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1.
Huan Jing Ke Xue ; 45(6): 3375-3388, 2024 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-38897759

RESUMEN

The vegetation phenology of the Qinghai-Xizang Plateau is changing significantly in the context of climate change. However, there are many hydrothermal factors affecting the phenology, and few studies have focused on the effects of multiple factors on the phenology of the Qinghai-Xizang Plateau, resulting in a lack of understanding of the mechanisms underlying phenological changes on the Qinghai-Xizang Plateau. In this study, we used remote sensing data interpretation to analyze the spatial and temporal variability of grassland phenology on the Qinghai-Xizang Plateau from 2002 to 2021, focusing on precipitation, temperature, altitude, soil, and other aspects to reveal the dominant factors of phenological variability using an interpretable machine learning method (SHAP) and to quantify the interactive effects of multiple factors on phenology. The results showed that:① The growing season start (SOS) of grasslands on the Qinghai-Xizang Plateau mostly ranged from 110 to 150 d, with 56.32 % of grasslands showing an early SOS trend; the growing season end (EOS) mostly ranged from 290-320 d, with 67.65 % of grasslands showing a delayed EOS trend; and the growing season length (LOS) mostly ranged from 120 to 210 d, with 65.50 % of the grasslands showing a trend towards longer growing season lengths. ② SOS in grasslands on the Qinghai-Xizang Plateau was mainly influenced by moisture conditions, in which soil moisture between 10 and 25 kg·m-2 in the 0-10 cm soil layer in March promoted the advancement of SOS and peaked at approximately 20 kg·m-2. EOS was mainly influenced by temperature, with higher temperatures in September and October having a stronger effect on EOS latency promotion and peaking at over 8 ℃ and -0.5 ℃, respectively. The main influencing factors of LOS were more consistent with SOS, in which soil moisture between 15 and 25 kg·m-2 in the 0-10 cm soil layer in March promoted the prolongation of LOS and peaked at approximately 18 kg·m-2. ③ There was an obvious interactive effect of water and heat and other factors on phenology; after soil moisture reached 20 kg·m-2 in the 0-10 cm soil layer in March, SOS was more advanced in low-precipitation and low-altitude areas. Better moisture conditions were more conducive to EOS delay at temperatures above 0 ℃ in October, and soil moisture in high precipitation areas promoted LOS prolongation more when soil moisture was between 12 and 22 kg·m-2 in 0-10 cm in March. The results also demonstrated that interpretable machine learning methods could provide a new approach to the analysis of the multifactorial effects of phenological change.


Asunto(s)
Cambio Climático , Pradera , Aprendizaje Automático , Estaciones del Año , China , Altitud , Tecnología de Sensores Remotos , Monitoreo del Ambiente/métodos , Suelo/química , Temperatura , Lluvia , Poaceae/crecimiento & desarrollo
2.
Opt Express ; 32(8): 13672-13687, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38859331

RESUMEN

Ronchi lateral shearing interferometry is a promising wavefront sensing technology with the advantages of simple structure and no reference light, which can realize a high-precision wavefront aberration measurement. To obtain shear information in both directions, the conventional double-Ronchi interferometer sequentially applies two orthogonal one-dimensional Ronchi gratings as the object-plane splitting element of the optics under test. Simultaneously, another Ronchi grating is positioned on the image plane in the same orientation to capture two sets of interferograms, thereby enabling two-dimensional wavefront reconstruction. Mechanical errors will inevitably be introduced during grating conversion, affecting reconstruction accuracy. Based on this, we propose a lateral shearing interferometry applying double-checkerboard grating. Only unidirectional phase shift is needed to obtain shear information in two directions while evading the grating conversion step, aiming to streamline operational processes and mitigate the potential for avoidable errors. We employ scalar diffraction theory to analyze the full optical path propagation process of the double-checkerboard shearing interferometry and introduce a new reconstruction algorithm to effectively extract the two-dimensional shear phase by changing the grating morphology, suppressing the aliasing effect of irrelevant diffraction orders. We reduce the fitting error through iterative optimization to realize high-precision wavefront reconstruction. Compared with conventional Ronchi lateral shearing interferometry, the proposed method exhibits better robustness and stability in noisy environments.

