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1.
Nature ; 627(8004): 553-558, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38480895

RESUMEN

Ranging from subcellular organelle biogenesis to embryo development, the formation of self-organized structures is a hallmark of living systems. Whereas the emergence of ordered spatial patterns in biology is often driven by intricate chemical signalling that coordinates cellular behaviour and differentiation1-4, purely physical interactions can drive the formation of regular biological patterns such as crystalline vortex arrays in suspensions of spermatozoa5 and bacteria6. Here we discovered a new route to self-organized pattern formation driven by physical interactions, which creates large-scale regular spatial structures with multiscale ordering. Specifically we found that dense bacterial living matter spontaneously developed a lattice of mesoscale, fast-spinning vortices; these vortices each consisted of around 104-105 motile bacterial cells and were arranged in space at greater than centimetre scale and with apparent hexagonal order, whereas individual cells in the vortices moved in coordinated directions with strong polar and vortical order. Single-cell tracking and numerical simulations suggest that the phenomenon is enabled by self-enhanced mobility in the system-that is, the speed of individual cells increasing with cell-generated collective stresses at a given cell density. Stress-induced mobility enhancement and fluidization is prevalent in dense living matter at various scales of length7-9. Our findings demonstrate that self-enhanced mobility offers a simple physical mechanism for pattern formation in living systems and, more generally, in other active matter systems10 near the boundary of fluid- and solid-like behaviours11-17.


Asunto(s)
Bacterias , Movimiento , Bacterias/citología , Rastreo Celular , Modelos Biológicos , Suspensiones
2.
Proc Natl Acad Sci U S A ; 120(30): e2219708120, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-37459530

RESUMEN

Interaction between active materials and the boundaries of geometrical confinement is key to many emergent phenomena in active systems. For living active matter consisting of animal cells or motile bacteria, the confinement boundary is often a deformable interface, and it has been unclear how activity-induced interface dynamics might lead to morphogenesis and pattern formation. Here, we studied the evolution of bacterial active matter confined by a deformable boundary. We found that an ordered morphological pattern emerged at the interface characterized by periodically spaced interfacial protrusions; behind the interfacial protrusions, bacterial swimmers self-organized into multicellular clusters displaying +1/2 nematic defects. Subsequently, a hierarchical sequence of transitions from interfacial protrusions to creeping branches allowed the bacterial active drop to rapidly invade surrounding space with a striking self-similar branch pattern. We found that this interface patterning is geometrically controlled by the local curvature of the interface, a phenomenon we denote as collective curvature sensing. Using a continuum active model, we revealed that the collective curvature sensing arises from enhanced active stresses near high-curvature regions, with the active length scale setting the characteristic distance between the interfacial protrusions. Our findings reveal a protrusion-to-branch transition as a unique mode of active matter invasion and suggest a strategy to engineer pattern formation of active materials.


Asunto(s)
Bacterias
3.
Nano Lett ; 24(2): 724-732, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38166126

RESUMEN

Photothermal membrane distillation (PMD) has emerged as a promising and sustainable approach for seawater desalination and wastewater purification. However, the wide application of the technique is severely impeded by low freshwater production and membrane fouling/wetting issues. Herein, we developed an advanced hydrogel-engineered membrane with simultaneously enhanced photothermal conversion capacity and desired fouling and wetting resistance for PMD. By the synergies of photothermal Ti3C2Tx MXene nanosheets and the tannic acid-Fe3+ network in the hydrogel, the membrane was endowed with excellent surface self-heating ability, yielding the highest freshwater production rate (1.71 kg m-2 h-1) and photothermal efficiency among the fabricated hydrogel composite membranes under 1 sun irradiation. Meanwhile, the PMD membrane could robustly resist oil-induced fouling and surfactant-induced wetting, significantly extending the membrane lifespan in treating contaminated saline water. Furthermore, when desalinating real seawater, the membrane exhibited superior durability with a stable vapor flux and excellent ion rejection (e.g., 99.24% for boron) for 100 h.

