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1.
Nano Lett ; 24(14): 4165-4171, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38534019

RESUMEN

An electrical-controllable antiferromagnet tunnel junction is a key goal in spintronics, holding immense promise for ultradense and ultrastable antiferromagnetic memory with high processing speed for modern information technology. Here, we have advanced toward this goal by achieving an electrical-controllable antiferromagnet-based tunnel junction of Pt/Co/Pt/Co/IrMn/MgO/Pt. The exchange coupling between antiferromagnetic IrMn and Co/Pt perpendicular magnetic multilayers results in the formation of an interfacial exchange bias and exchange spring in IrMn. Encoding information states "0" and "1" is realized through the exchange spring in IrMn, which can be electrically written by spin-orbit torque switching with high cyclability and electrically read by antiferromagnetic tunneling anisotropic magnetoresistance. Combining spin-orbit torque switching of both exchange spring and exchange bias, a 16 Boolean logic operation is successfully demonstrated. With both memory and logic functionalities integrated into our electrically controllable antiferromagnetic-based tunnel junction, we chart the course toward high-performance antiferromagnetic logic-in-memory.

2.
Nano Lett ; 24(18): 5420-5428, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38666707

RESUMEN

Artificial intelligence has surged forward with the advent of generative models, which rely heavily on stochastic computing architectures enhanced by true random number generators with adjustable sampling probabilities. In this study, we develop spin-orbit torque magnetic tunnel junctions (SOT-MTJs), investigating their sigmoid-style switching probability as a function of the driving voltage. This feature proves to be ideally suited for stochastic computing algorithms such as the restricted Boltzmann machines (RBM) prevalent in pretraining processes. We exploit SOT-MTJs as both stochastic samplers and network nodes for RBMs, enabling the implementation of RBM-based neural networks to achieve recognition tasks for both handwritten and spoken digits. Moreover, we further harness the weights derived from the preceding image and speech training processes to facilitate cross-modal learning from speech to image generation. Our results clearly demonstrate that these SOT-MTJs are promising candidates for the development of hardware accelerators tailored for Boltzmann neural networks and other stochastic computing architectures.

3.
EMBO J ; 39(4): e102856, 2020 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-31922267

RESUMEN

Plant pattern recognition receptors (PRRs) perceive pathogen-associated molecular patterns (PAMPs) to activate immune responses. Medium-chain 3-hydroxy fatty acids (mc-3-OH-FAs), which are widely present in Gram-negative bacteria, were recently shown to be novel PAMPs in Arabidopsis thaliana. The Arabidopsis PRR LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) is a G-type lectin receptor-like kinase that recognizes mc-3-OH-FAs and subsequently mounts an immune response; however, the mechanisms underlying LORE activation and downstream signaling are unexplored. Here, we report that one of the mc-3-OH-FAs, 3-OH-C10:0, induces phosphorylation of LORE at tyrosine residue 600 (Y600). Phosphorylated LORE subsequently trans-phosphorylates the receptor-like cytoplasmic kinase PBL34 and its close paralogs, PBL35 and PBL36, and therefore activates plant immunity. Phosphorylation of LORE Y600 is required for downstream phosphorylation of PBL34, PBL35, and PBL36. However, the Pseudomonas syringae effector HopAO1 targets LORE, dephosphorylating the tyrosine-phosphorylated Y600 and therefore suppressing the immune response. These observations uncover the mechanism by which LORE mediates signaling in response to 3-OH-C10:0 in Arabidopsis.


Asunto(s)
Arabidopsis/inmunología , Enfermedades de las Plantas/inmunología , Inmunidad de la Planta/genética , Pseudomonas syringae/inmunología , Arabidopsis/genética , Arabidopsis/microbiología , Regulación de la Expresión Génica de las Plantas , Lectinas/metabolismo , Lipopolisacáridos/administración & dosificación , Fosforilación , Enfermedades de las Plantas/microbiología , Receptores de Reconocimiento de Patrones/genética , Receptores de Reconocimiento de Patrones/metabolismo , Transducción de Señal , Tirosina/metabolismo
4.
Small ; 20(10): e2306736, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37880862

