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1.
Proc Natl Acad Sci U S A ; 120(22): e2217595120, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37216536

RESUMO

The sense of taste starts with activation of receptor cells in taste buds by chemical stimuli which then communicate this signal via innervating oral sensory neurons to the CNS. The cell bodies of oral sensory neurons reside in the geniculate ganglion (GG) and nodose/petrosal/jugular ganglion. The geniculate ganglion contains two main neuronal populations: BRN3A+ somatosensory neurons that innervate the pinna and PHOX2B+ sensory neurons that innervate the oral cavity. While much is known about the different taste bud cell subtypes, considerably less is known about the molecular identities of PHOX2B+ sensory subpopulations. In the GG, as many as 12 different subpopulations have been predicted from electrophysiological studies, while transcriptional identities exist for only 3 to 6. Importantly, the cell fate pathways that diversify PHOX2B+ oral sensory neurons into these subpopulations are unknown. The transcription factor EGR4 was identified as being highly expressed in GG neurons. EGR4 deletion causes GG oral sensory neurons to lose their expression of PHOX2B and other oral sensory genes and up-regulate BRN3A. This is followed by a loss of chemosensory innervation of taste buds, a loss of type II taste cells responsive to bitter, sweet, and umami stimuli, and a concomitant increase in type I glial-like taste bud cells. These deficits culminate in a loss of nerve responses to sweet and umami taste qualities. Taken together, we identify a critical role of EGR4 in cell fate specification and maintenance of subpopulations of GG neurons, which in turn maintain the appropriate sweet and umami taste receptor cells.


Assuntos
Papilas Gustativas , Paladar , Paladar/fisiologia , Gânglio Geniculado/metabolismo , Língua/inervação , Papilas Gustativas/metabolismo , Fatores de Transcrição/metabolismo , Células Receptoras Sensoriais/metabolismo
2.
PLoS Genet ; 19(6): e1010814, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37384781

RESUMO

Meta-diamides (e.g. broflanilide) and isoxazolines (e.g. fluralaner) are novel insecticides that target the resistant to dieldrin (RDL) subunit of insect γ-aminobutyric acid receptors (GABARs). In this study, we used in silico analysis to identify residues that are critical for the interaction between RDL and these insecticides. Substitution of glycine at the third position (G3') in the third transmembrane domain (TMD3) with methionine (G3'M TMD3), which is present in vertebrate GABARs, had the strongest effect on fluralaner binding. This was confirmed by expression of RDL from the rice stem borer, Chilo suppressalis (CsRDL) in oocytes of the African clawed frog, Xenopus laevis, where the G3'MTMD3 mutation almost abolished the antagonistic action of fluralaner. Subsequently, G3'MTMD3 was introduced into the Rdl gene of the fruit fly, Drosophila melanogaster, using the CRISPR/Cas9 system. Larvae of heterozygous lines bearing G3'MTMD3 did not show significant resistance to avermectin, fipronil, broflanilide, and fluralaner. However, larvae homozygous for G3'MTMD3 were highly resistant to broflanilide and fluralaner whilst still being sensitive to fipronil and avermectin. Also, homozygous lines showed severely impaired locomotivity and did not survive to the pupal stage, indicating a significant fitness cost associated with G3'MTMD3. Moreover, the M3'GTMD3 mutation in the mouse Mus musculus α1ß2 GABAR increased sensitivity to fluralaner. Taken together, these results provide convincing in vitro and in vivo evidence for both broflanilide and fluralaner acting on the same amino acid site, as well as insights into potential mechanisms leading to target-site resistance to these insecticides. In addition, our findings could guide further modification of isoxazolines to achieve higher selectivity for the control of insect pests with minimal effects on mammals.


Assuntos
Inseticidas , Receptores de GABA , Animais , Camundongos , Receptores de GABA/genética , Receptores de GABA/metabolismo , Dieldrin , Inseticidas/farmacologia , Inseticidas/química , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Larva/metabolismo , Mamíferos/metabolismo
3.
Brief Bioinform ; 24(2)2023 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-36880207

RESUMO

Protein-protein interactions (PPIs) carry out the cellular processes of all living organisms. Experimental methods for PPI detection suffer from high cost and false-positive rate, hence efficient computational methods are highly desirable for facilitating PPI detection. In recent years, benefiting from the enormous amount of protein data produced by advanced high-throughput technologies, machine learning models have been well developed in the field of PPI prediction. In this paper, we present a comprehensive survey of the recently proposed machine learning-based prediction methods. The machine learning models applied in these methods and details of protein data representation are also outlined. To understand the potential improvements in PPI prediction, we discuss the trend in the development of machine learning-based methods. Finally, we highlight potential directions in PPI prediction, such as the use of computationally predicted protein structures to extend the data source for machine learning models. This review is supposed to serve as a companion for further improvements in this field.