4.
J Am Chem Soc ; 146(25): 16963-16970, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38691630

RESUMEN

Despite the significant achievements in dearomatization and C-H functionalization of arenes, the arene ring-opening remains a largely unmet challenge and is underdeveloped due to the high bond dissociation energy and strong resonance stabilization energy inherent in aromatic compounds. Herein, we demonstrate a novel carbene assisted strategy for arene ring-opening. The understanding of the mechanism by our DFT calculations will stimulate wide application of bulk arene chemicals for the synthesis of value-added polyconjugated chain molecules. Various aryl azide derivatives now can be directly converted into valuable polyconjugated enynes, avoiding traditional synthesis including multistep unsaturated precursors, poor selectivity control, and subsequent transition-metal catalyzed cross-coupling reactions. The simple conditions required were demonstrated in the late-stage modification of complex molecules and fused ring compounds. This chemistry expands the horizons of carbene chemistry and provides a novel pathway for arene ring-opening.

5.
Small ; 20(27): e2311421, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38282177

RESUMEN

To improve ion transport kinetics and electronic conductivity between the different phases in sodium/lithium-ion battery (LIB/SIB) anodes, heterointerface engineering is considered as a promising strategy due to the strong built-in electric field. However, the lattice mismatch and defects in the interphase structure can lead to large grain boundary resistance, reducing the ion transport kinetics and electronic conductivity. Herein, monometallic selenide Fe3Se4-Fe7Se8 semi-coherent heterointerface embedded in 3D connected Nitrogen-doped carbon yolk-shell matrix (Fe3Se4-Fe7Se8@NC) is obtained via an in situ phase transition process. Such semi-coherent heterointerface between Fe3Se4 and Fe7Se8 shows the matched interfacial lattice and strong built-in electric field, resulting in the low interface impedance and fast reaction kinetics. Moreover, the yolk-shell structure is designed to confine all monometallic selenide Fe3Se4-Fe7Se8 semi-coherent heterointerface nanoparticles, improving the structural stability and inhibiting the volume expansion effect. In particular, the 3D carbon bridge between multi-yolks shell structure improves the electronic conductivity and shortens the ion transport path. Therefore, the efficient reversible pseudocapacitance and electrochemical conversion reaction are enabled by the Fe3Se4-Fe7Se8@NC, leading to the high specific capacity of 439 mAh g-1 for SIB and 1010 mAh g-1 for LIB. This work provides a new strategy for constructing heterointerface of the anode for secondary batteries.

6.
Am J Pathol ; 193(4): 430-441, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36690077

RESUMEN

Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, is implicated in intervertebral disc degeneration (IDD). The current study explored the role of Fer-1 in IDD via the toll-like receptor 4 (TLR4)/NF-κB signaling pathway. IDD-related gene expression microarray GSE124272 and high-throughput sequencing data set GSE175710 were obtained through the Gene Expression Omnibus database. Differentially expressed genes in IDD were identified, followed by implementation of protein-protein interaction network analysis and receiver operating characteristic curve analysis. The main pathways in IDD were obtained through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses, and target genes of Fer-1 were obtained through PubChem and PharmMapper websites. Finally, GPX4, FTH, and TLR4 expression was determined in a IDD rat model. Three key co-expression modules involved in IDD were obtained through Weighted Gene Co-Expression Network Analysis. Thirteen differentially expressed genes were found to be associated with IDD, and eight key genes (TLR4, BCL2A1, CXCL1, IL1R1, NAMPT, SOCS3, XCL1, and IRAK3) were found to affect IDD. These eight key genes had the diagnostic potential for IDD. The NF-κB signaling pathway was shown to play a predominant role in IDD development. Network pharmacologic analysis indicated a role of Fer-1 in suppressing ferroptosis and ameliorating IDD via the TLR4/NF-κB signaling pathway, which was verified by an in vivo animal experiment. The study showed that Fer-1 down-regulates TLR4 to inactivate NF-κB signaling pathway, suppressing ferroptosis and ultimately alleviating IDD in rats.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Ratas , Animales , FN-kappa B/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Transducción de Señal/fisiología
7.
Plant Physiol ; 193(3): 2232-2247, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37534747

