
Inteligencia Artificial , Neoplasias , Humanos , Multiómica , Neoplasias/diagnóstico , Neoplasias/genética , Aprendizaje
2.
Proc Natl Acad Sci U S A ; 119(46): e2214164119, 2022 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-36343234

RESUMEN

A quantitative understanding of the coupled dynamics of flow and particles in aerosol and droplet transmission associated with speech remains elusive. Here, we summarize an effort that integrates insights into flow-particle dynamics induced by the production plosive sounds during speech with skin-integrated electronic systems for monitoring the production of these sounds. In particular, we uncover diffusive and ballistic regimes separated by a threshold particle size and characterize the Lagrangian acceleration and pair dispersion. Lagrangian dynamics of the particles in the diffusive regime exhibit features of isotropic turbulence. These fundamental findings highlight the value in skin-interfaced wireless sensors for continuously measuring critical speech patterns in clinical settings, work environments, and the home, based on unique neck biomechanics associated with the generation of plosive sounds. We introduce a wireless, soft device that captures these motions to enable detection of plosive sounds in multiple languages through a convolutional neural network approach. This work spans fundamental flow-particle physics to soft electronic technology, with implications in monitoring and studying critical speech patterns associated with aerosol and droplet transmissions relevant to the spread of infectious diseases.


Asunto(s)
Electrónica , Habla , Aerosoles , Tamaño de la Partícula , Movimiento (Física)
3.
Proc Natl Acad Sci U S A ; 119(45): e2211228119, 2022 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-36322742

RESUMEN

Magnetic targeting is one of the most promising approaches for improving the targeting efficiency by which magnetic drug carriers are directed using external magnetic fields to reach their targets. As a natural magnetic nanoparticle (MNP) of biological origin, the magnetosome is a special "organelle" formed by biomineralization in magnetotactic bacteria (MTB) and is essential for MTB magnetic navigation to respond to geomagnetic fields. The magnetic targeting of magnetosomes, however, can be hindered by the aggregation and precipitation of magnetosomes in water and biological fluid environments due to the strong magnetic attraction between particles. In this study, we constructed a magnetosome-like nanoreactor by introducing MTB Mms6 protein into a reverse micelle system. MNPs synthesized by thermal decomposition exhibit the same crystal morphology and magnetism (high saturation magnetization and low coercivity) as natural magnetosomes but have a smaller particle size. The DSPE-mPEG-coated magnetosome-like MNPs exhibit good monodispersion, penetrating the lesion area of a tumor mouse model to achieve magnetic enrichment by an order of magnitude more than in the control groups, demonstrating great prospects for biomedical magnetic targeting applications.


Asunto(s)
Magnetosomas , Magnetospirillum , Nanopartículas , Neoplasias , Ratones , Animales , Proteínas Bacterianas/metabolismo , Magnetosomas/química , Bacterias Gramnegativas/metabolismo , Nanopartículas/química , Campos Magnéticos , Neoplasias/metabolismo , Magnetospirillum/metabolismo
4.
J Proteome Res ; 23(9): 4139-4150, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39129220

RESUMEN

In this study, we utilized the Olink Cardiovascular III panel to compare the expression levels of 92 cardiovascular-related proteins between patients with dilated cardiomyopathy combined with heart failure (DCM-HF) (n = 20) and healthy normal people (Normal) (n = 18). The top five most significant proteins, including SPP1, IGFBP7, F11R, CHI3L1, and Plaur, were selected by Olink proteomics. These proteins were further validated using ELISA in plasma samples collected from an additional cohort. ELISA validation confirmed significant increases in SPP1, IGFBP7, F11R, CHI3L1, and Plaur in DCM-HF patients compared to healthy controls. GO and KEGG analysis indicated that NT-pro BNP, SPP1, IGFBP7, F11R, CHI3L1, Plaur, BLM hydrolase, CSTB, Gal-4, CCL15, CDH5, SR-PSOX, and CCL2 were associated with DCM-HF. Correlation analysis revealed that these 13 differentially expressed proteins have strong correlations with clinical indicators such as LVEF and NT-pro BNP, etc. Additionally, in the GEO-DCM data sets, the combined diagnostic value of these five core proteins AUC values of 0.959, 0.773, and 0.803, respectively indicating the predictive value of the five core proteins for DCM-HF. Our findings suggest that these proteins may be useful biomarkers for the diagnosis and prediction of DCM-HF, and further research is prompted to explore their potential as therapeutic targets.