3.
Sci Rep ; 14(1): 12637, 2024 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-38825605

RESUMEN

Osteoporosis (OP) is a bone metabolism disease that is associated with inflammatory pathological mechanism. Nonetheless, rare studies have investigated the diagnostic effectiveness of immune-inflammation index in the male population. Therefore, it is interesting to achieve early diagnosis of OP in male population based on the inflammatory makers from blood routine examination. We developed a prediction model based on a training dataset of 826 Chinese male patients through a retrospective study, and the data was collected from January 2022 to May 2023. All participants underwent the dual-energy X-ray absorptiometry (DXEA) and blood routine examination. Inflammatory markers such as systemic immune-inflammation index (SII) and platelet-to-lymphocyte ratio (PLR) was calculated and recorded. We utilized the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection. Multivariable logistic regression analysis was applied to construct a predicting model incorporating the feature selected in the LASSO model. This predictive model was displayed as a nomogram. Receiver operating characteristic (ROC) curve, C-index, calibration curve, and clinical decision curve analysis (DCA) to evaluate model performance. Internal validation was test by the bootstrapping method. This study was approved by the Ethic Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Ethic No. JY2023012) and conducted in accordance with the relevant guidelines and regulations. The predictive factors included in the prediction model were age, BMI, cardiovascular diseases, cerebrovascular diseases, neuropathy, thyroid diseases, fracture history, SII, PLR, C-reactive protein (CRP). The model displayed well discrimination with a C-index of 0.822 (95% confidence interval: 0.798-0.846) and good calibration. Internal validation showed a high C-index value of 0.805. Decision curve analysis (DCA) showed that when the threshold probability was between 3 and 76%, the nomogram had a good clinical value. This nomogram can effectively predict the incidence of OP in male population based on SII and PLR, which would help clinicians rapidly and conveniently diagnose OP with men in the future.


Asunto(s)
Inflamación , Nomogramas , Osteoporosis , Humanos , Masculino , Osteoporosis/diagnóstico , Osteoporosis/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Inflamación/sangre , Inflamación/diagnóstico , China/epidemiología , Factores de Riesgo , Biomarcadores/sangre , Absorciometría de Fotón , Curva ROC , Adulto , Medición de Riesgo/métodos
4.
Chem Asian J ; 19(13): e202400375, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38693700

RESUMEN

Methane and its oxidation product (i. e., CO2) are both greenhouse gases. In the product chain of CO hydrogenation to hydrocarbon reaction, methane is also an unwanted product due to its poor added value. Herein we investigated the effect of structure-directing agent urotropine on cobalt-based catalyst supported on Al-O-Zn type carrier and achieved an initial and pioneering exploration of methane-free CO hydrogenation to hydrocarbon reaction at mild CO conversion range. The catalyst modified by urotropine has a nanoflower micromorphology and can significantly change the reaction performance, almost completely eliminating the ability of the catalyst to inhibit C-C coupling within a mild CO conversion range, that is, it can produce no or less C1-C4 gaseous hydrocarbons, while rich in condensed hydrocarbons (i. e., C5+ hydrocarbon selectivity can reach as high as 92.8 %-100.0 %).

5.
Int J Pharm ; 657: 124127, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38621611

RESUMEN

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by a positive feedback loop between cytokine storm and macrophages and lymphocytes overactivation, which could serve as a valid therapeutic target for HLH treatment. In this study, the clinically extensively used JAK1/2 inhibitor ruxolitinib was encapsulated into macrophage membrane-coated nanoparticles (M@NP-R) with high drug-loading efficiency for targeted HLH treatment. In vitro and in vivo studies demonstrated that M@NP-R not only efficiently adsorbed extracellular proinflammation cytokines, like IFN-γ and IL-6 to alleviate the cytokine storm, but also effectively dampened macrophage activation and proliferation by intracellular JAK/STAT signaling pathway inhibition. M@NP-R treatment significantly ameliorated the clinical and laboratory manifestations of HLH in mouse models, including trilineage cytopenia, hypercytokinemia, organomegaly, hepatorenal dysfunction, and tissue inflammation. Importantly, M@NP-R significantly enhanced the survival of the lethal HLH mice. Altogether, M@NP-R successfully blocked the positive feedback loop between the cytokine storm and macrophage overactivation by depleting extracellular inflammatory cytokines and inhibiting the intracellular JAK/STAT signaling pathway, both of which worked synergistically in HLH treatment. As ruxolitinib has already been extensively used in clinics with favorable safety, and M@NP is biodegradable and highly biocompatible, M@NP-R has good prospects for clinical translation.