Assuntos
Aprendizado de Máquina , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Proteínas/metabolismo , Biologia Computacional/métodos
4.
Nano Lett ; 24(22): 6706-6713, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38775232

RESUMO

Three-photon fluorescence microscopy (3PFM) is a promising brain research tool with submicrometer spatial resolution and high imaging depth. However, only limited materials have been developed for 3PFM owing to the rigorous requirement of the three-photon fluorescence (3PF) process. Herein, under the guidance of a band gap engineering strategy, CdTe/CdSe/ZnS quantum dots (QDs) emitting in the near-infrared window are designed for constructing 3PF probes. The formation of type II structure significantly increased the three-photon absorption cross section of QDs and caused the delocalization of electron-hole wave functions. The time-resolved transient absorption spectroscopy confirmed that the decay of biexcitons was significantly suppressed due to the appropriate band gap alignment, which further enhanced the 3PF efficiency of QDs. By utilizing QD-based 3PF probes, high-resolution 3PFM imaging of cerebral vasculature was realized excited by a 1600 nm femtosecond laser, indicating the possibility of deep brain imaging with these 3PF probes.


Assuntos
Encéfalo , Pontos Quânticos , Pontos Quânticos/química , Encéfalo/diagnóstico por imagem , Fótons , Animais , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Compostos de Cádmio/química , Sulfetos/química , Camundongos , Compostos de Zinco/química , Telúrio/química , Compostos de Selênio/química , Humanos
5.
J Neurosci ; 43(24): 4405-4417, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37188512

RESUMO

Although NG2 is known to be selectively expressed in oligodendrocyte precursor cells (OPCs) for many years, its expressional regulation and functional involvement in oligodendrocyte differentiation have remained elusive. Here, we report that the surface-bound NG2 proteoglycan can physically bind to PDGF-AA and enhances PDGF receptor alpha (PDGFRα) activation of downstream signaling. During differentiation stage, NG2 protein is cleaved by A disintegrin and metalloproteinase with thrombospondin motifs type 4 (Adamts4), which is highly upregulated in differentiating OPCs but gradually downregulated in mature myelinating oligodendrocytes. Genetic ablation of Adamts4 gene impedes NG2 proteolysis, leading to elevated PDGFRα signaling but impaired oligodendrocyte differentiation and axonal myelination in both sexes of mice. Moreover, Adamts4 deficiency also lessens myelin repair in adult brain tissue following Lysophosphatidylcholine-induced demyelination. Thus, Adamts4 could be a potential therapeutic target for enhancing oligodendrocyte differentiation and axonal remyelination in demyelinating diseases.SIGNIFICANCE STATEMENT NG2 is selectively expressed in OPCs and downregulated during differentiation stage. To date, the molecular mechanism underlying the progressive removal of NG2 surface proteoglycan in differentiating OPCs has been unknown. In this study, we demonstrate that ADAMTS4 released by differentiating OPCs cleaves surface NG2 proteoglycan, attenuates PDGFRα signaling, and accelerates oligodendrocyte differentiation. In addition, our study also suggests ADAMTS4 as a potential therapeutic target for promoting myelin recovery in demyelinating diseases.


Assuntos
Doenças Desmielinizantes , Remielinização , Masculino , Feminino , Camundongos , Animais , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Bainha de Mielina/metabolismo , Proteoglicanas/genética , Oligodendroglia/metabolismo , Diferenciação Celular/fisiologia , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/metabolismo
6.
Plant J ; 115(2): 369-385, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37009644