Asunto(s)
Biomarcadores , Cardiomiopatía Dilatada , Insuficiencia Cardíaca , Proteómica , Cardiomiopatía Dilatada/sangre , Cardiomiopatía Dilatada/diagnóstico , Humanos , Biomarcadores/sangre , Proteómica/métodos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Osteopontina/sangre , Péptido Natriurético Encefálico/sangre , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 1 Similar a Quitinasa-3/sangre , Fragmentos de Péptidos/sangre , Estudios de Casos y Controles , Adulto , Ensayo de Inmunoadsorción Enzimática
5.
J Am Chem Soc ; 146(29): 20205-20212, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39007348

RESUMEN

Incipient ferroelectrics have emerged as an attractive class of functional materials owing to their potential to be engineered for exotic ferroelectric behavior, holding great promise for expanding the ferroelectric family. However, thus far, their artificially engineered ferroelectricity has fallen far short of rivaling classic ferroelectrics. In this study, we address this challenge by developing a superfine nanodomain engineering strategy. By applying this approach to representative incipient ferroelectric of SrTiO3-based films, we achieve unprecedentedly strong ferroelectricity, not only surpassing previous records for incipient ferroelectrics but also being comparable to classic ferroelectrics. The remanent polarization of the thin film reaches up to 17.0 µC cm-2 with an ultrahigh Curie temperature of 973 K. Atomic-scale investigations elucidate the origin of this robust ferroelectricity in the emergent high-density superfine nanodomains spanning merely 3-10 unit cells. Combining experimental results with theoretical assessments, we unveil the underlying mechanism, where the intentionally introduced diluted foreign Fe element creates a deeper Landau energy well and promotes a short-range ordering of polarization. Our developed strategy significantly streamlines the design of unconventional ferroelectrics, providing a versatile pathway for exploring new and superior ferroelectric materials.

6.
Anal Chem ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014519

RESUMEN

Liver injury significantly affects a patient's health and quality of life. However, timely and convenient diagnosis of this disease via whole blood detection remains challenging due to the lack of user-friendly and fast readout blood test methods. Herein, we developed such a method for the swift auxiliary diagnosis of liver injury via whole blood detection using a customed point-of-care testing (POCT) system consisting of a biothiols-activatable chemiluminescent probe and a hand-held POCT device. Biothiols served as the target to build the activable chemiluminescence probe due to their abnormal level in liver injury. Compared with fluorescent and electrical POCTs, this method is more convenient and has strong universality. By incorporating cyclodextrin via host-guest chemistry, we intensified chemiluminescence while mitigating chemical hemolysis caused by the dissolution of organic molecules, making this system suitable for whole blood analysis. Preliminary assessments in aqueous solutions, living cells, and mouse models confirmed its sensitivity, reliability, and feasibility. Simply mixing blood with the probe for 30 min yielded a clear signal readout within 15 s on the POCT device. Utilizing this portable detector, the reduced biothiol level was tested in 18 liver injury patient blood samples, and the results were similar to those measured by a commercial kit and in vivo imaging system. Thus, this work provides a universal platform for the fast and convenient detection of other biomarkers in whole blood samples and opens up possibilities for the rapid clinical diagnosis of diseases, enabling patients to conduct home self-examinations with ease.

7.
Small ; 20(6): e2306466, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37775327

RESUMEN

Proteins exhibit complex and diverse multi-dimensional structures, along with a wide range of functional groups capable of binding metal ions. By harnessing the unique characteristics of proteins, it is possible to enhance the synthesis of metal-organic frameworks (MOFs) and modify their morphology. Here, the utilization of biomineralized bovine serum albumin (BSA) protein as a template for synthesizing Mil-100 with superior microwave absorption (MA) properties is investigated. The multi-dimensional structure and abundant functional groups of biomineralized BSA protein make it an ideal candidate for guiding the synthesis of Mil-100 with intricate network structures. The BSA@Mil-100 synthesized using this method exhibits exceptional uniformity and monodispersity of nanocrystals. The findings suggest that the BSA protein template significantly influences the regulation of nanocrystal and microstructure formation of Mil-100, resulting in a highly uniform and monodisperse structure. Notably, the synthesized 2-BSA@Mil-100 demonstrates a high reflection loss value of -58 dB at 8.85 GHz, along with a maximum effective absorption bandwidth value of 6.79 GHz, spanning from 6.01 to 12.8 GHz. Overall, this study highlights the potential of utilizing BSA protein as a template for MOF synthesis, offering an effective strategy for the design and development of high-performance MA materials.