Asunto(s)
Síndrome de Liberación de Citoquinas , Citocinas , Linfohistiocitosis Hemofagocítica , Macrófagos , Nanopartículas , Nitrilos , Pirazoles , Pirimidinas , Animales , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Pirazoles/administración & dosificación , Pirazoles/farmacología , Pirimidinas/administración & dosificación , Pirimidinas/farmacología , Ratones , Citocinas/metabolismo , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Células RAW 264.7 , Modelos Animales de Enfermedad , Masculino , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/administración & dosificación , Humanos
6.
Biomed Pharmacother ; 175: 116571, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38677248

RESUMEN

Diabetes can lead to a disorder of bone-fat balance, a significant cause of osteoporosis due to changes in environmental factors. Baicalin (Bai), an active ingredient of Scutellaria baicalensis, has been confirmed to possess antioxidant, hypoglycemic, and anti-osteoporotic effects. However, a comprehensive understanding of Bai's influence on diabetic osteoporosis (DOP), including its effects and underlying mechanisms, remains elusive. This study investigated Bai's impact on the bone-fat equilibrium in rats with DOP. The results indicated that Bai alleviated bone damage in DOP by promoting osteogenesis and inhibiting adipogenesis. Concurrently, through bioinformatics analysis, it was suggested that Bai's mechanism of action might involve the P38-MAPK pathway. In vitro, Bai was found to enhance the development of bone marrow mesenchymal stem cells (BMSCs) towards osteogenic lineages while suppressing their differentiation towards adipogenic lineages. It was discovered that Bai's promotion of BMSC osteogenic differentiation depends on the P38-MAPK pathway. Additionally, the synergistic effect mediated by Bai and P38-MAPK inhibitor suppressed BMSC adipogenic differentiation. Our research indicates that the P38-MAPK pathway play a role in Bai's effects on the osteogenic-adipogenic differentiation of BMSCs, showcasing the potential for DOP treatment. This study highlights Bai's ability to regulate the equilibrium between bone and fat, presenting a novel approach to adressing DOP.


Asunto(s)
Adipogénesis , Diferenciación Celular , Flavonoides , Células Madre Mesenquimatosas , Osteogénesis , Osteoporosis , Ratas Sprague-Dawley , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Flavonoides/farmacología , Flavonoides/uso terapéutico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Osteoporosis/tratamiento farmacológico , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Masculino , Ratas , Diferenciación Celular/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/patología , Células Cultivadas
7.
Mol Biol Rep ; 51(1): 67, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38170368

RESUMEN

BACKGROUND: HucMSCs had shown promising efficacy in treating childhood diseases, but oxidative stress induced by the poor microenvironment at the site of damage resulted in low cell survival after transplantation, thus preventing the cells from maximizing therapeutic efficacy. Therefore, this study aimed to investigate the role and mechanism of keap1 in oxidative stress injury of human umbilical cord mesenchymal stem cells (hucMSCs), and to provide theoretical support for improving the efficacy of stem cell therapy. METHODS: The hucMSCs were treated with hypoxic low-sugar-free serum (GSDH) to mimic the damaged site microenvironment after implantation. Adenoviral overexpression of keap1 gene of hucMSCs was performed in vitro, and cell proliferation ability was detected by CCK8 assay, crystal violet staining assay, and cell cycle assay. Cellular redox level was assessed by Amplex Red, MDA, and GSH/GSSG kit. Mitochondrial morphology was evaluated by mitotracker Red staining. ATP production was estimated by ATP detection kit. The mRNA and protein expression levels were tested by western blotting and RT-qPCR. RESULTS: GSDH treatment substantially upregulated keap1 expression. Subsequently, we found that overexpression of keap1 notably inhibited cell proliferation and caused cells to stagnate in G1 phase. At the same time, overexpression of keap1 induced the production of large amounts of H2O2 and the accumulation of MDA, but suppressed the GSH/GSSG ratio and the expression of antioxidant proteins NQO1 and SOD1, which caused oxidative stress damage. Overexpression of keap1 induced cells to produce a large number of dysfunctional mitochondria resulting in reduced ATP production. Moreover, Overexpression of keap1 significantly decreased the IKKß protein level, while upregulating IkB mRNA levels and downregulating P50 mRNA levels. CONCLUSIONS: Overexpression of keap1 may induce oxidative stress injury in hucMSCs by down-regulating IKKß expression and inhibiting NF-κB pathway activation. This implies the importance of keap1 in hucMSCs and it may be a potential gene for genetic modification of hucMSCs.