RESUMO

Maintenance of stable mitochondrial respiratory chains could enhance adaptability to high temperature, but the potential mechanism was not elucidated clearly in plants. In this study, we identified and isolated a TrFQR1 gene encoding the flavodoxin-like quinone reductase 1 (TrFQR1) located in mitochondria of leguminous white clover (Trifolium repens). Phylogenetic analysis indicated that amino acid sequences of FQR1 in various plant species showed a high degree of similarities. Ectopic expression of TrFQR1 protected yeast (Saccharomyces cerevisiae) from heat damage and toxic levels of benzoquinone, phenanthraquinone and hydroquinone. Transgenic Arabidopsis thaliana and white clover overexpressing TrFQR1 exhibited significantly lower oxidative damage and better photosynthetic capacity and growth than wild-type in response to high-temperature stress, whereas AtFQR1-RNAi A. thaliana showed more severe oxidative damage and growth retardation under heat stress. TrFQR1-transgenic white clover also maintained better respiratory electron transport chain than wild-type plants, as manifested by significantly higher mitochondrial complex II and III activities, alternative oxidase activity, NAD(P)H content, and coenzyme Q10 content in response to heat stress. In addition, overexpression of TrFQR1 enhanced the accumulation of lipids including phosphatidylglycerol, monogalactosyl diacylglycerol, sulfoquinovosyl diacylglycerol and cardiolipin as important compositions of bilayers involved in dynamic membrane assembly in mitochondria or chloroplasts positively associated with heat tolerance. TrFQR1-transgenic white clover also exhibited higher lipids saturation level and phosphatidylcholine:phosphatidylethanolamine ratio, which could be beneficial to membrane stability and integrity during a prolonged period of heat stress. The current study proves that TrFQR1 is essential for heat tolerance associated with mitochondrial respiratory chain, cellular reactive oxygen species homeostasis, and lipids remodeling in plants. TrFQR1 could be selected as a key candidate marker gene to screen heat-tolerant genotypes or develop heat-tolerant crops via molecular-based breeding.


Assuntos
Arabidopsis , Trifolium , Trifolium/genética , Trifolium/metabolismo , Flavodoxina/genética , Flavodoxina/metabolismo , Diglicerídeos/metabolismo , Filogenia , Temperatura , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Oxidativo , Arabidopsis/genética , Arabidopsis/metabolismo , Homeostase , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo
7.
Anal Chem ; 96(13): 5315-5322, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38511619

RESUMO

Photoacoustic imaging (PAI) in the second near-infrared region (NIR-II), due to deeper tissue penetration and a lower background interference, has attracted widespread concern. However, the development of NIR-II nanoprobes with a large molar extinction coefficient and a high photothermal conversion efficiency (PCE) for PAI and photothermal therapy (PTT) is still a big challenge. In this work, the NIR-II CuTe nanorods (NRs) with large molar extinction coefficients ((1.31 ± 0.01) × 108 cm-1·M-1 at 808 nm, (7.00 ± 0.38) × 107 cm-1·M-1 at 1064 nm) and high PCEs (70% at 808 nm, 48% at 1064 nm) were synthesized by living Staphylococcus aureus (S. aureus) cells as biosynthesis factories. Due to the strong light-absorbing and high photothermal conversion ability, the in vitro PA signals of CuTe NRs were about 6 times that of indocyanine green (ICG) in both NIR-I and NIR-II. In addition, CuTe NRs could effectively inhibit tumor growth through PTT. This work provides a new strategy for developing NIR-II probes with large molar extinction coefficients and high PCEs for NIR-II PAI and PTT.


Assuntos
Nanopartículas , Nanotubos , Técnicas Fotoacústicas , Fototerapia/métodos , Técnicas Fotoacústicas/métodos , Staphylococcus aureus , Nanomedicina Teranóstica/métodos
8.
BMC Cancer ; 24(1): 138, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38281032

