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1.
Nat Commun ; 15(1): 4458, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796508

RESUMEN

The impact of interbasin linkage on the weather/climate and ecosystems is significantly broader and profounder than that of only appearing in an individual basin. Here, we reveal that a decadal linkage of sea surface temperature (SST) has emerged between western Australian coast and western-central tropical Pacific since 1985, associated with continuous intensification of decadal variabilities (8-16 years). The rapid SST changes in both tropical Indian Ocean and Indo-Pacific warm pool in association to greenhouse gases and volcanoes are emerging factors resulting in enhanced decadal co-variabilities between these two regions since 1985. These SST changes induce enhanced convection variability over the Maritime Continent, leading to stronger easterlies in the western-central tropical Pacific during the warm phase off western Australian coast. The above changes bring about cooling in the western-central tropical Pacific and strengthened Leeuwin Current and anomalous cyclonic wind off western Australian coast, and ultimately resulting in enhanced coupling between these two regions. Our results suggest that enhanced decadal interbasin connections can offer further understanding of decadal changes under future warmer conditions.

2.
Cancer Cell ; 42(4): 682-700.e12, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38428409

RESUMEN

Cancer-associated fibroblasts (CAFs) exhibit considerable heterogeneity in advanced cancers; however, the functional annotation and mechanism of CAFs in early-stage cancers remain elusive. Utilizing single-cell RNA sequencing and spatial transcriptomic, we identify a previously unknown PDGFRα+ITGA11+ CAF subset in early-stage bladder cancer (BCa). Multicenter clinical analysis of a 910-case cohort confirms that PDGFRα+ITGA11+ CAFs are associated with lymphovascular invasion (LVI) and poor prognosis in early-stage BCa. These CAFs facilitate LVI and lymph node (LN) metastasis in early-stage BCa, as evidenced in a PDGFRα+ITGA11+ CAFs-specific deficient mouse model. Mechanistically, PDGFRα+ITGA11+ CAFs promote lymphangiogenesis via recognizing ITGA11 surface receptor SELE on lymphatic endothelial cells to activate SRC-p-VEGFR3-MAPK pathway. Further, CHI3L1 from PDGFRα+ITGA11+ CAFs aligns the surrounding matrix to assist cancer cell intravasation, fostering early-stage BCa LVI and LN metastasis. Collectively, our study reveals the crucial role of PDGFRα+ITGA11+ CAFs in shaping metastatic landscape, informing the treatment of early-stage BCa LVI.


Asunto(s)
Fibroblastos Asociados al Cáncer , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Animales , Humanos , Ratones , Fibroblastos Asociados al Cáncer/patología , Células Endoteliales , Fibroblastos/metabolismo , Cadenas alfa de Integrinas , Metástasis Linfática/patología , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo
3.
Front Microbiol ; 15: 1374406, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38362499

RESUMEN

[This corrects the article DOI: 10.3389/fmicb.2023.1284864.].