RESUMEN

Bacterial blight seriously affects the growth and production of cassava (Manihot esculenta Crantz), but disease resistance genes and the underlying molecular mechanism remain unknown. In this study, we found that LESION SIMULATING DISEASE 3 (MeLSD3) is essential for disease resistance in cassava. MeLSD3 physically interacts with SIRTUIN 1 (MeSRT1), inhibiting MeSRT1-mediated deacetylation modification at the acetylation of histone 3 at K9 (H3K9Ac). This leads to increased H3K9Ac levels and transcriptional activation of SUPPRESSOR OF BIR1 (SOBIR1) and FLAGELLIN-SENSITIVE2 (FLS2) in pattern-triggered immunity, resulting in immune responses in cassava. When MeLSD3 was silenced, the release of MeSRT1 directly decreased H3K9Ac levels and inhibited the transcription of SOBIR1 and FLS2, leading to decreased disease resistance. Notably, DELLA protein GIBBERELLIC ACID INSENSITIVE 1 (MeGAI1) also interacted with MeLSD3, which enhanced the interaction between MeLSD3 and MeSRT1 and further strengthened the inhibition of MeSRT1-mediated deacetylation modification at H3K9Ac of defense genes. In summary, this study illustrates the mechanism by which MeLSD3 interacts with MeSRT1 and MeGAI1, thereby mediating the level of H3K9Ac and the transcription of defense genes and immune responses in cassava.


Asunto(s)
Manihot , Xanthomonas axonopodis , Xanthomonas axonopodis/metabolismo , Manihot/genética , Manihot/metabolismo , Manihot/microbiología , Histonas/metabolismo , Resistencia a la Enfermedad/genética , Acetilación , Enfermedades de las Plantas/microbiología
8.
Ann Vasc Surg ; 102: 92-100, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38301851

RESUMEN

BACKGROUND: To quantitatively analyze histological and fiber structure of the superior mesenteric artery (SMA) wall and to further explore the possible relationship between the architecture and histology changes of vessel wall and the occurrence of related diseases. METHODS: Histological and fiber structure analysis were performed on SMA specimens obtained from 22 cadavers. The SMA specimens were divided into initial, curved, and distal segments, and each segment was separated into the anterior and posterior walls. RESULTS: From the initial to the curved to the distal segment, the ratio of elastin decreased (31.4% ± 6.0%, 21.1% ± 5.8%, 18.6% ± 4.7%, respectively; P < 0.001), whereas the ratio of smooth muscle actin (24.5% ± 8.7%, 30.5% ± 6.8%, 36.1% ± 7.3%, respectively; P < 0.001) increased. Elastic fiber longitudinal amplitude of angular undulation was highest in the initial segment [7° (3.25°, 15°)] and lowest in the curved segment [2° (1°, 5°)]. In SMA curved segment, the anterior wall, when compared with the posterior wall, demonstrated a lower ratio of elastin (19.0% ± 5.8% vs. 23.3% ± 5.0%; P = 0.010) and collagen (41.4% ± 12.3% vs. 49.0% ± 10.2%; P = 0.032), a lower elastic fiber longitudinal amplitude of angular undulation [1° (1°, 5°) vs. 3° (2°, 5.25°); P = 0.013], a lower average fiber diameter (8.06 ± 0.36 pixels vs. 8.45 ± 0.50 pixels; P = 0.005), and a lower average segment length (17.96 ± 1.59 pixels vs. 20.05 ± 2.33 pixels; P = 0.001). CONCLUSIONS: SMA wall structure varies along the circumferential and axial directions, the presence of dense undulated elastic fiber protects the SMA initial segment of from dissection and aneurysm, but highly cross-linked collagen fiber here increases the likelihood of plaque formation. In the anterior wall of the curved segment, lower elastin and collagen content, lower elastic fiber undulation, and higher degree of collagen fiber cross-linking leads to the occurrence of SMA dissection and aneurysm. In the distal segment, high levels of vascular smooth muscle cells and bundles of long collagen fiber offer protection against the development of SMA-related diseases.