8.
Small ; : e2403325, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39314054

RESUMEN

The solution-derived non-stoichiometric nickel oxide (NiOx) is a promising hole-injecting material for stable quantum dot light-emitting diodes (QLEDs). However, the carrier imbalance due to the misalignment of energy levels between the NiOx and polymeric hole-transporting layers (HTLs) curtails the device efficiency. In this study, the modification of the NiOx surface is investigated using either 3-cyanobenzoic acid (3-CN-BA) or 4-cyanobenzoic acid (4-CN-BA) in the QLED fabrication. Morphological and electrical analyses revealed that both 4-CN-BA and 3-CN-BA can enhance the work function of NiOx, reduce the oxygen vacancies on the NiOx surface, and facilitate a uniform morphology for subsequent HTL layers. Moreover, it is found that the binding configurations of dipole molecules as a function of the substitution position of the tail group significantly impact the work function of underlying layers. When integrated in QLEDs, the modification layers resulted in a significant improvement in the electroluminescent efficiency due to the enhancement of energy level alignment and charge balance within the devices. Specifically, QLEDs incorporating 4-CN-BA achieved a champion external quantum efficiency (EQE) of 20.34%, which is a 1.8X improvement in comparison with that of the devices utilizing unmodified NiOx (7.28%). Moreover, QLEDs with 4-CN-BA and 3-CN-BA modifications exhibited prolonged operational lifetimes, indicating potential for practical applications.

9.
PLoS Pathog ; 18(2): e1010299, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35171955

RESUMEN

Influenza A viruses (IAVs) continuously challenge the poultry industry and human health. Elucidation of the host factors that modulate the IAV lifecycle is vital for developing antiviral drugs and vaccines. In this study, we infected A549 cells with IAVs and found that host protein contactin-1 (CNTN1), a member of the immunoglobulin superfamily, enhanced viral replication. Bioinformatic prediction and experimental validation indicated that the expression of CNTN1 was reduced by microRNA-200c (miR-200c) through directly targeting. We further showed that CNTN1-modulated viral replication in A549 cells is dependent on type I interferon signaling. Co-immunoprecipitation experiments revealed that CNTN1 specifically interacts with MAVS and promotes its proteasomal degradation by removing its K63-linked ubiquitination. Moreover, we discovered that the deubiquitinase USP25 is recruited by CNTN1 to catalyze the deubiquitination of K63-linked MAVS. Consequently, the CNTN1-induced degradation cascade of MAVS blocked RIG-I-MAVS-mediated interferon signaling, leading to enhanced viral replication. Taken together, our data reveal novel roles of CNTN1 in the type I interferon pathway and regulatory mechanism of IAV replication.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Contactina 1/metabolismo , Proteína 58 DEAD Box/metabolismo , Virus de la Influenza A/metabolismo , Gripe Humana/virología , MicroARNs/metabolismo , Receptores Inmunológicos/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Células A549 , Interacciones Microbiota-Huesped , Humanos , Interferón Tipo I/metabolismo , Transducción de Señal , Ubiquitinación , Replicación Viral
10.
Clin Genet ; 105(4): 440-445, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38148155

RESUMEN

Nonobstructive azoospermia (NOA), the most severe manifestation of male infertility, lacks a comprehensive understanding of its genetic etiology. Here, a bi-allelic loss-of-function variant in REC114 (c.568C > T: p.Gln190*) were identified through whole exome sequencing (WES) in a Chinese NOA patient. Testicular histopathological analysis and meiotic chromosomal spread analysis were conducted to assess the stage of spermatogenesis arrested. Co-immunoprecipitation (Co-IP) and Western blot (WB) were used to investigate the influence of variant in vitro. In addition, our results revealed that the variant resulted in truncated REC114 protein and impaired interaction with MEI4, which was essential for meiotic DNA double-strand break (DSB) formation. As far as we know, this study presents the first report that identifies REC114 as the causative gene for male infertility. Furthermore, our study demonstrated indispensability of the REC114-MEI4 complex in maintaining DSB homoeostasis, and highlighted that the disruption of the complex due to the REC114 variant may underline the mechanism of NOA.