RESUMEN

Superionic halides have aroused interests in field of solid electrolytes such as Li2 ZrCl6 . However, they are still facing challenges including poor air stability which lacks in-depth investigation. Here, moisture instability of Li2 ZrCl6 is demonstrated and decomposition mechanism in air is clearly revealed. Li2 ZrCl6 decomposes into Li2 ZrO3 , ZrOCl2 ·xH2 O and LiCl during initial stage as halides upon moisture exposure. Later, these side products evolve into LiCl(H2 O) and Li6 Zr2 O7 after longer time exposure. More importantly, structure of destroyed halides cannot be recovered after postheating. Later, Indium is doped into Li2 ZrCl6 (9.7 × 10-5 S cm-1 ) to explore its effect on structure and properties. Crystal structure of ball-milled In-doped Li2 ZrCl6 electrolytes is converted from the Li3 YCl6 -like to Li3 InCl6 -like with increasing In content and ionic conductivity can also be enhanced (0.768-1.13) × 10-3 S cm-1 ). More importantly, good air stability of optimal Li2.8 Zr0.2 In0.8 Cl6 is achieved since halide hydrates are formed after air exposure instead of total decomposition and the hydrates can be restored to Li2.8 Zr0.2 In0.8 Cl6 after postheating. Moreover, reheated Li2.8 Zr0.2 In0.8 Cl6 after air exposure is successfully applied in solid-state LiNi0.8 Co0.1 Mn0.1 O2 /halides/Li6 PS5 Cl/Li-In battery. The results in this work can provide insights into air instability of Li2 ZrCl6 and effective strategy to regulate air stability of halides.

5.
Plant Cell ; 33(6): 2015-2031, 2021 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-33751120

RESUMEN

Acquisition of nutrients from different species is necessary for pathogen colonization. Iron is an essential mineral nutrient for nearly all organisms, but little is known about how pathogens manipulate plant hosts to acquire iron. Here, we report that AvrRps4, an effector protein delivered by Pseudomonas syringae bacteria to plants, interacts with and targets the plant iron sensor protein BRUTUS (BTS) to facilitate iron uptake and pathogen proliferation in Arabidopsis thaliana. Infection of rps4 and eds1 by P. syringae pv. tomato (Pst) DC3000 expressing AvrRps4 resulted in iron accumulation, especially in the plant apoplast. AvrRps4 alleviates BTS-mediated degradation of bHLH115 and ILR3(IAA-Leucine resistant 3), two iron regulatory proteins. In addition, BTS is important for accumulating immune proteins Enhanced Disease Susceptibility1 (EDS1) at both the transcriptional and protein levels upon Pst (avrRps4) infections. Our findings suggest that AvrRps4 targets BTS to facilitate iron accumulation and BTS contributes to RPS4/EDS1-mediated immune responses.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Proteínas Bacterianas/metabolismo , Interacciones Huésped-Patógeno/fisiología , Hierro/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/inmunología , Proteínas Bacterianas/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica de las Plantas , Mutación , Inmunidad de la Planta/genética , Plantas Modificadas Genéticamente , Pseudomonas syringae/metabolismo , Pseudomonas syringae/patogenicidad , Ubiquitina-Proteína Ligasas/genética
6.
Nano Lett ; 23(20): 9482-9490, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37818857

RESUMEN

Racetrack memories with magnetic skyrmions have recently been proposed as a promising storage technology. To be appealing, several challenges must still be faced for the deterministic generation of skyrmions, their high-fidelity transfer, and accurate reading. Here, we realize the first proof-of-concept of a 9-bit skyrmion racetrack memory with all-electrical controllable functionalities implemented in the same device. The key ingredient is the generation of a tailored nonuniform distribution of magnetic anisotropy via laser irradiation in order to (i) create a well-defined skyrmion nucleation center, (ii) define the memory cells hosting the information coded as the presence/absence of skyrmions, and (iii) improve the signal-to-noise ratio of anomalous Hall resistance measurements. This work introduces a strategy to unify previous findings and predictions for the development of a generation of racetrack memories with robust control of skyrmion nucleation and position, as well as effective skyrmion electrical detection.