Asunto(s)
Aneurisma , Arteria Mesentérica Superior , Humanos , Arteria Mesentérica Superior/diagnóstico por imagen , Resultado del Tratamiento , Elastina , Colágeno
9.
Biomed Chromatogr ; : e5948, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981997

RESUMEN

Epimedium is a traditional Chinese medicine with a wide range of clinical applications; however, there have been numerous reports of adverse reactions in recent years. The most common side effect of Epimedium is liver injury. In this study, the liquid chromatography-mass spectrometry (LC-MS) method has been established to study the components of Epimedium and to identify the components absorbed into the blood of rats. Bioinformatics was used to screen out potential toxic components, and the integrating metabolomics method was used to explore the molecular mechanism of Epimedium-induced liver injury. The chemical constituents of Epimedium were identified by LC-MS, and 62 compounds were obtained, including 57 flavonoids, four organic acids and one alkaloid. The toxicity network of "Epimedium-component-target-liver injury" was constructed using bioinformatics research methods, and then the key hepatotoxic component icaritin was identified. Integrating metabolomics was used to investigate the changes in the metabolic profile of L-02 cells with different durations of icaritin administration compared with the control group, and 106 different metabolites were obtained. A total of 14 potential biomarkers significantly associated with cell survival were screened by Pearson correlation analysis combined with the L-02 cell survival rate. Our study preliminarily revealed the mechanism of hepatotoxicity induced by Epimedium.

10.
Plant J ; 110(5): 1447-1461, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35352421

RESUMEN

Reactive oxygen species (ROS) overproduction leads to oxidative damage under almost all stress conditions. Lesion-Simulating Disease (LSD), a zinc finger protein, is an important negative regulator of ROS accumulation and cell death in plants. However, the in vivo role of LSD in cassava (Manihot esculenta) and the underlying molecular mechanisms remain elusive. Here, we found that MeLSD3 is essential for the oxidative stress response in cassava. MeLSD3 physically interacted with ascorbate peroxidase 2 (MeAPX2), thereby promoting its enzymatic activity. In addition, MeLSD3 also interacted with the nuclear factor YC15 (MeNF-YC15), which also interacted with nuclear factor YA2/4 (MeNF-YA2/4) and nuclear factor YB18 (MeNF-YB18) to form an MeNF-YC15-MeNF-YA2/4-MeNF-YB18 complex. Notably, MeLSD3 positively modulated the transcriptional activation of the MeNF-YC15-MeNF-YA2/4-MeNF-YB18 complex by interacting with the CCAAT boxes of the promoters of glutathione S-transferases U37/U39 (MeGST-U37/U39), activating their transcription. When one or both of MeLSD3 and the MeNF-YC15-MeNF-YA2/4-MeNF-YB18 complex were co-silenced, cassava showed decreased oxidative stress resistance, while overexpression of MeGST-U37/U39 alleviated the oxidative stress-sensitive phenotype of these silenced plants. This study illustrates the dual roles of MeLSD3 in promoting MeAPX2 activity and MeNF-YC15-MeGST-U37/U39 regulation, which underlie the oxidative stress response in cassava.