Asunto(s)
Azoospermia , Infertilidad Masculina , Humanos , Masculino , Azoospermia/genética , Azoospermia/patología , Pérdida de Heterocigocidad , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Testículo/patología , Meiosis/genética , Proteínas de Ciclo Celular/genética
11.
Cardiovasc Diabetol ; 23(1): 215, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907337

RESUMEN

BACKGROUND: Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. METHODS: A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan-Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. RESULTS: During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan-Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05-1.71), 1.52 (1.19-1.93), and 1.84 (1.45-2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. CONCLUSIONS: An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual's glucose metabolism status.


Asunto(s)
Biomarcadores , Glucemia , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Anciano , Glucemia/metabolismo , Biomarcadores/sangre , China/epidemiología , Medición de Riesgo , Incidencia , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/diagnóstico , Factores de Tiempo , Estudios Longitudinales , Pronóstico , Resistencia a la Insulina , Triglicéridos/sangre , HDL-Colesterol/sangre , Dislipidemias/sangre , Dislipidemias/epidemiología , Dislipidemias/diagnóstico , Aterosclerosis/sangre , Aterosclerosis/epidemiología , Aterosclerosis/diagnóstico , Estudios Prospectivos
12.
Toxicol Appl Pharmacol ; 486: 116947, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38688426

RESUMEN

AIMS: SERCA2, one of the P-type pumps encoded by gene ATP2A2, is the only calcium reflux channel of the endoplasmic reticulum (ER) and participates in maintaining calcium homeostasis. The present study was designed to explore SERCA2 expression pattern in auditory hair cells and the possible mechanism underlying the effects of SERCA2 on cisplatin-induced ototoxicity. MAIN METHODS: The SERCA2 expression pattern in cochlea hair cells and HEI-OC1 cells was measured by Western blot (WB) and immunofluorescence staining. The apoptosis and its related factors were detected by TUNEL assay and WB. The expression levels of ER stress-related factors, ATF6, PERK, IRE1α, and GRP78, were measured via WB. As for the determination of SERCA2 overexpression and knockdown, plasmids and lentiviral vectors were constructed, respectively. KEY FINDINGS: We found that SERCA2 was highly expressed in cochlea hair cells and HEI-OC1 cells. Of note, the level of SERCA2 expression in neonatal mice was remarkably higher than that in adult mice. Under the exposure of 30 µM cisplatin, SERCA2 was down-regulated significantly compared with the control group. In addition, cisplatin administration triggered the occurrence of ER stress and apoptosis. Those events were reversed by overexpressing SERCA2. On the contrary, SERCA2 knockdown could aggravate the above processes. SIGNIFICANCE: The findings from the present study disclose, for the first time, that SERCA2 is abundantly expressed in cochlea hair cells, and the suppression of SERCA2 caused by cisplatin could trigger ER homeostasis disruption, thereby implying that SERCA2 might be a promising target to prevent cisplatin-induced cytotoxicity of hair cells.


Asunto(s)
Apoptosis , Cisplatino , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Células Ciliadas Auditivas , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico , Cisplatino/toxicidad , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Apoptosis/efectos de los fármacos , Células Ciliadas Auditivas/efectos de los fármacos , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patología , Línea Celular , Antineoplásicos/toxicidad , Masculino , Ototoxicidad/prevención & control
13.
Respir Res ; 25(1): 365, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39385167