RESUMO

BACKGROUND: Central nervous system (CNS) tumors are the most common solid tumors in children and the leading cause of cancer-related death in the latter. Currently, the incidence rate exceeds that of leukemia and ranks first in the incidence of malignant tumors in children. METHODS: The epidemiological data on childhood CNS tumors were collected from the Chinese Cancer Registry Annual Report. The annual percent change (APC) of incidence and mortality-rate changes were estimated via Joinpoint regression. Due to a lack of pertinent data, we performed a system review on the clinical-pathological characteristics in Chinese publications. RESULTS: There was no significant increase in the incidence rate (APC: -0.1, 95% CI: -1.5 to 1.3), but there was a significant increase in the mortality rate (APC: 1.8, 95% CI: 0.3 to 3.4) for childhood CNS tumors. In the subgroup analysis, there were significant increases in both the incidence and mortality rates in rural areas (APC in the incidence: 6.2, 95% CI: 2.4 to 10.2; APC in mortality: 4.4, 95% CI: 0.4 to 8.4). The most common location and type of childhood CNS were, respectively, the cerebral hemisphere (25.5%, 95% CI: 21.7% to 29.4%) and astrocytomas (26.8%, 95% CI: 23.9% to 29.6%). CONCLUSIONS: The epidemiological trends, and the relevant prediction, highlighted the need to pay continual attention to childhood CNS tumors, and the clinicopathology evinced its own distinctive characteristics. Timely detection and effective treatment must be further promoted regarding childhood CNS tumors with a view to decreasing the disease burden, especially in rural areas.


Assuntos
Neoplasias do Sistema Nervoso Central , Leucemia , Criança , Humanos , Neoplasias do Sistema Nervoso Central/epidemiologia , China/epidemiologia , Incidência , Sistema de Registros
9.
Cell Commun Signal ; 22(1): 357, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987851

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155-/- mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated ß-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.


Assuntos
Senescência Celular , Células Epiteliais , Exossomos , Túbulos Renais , Macrófagos , MicroRNAs , Telômero , MicroRNAs/genética , MicroRNAs/metabolismo , Senescência Celular/genética , Exossomos/metabolismo , Exossomos/genética , Animais , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Macrófagos/metabolismo , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Camundongos , Telômero/genética , Telômero/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Masculino , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Fibrose/genética , Angiotensina II
10.
BMC Gastroenterol ; 24(1): 40, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238700

RESUMO

BACKGROUND: The weight-adjusted-waist index (WWI) is a novel obesity index, and gallstones are associated with obesity. This study aimed to investigate the possible relationship between WWI and gallstones. METHODS: The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between WWI and gallstones incidence. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. RESULTS: The study comprised 8004 participants over the age of 20, including 833 reported with gallstones. Participants in the higher WWI tertile tended to have a higher gallstones prevalence. In the final adjusted model, a positive association between WWI and gallstones prevalence was observed (OR = 1.34, 95% CI: 1.20‒1.49). Participants in the highest WWI tertile had a significantly 71% higher risk of gallstones than those in the lowest WWI tertile (OR = 1.71, 95% CI: 1.35‒2.17). A nonlinear correlation was found between the WWI and gallstones prevalence, with an inflection point of 12.7. CONCLUSIONS: Our study found that higher WWI levels connected with increased prevalence of gallstones. However, more prospective studies are needed to validate our findings.


Assuntos
Cálculos Biliares , Humanos , Cálculos Biliares/complicações , Inquéritos Nutricionais , Índice de Massa Corporal , Estudos Transversais , Obesidade/epidemiologia , Obesidade/complicações
11.
Environ Res ; 257: 119327, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38830391

RESUMO

Climate change mitigation requires simultaneous reduction of carbon emissions and air pollution. This study examines the synergy between pollution reduction and carbon reduction, identifying key variables and strategies to achieve this goal. Using a Geographical Detector model and a Coupling Degree of Coordination model, 108 cities in the Yangtze River Economic Belt (YREB) are investigated. Results show that while controlling PM2.5 has been more successful than managing carbon emissions in the YREB, synergy between pollution reduction and carbon emissions increased by an average of 7.2% from 2006 to 2019. Spatial analysis reveals higher synergy in upstream areas, indicating significant spatial diversity. The impact of pollution and emission reduction synergies is influenced by societal and environmental variables, including industry structure, technological innovation, energy structure, human capital quality, and economic basis. Synergy is amplified when natural limits align with high-quality development drivers such as technical innovation and the digital economy. Recommendations include enhancing city-to-city contact, improving energy and industrial structures, and fostering technological innovation to address regional variations in synergy levels.