Asunto(s)
Peróxido de Hidrógeno , Células Madre Mesenquimatosas , Niño , Humanos , Adenosina Trifosfato , Disulfuro de Glutatión/metabolismo , Peróxido de Hidrógeno/metabolismo , Quinasa I-kappa B/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Células Madre Mesenquimatosas/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , ARN Mensajero/metabolismo , Cordón Umbilical
8.
Opt Express ; 31(24): 40005-40017, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-38041311

RESUMEN

Recently, phase retrieval techniques have garnered significant attention with their exceptional flexibility. However, their application is limited in optical systems with high numerical aperture due to the disregarded polarization properties of the beam. In this paper, a fast wavefront sensing method for tightly focused systems is proposed. Firstly, a vector diffraction model based on the chirp-Z transform is established to analytically describe the focal spot using the modal coefficients of polynomials and diffraction basis vectors, which accommodating any pixel size and resolution, thereby enabling to break through sampling constraints and remove lateral errors. Additionally, a modified Newton-gradient second-order algorithm is introduced to simultaneously optimize wavefront in multiple polarization directions, without the need for diffraction operators during iterations. Both numerical simulations and error analysis confirm the efficacy and precision of the proposed wavefront sensing method.

9.
World J Microbiol Biotechnol ; 40(2): 46, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38114752

RESUMEN

The objective of this paper is to explore the function of the AOL-s00215g415 (Aog415) gene, which encodes for the synthesis of siderophore in the nematode trapping fungal model strain A. oligospora, in order to understand the relationship between siderophore biosynthesis and nematode trapping activity. After a through sequence analysis, it was determined that Aog415 is a siderophore-synthesizing NRPS. The product of this gene was then identified to be the hydroxamate siderophore desferriferrichrome, using mass spectrometry analysis. When compared to the WT strains, the Aog415 knockout strain exhibited a 60% decrease in siderophore content in fermentation broth. Additionally, the number of predatory rings of decreased by 23.21%, while the spore yield increased by 37.34%. The deletion of Aog415 did not affect the growth of A. oligospora in diverse nutrient medium. Lipid metabolism-related pathways were the primary targets of Aog415 disruption as revealed by the metabolomic analysis. In comparison to the WT, a significant reduction in the levels of glycerophospholipids, and glycolipids was observed in the mutation. The metabolic alteration in fatty acyls and amino acid-like molecules were significantly disrupted. The knockout of Aog415 impaired the biosynthesis of the hydroxamate siderophore desferriferrichrome, remodeled the flow of fatty acid in A. oligospora, and mainly reprogrammed the membrane lipid metabolism in cells. Desferriferrichrome, a hydroxamate siderophore affects the growth, metabolism and nematode trapping ability of A. oligospora by regulating iron intake and cell membrane homeostasis. Our study uncovered the significant contribution of siderophores to the growth and nematode trapping ability and constructed the relationship among siderophores biosynthesis, lipid metabolism and nematode trapping activity of A. oligospora, which provides a new insight for the development of nematode biocontrol agents based on nematode trapping fungi.


Asunto(s)
Nematodos , Animales , Nematodos/microbiología , Metaboloma , Fenotipo , Sideróforos , Lípidos
10.
J Cancer ; 14(18): 3397-3403, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38021157