7.
Metabolomics ; 19(10): 86, 2023 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-37776501

RESUMEN

INTRODUCTION: Femur head necrosis (FHN) is a challenging clinical disease with unclear underlying mechanism, which pathologically is associated with disordered metabolism. However, the disordered metabolism in cancellous bone of FHN was never analyzed by gas chromatography-mass spectrometry (GC-MS). OBJECTIVES: To elucidate altered metabolism pathways in FHN and identify putative biomarkers for the detection of FHN. METHODS: We recruited 26 patients with femur head necrosis and 22 patients with femur neck fracture in this study. Cancellous bone tissues from the femoral heads were collected after the surgery and were analyzed by GC-MS based untargeted metabolomics approach. The resulting data were analyzed via uni- and multivariate statistical approaches. The changed metabolites were used for the pathway analysis and potential biomarker identification. RESULTS: Thirty-seven metabolites distinctly changed in FHN group were identified. Among them, 32 metabolites were upregulated and 5 were downregulated in FHN. The pathway analysis showed that linoleic acid metabolism were the most relevant to FHN pathology. On the basis of metabolites network, L-lysine, L-glutamine and L-serine were deemed as the junctions of the whole metabolites. Finally, 9,12-octadecadienoic acid, inosine, L-proline and octadecanoic acid were considered as the potential biomarkers of FHN. CONCLUSION: This study provides a new insight into the pathogenesis of FHN and confirms linoleic acid metabolism as the core.


Asunto(s)
Necrosis de la Cabeza Femoral , Metabolómica , Humanos , Cromatografía de Gases y Espectrometría de Masas/métodos , Metabolómica/métodos , Ácido Linoleico , Hueso Esponjoso , Biomarcadores
8.
Nano Lett ; 22(17): 6857-6865, 2022 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-35849087

RESUMEN

Perpendicularly magnetized structures that are switchable using a spin current under field-free conditions can potentially be applied in spin-orbit torque magnetic random-access memory (SOT-MRAM). Several structures have been developed; however, new structures with a simple stack structure and MRAM compatibility are urgently needed. Herein, a typical structure in a perpendicular spin-transfer torque MRAM, the Pt/Co multilayer and its synthetic antiferromagnetic counterpart with perpendicular magnetic anisotropy, was observed to possess an intrinsic interlayer chiral interaction between neighboring magnetic layers, namely, the interlayer Dzyaloshinskii-Moriya interaction (DMI) effect. Furthermore, using a current parallel to the eigenvector of the interlayer DMI, we switched the perpendicular magnetization of both structures without a magnetic field, owing to the additional symmetry breaking introduced by the interlayer DMI. This SOT switching scheme realized in the Pt/Co multilayer and its synthetic antiferromagnet structure may open a new avenue toward practical perpendicular SOT-MRAM and other SOT devices.

9.
Sleep Breath ; 23(1): 259-267, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29992456

RESUMEN

PURPOSE: Obstructive sleep apnea (OSA) is induced by obstruction of the upper airway, which can raise multiple health risks. This study is designed to reveal the key genes involved in OSA. METHODS: GSE38792 was extracted from Gene Expression Omnibus database, including ten visceral adipose tissues from OSA patients and eight visceral adipose tissues from normal controls. Differential expression analysis was conducted using limma package, and then the functions of the differentially expressed genes (DEGs) were analyzed using DAVID database, followed by protein-protein interaction (PPI) network, and integrated regulatory network analysis was performed using Cytoscape software. RESULTS: A total of 368 DEGs (176 upregulated and 192 downregulated) were identified in OSA samples. Epstein-Barr virus infection (involving IL10RB, MAPK9, and MAPK10) and olfactory transduction were the main pathways separately enriched for the upregulated genes and the downregulated genes. After the PPI network was built, the top ten network nodes (such as TXN) were selected according to node degrees. Two significant PPI network modules were identified. Moreover, the integrated regulatory network was constructed. CONCLUSION: IL10RB, MAPK9, MAPK10, and TXN might function in the pathogenesis of OSA.


Asunto(s)
Biología Computacional , Apnea Obstructiva del Sueño/genética , Tejido Adiposo/metabolismo , Regulación hacia Abajo/genética , Infecciones por Virus de Epstein-Barr/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes/genética , Humanos , Subunidad beta del Receptor de Interleucina-10/genética , Proteína Quinasa 10 Activada por Mitógenos/genética , Proteína Quinasa 9 Activada por Mitógenos/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Dominios y Motivos de Interacción de Proteínas/genética , Valores de Referencia , Tiorredoxinas/genética , Regulación hacia Arriba/genética
10.
Clin Infect Dis ; 67(suppl_2): S249-S255, 2018 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-30423040

