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 , SuspensionesRESUMEN
Microbial communities such as biofilms are commonly found at interfaces. However, it is unclear how the physical environment of interfaces may contribute to the development and behavior of surface-associated microbial communities. Combining multimode imaging, single-cell tracking, and numerical simulations, here, we found that activity-induced interface bulging promotes colony biofilm formation in Bacillus subtilis swarms presumably via segregation and enrichment of sessile cells in the bulging area. Specifically, the diffusivity of passive particles is ~50% lower inside the bulging area than elsewhere, which enables a diffusion-trapping mechanism for self-assembly and may account for the enrichment of sessile cells. We also uncovered a quasilinear relation between cell speed and surface-packing density that underlies the process of active interface bulging. Guided by the speed-density relation, we demonstrated reversible formation of liquid bulges by manipulating the speed and local density of cells with light. Over the course of development, the active bulges turned into striped biofilm structures, which eventually give rise to a large-scale ridge pattern. Our findings reveal a unique physical mechanism of biofilm formation at air-solid interface, which is pertinent to engineering living materials and directed self-assembly in active fluids.
Asunto(s)
Bacillus subtilis , Biopelículas , Bacillus subtilis/fisiología , Biopelículas/crecimiento & desarrolloRESUMEN
Pachynema progression contributes to the completion of prophase I. Nevertheless, the regulation of this significant meiotic process remains poorly understood. In this study, we identified a novel testis-specific protein HSF5, which regulates pachynema progression during male meiosis in a manner dependent on chromatin-binding. Deficiency of HSF5 results in meiotic arrest and male infertility, characterized as unconventional pachynema arrested at the mid-to-late stage, with extensive spermatocyte apoptosis. Our scRNA-seq data confirmed consistent expressional alterations of certain driver genes (Sycp1, Msh4, Meiob, etc.) crucial for pachynema progression in Hsf5-/- individuals. HSF5 was revealed to primarily bind to promoter regions of such key divers by CUT&Tag analysis. Also, our results demonstrated that HSF5 biologically interacted with SMARCA5, SMARCA4 and SMARCE1, and it could function as a transcription factor for pachynema progression during meiosis. Therefore, our study underscores the importance of the chromatin-associated HSF5 for the differentiation of spermatocytes, improving the protein regulatory network of the pachynema progression.
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)
BacteriasRESUMEN
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.
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.
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.
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/fisiologíaRESUMEN
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/microbiologíaRESUMEN
AGO2 plays a vital role in small RNA-guided gene silencing, which has been implied in the tumorigenesis of different types of tumors. Fundamentally, increased expression of AGO2 protein is associated with cancer progression and metastasis. This study aims to investigate the molecular mechanism by which AGO2 promotes tumorigenesis in colorectal cancer (CRC). Databases were used to analyze the expression levels of AGO2 in CRC and confirmed by a quantitative reverse transcriptase-PCR (qRT-PCR) assay in CRC tissues and normal adjacent tissues collected from 25 CRC patients. CRISPR/Cas9-mediated genome editing was used to knockout the AGO2 in HCT116 cells as a model system for colorectal cancers. The cell proliferation, migration and invasion ability of HCT116 cells were detected by CCK-8 assay, Wound scratch assay and Transwell assay. Moreover, the quantities of miRNA binding with AGO2 were detected by RNA-Binding Protein Immunoprecipitation (RIP-Assay). We demonstrated that AGO2 was aberrantly high-expressed in 25 matched-tissue pairs of colorectal cancer and para-carcinoma tissue. The following functional experiments verified that knockout of AGO2 suppressed cell proliferation, migration and tumorigenesis to hamper the aggressiveness of CRC. Our study also suggests a possible link between AGO2 and miRNA in RISC. AGO2 was elevated in CRC and knockout of AGO2 suppressed proliferation and tumorigenicity of CRC cells. Moreover, RISC formation and the function of miRNAs are also subject to AGO2. AGO2 may be a meaningful target for CRC therapy.
Asunto(s)
Proteínas Argonautas , Sistemas CRISPR-Cas , Carcinogénesis , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , MicroARNs , Humanos , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Proliferación Celular/genética , Sistemas CRISPR-Cas/genética , Movimiento Celular/genética , Carcinogénesis/genética , Carcinogénesis/patología , Células HCT116 , MicroARNs/genética , MicroARNs/metabolismo , Técnicas de Inactivación de GenesRESUMEN
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 , ColágenoRESUMEN
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.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Biología Computacional , Epimedium , Flavonoides , Metabolómica , Ratas Sprague-Dawley , Epimedium/química , Metabolómica/métodos , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Ratas , Flavonoides/química , Flavonoides/farmacología , Masculino , Humanos , Cromatografía Liquida/métodos , Línea Celular , Espectrometría de Masas/métodos , Medicamentos Herbarios Chinos/química , Metaboloma/efectos de los fármacos , Supervivencia Celular/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. METHODS: A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. RESULTS: After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. CONCLUSIONS: Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure.
RESUMEN
Boron (B) deficiency has been shown to inhibit root cell growth and division. However, the precise mechanism underlying B deficiency-mediated root tip growth inhibition remains unclear. In this study, we investigated the role of BnaA3.NIP5;1, a gene encoding a boric acid channel, in Brassica napus (B. napus). BnaA3.NIP5;1 is expressed in the lateral root cap and contributes to B acquisition in the root tip. Downregulation of BnaA3.NIP5;1 enhances B sensitivity in B. napus, resulting in reduced shoot biomass and impaired root tip development. Transcriptome analysis was conducted on root tips from wild-type B. napus (QY10) and BnaA3.NIP5;1 RNAi lines to assess the significance of B dynamics in meristematic cells during seedling growth. Differentially expressed genes (DEGs) were significantly enriched in plant circadian rhythm and nitrogen (N) metabolism pathways. Notably, the circadian-rhythm-related gene HY5 exhibited a similar B regulation pattern in Arabidopsis to that observed in B. napus. Furthermore, Arabidopsis mutants with disrupted circadian rhythm (hy5/cor27/toc1) displayed heightened sensitivity to low B compared to the wild type (Col-0). Consistent with expectations, B deficiency significantly disrupted N metabolism in B. napus roots, affecting nitrogen concentration, nitrate reductase enzyme activity, and glutamine synthesis. Interestingly, this disruption was exacerbated in BnaA3NIP5;1 RNAi lines. Overall, our findings highlight the critical role of B dynamics in root tip cells, impacting circadian rhythm and N metabolism, ultimately leading to retarded growth. This study provides novel insights into B regulation in root tip development and overall root growth in B. napus.
Asunto(s)
Boro , Brassica napus , Ritmo Circadiano , Regulación de la Expresión Génica de las Plantas , Nitrógeno , Raíces de Plantas , Brassica napus/genética , Brassica napus/metabolismo , Brassica napus/crecimiento & desarrollo , Boro/metabolismo , Boro/deficiencia , Nitrógeno/metabolismo , Nitrógeno/deficiencia , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Ritmo Circadiano/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Plantones/metabolismo , Plantones/crecimiento & desarrollo , Plantones/genética , Perfilación de la Expresión Génica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismoRESUMEN
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/metabolismoRESUMEN
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 , HemodinámicaRESUMEN
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/metabolismoRESUMEN
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 TumoralRESUMEN
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 adversosRESUMEN
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.