RESUMEN

Background: Ovarian cancer (OC) represents the seventh most lethal female tumors worldwide. The combination of PARP inhibitor (PARPi) and angiogenic inhibitor has been shown to be effective as a first-line or second-line maintenance regimen to synergistically exert antitumor effects, which prompts us to further evaluate the therapeutic effect of the combination of PARP inhibitor Niraparib and anti-angiogenic Brivanib on OC. Method:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay were applied to evaluate the anti-proliferative effect of Niraparib, Brivanib, or the combination treatment on OC cells. The Annexin V-FITC/PI apoptotic assay was adopted to detect cell apoptosis. Tumor xenograft experiment and immunohistochemical (IHC) analysis were performed to evaluate the effect of single or combination treatment on the tumorigenicity of OC in vivo. Results: Our current findings revealed that OC cells harboring BRAC1/2 mutations were more sensitive to Niraparib treatment compared to those with BRAC wild-type, and the addition of Brivanib enhanced programmed cell death (PCD) to sensitize OC cells with BRAC mutations to Niraparib treatment in vitro and in vivo. Conclusion: Our work illustrates that the combination regimen of PARPi and angiogenic inhibitor treatment should be beneficial for the OC patients with BRAC mutations, at least partially owing to the induction of multiple forms of programmed cell death (PCD).

11.
Acta Pharm Sin B ; 13(9): 3817-3833, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37719368

RESUMEN

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.

12.
J Transl Med ; 21(1): 581, 2023 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-37649075

RESUMEN

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are seed cells that can be used for alternative treatment of myocardial damage. However, their immaturity limits their clinical application. Mitochondrial development accompanies cardiomyocyte maturation, and PINK1 plays an important role in the regulation of mitochondrial quality. However, the role and mechanism of PINK1 in cardiomyocyte development remain unclear. METHODS: We used proteomic and phosphoproteomic to identify protein and phosphosite changes in hiPSC-CMs deficient in PINK1. Bioinformatics analysis was performed to identify the potential biological functions and regulatory mechanisms of these differentially expressed proteins and validate potential downstream mechanisms. RESULTS: Deletion of PINK1 resulted in mitochondrial structural breakdown and dysfunction, accompanied by disordered myofibrils arrangement. hiPSC-CMs deficient in PINK1 exhibited significantly decreased expression of mitochondrial ATP synthesis proteins and inhibition of the oxidative phosphorylation pathway. In contrast, the expression of proteins related to cardiac pathology was increased, and the phosphoproteins involved in cytoskeleton construction were significantly altered. Mechanistically, PINK1 deletion damaged the mitochondrial cristae of hiPSC-CMs and reduced the efficiency of mitochondrial respiratory chain assembly. CONCLUSION: The significantly differentially expressed proteins identified in this study highlight the important role of PINK1 in regulating mitochondrial quality in hiPSC-CMs. PINK1-mediated mitochondrial respiratory chain assembly is the basis for mitochondrial function. Whereas the cytoskeleton may be adaptively altered in response to mitochondrial dysfunction caused by PINK1 deletion, inadequate energy supply hinders myocardial development. These findings facilitate the exploration of the mechanism of PINK1 in cardiomyocyte development and guide efforts to promote the maturation of hiPSC-CMs.


Asunto(s)
Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Humanos , Proteómica , Mitocondrias , Proteínas Mitocondriales , Proteínas Quinasas/genética
13.
Front Microbiol ; 14: 1210288, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37520361

RESUMEN

In this study, the function of a non-ribosomal peptide synthetase-like (NRPS-like) encoding gene AOL_s00188g306 (g306) was investigated to reveal the association between NRPS and nematocidal activity in the nematode-trapping fungus Arthrobotrys oligospora. Sequence analysis indicated that the encoded product of g306 is an adenylation domain of non-ribosomal peptide synthetases and extended short-chain dehydrogenase/reductase domain-containing proteins, and displays a wide substrate spectrum. The Δg306 mutants were more sensitive to chemical stressors than the wild type. Disruption of g306 impeded the nematocidal efficiency of A. oligospora. Metabolomics analysis showed that secondary metabolite biosynthesis and lipid metabolism were altered in the mutants. The phenotypic changes in the mutants can be attributed to the down-regulation of various metabolites, including fatty acyls, prenol lipids, steroidsand steroid derivative, and amino acid derivatives, identified in the present study. This study investigated the association between the non-ribosomal polypeptide-encoding gene g306 and nematicidal activity in A. oligospora, providing a reference for resolving the predation mechanism of nematode-trapping fungus.