4.
Mol Neurobiol ; 61(4): 2136-2150, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37858031

RESUMEN

Our previous studies have discovered that long non-coding RNA (lncRNA) MALAT1 and its target microRNA-125b-5p (miR-125b-5p) are implicated in neurological diseases via regulating neuroinflammation and neuronal injury. This study aimed to further explore the relationship between lncRNA MALAT1 and miR-125b-5p, as well as their effect on microglial activation, neuroinflammation, and neural apoptosis in spinal cord injury (SCI). Primary microglia from Sprague Dawley rats were stimulated with lipopolysaccharide (LPS). Then, microglia were transfected with lncRNA MALAT1 overexpression or knock-down adenovirus-associated virus with or without miR-125b-5p mimic. The culture medium of microglia was incubated with primary neurons. SCI rats were established for in vivo validation. LncRNA MALAT1 expression was reduced by LPS treatment in a dose-dependent manner. LncRNA MALAT1 overexpression suppressed the microglial M1 polarization (decreased iNOS but increased ARG1), neuroinflammation (declined PTGS2, TNF-α, IL-1ß, and IL-6), and microglia-induced neural apoptosis (lower TUNEL positive cells and C-caspase3 but higher BCL2) under LPS treatment; its knock-down displayed the opposite trend. Moreover, lncRNA MALAT1 directly bound to and negatively regulated miR-125b-5p. MiR-125b-5p mimic promoted microglial M1 polarization, neuroinflammation, and microglia-induced neural apoptosis following LPS treatment; also, it could attenuate the effect of lncRNA MALAT1. Further in vivo study displayed that lncRNA MALAT1 overexpression elevated the Basso-Beattie-Bresnahan motor function score and improved neural injury. Also, in vivo validation indicated a similar effect of lncRNA MALAT1 on microglial polarization and neuroinflammation as in vitro. LncRNA MALAT1 improves SCI recovery via miR-125b-5p mediated microglial M1 polarization, neuroinflammation, and neural apoptosis.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Traumatismos de la Médula Espinal , Ratas , Animales , MicroARNs/genética , ARN Largo no Codificante/genética , Microglía/metabolismo , Enfermedades Neuroinflamatorias , Ratas Sprague-Dawley , Lipopolisacáridos/farmacología , Inflamación/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Apoptosis , Médula Espinal/metabolismo
5.
Cancer Res ; 84(3): 434-448, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-37991737

RESUMEN

Aberrant gene expression is a prominent feature of metastatic cancer. Translational initiation is a vital step in fine-tuning gene expression. Thus, exploring translation initiation regulators may identify therapeutic targets for preventing and treating metastasis. Herein, we identified that DHCR24 was overexpressed in lymph node (LN) metastatic bladder cancer and correlated with poor prognosis of patients. DHCR24 promoted lymphangiogenesis and LN metastasis of bladder cancer in vitro and in vivo. Mechanistically, DHCR24 mediated and recognized the SUMO2 modification at lysine 108 of hnRNPA2B1 to foster TBK1 mRNA circularization and eIF4F initiation complex assembly by enhancing hnRNPA2B1-eIF4G1 interaction. Moreover, DHCR24 directly anchored to TBK1 mRNA 3'-untranslated region to increase its stability, thus forming a feed forward loop to elevate TBK1 expression. TBK1 activated PI3K/Akt signaling to promote VEGFC secretion, resulting in lymphangiogenesis and LN metastasis. DHCR24 silencing significantly impeded bladder cancer lymphangiogenesis and lymphatic metastasis in a patient-derived xenograft model. Collectively, these findings elucidate DHCR24-mediated translation machinery that promotes lymphatic metastasis of bladder cancer and supports the potential application of DHCR24-targeted therapy for LN-metastatic bladder cancer. SIGNIFICANCE: DHCR24 is a SUMOylation regulator that controls translation initiation complex assembly and orchestrates TBK1 mRNA circularization to activate Akt/VEGFC signaling, which stimulates lymphangiogenesis and promotes lymph node metastasis in bladder cancer.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Neoplasias de la Vejiga Urinaria , Humanos , Metástasis Linfática , ARN Mensajero/genética , ARN Mensajero/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sumoilación , Línea Celular Tumoral , Neoplasias de la Vejiga Urinaria/patología , Linfangiogénesis/genética
6.
Signal Transduct Target Ther ; 8(1): 426, 2023 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-37925421

RESUMEN

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Vesículas Extracelulares , Neoplasias Pulmonares , ARN Circular , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Células Endoteliales/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/patología , Metástasis Linfática , Sumoilación/genética , Factores de Transcripción , ARN Circular/genética
7.
Front Microbiol ; 14: 1284864, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38029206