Asunto(s)
Manihot , Manihot/genética , Manihot/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo
11.
Neuroimage ; 271: 120019, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36914108

RESUMEN

Studies of resting-state functional connectivity (rsFC) have provided rich insights into the structures and functions of the human brain. However, most rsFC studies have focused on large-scale brain connectivity. To explore rsFC at a finer scale, we used intrinsic signal optical imaging to image the ongoing activity of the anesthetized macaque visual cortex. Differential signals from functional domains were used to quantify network-specific fluctuations. In 30-60 min resting-state imaging, a series of coherent activation patterns were observed in all three visual areas we examined (V1, V2, and V4). These patterns matched the known functional maps (ocular dominance, orientation, color) obtained in visual stimulation conditions. These functional connectivity (FC) networks fluctuated independently over time and exhibited similar temporal characteristics. Coherent fluctuations, however, were observed from orientation FC networks in different areas and even across two hemispheres. Thus, FC in the macaque visual cortex was fully mapped both on a fine scale and over a long range. Hemodynamic signals can be used to explore mesoscale rsFC in a submillimeter resolution.


Asunto(s)
Conectoma , Macaca fascicularis , Descanso , Corteza Visual , Macaca fascicularis/fisiología , Corteza Visual/irrigación sanguínea , Corteza Visual/fisiología , Corteza Visual/ultraestructura , Masculino , Animales , Descanso/fisiología , Estimulación Luminosa , Imagen Óptica , Hemodinámica
12.
Mol Med ; 29(1): 30, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36858954

RESUMEN

BACKGROUND: Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based on transcriptome sequencing data. METHODS: Streptozotocin (STZ)-induced diabetes mellitus type 1 (T1DM) rats were used to obtain the nucleus pulposus tissues for transcriptome sequencing. Next, differentially expressed genes (DEGs) in transcriptome sequencing data and GSE34000 microarray dataset were obtained and intersected to acquire the candidate genes. Moreover, GO and KEGG enrichment analyses were performed to analyze the cellular functions and molecular signaling pathways primarily regulated by candidate DEGs. RESULTS: A total of 35 key genes involved in IDD of T1DM rats were mainly enriched in the extracellular matrix (ECM) and cytokine adhesion binding-related pathways. NLRP3 inflammasome activation promoted the pyroptosis of nucleus pulposus cells (NPCs). Besides, BMP7 could affect the IDD of T1DM rats by regulating the inflammatory responses. Additionally, NPCs were isolated from STZ-induced T1DM rats to illustrate the effects of BMP7 on IDD of T1DM rats using the ectopic expression method. Both in vitro and in vivo experiments validated that BMP7 alleviated IDD of T1DM rats by inhibiting NLRP3 inflammasome activation and pyroptosis of NPCs. CONCLUSION: Collectively, our findings provided novel mechanistic insights for understanding of the role of BMP7 in IDD of T1DM, and further highlighted BMP7 as a potential therapeutic target for preventing IDD in T1DM.


Asunto(s)
Proteína Morfogenética Ósea 7 , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Degeneración del Disco Intervertebral , Núcleo Pulposo , Animales , Ratas , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Estreptozocina , Proteína Morfogenética Ósea 7/metabolismo
13.
Clin Exp Immunol ; 214(3): 249-259, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-37586053

RESUMEN

Mounting evidence has indicated the essential role of tissue-resident memory T (TRM) cells for frontline protection against viral infection and for cancer immune surveillance (Mueller SN, Mackay LK. Tissue-resident memory T cells: local specialists in immune defense. Nat Rev Immunol 2016, 16, 79-89. doi:10.1038/nri.2015.3.). TRM cells are transcriptionally, phenotypically, and functionally distinct from circulating memory T (Tcirm) cells. It is necessary to understand the unique ontogenetic mechanism, migratory regulation, and biological function of TRM cells. In this review, we discuss recent insights into cellular mechanisms and discrete responsiveness in different tissue microenvironments underlying TRM cell development. We also emphasize the translational potential of TRM cells by focusing on their establishment in association with improved protection in mucosal tissues against various types of diseases and effective strategies for eliciting TRM cells in both pre-clinical and clinical studies.