14.
Genes Dis ; 10(5): 2151-2166, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37492732

RESUMEN

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have attracted attention in the field of regenerative medicine due to their potential ability to repair damaged hearts. However, the immature phenotype of these cells limits their clinical application. Cardiomyocyte maturation is accompanied by changes in mitochondrial quality. PTEN-induced putative kinase 1 (PINK1) has been linked to mitochondrial quality control. However, whether the changes in mitochondrial quality in hiPSC-CMs are associated with PINK1, and the impact of PINK1 on hiPSC-CMs development are not clear. In this study, we found that knockdown of PINK1 in hiPSC-CMs resulted in mitochondrial fragmentation and impaired mitochondrial functions such as mitophagy and mitochondrial biogenesis. PINK1 deletion also inhibited the maturation of hiPSC-CMs, reverting them to a naive structural and functional state. We found that restoring the mitochondrial structure did not completely rescue the mitochondrial dysfunction caused by PINK1 deletion, while activation of PINK1 kinase activity using kinetin promoted mitochondrial fusion, increased the mitochondrial membrane potential and ATP production, and maintained the development and maturation of hiPSC-CMs. In conclusion, PINK1 regulates the mitochondrial structure and function of hiPSC-CMs, and is essential for the maturation of hiPSC-CMs.

15.
Genes Dis ; 10(4): 1279-1290, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37397565

RESUMEN

Circadian rhythm refers to the inherent 24-h cycle oscillation of biochemical, physiological and behavioral functions, which is almost universal in eukaryotes. At least 14 core clock genes have been reported to form multiple chain feedback loops that confer intrinsic circadian rhythmicity onto the molecular clock. Accumulating evidence has shown that the circadian gene dysfunction resulted from single nucleotide polymorphisms (SNPs), deletions, epigenetic modification, and deregulation is strongly associated with cancer risk. In the present review, we describe the composition of circadian rhythm system. We highlight the function and mechanism of clock genes in cancer pathogenesis and progression. Moreover, their potential clinical implications as prognostic biomarkers and therapeutic targets have been addressed.

16.
J Hazard Mater ; 457: 131699, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37270960

RESUMEN

Microplastics (MPs) as emerging contaminants have accumulated extensively in agricultural ecosystems and are known to exert important effects on biogeochemical processes. However, how MPs in paddy soils influence the conversion of mercury (Hg) to neurotoxic methylmercury (MeHg) remains poorly understood. Here, we evaluated the effects of MPs on Hg methylation and associated microbial communities in microcosms using two typical paddy soils in China (i.e., yellow and red soils). Results showed that the addition of MPs significantly increased MeHg production in both soils, which could be related to higher Hg methylation potential in the plastisphere than in the bulk soil. We found significant divergences in the community composition of Hg methylators between the plastisphere and the bulk soil. In addition, the plastisphere had higher proportions of Geobacterales in the yellow soil and Methanomicrobia in the red soil compared with the bulk soil, respectively; and plastisphere also had more densely connected microbial groups between non-Hg methylators and Hg methylators. These microbiota in the plastisphere are different from those in the bulk soil, which could partially account for their distinct MeHg production ability. Our findings suggest plastisphere as a unique biotope for MeHg production and provide new insights into the environment risks of MP accumulation in agricultural soils.


Asunto(s)
Mercurio , Compuestos de Metilmercurio , Microbiota , Oryza , Contaminantes del Suelo , Compuestos de Metilmercurio/química , Suelo/química , Plásticos , Contaminantes del Suelo/análisis , Mercurio/análisis , Oryza/química
17.
Ecol Evol ; 13(5): e10135, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37250442

RESUMEN

Noninvasive genetic sampling greatly facilitates studies on the genetics, ecology, and conservation of threatened species. Species identification is often a prerequisite for noninvasive sampling-based biological studies. Due to the low quantity and quality of genomic DNA from noninvasive samples, high-performance short-target PCR primers are necessary for DNA barcoding applications. The order Carnivora is characterized by an elusive habit and threatened status. In this study, we developed three pairs of short-target primers for identifying Carnivora species. The COI279 primer pair was suitable for samples with better DNA quality. The COI157a and COI157b primer pairs performed well for noninvasive samples and reduced the interference of nuclear mitochondrial pseudogenes (numts). COI157a could effectively identify samples from Felidae, Canidae, Viverridae, and Hyaenidae, while COI157b could be applied to samples from Ursidae, Ailuridae, Mustelidae, Procyonidae, and Herpestidae. These short-target primers will facilitate noninvasive biological studies and efforts to conserve Carnivora species.