RESUMEN

Introduction: Biodiversity maintenance and its underlying mechanisms are central issues of ecology. However, predicting the composition turnovers of microbial communities at multiple spatial scales remains greatly challenging because they are obscured by the inconsistent impacts of climatic and local edaphic conditions on the assembly process. Methods: Based on the Illumina MeSeq 16S/18S rRNA sequencing technology, we investigated soil bacterial and eukaryotic communities in biocrusts with different successional levels at a subcontinental scale of Northern China. Results: Results showed that irrespective of spatial scale, bacterial α diversity increased but eukaryotic diversity decreased with the primary succession, whereas both ß diversities decreased at the subcontinental scale compared with smaller scales, indicating that the biogeographic pattern of soil microorganisms was balanced by successional convergence and distance decay effect. We found that the convergence of bacterial and eukaryotic communities was attributed to the turnovers of generalist and specialist species, respectively. In this process, edaphic and climatic factors showed unique roles in the changes of diversity at local/subcontinental scales. Moreover, the taxonomic diversity tended to be more susceptible to climatic and edaphic conditions, while biotic factors (photosynthesis and pigments) were more important to phylogenetic diversity. Conclusion: Taken together, our study provided comprehensive insights into understanding the pattern of microbial diversity at multiple spatial scales of drylands.

8.
Micromachines (Basel) ; 14(10)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37893251

RESUMEN

Jet noise is a common problem in minimum quantity lubrication (MQL) technology. This should be given great attention because of its serious impacts on the physical and mental health of the operators. In this study, a micro-grooved nozzle is proposed based on the noise reduction concept of biological micro-grooves. The flow field and acoustic characteristics of an original nozzle and a micro-grooved nozzle were investigated numerically to help better understand the noise reduction mechanism. The reasons for noise generation and the effects of the length (L), width (W) and depth (δ) of the micro-grooves on noise reduction were analyzed. It was found that jet noise is generated by the large-scale vortex ring structure and the pressure fluctuations caused by its motion. The overall sound pressure level (OASPL) decreased with the increases in W and δ, and increased with the increase in L. Among of them, δ has the greatest effect on noise reduction. The maximum noise reduction achieved was 6.66 dB, as verified by the OASPL test. Finally, the noise reduction mechanism was discussed in terms of the flow field, vorticity and the frequency characteristics. Micro-grooves can enhance the mixing of airflow inside the nozzle and accelerate the process of large-scale vortices breaking into smaller-scale vortices. It also reduces the sound pressure level (SPL) of middle frequencies, as well as the SPL of high frequencies on specific angles.

9.
J Exp Clin Cancer Res ; 42(1): 191, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37528489

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) circularized by back-splicing of pre-mRNA are widely expressed and affected the proliferation, invasion and metastasis of bladder cancer (BCa). However, the mechanism underlying circRNA biogenesis in mediating the distant metastasis of BCa still unexplored. METHODS: RNA sequencing data between BCa and normal adjacent tissues was applied to identify the differentially expressed circRNAs. The functions of circNIPBL in BCa were investigated via a series of biochemical experiments. The Clinical significance of circNIPBL was examined in a cohort of larger BCa tissues. RESULTS: In the present study, we identified a novel circRNA (hsa_circ_0001472), circNIPBL, which was significantly upregulated and had great influence on the poor prognosis of patients with BCa. Functionally, circNIPBL promotes BCa metastasis in vitro and in vivo. Mechanistically, circNIPBL upregulate the expression of Wnt5a and activated the Wnt/ß-catenin signaling pathway via directly sponged miR-16-2-3p, leading to the upregulation of ZEB1, which triggers the EMT of BCa. Moreover, we revealed that ZEB1 interacted with the flanking introns of exons 2-9 on NIPBL pre-mRNA to trigger circNIPBL biogenesis, thus forming a positive feedback loop. Importantly, circNIPBL overexpression significantly facilitated the distant metastasis of BCa in the orthotopic bladder cancer model, while silencing ZEB1 remarkably blocked the effects of metastasis induced by circNIPBL overexpression. CONCLUSIONS: Our study highlights that circNIPBL-induced Wnt signaling pathway activation triggers ZEB1-mediated circNIPBL biogenesis, which forms a positive feedback loop via the circNIPBL/miR-16-2-3p/Wnt5a/ZEB1 axis, supporting circNIPBL as a novel therapeutic target and potential biomarker for BCa patients.