RESUMEN

BACKGROUND: Pulmonary hypertension (PH) is marked by elevated pulmonary artery pressures due to various causes, impacting right heart function and survival. Disulfidptosis, a newly recognized cell death mechanism, may play a role in PH, but its associated genes (DiGs) are not well understood in this context. This study aims to define the diagnostic relevance of DiGs in PH. METHODS: Using GSE11726 data, we analyzed DiGs and their immune characteristics to identify core genes influencing PH progression. Various machine learning models, including RF, SVM, GLM, and XGB, were compared to determine the most effective diagnostic model. Validation used datasets GSE57345 and GSE48166. Additionally, a CeRNA network was established, and a hypoxia-induced PH rat model was used for experimental validation with Western blot analysis. RESULTS: 12 DiGs significantly associated with PH were identified. The XGB model excelled in diagnostic accuracy (AUC = 0.958), identifying core genes DSTN, NDUFS1, RPN1, TLN1, and MYH10. Validation datasets confirmed the model's effectiveness. A CeRNA network involving these genes, 40 miRNAs, and 115 lncRNAs was constructed. Drug prediction suggested therapeutic potential for folic acid, supported by strong molecular docking results. Experimental validation in a rat model aligned with these findings. CONCLUSION: We uncovered the distinct expression patterns of DiGs in PH, identified core genes utilizing an XGB machine-learning model, and established a CeRNA network. Drugs targeting the core genes were predicted and subjected to molecular docking. Experimental validation was also conducted for these core genes.


Asunto(s)
Hipertensión Pulmonar , Animales , Ratas , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/diagnóstico , Masculino , Humanos , Ratas Sprague-Dawley , Aprendizaje Automático , Bases de Datos Genéticas , Redes Reguladoras de Genes , Modelos Animales de Enfermedad
14.
Biotechnol Bioeng ; 121(7): 2133-2146, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38634289

RESUMEN

L-cysteine is an important sulfur-containing amino acid being difficult to produce by microbial fermentation. Due to the lack of high-throughput screening methods, existing genetically engineered bacteria have been developed by simply optimizing the expression of L-cysteine-related genes one by one. To overcome this limitation, in this study, a biosensor-based approach for multilevel biosynthetic pathway optimization of L-cysteine from the DecR regulator variant of Escherichia coli was applied. Through protein engineering, we obtained the DecRN29Y/C81E/M90Q/M99E variant-based biosensor with improved specificity and an 8.71-fold increase in dynamic range. Using the developed biosensor, we performed high-throughput screening of the constructed promoter and RBS combination library, and successfully obtained the optimized strain, which resulted in a 6.29-fold increase in L-cysteine production. Molecular dynamics (MD) simulations and electrophoretic mobility shift analysis (EMSA) showed that the N29Y/C81E/M90Q/M99E variant had enhanced induction activity. This enhancement may be due to the increased binding of the variant to DNA in the presence of L-cysteine, which enhances transcriptional activation. Overall, our biosensor-based strategy provides a promising approach for optimizing biosynthetic pathways at multiple levels. The successful implementation of this strategy demonstrates its potential for screening improved recombinant strains.


Asunto(s)
Técnicas Biosensibles , Cisteína , Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Cisteína/metabolismo , Cisteína/genética , Cisteína/biosíntesis , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Ingeniería Metabólica/métodos , Ingeniería de Proteínas/métodos , Vías Biosintéticas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
15.
Artículo en Inglés | MEDLINE | ID: mdl-38904989