Asunto(s)
Neoplasias , Virosis , Humanos , Memoria Inmunológica , Células T de Memoria , Linfocitos T CD8-positivos , Microambiente Tumoral
14.
J Cardiovasc Electrophysiol ; 34(11): 2273-2282, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37694672

RESUMEN

BACKGROUND: Substrate-based ablation can treat uninducible or hemodynamically instability scar-related ventricular tachycardia (VT). However, whether a correlation exists between the critical VT isthmus and late activation zone (LAZ) during sinus rhythm (SR) is unknown. OBJECTIVE: To demonstrate the structural and functional properties of abnormal substrates and analyze the link between the VT circuit and abnormal activity during SR. METHODS: Thirty-six patients with scar-related VT (age, 50.0 ± 13.7 years and 86.1% men) who underwent VT ablation were reviewed. The automatic rhythmia ultrahigh resolution mapping system was used for electroanatomic substrate mapping. The clinical characteristics and mapping findings, particularly the LAZ characteristics during SR and VT, were analyzed. To determine the association between the LAZ during the SR and VT circuits, the LAZ was defined as five activation patterns: entrance, exit, core, blind alley, and conduction barrier. RESULTS: Forty-five VTs were induced in 36 patients, 91.1% of which were monomorphic. The LAZ of all patients was mapped during the SR and VT circuits, and the consistency of the anatomical locations of the LAZ and VT circuits was analyzed. Using the ultrahigh resolution mapping system, interconversion patterns, including the bridge, T, puzzle, maze, and multilayer types, were identified. VT ablation enabled precise ablation of abnormal late potential conduction channels. CONCLUSION: Five interconversion patterns of the LAZ during the SR and VT circuits were summarized. These findings may help formulate more precise substrate-based ablation strategies for scar-related VT and shorter procedure times.


Asunto(s)
Ablación por Catéter , Taquicardia Ventricular , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Cicatriz , Técnicas Electrofisiológicas Cardíacas , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiología , Taquicardia Ventricular/cirugía , Frecuencia Cardíaca , Factores de Tiempo , Ablación por Catéter/efectos adversos
15.
Environ Sci Technol ; 57(23): 8467-8475, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37256786

RESUMEN

Residential emissions significantly contribute to air pollution. To address this issue, a clean heating campaign was implemented to replace coal with electricity or natural gas among 13.9 million rural households in northern China. Despite great success, the cost-benefits and environmental equity of this campaign have never been fully investigated. Here, we modeled the environmental and health benefits, as well as the total costs of the campaign, and analyzed the inequality and inequity. We found that even though the campaign decreased only 1.1% of the total energy consumption, PM2.5 emissions and PM2.5 exposure experienced 20% and 36% reduction, respectively, revealing the amplification effects along the causal pathway. Furthermore, the number of premature deaths attributable to residential emissions reduced by 32%, suggesting that the campaign was highly beneficial. Governments and residents shared the cost of 2,520 RMB/household. However, the benefits and the costs were unevenly distributed, as the residents in mountainous areas were not only less benefited from the campaign but also paid more because of the higher costs, resulting in a notably lower cost-effectiveness. Moreover, villages in less developed areas tended to choose natural gas with a lower initial investment but a higher total cost (2,720 RMB/household) over electricity (2,190 RMB/household). With targeted investment and subsidies in less developed areas and the promotion of electricity and other less expensive alternatives, the multidevelopment goals of improved air quality, reduced health impacts, and reduced inequity in future clean heating interventions could be achieved.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Análisis Costo-Beneficio , Material Particulado/análisis , Calefacción , Gas Natural , Contaminación del Aire/análisis , China , Contaminantes Atmosféricos/análisis
16.
Phys Chem Chem Phys ; 25(43): 29656-29663, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37882236