Assuntos
Rios , China , Rios/química , Poluição do Ar/prevenção & controle , Poluição do Ar/análise , Mudança Climática , Monitoramento Ambiental/métodos , Cidades , Material Particulado/análise , Poluentes Atmosféricos/análise
12.
Environ Res ; 251(Pt 2): 118723, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490625

RESUMO

For better understanding the mechanism of microbial strains promoting methane production, four strains Hungatella xylanolytica A5, Bacillus licheniformis B1, Paraclostridium benzoelyticum C2 and Advenella faeciporci E1 were inoculated into anaerobic digestion systems. After bioaugmentation, the cumulative methane production of A5, B1, C2 and E1 groups elevated by 11.68%, 8.20%, 18.21% and 15.67% compared to CK group, respectively. The metagenomic analysis revealed that the species diversity and uniformity of the experimental groups was improved, and hydrolytic acidifying bacteria, represented by Clostridiaceae, Anaerolineaceae and Oscillospiraceae, and methanogens, such as Methanotrichaceae and Methanobacteriaceae, were enriched. Meanwhile, the abundance of key genes in carbohydrate, pyruvate and methane metabolism was increased in the inoculated groups, providing reasonable reasons for more methane production. The strengthening mechanism of microbial strains in this study offered a theoretical foundation for selecting a suitable bioaugmentation strategy to solve the problems of slow start-up and low methane production in anaerobic digestion.


Assuntos
Metagenoma , Metano , Metano/metabolismo , Anaerobiose , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Reatores Biológicos/microbiologia , Perda e Desperdício de Alimentos
13.
Environ Res ; 246: 118023, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38145733

RESUMO

Pesticides represent one of the largest intentional inputs of potentially hazardous compounds into agricultural soils. However, as an important vegetable producing country, surveys on pesticide residues in soils of vegetable production areas are scarce in China. This study presented the occurrence, spatial distribution, correlation between vegetable types and pesticides, and ecological risk evaluation of 94 current-use pesticides in 184 soil samples from vegetable production areas of Zhejiang province (China). The ecological risks of pesticides to soil biota were evaluated with toxicity exposure ratios (TERs) and risk quotient (RQ). The pesticide concentrations varied largely from below the limit of quantification to 20703.06 µg/kg (chlorpyrifos). The situation of pesticide residues in Jiaxing is more serious than in other cities. Soils in the vegetable areas are highly diverse in pesticide combinations. Eisenia fetida suffered exposure risk from multiple pesticides. The risk posed by chlorpyrifos, which exhibited the highest RQs at all scenarios, was worrisome. Only a few pesticides accounted for the overall risk of a city, while the other pesticides make little or zero contribution. This work will guide the appropriate use of pesticides and manage soil ecological risks, achieving green agricultural production.


Assuntos
Clorpirifos , Resíduos de Praguicidas , Praguicidas , Poluentes do Solo , Praguicidas/toxicidade , Praguicidas/análise , Resíduos de Praguicidas/toxicidade , Resíduos de Praguicidas/análise , Solo/química , Verduras , Monitoramento Ambiental , Medição de Risco , Poluentes do Solo/toxicidade , Poluentes do Solo/análise
14.
Mol Ther ; 31(5): 1437-1450, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35982620

RESUMO

Tubular epithelial cells (TECs) exposed to hypoxia incite tubulointerstitial inflammation (TII), while the exact mechanism is unclear. In this study, we identified that hypoxia evoked tubule injury as evidenced by tubular hypoxia-inducible factor-1α and kidney injury molecule-1 (KIM-1) expression and that renal small extracellular vesicle (sEV) production was increased with the development of TII after ischemia-reperfusion injury (IRI). Intriguingly, KIM-1-positive tubules were surrounded by macrophages and co-localized with sEVs. In vitro, KIM-1 expression and sEV release were increased in hypoxic TECs and the hypoxia-induced inflammatory response was ameliorated when KIM-1 or Rab27a, a master regulator of sEV secretion, was silenced. Furthermore, KIM-1 was identified to mediate hypoxic TEC-derived sEV (Hypo-sEV) uptake by TECs. Phosphatidylserine (PS), a ligand of KIM-1, was present in Hypo-sEVs as detected by nanoflow cytometry. Correspondingly, the inflammatory response induced by exogenous Hypo-sEVs was attenuated when KIM-1 was knocked down. In vivo, exogenous-applied Hypo-sEVs localized to KIM-1-positive tubules and exacerbated TII in IRI mice. Our study demonstrated that KIM-1 expressed by injured tubules mediated sEV uptake via recognizing PS, which participated in the amplification of tubule inflammation induced by hypoxia, leading to the development of TII in ischemic acute kidney injury.