RESUMEN

Background: Vancomycin is a first-line antibiotic used for the treatment of severe gram-positive bacterial infections. Clinical guidelines recommend that the vancomycin trough concentration be 10-15 mg/L for regular infections and 15-20 mg/L for severe infections. We investigated whether increasing the vancomycin concentration would result in better clinical outcomes with sustainable adverse effects (AEs) in the Chinese population. Methods: A prospective, open, multicenter clinical observational study was performed in patients with gram-positive bacterial infections from 13 teaching hospitals. Patients received vancomycin therapeutic drug monitoring. Clinical, microbiological, and laboratory data were collected. Results: In total, 510 patients were enrolled, and 470 were evaluable, of whom 370 were adults and 100 were children; 35.53% had methicillin-resistant Staphylococcus aureus infections (vancomycin 50% minimum inhibitory concentration [MIC50] = 1, 90% minimum inhibitory concentration [MIC90] = 1), and 23.19% had Enterococcus species infections (vancomycin MIC50 = 1, MIC90 = 2). The average trough concentration was 10.54 ± 8.08 mg/L in adults and 6.74 ± 8.93 mg/L in children. The infection was eradicated in 86.22% of adults and 96% of children. Thirty-six vancomycin-related nephrotoxicity cases were reported in the enrolled population. No severe AEs or deaths were related to vancomycin therapy. Logistic regression analysis showed that trough concentration had no relationship with clinical outcomes (adults P = .75, children P = .68) but was correlated with adult nephrotoxicity (P < .0001). Vancomycin trough concentration had an applicable cut point at 13 mg/L. Conclusions: Our study shows that vancomycin trough concentration has no statistical correlation with clinical outcomes, and is an indicator of nephrotoxicity in the observed population. We found no evidence that increasing vancomycin trough concentration to 15-20 mg/L can benefit Chinese patients with complicated infections. Clinical Trials Registration: ChiCTR-OPC-16007920.


Asunto(s)
Antibacterianos/uso terapéutico , Monitoreo de Drogas , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Vancomicina/uso terapéutico , Adolescente , Anciano , Niño , Preescolar , China , Relación Dosis-Respuesta a Droga , Femenino , Hospitales de Enseñanza , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Prospectivos
11.
Clin Infect Dis ; 67(suppl_2): S256-S262, 2018 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-30423042

RESUMEN

Background: Our aims in this prospective study were to evaluate the correlations between pharmacokinetic/pharmacodynamic (PK/PD) indices and the clinical/microbiological efficacy of vancomycin and to identify an appropriate PK/PD target in the Chinese population to guide vancomycin treatment in the clinic. Methods: Adult patients from 11 hospitals in China with gram-positive infections who received vancomycin therapy for ≥5 days and who were under therapeutic drug monitoring (TDM) were enrolled in this study. A 1-compartment population PK model was established and validated. The correlations between PK/PD indices (Cmin, Cmax, 0-24 hour area under the curve (AUC0-24), and AUC0-24/minimum inhibitory concentration (MIC) and clinical outcomes (clinical efficacy and bacterial eradication) were evaluated. Results: In total, 402 adult Chinese patients were enrolled. Among them, 380 patients were evaluable for PK analysis, and 334 were evaluable for PK/PD analysis. In the final population PK model, creatinine clearance (CLCR) was the significant covariate on CL (typical value, 3.87 L/hour; between-subject variability (BSV), 12.5%), and age was the significant covariate on volume of distribution (V) (typical value, 45.1 L; BSV, 24.8%). The univariate analysis showed that Cmax, AUC0-24, and AUC0-24/MIC were significantly different or marginally significantly different (P values were 0.009, 0.0385, and 0.0509, respectively) between microbiological outcome groups with coagulase-negative Staphylococcus infections. However, there were no significant differences (P > .05) in the above PK parameters by multivariate logistic regression analysis, indicating there was no independently associated factor. Conclusions: No significant correlations were identified between PK/PD indices and the clinical or microbiological efficacy of vancomycin in Chinese patients. The necessity of vancomycin TDM based on trough concentration and the current treatment target of AUC0-24/MIC ≥400 need to be further evaluated and confirmed in additional prospective studies.