Asunto(s)
MicroARNs , Neoplasias de la Vejiga Urinaria , Humanos , ARN Circular/genética , Vía de Señalización Wnt , beta Catenina/metabolismo , Precursores del ARN , Línea Celular Tumoral , Movimiento Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Proteínas de Ciclo Celular/genética
10.
Neuroscience ; 529: 88-98, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37286157

RESUMEN

Long noncoding RNA nuclear enriched abundant transcript 1 (lnc-NEAT1) is closely implicated in neurological diseases, while its implication in Alzheimer's disease (AD) is rarely reported. This study aimed to investigate the effect of lnc-NEAT1 knockdown on neuron injury, inflammation, and oxidative stress in AD, as well as its interaction with downstream targets and pathways. APPswe/PS1dE9 transgenic mice were injected with negative control or lnc-NEAT1 interference lentivirus. Besides, AD cellular model was constructed by amyloid ß treatment in mice primary neuron cells; then, knockdown of lnc-NEAT1 and microRNA-193a was performed alone or in combination. In vivo experiments revealed that Lnc-NEAT1 knockdown improved cognition in AD mice reflected by Morrison water maze and Y-maze assays. Besides, lnc-NEAT1 knockdown reduced injury and apoptosis, decreased inflammatory cytokine levels, repressed oxidative stress level, and activated adenosine cyclophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and nuclear factor erythroid 2-related factor 2 (NRF2)/nicotinamide adenine dinucleotide phosphate dehydrogenase 1 (NQO1) pathways in hippocampi of AD mice. Notably, lnc-NEAT1 down-regulated microRNA-193a both in vitro and in vivo and acted as a decoy of microRNA-193a. In vitro experiments showed that lnc-NEAT1 knockdown decreased apoptosis and oxidative stress, improved cell viability, also activated CREB/BDNF and NRF2/NQO1 pathways in AD cellular model. Meanwhile, microRNA-193a knockdown showed the opposite effects, which also attenuated lnc-NEAT1 knockdown-mediated reduction in injury, oxidative stress, and CREB/BDNF and NRF2/NQO1 pathways of AD cellular model. In conclusion, lnc-NEAT1 knockdown reduces neuron injury, inflammation, and oxidative stress through activating microRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways in AD.


Asunto(s)
Enfermedad de Alzheimer , MicroARNs , ARN Largo no Codificante , Animales , Ratones , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides , Apoptosis/genética , Factor Neurotrófico Derivado del Encéfalo , Inflamación/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Factor 2 Relacionado con NF-E2/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
11.
J Tissue Eng ; 14: 20417314231180033, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37333896

RESUMEN

Spinal cord injury (SCI) is a serious refractory disease of the central nervous system (CNS), which mostly caused by high-energy trauma. Existing interventions such as hormone shock and surgery are insufficient options, which relate to the secondary inflammation and neuronal dysfunction. Hydrogel with neuron-protective behaviors attracts tremendous attention, and black phosphorus quantum dots (BPQDs) encapsulating with Epigallocatechin-3-gallate (EGCG) hydrogels (E@BP) is designed for inflammatory modulation and SCI treatment in this study. E@BP displays good stability, biocompatibility and safety profiles. E@BP incubation alleviates lipopolysaccharide (LPS)-induced inflammation of primary neurons and enhances neuronal regeneration in vitro. Furthermore, E@BP reconstructs structural versus functional integrity of spinal cord tracts, which promotes recovery of motor neuron function in SCI rats after transplantation. Importantly, E@BP restarts the cell cycle and induces nerve regeneration. Moreover, E@BP diminishes local inflammation of SCI tissues, characterized by reducing accumulation of astrocyte, microglia, macrophages, and oligodendrocytes. Indeed, a common underlying mechanism of E@BP regulating neural regenerative and inflammatory responses is to promote the phosphorylation of key proteins related to AKT signaling pathway. Together, E@BP probably repairs SCI by reducing inflammation and promoting neuronal regeneration via the AKT signaling pathway.

12.
Adv Atmos Sci ; 40(6): 963-974, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36643611

RESUMEN

Changes in ocean heat content (OHC), salinity, and stratification provide critical indicators for changes in Earth's energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth's climate system. In 2022, the world's oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum. According to IAP/CAS data, the 0-2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ (1 Zetta Joules = 1021 Joules); and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins (the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the "salty gets saltier-fresh gets fresher" pattern, also reached its highest level on record in 2022, implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Niña event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.