Assuntos
Vesículas Extracelulares , Traumatismo por Reperfusão , Animais , Camundongos , Células Epiteliais/metabolismo , Vesículas Extracelulares/metabolismo , Hipóxia/metabolismo , Inflamação/metabolismo , Rim/metabolismo , Traumatismo por Reperfusão/metabolismo
15.
Cell Mol Life Sci ; 80(9): 252, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37587272

RESUMO

White adipose tissue (WAT) is important for regulating the whole systemic energy homeostasis. Excessive WAT accumulation further contributes to the development of obesity and obesity-related illnesses. More detailed mechanisms for WAT lipid metabolism reprogramming, however, are still elusive. Here, we report the abnormally high expression of a circular RNA (circRNA) mmu_circ_0001874 in the WAT and liver of mice with obesity. mmu_circ_0001874 interference achieved using a specific adeno-associated virus infects target tissues, down-regulating lipid accumulation in the obesity mice WAT, and liver tissues. Mechanistically, miR-24-3p directly interacts with the lipid metabolism effect of mmu_circ_0001874 and participates in adipogenesis and lipid accumulation by targeting Igf2/PI3K-AKT-mTOR axis. Moreover, mmu_circ_0001874 binds to Igf2bp2 to interact with Ucp1, up-regulating Ucp1 translation and increasing thermogenesis to decrease lipid accumulation. In conclusion, our data highlight a physiological role for circRNA in lipid metabolism reprogramming and suggest mmu_circ_0001874/miR-24-3p/Igf2/PI3K-AKT-mTOR and mmu_circ_0001874/Igf2bp2/Ucp1 axis may represent a potential mechanism for controlling lipid accumulation in obesity.


Assuntos
Metabolismo dos Lipídeos , MicroRNAs , Animais , Camundongos , Metabolismo dos Lipídeos/genética , Lipídeos , MicroRNAs/genética , Obesidade/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Circular/genética , Serina-Treonina Quinases TOR/genética , Proteína Desacopladora 1
16.
Med Sci Monit ; 30: e942231, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183217

RESUMO

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) is a mature and popular surgery for treatment of lumbar disc herniation (LDH). The main objective of our study was to identify risk factors for residual low back pain after PELD and to improve postoperative management. MATERIAL AND METHODS We retrospectively analyzed the clinical and imaging data of 251 patients who underwent PELD for LDH. We defined residual LBP as visual analog scale (VAS) score for LBP ≥3 at 2 years postoperatively, and severe LBP was defined as VAS for LBP ≥7.5. The clinical and imaging data were analyzed by comparing patients with VAS scores ≥3 and <3, and univariate analysis and multivariable logistic regression analysis were applied to predict the risk factors for residual LBP. RESULTS There were 56 (22.3%) patients with LBP VAS ≥3 at 2 years postoperatively. Multivariable logistic regression analysis demonstrated that severe baseline VAS for LBP (P<0.001), MCs type I (P=0.006), and severe fatty infiltration of the paravertebral muscles (P<0.001) were independent risk factors for residual LBP after PELD. CONCLUSIONS In patients with LDH, MCs type I, severe baseline LBP, and fatty infiltration of the paravertebral muscles were predictive factors for residual LBP after PELD. Our study suggests that spine surgeons should pay more attention to these imaging parameters, which may be a helpful indicator for the choice of surgical modality.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Dor Lombar , Humanos , Dor Lombar/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Estudos Retrospectivos , Vértebras Lombares/cirurgia
17.
Ecotoxicol Environ Saf ; 277: 116374, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677072

RESUMO

Farmland soil organisms frequently encounter pesticide mixtures presented in their living environment. However, the underlying toxic mechanisms employed by soil animals to cope with such combined pollution have yet to be explored. This investigation aimed to reveal the changes in cellular and mRNA levels under chlorpyrifos (CPF) and lambda-cyhalothrin (LCT) co-exposures in earthworms (Eisenia fetida). Results exhibited that the combination of CPF and LCT triggered an acute synergistic influence on the animals. Most exposures resulted in significant alterations in the activities of total superoxide dismutase (T-SOD), copper/zinc superoxide dismutase (Cu/Zn-SOD), caspase 3, and carboxylesterase (CarE) compared to the basal level. Moreover, when exposed to chemical mixtures, the transcription levels of four genes [heat shock protein 70 (hsp70), gst, sod, and calreticulin (crt)] also displayed more pronounced changes compared with their individual exposures. These changes in determined parameters indicated the occurrence of oxidative stress, cell death, detoxification dysfunction, and endoplasmic reticulum damage after co-exposure to CPF and LCT in E. fetida. The comprehensive examination of mixture toxicities of CPF and LCT at different endpoints would help to understand the overall toxicity they cause to soil invertebrates. The augmented deleterious effect of these pesticides in a mixture suggested that mixture toxicity assessment was necessary for the safety evaluation and application of pesticide mixtures.