18.
Chemistry ; 29(37): e202300662, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37040121

RESUMEN

Developing a straightforward and effective hydrophobic modification for metal-organic frameworks (MOFs) under mild conditions is meaningful for MOF applications. Here, a post-synthetic modification approach assisted with metal hydroxyl groups at room temperature is reported to induce hydrophobicity in the hydrophilic UiO-66. The bonding between Zr-OH in UiO-66 and n-tetradecylphosphonic acid (TDPA) is the vital force for the modifier TDPA. Superhydrophobic and superoleophilic composites were constructed for efficient oil-water separation by coating TDPA-modified UiO-66 (P-UiO-66) on commercial melamine sponges (MS) and filter papers (FP) with water contact angles of 153.2° and 155.6°, respectively. The P-UiO-66/MS composite could quickly and selectively absorb oily liquids up to 43 times its weight from water. The P-UiO-66/MS achieved continuous oil collection with high separation efficiencies (≥99.4 %). In addition, P-UiO-66/FP and P-UiO-66/MS showed high separation efficiencies for water-in-oil emulsions (≥98.5 %) and oil-in-water emulsions, respectively, with high resistance to low/high temperatures and acid/base conditions. The metal hydroxyl group-assisted post-synthetic modification strategy offers a facile and broad way to prepare hydrophobic MOFs for promising applications in environmental fields.

19.
Free Radic Biol Med ; 195: 270-282, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36596388

RESUMEN

The metabolic patterns and energetics of human induced pluripotent stem cell-derived cardiomyocytes (HiPSC-CMs) are much less than those of normal adult cardiomyocytes, which has limited their application in disease therapy and regenerative medicine. It has been demonstrated that SIRT3, a mitochondria-target deacetylase, controls mitochondrial metabolism in physiological and pathological conditions. In this research, We investigated the role and regulatory mechanism of SIRT3 in energy metabolism in HiPSC-CMs. We found that the expression of SIRT3 was increased during the differentiation and maturation of HiPSC-CMs. Knocking down SIRT3 impaired mitochondrial structure, mitochondrial respiration capacity, and fatty acid oxidation but enhanced glycolysis. However, honokiol, a pharmacological activator of SIRT3, improved the mitochondrial ultrastructure and energetics, and promoted oxidative phosphorylation in HiPSC-CMs. Furthermore, SIRT3 regulated the acetylation of OPA1, and the knockdown of OPA1 blocked the promotion of energy metabolism by honokiol, meanwhile, knocking down OPA1 impaired mitochondrial fusion, mitochondrial respiration capacity, and fatty acid oxidation which were reversed by M1 (a mitochondrial fusion promoter) in HiPSC-CMs. In summary, SIRT3 regulated energetics and promoted metabolism remodeling by targeting the OPA1-controlled mitochondrial dynamics in HiPSC-CMs, and targeting SIRT3 may have revelatory implications in the treatment of cardiovascular diseases and the application of HiPSC-CMs to regenerative medicine.


Asunto(s)
Células Madre Pluripotentes Inducidas , Sirtuina 3 , Humanos , Diferenciación Celular , Ácidos Grasos/metabolismo , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Dinámicas Mitocondriales , Miocitos Cardíacos/metabolismo , Sirtuina 3/genética , Sirtuina 3/metabolismo
20.
Lab Chip ; 23(3): 475-484, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36688448

RESUMEN

Angiogenesis, the formation of new blood vessels from existing vessels, has been associated with more than 70 diseases. Although numerous studies have established angiogenesis models, only a few indicators can be used to analyze angiogenic structures. In the present study, we developed an image-processing pipeline based on deep learning to analyze and quantify angiogenesis. We utilized several image-processing algorithms to quantify angiogenesis, including a deep learning-based cell nuclear segmentation algorithm and image skeletonization. This method could quantify and measure changes in blood vessels in response to biochemical gradients using 16 indicators, including length, width, number, and nuclear distribution. Moreover, this procedure is highly efficient for the three-dimensional quantitative analysis of angiogenesis and can be applied to diverse angiogenesis investigations.


Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Dispositivos Laboratorio en un Chip
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