13.
Int J Pharm ; 632: 122581, 2023 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-36608806

RESUMEN

Oxidative stress, characterized by excessive accumulation of reactive oxygen species (ROS), is involved in acute myocardial infarction (AMI)-related pathological processes and vascular reperfusion therapy injury. Alpha lipoic acid (LA) exhibits excellent antioxidant properties, however, its application is limited by inherent characteristics, including rapid clearance and extensive volume distribution. In this study, we hypothesized that scavenging cardiac ROS using adequately delivered LA could promote heart repair. Here, we report a new strategy for dynamic-release LA to treat AMI disease. In particular, this involves using poly(lactic-co-glycolic) (PLGA) copolymers as carriers to form a thin film (LA@PLGA) via electrospinning technology to achieve controlled release of LA, which essentially blocking local ROS production in damaged hearts. The drug-loading capacity and capsulation efficiency of this compound film could be regulated by determining the dose proportions of LA and PLGA. The incubation of LA@PLGA showed strong anti-oxidative activity and anti-apoptosis effect in hydrogen peroxide-administered primary cardiomyocytes. Patching LA@PLGA on the infarcted cardiac surfaces of AMI mice dramatically improved heart functions and reduced cardiac fibrosis throughout ventricular remodeling process. Importantly, the attenuation of detrimental pathologies was observed, including oxidative stress, senescence, DNA damage, cytokine-related processes, apoptosis, and ferroptosis. These results suggest that PLGA-carried LA can reduce ROS damage and restore heart function after myocardial damage, demonstrating a great potential for LA drugs in treating AMI disease.


Asunto(s)
Infarto del Miocardio , Ácido Tióctico , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Estrés Oxidativo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología
14.
Neuroscience ; 510: 82-94, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36581132

RESUMEN

PR-957 [low molecular mass polypeptide (LMP)-7 selective inhibitor] regulates T helper (Th) cell differentiation and inflammatory response in multiple neurological diseases. Hence, this study aimed to explore the effect of PR-957 on Th1/Th2/Th17 cell differentiation, therapeutic efficacy and its potential mechanisms in Alzheimer's disease (AD). The LMP7 expressions in peripheral blood mononuclear cells from 30 AD patients and 30 healthy controls (HC) were detected. PR-957 was added for the incubation of naive cluster of differentiation (CD)4+ T cells from AD patients, then SC79 [phosphorylated protein kinase B (pAKT) agonist] was added. LMP7, Th1 cells, and Th17 cells were upregulated, while Th2 cells were downregulated in AD patients compared to HC. Also, LMP7 was positively related to Th1 cells and Th17 cells, but it did not correlate with Th2 cells in AD patients. PR-957 treatment downregulated Th1 cells, Th17 cells, and their secreted cytokines as well as phosphorylated phosphoinositide 3-kinase (pPI3K)/PI3K and pAKT/AKT expressions in AD CD4+ T cells. SC79 addition upregulated pAKT/AKT expression, Th1 cells, and Th17 cells, while downregulated Th2 cells; also SC79 could alleviate the effect of PR-957 on regulating PI3K/AKT pathway and Th1, Th2, and Th17 cell differentiation in AD CD4+ T cells. Furthermore, PR-957 attenuated cognitive impairment and neurofibrillary tangle; also it inhibited Th17 cell differentiation and PI3K/AKT pathway in the brain and spleen of AD mice. In conclusion, PR-957 suppresses Th1 and Th17 cell differentiation, attenuates neural injury and improves cognitive function via inactivating PI3K/AKT pathway in AD.


Asunto(s)
Enfermedad de Alzheimer , Células Th17 , Animales , Ratones , Células Th17/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Enfermedad de Alzheimer/metabolismo , Leucocitos Mononucleares , Diferenciación Celular
15.
Artículo en Inglés | MEDLINE | ID: mdl-36429880