Asunto(s)
Antibacterianos/farmacocinética , Monitoreo de Drogas , Vancomicina/farmacocinética , Anciano , Antibacterianos/uso terapéutico , Área Bajo la Curva , China , Femenino , Hospitales , Humanos , Pacientes Internos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Modelos Estadísticos , Estudios Prospectivos , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus/efectos de los fármacos , Resultado del Tratamiento , Vancomicina/uso terapéutico
12.
Plant Physiol ; 174(4): 2501-2514, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28696275

RESUMEN

Plant surface-localized pathogen recognition receptors (PRRs) perceive conserved microbial features, termed pathogen-associated molecular patterns (PAMPs), resulting in disease resistance. PAMP perception leads to calcium influx, MAPK activation, a burst of reactive oxygen species (ROS) mediated by RbohD, accumulation of the defense hormone salicylic acid (SA), and callose deposition. Lectin receptor-like kinases (LecRKs) belong to a specific PRR family and are important players in plant innate immunity. Here, we report that LecRK-IX.2 is a positive regulator of PRR-triggered immunity. Pathogen infection activated the transcription of Arabidopsis (Arabidopsis thaliana) LecRK-IX.2, and the LecRK-IX.2 knockout lines exhibited enhanced susceptibility to virulent Pseudomonas syringae pv tomato DC3000. In addition, LecRK-IX.2 is capable of inducing RbohD phosphorylation, likely by recruiting calcium-dependent protein kinases to trigger ROS production in Arabidopsis. Overexpression of LecRK-IX.2 resulted in elevated ROS and SA and enhanced systemic acquired resistance to P. syringae pv tomato DC3000. Our data highlight the importance of LecRKs in plant immune signaling and SA accumulation.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , Lectinas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Ácido Salicílico/metabolismo , Transducción de Señal , Arabidopsis/genética , Arabidopsis/inmunología , Arabidopsis/microbiología , Muerte Celular , Resistencia a la Enfermedad , Flagelina/metabolismo , Regulación de la Expresión Génica de las Plantas , Modelos Biológicos , Mutación/genética , Fenotipo , Fosforilación , Enfermedades de las Plantas/microbiología , Inmunidad de la Planta , Unión Proteica , Proteínas Quinasas/metabolismo , Pseudomonas syringae/fisiología
13.
BMC Pulm Med ; 18(1): 21, 2018 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-29375033

RESUMEN

BACKGROUND: Chyloptysis is reflux of chyle into the lungs and is a rare manifestation of primary chylous disorders. CASE PRESENTATION: Over 29 months, on the basis of x-rays, a 33-year-old female was repeatedly misdiagnosed with recurrent right-sided pneumonia; her symptoms included a recurrent cough, the appearance of cheese-like sputum, and diffuse pulmonary exudates. There was a history that abundant fluid in the pericardium was confirmed with echocardiography to have been present and asymptomatic for 4 years. Lymphangiography and surgery confirmed that the terminal portion of the thoracic duct was compressed by thick fibrous tissue and the vascular sheath of the internal jugular vein. Chyloptysis caused by high peribronchial lymphatic pressure was diagnosed and surgical intervention relieved the symptoms. CONCLUSION: Chyloptysis is rare and easy to misdiagnose but is a typical symptom of chylous reflux syndrome.


Asunto(s)
Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Linfáticas/diagnóstico por imagen , Derrame Pericárdico/diagnóstico por imagen , Neumonía/diagnóstico , Conducto Torácico/diagnóstico por imagen , Adulto , Quilo , Constricción Patológica , Tos , Errores Diagnósticos , Ecocardiografía , Femenino , Humanos , Linfografía
14.
Mol Plant Microbe Interact ; 30(6): 502-512, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28353399

RESUMEN

Bacterial pathogen Pseudomonas syringae delivers diverse type III effectors into host cells to interfere with their immune responses. One of the effectors, AvrB, targets a host guardee protein RIN4 and induces RIN4 phosphorylation in Arabidopsis. Phosphorylated RIN4 activates the immune receptor RPM1 to mount defense. AvrB-induced RIN4 phosphorylation depends on RIPK, a receptor-like cytoplasmic kinase (RLCK). In this study, we found several other RLCKs that were also able to phosphorylate RIN4. We demonstrated that these RLCKs formed a complex with RIPK and were functionally redundant to RIPK. We also found that unphosphorylated RIN4 was epistatic to phosphorylated RIN4 in terms of RPM1 activation. AvrB-induced RLCK gene expression and phosphorylated RIN4-triggered RPM1 activation required RAR1, a central regulator in plant innate immunity. Our results unravel a mechanism in which plants employ multiple kinases to hyperphosphorylate the guardee protein RIN4 to ensure immune activation during pathogen invasion.


Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Proteínas Bacterianas/genética , Proteínas Portadoras/genética , Pseudomonas syringae/genética , Receptores Citoplasmáticos y Nucleares/genética , Arabidopsis/metabolismo , Arabidopsis/microbiología , Proteínas de Arabidopsis/metabolismo , Proteínas Portadoras/metabolismo , Regulación de la Expresión Génica de las Plantas , Interacciones Huésped-Patógeno/genética , Péptidos y Proteínas de Señalización Intracelular , Mutación , Fosforilación , Plantas Modificadas Genéticamente , Unión Proteica , Pseudomonas syringae/fisiología , Receptores Citoplasmáticos y Nucleares/metabolismo
15.
Respirol Case Rep ; 12(6): e01391, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38831800

RESUMEN

Odontogenic infections can spread to the respiratory tract. Despite the known role of Tannerella forsythia as the primary pathogen in periodontitis, the association between T. forsythia infection and risk of pneumonia or lung abscess remains unknown. In this report, we present a case of lung abscess caused by T. forsythia infection. The pathogen was detected by metagenomic next-generation sequencing (mNGS) in the bronchoalveolar lavage fluid of the patient. The clinical characteristics and possible mechanisms of the infection are discussed. T. forsythia is a conditional pathogen that can cause lung abscess in the presence of helper bacteria and reduced host immune status. The course of treatment should be personalized and might be longer than 3 months.

16.
Cell Signal ; 124: 111399, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39251054

RESUMEN

BACKGROUND: Osteoarthritis (OA) is a prevalent ailment characterized by the gradual degradation of joints, resulting in discomfort and restricted movement. The recently proposed mechanism of ferroptosis is intricately associated with the initiation and progression of OA. Our study found that the long non-coding RNA HOXA11-AS reduces ferroptosis by increasing the expression of SLC3A2 through the transcription factor POU2F2. MATERIALS AND METHODS: HOXA11-AS was identified through lncRNA microarray analysis, and its impact on chondrocytes and extracellular matrix was assessed using real-time quantitative PCR, western blotting, and CCK8 assays. Subsequently, overexpression of HOXA11-AS in the knee joints of mice confirmed its protective efficacy on chondrocyte phenotype in the OA model. The involvement of HOXA11-AS in regulating ferroptosis via SLC3A2 was further validated through RNA sequencing analysis of mouse cartilage and the assessment of malondialdehyde levels and glutathione peroxidase activity. Finally, a combination of RNA sequencing, pull-down assays, mass spectrometry (MS), and chromatin immunoprecipitation (ChIP) techniques was employed to identify POU2F2 as the crucial transcription factor responsible for repressing the expression of SLC3A2, which can be effectively inhibited by HOXA11-AS. RESULTS: Our study demonstrated that HOXA11-AS effectively enhanced the metabolic homeostasis of chondrocytes, and alleviated the progression of OA in vitro and in vivo experiments. Furthermore, HOXA11-AS was found to enhance SLC3A2 expression, a key regulator of ferroptosis, by interacting with the transcriptional repressor POU2F2. CONCLUSIONS: HOXA11-AS promotes SLC3A2 expression and inhibits chondrocyte ferroptosis, by binding to the transcriptional repressor POU2F2, offering a promising and innovative therapeutic approach for OA.

17.
Hortic Res ; 11(8): uhae162, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108578

RESUMEN

Ralstonia solanacearum (Rso) causes destructive bacterial wilt across a broad range of host plants by delivering a repertoire of type III effectors. In the present study, we determined that the deletion of the type III effector RipAF1 resulted in increased virulence on Nicotiana benthamiana, Solanum lycopersicum, and Capsicum annuum plants. RipAF1 showed ADP-ribosylation activity in vivo and in vitro. Transient overexpression of RipAF1 suppressed jasmonic acid (JA) signaling and induced salicylic acid (SA) signaling. The ADP-ribosylation activity of RipAF1 was essential for JA and SA signaling mediation. Host fibrillin FBN1 was identified as a RipAF1-interactor that is ADP-ribosylated by RipAF1 directly. Most importantly, the ADP-ribosylation of conserved residues of FBN1 contributes to its localization to the plasma membrane and leads to the suppression of JA signaling and induction of SA signaling. We concluded that RipAF1 mediates antagonistic crosstalk between JA and SA signaling pathways by ADP-ribosylation of FBN1.