RESUMEN

A toll-like receptor 4/myeloid differentiation factor 2 complex (TLR4/MD2) has been identified as a non-classical opioid receptor capable of recognizing morphine isomers and activating microglia in a non-enantioselective manner. Additionally, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), the major metabolites of morphine, possess similar chemical structures but exhibit distinct effects on TLR4 signaling. However, the specific mechanisms by which morphine isomers and morphine metabolites are recognized by the innate immune receptor TLR4/MD2 are not well understood. Herein, molecular dynamics simulations were performed to dissect the molecular recognition of TLR4/MD2 with morphine isomers, M3G and M6G. Morphine and its (+)-enantiomer, dextro-morphine ((+)-morphine), were found to have comparable binding free energies as well as similar interaction modes when interacting with (TLR4/MD2)2. Binding with morphine and (+)-morphine caused the motion of the F126 loop towards the inside of the MD2 cavity, which stabilizes (TLR4/MD2)2 with similar dimerization interfaces. The binding free energies of M3G and M6G with (TLR4/MD2)2, while lower than those of morphine isomers, were comparable to each other. However, the binding behaviors of M3G and M6G exhibited contrasting patterns when interacting with (TLR4/MD2)2. The glucuronide group of M3G bound to the gating loop of MD2 and formed strong interactions with TLR4*, which stabilizes the active heterotetrameric complex. In contrast, M6G was situated in cavity A of MD2, where the critical interactions between M6G and the residues of TLR4* were lost, resulting in fluctuation of (TLR4/MD2)2 away from the active conformation. These results indicate that the pivotal interactions at the dimerization interface between MD2 and TLR4* in M6G-bound (TLR4/MD2)2 were considerably weaker than those in M3G-bound (TLR4/MD2)2, which partially explains why M6G fails to activate TLR4 signaling. The discoveries from this study will offer valuable insights for the advancement of next-generation TLR4 small molecule modulators based on opioids.


Asunto(s)
Morfina , Receptor Toll-Like 4 , Morfina/metabolismo , Derivados de la Morfina , Simulación por Computador , Inmunidad Innata
17.
Sensors (Basel) ; 23(23)2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38067831

RESUMEN

In recent years, deep convolutional neural networks (CNNs) have made significant progress in single-image super-resolution (SISR) tasks. Despite their good performance, the single-image super-resolution task remains a challenging one due to problems with underutilization of feature information and loss of feature details. In this paper, a multi-scale recursive attention feature fusion network (MSRAFFN) is proposed for this purpose. The network consists of three parts: a shallow feature extraction module, a multi-scale recursive attention feature fusion module, and a reconstruction module. The shallow features of the image are first extracted by the shallow feature extraction module. Then, the feature information at different scales is extracted by the multi-scale recursive attention feature fusion network block (MSRAFFB) to enhance the channel features of the network through the attention mechanism and fully fuse the feature information at different scales in order to improve the network's performance. In addition, the image features at different levels are integrated through cross-layer connections using residual connections. Finally, in the reconstruction module, the upsampling capability of the deconvolution module is used to enlarge the image while extracting its high-frequency information in order to obtain a sharper high-resolution image and achieve a better visual effect. Through extensive experiments on a benchmark dataset, the proposed network model is shown to have better performance than other models in terms of both subjective visual effects and objective evaluation metrics.

18.
Int J Mol Sci ; 24(19)2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37833932

RESUMEN

Energy metabolism is a fundamental process in all organisms. During silkworm (Bombyx mori) embryonic development, there is a high demand for energy due to continuous cell proliferation and differentiation. Estrogen-related receptors (ERRs) are transcriptional regulatory factors that play crucial roles in mammalian energy storage and expenditure. Although most insects have one ERR gene, it also participates in the regulation of energy metabolism, including carbohydrate metabolism in Drosophila, Aphid, and Silkworm. However, no study has reported the direct impact of energy metabolism on embryonic development in silkworms. In this study, we used transgenic technology to increase silkworm (B. mori; Bm) BmERR expression during embryonic development and explored the impact of energy on embryonic development. We found no significant change in the quality of silkworm eggs compared to that of wild-type silkworms. However, there was an increase in the consumption of vitellin, a major nutrient in embryos. This resulted in a decrease in glucose content and a significant increase in ATP content. These findings provide evidence that the acceleration of energy metabolism promotes embryonic development and enhances the motility of hatched silkworms. In addition, these results provide a novel perspective on the relationship between energy metabolism and embryonic development in other insects.