RESUMEN

Resilience can improve the adaptability of coal miners to high-hazard and high-stress environments. After facing setbacks or adversities, resilience can enable coal miners to recover from bad mental states and have an optimistic safety attitude and positive safety behaviors. However, how resilience affects safety behavior and the role of safety attitude in the relationship have not been clear. This study systematically reviewed previous research on resilience, safety attitude, and safety behavior. By recovering 639 valid questionnaires, the validity and reliability of the resilience scale, safety attitude scale, and safety behavior scale for coal miners were verified. Hierarchical regression analysis explored the relationships between resilience, safety attitude, and safety behavior. Studies have shown that resilience positively affects safety attitude and safe behavior. Safety attitude positively affects safety behaviors and plays a role as a partial mediator in the impact of resilience on safe behavior. The theoretical contribution is that the resilience of miners has a positive impact on safety behavior. Moreover, resilience can also act on safety behaviors through the partial intermediation of safety attitude. The practical contribution is that managers of coal mining companies can promote the resilience and safety attitude of coal miners to improve safety behaviors and prevent accidents.


Asunto(s)
Mineros , Humanos , Reproducibilidad de los Resultados , Conductas Relacionadas con la Salud , China , Carbón Mineral
16.
Nat Commun ; 13(1): 6410, 2022 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-36302781

RESUMEN

Low-lying island nations like Indonesia are vulnerable to sea level Height EXtremes (HEXs). When compounded by marine heatwaves, HEXs have larger ecological and societal impact. Here we combine observations with model simulations, to investigate the HEXs and Compound Height-Heat Extremes (CHHEXs) along the Indian Ocean coast of Indonesia in recent decades. We find that anthropogenic sea level rise combined with decadal climate variability causes increased occurrence of HEXs during 2010-2017. Both HEXs and CHHEXs are driven by equatorial westerly and longshore northwesterly wind anomalies. For most HEXs, which occur during December-March, downwelling favorable northwest monsoon winds are enhanced but enhanced vertical mixing limits surface warming. For most CHHEXs, wind anomalies associated with a negative Indian Ocean Dipole (IOD) and co-occurring La Niña weaken the southeasterlies and cooling from coastal upwelling during May-June and November-December. Our findings emphasize the important interplay between anthropogenic warming and climate variability in affecting regional extremes.


Asunto(s)
El Niño Oscilación del Sur , Viento , Estaciones del Año , Indonesia , Océano Índico
17.
Diagn Microbiol Infect Dis ; 104(4): 115801, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36130430

RESUMEN

Timely identification of respiratory pathogens guides specific treatment, reduces hospital costs and minimizes the excessive use of antibiotics. A new multiplex real-time PCR panel was developed based on an automatic molecular detection and analysis system (AutoMolec system), consisting of three separate internally controlled assays. Mycoplasma pneumoniae, Chlamydia pneumoniae, adenovirus, human metapneumovirus, influenza B virus, respiratory syncytial virus and human parainfluenza virus 1-3 may be directly detected in original samples. The system's clinical performance was evaluated by comparison with an approved commercial kit, using 517 clinical samples. The limit of detection of the AutoMolec mRT-PCR panel ranged from 4 × 10-4 ∼3.3 TCID50/mL and no cross-reaction with common respiratory pathogens was observed. The AutoMolec mRT-PCR panel had 99.09% sensitivity and 100.0% specificity and overall detection consistency was 99.61%, making it comparable to that of the commercial kit. Therefore, the AutoMolec mRT-PCR panel has great potential for routine screening of respiratory infection in China.


Asunto(s)
Metapneumovirus , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa Multiplex , Infecciones del Sistema Respiratorio/diagnóstico , Metapneumovirus/genética , Sensibilidad y Especificidad
18.
Sci Rep ; 12(1): 9182, 2022 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-35654939

RESUMEN

The intraseasonal variability of the intermediate water (IW) and its characteristics east of Taiwan are studied utilizing 17 months of long-term, continuous and synchronous measurements of temperature, salinity and current from mooring sites deployed at 122° E/23° N from January 2016 to May 2017. Direct measurements revealed water masses east of Taiwan alternately show complete South China Sea Intermediate Water or North Pacific Intermediate Water (NPIW) characteristics, mostly in a mixed state, with NPIW dominating 70% of the time. For the first time, it is demonstrated that the variation of IW with periods of ~ 80 days is mainly related to mesoscale eddies. Anticyclonic (cyclonic) eddies corresponding to an increase (decrease) in temperature and salinity in the intermediate layer. Further mechanism analysis indicates the vertical motion of the water mass inside the eddies is one of the reasons for the thermohaline change in the intermedaiter layer. In addition, the anticyclonic eddies may increase the salinity concentration gradient across the Luzon Strait, and the enhanced advection is favorable to the outflow of water masses in the South China Sea. When the cyclonic eddies acts on the eastern part of Taiwan, the influence of the northward advection is weakened and the southward flow on its left side is more favorable to the transport of NPIW.