18.
Adv Sci (Weinh) ; 11(23): e2402182, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38622896

RESUMEN

The incorporation of randomness into stochastic computing can provide ample opportunities for applications such as simulated annealing, non-polynomial hard problem solving, and Bayesian neuron networks. In these cases, a considerable number of random numbers with an accurate and configurable probability distribution function (PDF) are indispensable. Preferably, these random numbers are provided at the hardware level to improve speed, efficiency, and parallelism. In this paper, how spin-orbit torque magnetic tunnel junctions (SOT-MTJs) with high barriers are suitable candidates for the desired true random number generators is demonstrated. Not only do these SOT-MTJs perform excellently in speed and endurance, but their randomness can also be conveniently and precisely controlled by a writing voltage, which makes them a well-performed Bernoulli bit. By utilizing these SOT-MTJ-based Bernoulli bits, any PDF, including Gaussian, uniform, exponential, Chi-square, and even arbitrarily defined distributions can be realized. These PDF-configurable true random number generators can then promise to advance the development of stochastic computing and broaden the applications of the SOT-MTJs.

19.
Oncol Lett ; 27(3): 106, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38298427

RESUMEN

Microwave ablation (MWA) is a key alternative therapy to conventional surgery for the treatment of lung cancer. In addition to eliminating local tumors, MWA may promote antitumor immunological responses, such as abscopal effects in distant lesions. However, the intensity of MWA is limited and the underlying mechanisms are not well-defined. The present study assessed the impact of MWA on immune cell subsets and cytokines in patients with lung cancer. A total of 45 patients with lung cancer who underwent percutaneous lung tumor MWA were enrolled. Peripheral blood samples were collected before and 24 h after MWA and changes in immune cell subsets [lymphocytes, CD3+, CD4+ and CD8+ T cells, B cells and natural killer (NK) cells] and serum cytokine levels (IL-1ß, IL-2, IL-4-6, IL-8, IL-10, IL-12p70, IL-17A and F, IL-22, TNF-α, TNF-ß and IFN-γ) were assessed by flow cytometry and ELISA. The number of total lymphocytes, CD4+ T and NK cells in the peripheral blood significantly decreased 24 h after MWA, while number of CD8+ T cells remained stable, leading to a higher proportion of CD8+ T cells. In addition, the serum levels of IL-2, IL-1ß, IL-6, IL-12p70, IL-22, TNF-α and IFN-γ were significantly increased 24 h after MWA, indicating a T helper 1 type immune response. The immune response in patients with advanced stage disease was comparable with patients in the early stage group; however, the number of total lymphocytes and CD3+ T cells significantly decreased and the ratio of CD4/CD8 and IL-2 levels significantly increased. The early immune response after MWA may contribute to systemic antitumor immunity in patients with both early and advanced disease. Thus, MWA may exhibit potential as a local therapy and trigger abscopal effects in distant lesions in patients with lung cancer.

20.
Food Chem ; 443: 138556, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38290299

RESUMEN

Potato is one of the most important crops worldwide, to feed a fast-growing population. In addition to providing energy, fiber, vitamins, and minerals, potato storage proteins are considered as one of the most valuable sources of non-animal proteins due to their high essential amino acid (EAA) index. However, low tuber protein content and limited knowledge about potato storage proteins restrict their widespread utilization in the food industry. Here, we report a proof-of-concept study, using deep learning-based protein design tools, to characterize the biological and chemical characteristics of patatins, the major potato storage proteins. This knowledge was then employed to design multiple cysteines on the patatin surface to build polymers linked by disulfide bonds, which significantly improved viscidity and nutrient of potato flour dough. Our study shows that deep learning-based protein design strategies are efficient to characterize and to create novel proteins for future food sources.


Asunto(s)
Aprendizaje Profundo , Solanum tuberosum , Solanum tuberosum/química , Proteínas de Plantas/metabolismo , Tubérculos de la Planta/química , Carbohidratos/análisis
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