Asunto(s)
Bombyx , Receptores de Estrógenos , Animales , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Bombyx/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Desarrollo Embrionario/genética , Factores de Transcripción/metabolismo , Estrógenos/metabolismo , Mamíferos/metabolismo
19.
Int J Mol Sci ; 24(23)2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-38068875

RESUMEN

Melatonin has been proved to be involved in testosterone synthesis, but whether melatonin participates in testosterone synthesis by regulating miRNA in Leydig cells is still unclear. The purpose of this study is to clarify the mechanism of melatonin on Leydig cells testosterone synthesis from the perspective of miRNA. Our results showed that melatonin could significantly inhibit testosterone synthesis in rooster Leydig cells. miR-7481-3p and CXCL14 were selected as the target of melatonin based on RNA-seq and miRNA sequencing. The results of dual-luciferase reporter assays showed that miR-7481-3p targeted the 3'-UTR of CXCL14. The overexpression of miR-7481-3p significantly inhibited the expression of CXCL14 and restored the inhibitory role of melatonin testosterone synthesis and the expression of StAR, CYP11A1, and 3ß-HSD in rooster Leydig cells. Similarly, interference with CXCL14 could reverse the inhibitory effect of melatonin on the level of testosterone synthesis and the expression of StAR, CYP11A1, and 3ß-HSD in rooster Leydig cells. The RNA-seq results showed that melatonin could activate the PI3K/AKT signal pathway. Interference with CXCL14 significantly inhibited the phosphorylation level of PI3K and AKT, and the inhibited PI3K/AKT signal pathway could reverse the inhibitory effect of CXCL14 on testosterone synthesis and the expression of StAR, CYP11A1 and 3ß-HSD in rooster Leydig cells. Our results indicated that melatonin inhibits testosterone synthesis by targeting miR-7481-3p/CXCL14 and inhibiting the PI3K/AKT pathway.


Asunto(s)
Células Intersticiales del Testículo , Melatonina , MicroARNs , Testosterona , Animales , Masculino , Pollos/genética , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Células Intersticiales del Testículo/metabolismo , Melatonina/farmacología , Melatonina/metabolismo , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Testosterona/metabolismo
20.
J Exerc Sci Fit ; 21(2): 210-217, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36923209

RESUMEN

Background: Upper limb balance is one of the important physical fitness parameters for all populations, especially overhead athletes like swimmers. Upper extremity star excursion balance test (UESEBT) is a comprehensive dynamic balance assessment, this study aims to explore the reliability and validity of UESEBT among adolescent swimmers. Methods: This cross-sectional study recruited 70 adolescent swimmers. All participants were required to complete UESEBT, upper quarter Y-balance test (UQYBT), maximal isometric strength (MIS) tests in upper limb, closed kinetic chain upper extremity stability test (CKCUEST), trunk flexor endurance test (TFET) and lateral trunk endurance test (LTET). The intra- and inter-operator reliability and the correlation of UESEBT with other physical performances were conducted. Results: For reliability, the intra- and inter-operator reliability of all directions and composite score were high-to-excellent (ICC = 0.706-1.000) among all participants. For validity, the UESEBT has a moderate-to-strong correlation with UQYBT (r = 0.42-0.72, p < 0.001), and a weak-to moderate one with CKCUEST (r = 0.25-0.42, p < 0.05). Furthermore, the UESEBT performance showed weak-to-moderate correlations with MIS (r = 0.24-0.44, p < 0.05). UESEBT was correlated to LTET (r = 0.24-0.33, p < 0.05) whereas no relationship was found with TFET. Conclusions: UESEBT was a reliable and valid tool to screen upper extremity dynamic balance among adolescent swimmers. UESEBT provides more detailed information in eight directions to assess the upper limb sport performance. Further study should explore the prediction ability of UESEBT for injury.

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