19.
Transl Oncol ; 22: 101463, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35691247

RESUMEN

BACKGROUND: A-kinase interacting protein 1 (AKIP1) is recently implicated in the pathogenesis of several solid tumors, while its role in glioblastoma multiforme (GBM) is largely unknown. Therefore, the current study aimed to investigate the effect of AKIP1 on GBM cell malignant behaviors, stemness, and its underlying molecular mechanisms. METHODS: U-87 MG and A172 cells were transfected with control or AKIP1 overexpression plasmid; control or AKIP1 siRNA plasmid. Then cell proliferation, apoptosis, invasion, CD133+ cell proportion, and sphere formation assays were performed. Furthermore, RNA-Seq was performed in U-87 MG cells. Besides, AKIP1 expression was detected in 25 GBM and 25 low-grade glioma (LGG) tumor samples. RESULTS: AKIP1 was increased in several GBM cell lines compared to the control cell line. After transfections, it was found that AKIP1 overexpression increased cell invasion, CD133+ cell proportion, and sphere formation ability while less affecting cell proliferation or cell apoptosis in U-87 MG and A172 cells. Moreover, AKIP1 siRNA achieved the opposite effect in these cells, except that it inhibited cell proliferation but induced cell apoptosis to some extent. Subsequent RNA-Seq assay showed several critical carcinogenetic pathways, such as PI3K/AKT, Notch, EGFR tyrosine kinase inhibitor resistance, Ras, ErbB, mTOR pathways, etc. were potentially related to the function of AKIP1 in U-87 MG cells. Clinically, AKIP1 expression was higher in GBM tissues than in LGG tissues, which was also correlated with the poor prognosis of GBM to some degree. CONCLUSIONS: AKIP1 regulates the malignant behaviors and stemness of GBM via regulating multiple carcinogenetic pathways.

20.
Front Microbiol ; 13: 848908, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35495652

RESUMEN

Archaea exhibit strong community heterogeneity with microhabitat gradients and are a non-negligible part of biocrust's microorganisms. The study on archaeal biogeography in biocrusts could provide new insights for its application in environmental restoration. However, only a few studies on assembly processes and co-occurrence patterns of the archaeal community in patchy biocrusts have been reported, especially considering the number of species pools (SPs). Here, we comprehensively collected biocrusts across 3,500 km of northern China. Different successional biocrusts from various regions contain information of local climate and microenvironments, which can shape multiple unique archaeal SPs. The archaeal community differences in the same successional stage exceeded the variations between successional stages, which was due to the fact that the heterogeneous taxa tended to exchange between unknown patches driven by drift. We also comparatively studied the driving forces of community heterogeneity across three to ten SPs, and assembly and co-occurrence patterns were systematically analyzed. The results revealed that the impact of spatial factors on biogeographic patterns was greater than that of environmental and successional factors and that impact decreased with the number of SPs considered. Meanwhile, community heterogeneity at the phylogenetic facet was more sensitive to these driving factors than the taxonomic facet. Subgroups 1 (SG1) and 2 (SG2) of the archaeal communities in biocrusts were dominated by Nitrososphaeraceae and Haloarchaea, respectively. The former distribution pattern was associated with non-salinity-related variables and primarily assembled by drift, whereas the latter was associated with salinity-related variables and primarily assembled by homogeneous selection. Finally, network analysis indicated that the SG1 network had a higher proportion of competition and key taxa than the SG2 network, but the network of SG2 was more complex. Our study suggested that the development of the archaeal community was not consistent with biocrusts succession. The dominant taxa may determine the patterns of community biogeography, assembly, and co-occurrence.

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