RESUMEN

TwoGram-stain-positive and rod-shaped actinomycetes (strains CDC186T and CDC192) were isolated from sputum samples of a patient in Chongqing, PR China, and were investigated to determine their taxonomic status. The results of phylogenetic analysis based on the 16S rRNA gene indicated that CDC186T and CDC192 represented members of the genus Nocardia, and the sequence similarity with Nocardia beijingensis DSM 44636T was the highest, at 99.71 and 99.78 %, respectively. The DNA G+C content of both CDC186T and CDC192 was 69.1 %. Genomic diversity analysis revealed that the average nucleotide identity and in silico DNA‒DNA hybridisation values between the two novel strains and closely related species were significantly below the thresholds of 95-96 and 70 %, respectively, but these values between the two novel strains were 99.96 and 99.90 %, respectively. The phylogenetic relationship based on the dapb1 gene and the single-copy core genes further indicated that the two novel strains were clustered in separate branch adjacent to N. beijingensis DSM 44636T. Growth occurred within the ranges of 20-42 °C, pH 6.0-9.0 and NaCl concentrations of 0.5-4.5 % (w/v). The major fatty acids of CDC186T and CDC192 were C16 : 0 and C18 : 0 10-methyl [tuberculostearic acid (TBSA)]. The predominant respiratory menaquinone was MK-9. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, one unidentified glycolipid, one unidentified phospholipid and one unidentified phosphoglycolipid. All the genomes of the studied strains were annotated with virulence factor (VF)-associated genes homologous to those of Mycobacterium tuberculosis, and the results of susceptibility testing indicated that CDC186T and CDC192 were resistant to amoxicillin-clavulanic acid and tigecycline. On the basis of chemotaxonomic characteristics and the results of phylogenetic analyses, strains CDC186T and CDC192 represent a novel species within the genus Nocardia, for which the name Nocardia implantans sp. nov. is proposed. The type strain is CDC186T (=GDMCC 4.206T= JCM 34959T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Nocardiosis , Nocardia , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Esputo , Nocardia/aislamiento & purificación , Nocardia/genética , Nocardia/clasificación , Humanos , ARN Ribosómico 16S/genética , China , ADN Bacteriano/genética , Ácidos Grasos/análisis , Ácidos Grasos/química , Nocardiosis/microbiología , Esputo/microbiología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Genoma Bacteriano
16.
Inorg Chem ; 63(32): 15098-15104, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39072372

RESUMEN

Interfacial strain engineering can induce structural transformation and introduce new physical properties into materials, which is an effective method to prepare new multifunctional materials. However, interfacial strain has a limited spatial impact size. For example, in 2D thin films, the critical thickness of biaxial strain is typically less than 20 nm, which is not conducive to the maintenance of a strained structure and properties in thick film materials. The construction of a 3D interface can solve this problem. The large lattice mismatch between the BaZrO3 thin film and the substrate can induce the out-of-phase boundary (OPB) structure, which can extend along the thickness direction with the stacking of atoms. The lattice distortion at the OPB structure can provide a clamping effect for each layer of atoms, thus expanding the spatial influence range of biaxial strain. As a result, the uniform in-plane strain distribution and strain-induced ferroelectricity (Pr = 13 µC/cm2) are maintained along the thickness direction in BaZrO3 films.

17.
BMC Infect Dis ; 24(1): 1016, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304798

RESUMEN

BACKGROUND: Nocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue. METHODS: BALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested. RESULTS: Intraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes. CONCLUSION: The study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.


Asunto(s)
Encéfalo , Citocinas , Ratones Endogámicos BALB C , Nocardiosis , Nocardia , Animales , Nocardia/genética , Nocardiosis/microbiología , Nocardiosis/inmunología , Ratones , Citocinas/sangre , Femenino , Encéfalo/microbiología , Encéfalo/patología , Pulmón/microbiología , Pulmón/patología , Modelos Animales de Enfermedad , Carga Bacteriana
18.
Environ Res ; 244: 117946, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38104915

RESUMEN

The industrialization of hydrogen production through dark fermentation of food waste faces challenges, such as low yields and unpredictable fermentation processes. Biochar has emerged as a promising green additive to enhance hydrogen production in dark fermentation. Our study demonstrated that the introduction of Fe-modified biochar (Fe-L600) significantly boosted hydrogen production during thermophilic dark fermentation of food waste. The addition of Fe-L600 led to a remarkable 31.19% increase in hydrogen yield and shortened the time needed for achieving stabilization of hydrogen production from 18 h to 12 h. The metabolite analysis revealed an enhancement in the butyric acid pathway as the molar ratio of acetic acid to butyric acid decreased from 3.09 to 2.69 but hydrogen yield increased from 57.12 ± 1.48 to 76.78 ± 2.77 mL/g, indicating Fe-L600 improved hydrogen yield by regulating crucial metabolic pathways of hydrogen production. The addition of Fe-L600 also promoted the release of Fe2+ and Fe3+ and increased the concentrations of Fe2+ and Fe3+ in the fermentation system, which might promote the activity of hydrogenase and ferredoxin. Microbial community analysis indicated a substantial increase in the relative abundance of Thermoanaerobacterium after thermophilic dark fermentation. The relative abundances of microorganisms responsible for hydrolysis and acidogenesis were also observed to be improved in the system with Fe-L600 addition. This research provides a feasible strategy for improving hydrogen production of food waste and deepens the understanding of the mechanisms of biochar.