Assuntos
Clorpirifos , Proteínas de Choque Térmico HSP70 , Nitrilas , Oligoquetos , Estresse Oxidativo , Piretrinas , Poluentes do Solo , Superóxido Dismutase , Animais , Oligoquetos/efeitos dos fármacos , Clorpirifos/toxicidade , Piretrinas/toxicidade , Nitrilas/toxicidade , Superóxido Dismutase/metabolismo , Poluentes do Solo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Carboxilesterase/metabolismo , Inseticidas/toxicidade , Caspase 3/metabolismo , Caspase 3/genética , Calreticulina/genética , Calreticulina/metabolismo , Glutationa Transferase/metabolismo , Glutationa Transferase/genética
18.
Sensors (Basel) ; 24(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38400336

RESUMO

By precisely controlling the distance between two train sets, virtual coupling (VC) enables flexible coupling and decoupling in urban rail transit. However, relying on train-to-train communication for obtaining the train distance can pose a safety risk in case of communication malfunctions. In this paper, a distance-estimation framework based on monocular vision is proposed. First, key structure features of the target train are extracted by an object-detection neural network, whose strategies include an additional detection head in the feature pyramid, labeling of object neighbor areas, and semantic filtering, which are utilized to improve the detection performance for small objects. Then, an optimization process based on multiple key structure features is implemented to estimate the distance between the two train sets in VC. For the validation and evaluation of the proposed framework, experiments were implemented on Beijing Subway Line 11. The results show that for train sets with distances between 20 m and 100 m, the proposed framework can achieve a distance estimation with an absolute error that is lower than 1 m and a relative error that is lower than 1.5%, which can be a reliable backup for communication-based VC operations.

19.
Sensors (Basel) ; 24(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38676244

RESUMO

Combining multiple devices for localization has important applications in the military field. This paper exploits the land-based short-wave platforms and satellites for fusion localization. The ionospheric reflection height error and satellite position errors have a great impact on the short-wave localization and satellite localization accuracy, respectively. In this paper, an iterative constrained weighted least squares (ICWLS) algorithm is proposed for these two kinds of errors. The algorithm converts the nonconvex equation constraints to linear constraints using the results of the previous iteration, thus ensuring convergence to the globally optimal solution. Simulation results show that the localization accuracy of the algorithm can reach the corresponding Constrained Cramér-Rao Lower Bound (CCRLB). Finally, the localization results of the two methods are fused using Kalman filtering. Simulations show that the fused localization accuracy is improved compared to the single-means localization.

20.
Sensors (Basel) ; 24(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38400507

RESUMO

There has been a significant shift in research focus in recent years toward laser-induced graphene (LIG), which is a high-performance material with immense potential for use in energy storage, ultrahydrophobic water applications, and electronic devices. In particular, LIG has demonstrated considerable potential in the field of high-precision human motion posture capture using flexible sensing materials. In this study, we investigated the surface morphology evolution and performance of LIG formed by varying the laser energy accumulation times. Further, to capture human motion posture, we evaluated the performance of highly accurate flexible wearable sensors based on LIG. The experimental results showed that the sensors prepared using LIG exhibited exceptional flexibility and mechanical performance when the laser energy accumulation was optimized three times. They exhibited remarkable attributes, such as high sensitivity (~41.4), a low detection limit (0.05%), a rapid time response (response time of ~150 ms; relaxation time of ~100 ms), and excellent response stability even after 2000 s at a strain of 1.0% or 8.0%. These findings unequivocally show that flexible wearable sensors based on LIG have significant potential for capturing human motion posture, wrist pulse rates, and eye blinking patterns. Moreover, the sensors can capture various physiological signals for pilots to provide real-time capturing.


Assuntos
Grafite , Dispositivos Eletrônicos Vestíveis , Humanos , Captura de Movimento , Eletrônica , Lasers
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