Asunto(s)
Carbón Orgánico , Alimento Perdido y Desperdiciado , Eliminación de Residuos , Fermentación , Alimentos , Ácido Butírico , Hidrógeno/metabolismo
19.
BMC Pregnancy Childbirth ; 24(1): 390, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802735

RESUMEN

BACKGROUND: The rising number of women giving birth at advanced maternal age has posed significant challenges in obstetric care in recent years, resulting in increased incidence of neonatal transfer to the Neonatal Intensive Care Unit (NICU). Therefore, identifying fetuses requiring NICU transfer before delivery is essential for guiding targeted preventive measures. OBJECTIVE: This study aims to construct and validate a nomogram for predicting the prenatal risk of NICU admission in neonates born to mothers over 35 years of age. STUDY DESIGN: Clinical data of 4218 mothers aged ≥ 35 years who gave birth at the Department of Obstetrics of the Second Hospital of Shandong University between January 1, 2017 and December 31, 2021 were reviewed. Independent predictors were identified by multivariable logistic regression, and a predictive nomogram was subsequently constructed for the risk of neonatal NICU admission. RESULTS: Multivariate logistic regression demonstrated that the method of prenatal screening, number of implanted embryos, preterm premature rupture of the membranes, preeclampsia, HELLP syndrome, fetal distress, premature birth, and cause of preterm birth are independent predictors of neonatal NICU admission. Analysis of the nomogram decision curve based on these 8 independent predictors showed that the prediction model has good net benefit and clinical utility. CONCLUSION: The nomogram demonstrates favorable performance in predicting the risk of neonatal NICU transfer after delivery by mothers older than 35 years. The model serves as an accurate and effective tool for clinicians to predict NICU admission in a timely manner.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Edad Materna , Nomogramas , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , China/epidemiología , Pueblos del Este de Asia , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Modelos Logísticos , Admisión del Paciente/estadística & datos numéricos , Nacimiento Prematuro/epidemiología , Diagnóstico Prenatal/métodos , Diagnóstico Prenatal/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo
20.
BMC Geriatr ; 24(1): 462, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802742

RESUMEN

BACKGROUND: The feasibility and safety of laparoscopic pancreatoduodenectomy (LPD) in elderly patients is still controversial. This study aimed to compare the clinical outcomes of LPD and open pancreatoduodenectomy (OPD) in elderly patients. METHODS: Clinical and follow-up data of elderly patients (≥ 65 years) who underwent LPD or OPD between 2015 and 2022 were retrospectively analyzed. A 1:1 propensity score-matching (PSM) analysis was performed to minimize differences between groups. Univariate and multivariate logistic regression analysis were used to select independent prognostic factors for 90-day mortality. RESULTS: Of the 410 elderly patients, 236 underwent LPD and 174 OPD. After PSM, the LPD group had a less estimated blood loss (EBL) (100 vs. 200 mL, P < 0.001), lower rates of intraoperative transfusion (10.4% vs. 19.0%, P = 0.029), more lymph node harvest (11.0 vs. 10.0, P = 0.014) and shorter postoperative length of stay (LOS) (13.0 vs. 16.0 days, P = 0.013). There were no significant differences in serious complications, reoperation, 90-day readmission and mortality rates (all P > 0.05). Multivariate logistic regression analysis showed that post-pancreatectomy hemorrhage (PPH) was an independent risk factor for 90-day mortality. Elderly patients with pancreatic ductal adenocarcinoma (PDAC) who underwent LPD or OPD had similar overall survival (OS) (22.5 vs.20.4 months, P = 0.672) after PSM. CONCLUSIONS: It is safe and feasible for elderly patients to undergo LPD with less EBL and a shorter postoperative LOS. There was no statistically significant difference in long-term survival outcomes between elderly PDAC patients who underwent LPD or OPD.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Puntaje de Propensión , Humanos , Pancreaticoduodenectomía/métodos , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/tendencias , Anciano , Masculino , Femenino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Laparoscopía/tendencias , Estudios Retrospectivos , Neoplasias Pancreáticas/cirugía , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Anciano de 80 o más Años , Factores de Tiempo , Tiempo de Internación/tendencias
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