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1.
Environ Sci Technol ; 58(19): 8215-8227, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38687897

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are extensively utilized in varieties of products and tend to accumulate in the human body including umbilical cord blood and embryos/fetuses. In this study, we conducted an assessment and comparison of the potential early developmental toxicity of perfluorooctanoic acid (PFOA), undecafluorohexanoic acid (PFHxA), heptafluorobutyric acid, perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate, and perfluorobutyric acid at noncytotoxic concentrations relevant to human exposure using models based on human embryonic stem cells in both three-dimensional embryoid body (EB) and monolayer differentiation configurations. All six compounds influenced the determination of cell fate by disrupting the expression of associated markers in both models and, in some instances, even led to alterations in the formation of cystic EBs. The expression of cilia-related gene IFT122 was significantly inhibited. Additionally, PFOS and PFOA inhibited ciliogenesis, while PFOA specifically reduced the cilia length. Transcriptome analysis revealed that PFOS altered 1054 genes and disrupted crucial signaling pathways such as WNT and TGF-ß, which play integral roles in cilia transduction and are critical for early embryonic development. These results provide precise and comprehensive insights into the potential adverse health effects of these six PFAS compounds directly concerning early human embryonic development.


Assuntos
Fluorocarbonos , Células-Tronco Embrionárias Humanas , Humanos , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Fluorocarbonos/toxicidade , Diferenciação Celular/efeitos dos fármacos
2.
BMC Cancer ; 24(1): 354, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504172

RESUMO

Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.


Assuntos
Neoplasias Colorretais , Interleucina-6 , Humanos , Animais , Camundongos , Interleucina-6/genética , ADP Ribose Transferases/genética , ADP Ribose Transferases/metabolismo , Receptor gp130 de Citocina/genética , Linhagem Celular Tumoral , Poli(ADP-Ribose) Polimerases/genética , Proliferação de Células , Neoplasias Colorretais/patologia , Proteínas Ligadas por GPI/metabolismo
3.
Brain Imaging Behav ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512647

RESUMO

Previous studies have provided evidence of structural and functional changes in the brains of patients with tension-type headache (TTH). However, investigations of functional connectivity alterations in TTH have been inconclusive. The present study aimed to investigate abnormal intrinsic functional connectivity patterns in patients with TTH through the voxel-wise degree centrality (DC) method as well as functional connectivity (FC) analysis. A total of 33 patients with TTH and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and were enrolled in the final study. The voxel-wise DC method was performed to quantify abnormalities in the local functional connectivity hubs. Nodes with abnormal DC were used as seeds for further FC analysis to evaluate alterations in functional connectivity patterns. In addition, correlational analyses were performed between abnormal DC and FC values and clinical features. Compared with HCs, patients with TTH had higher DC values in the left middle temporal gyrus (MTG.L) and lower DC values in the left anterior cingulate and paracingulate gyri (ACG.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Seed-based FC analyses revealed that patients with TTH showed greater connections between ACG.L and the right cerebellum lobule IX (CR-IX.R), and smaller connections between ACG.L and ACG.L. The MTG.L showed increased FC with the ACG.L, and decreased FC with the right caudate nucleus (CAU.R) and left precuneus (PCUN.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Additionally, the DC value of the MTG.L was negatively correlated with the DASS-depression score (p = 0.046, r=-0.350). This preliminary study provides important insights into the pathophysiological mechanisms of TTH.

4.
J Chromatogr A ; 1720: 464822, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38502989

RESUMO

α-Glucosidase plays a direct role in the metabolic pathways of starch and glycogen, any dysfunction in its activity could result in metabolic disease. Concurrently, this enzyme serves as a target for diverse drugs and inhibitors, contributing to the regulation of glucose metabolism in the human body. Here, an integrated analytical method was established to screen inhibitors of α-glucosidase. This step-by-step screening model was accomplished through the biosensing and affinity chromatography techniques. The newly proposed sensing program had a good linear relationship within the enzyme activity range of 0.25 U mL-1 to 1.25 U mL-1, which can quickly identify active ingredients in complex samples. Then the potential active ingredients can be captured, separated, and identified by an affinity chromatography model. The combination of the two parts was achieved by an immobilized enzyme technology and a microdevice for reaction, and the combination not only ensured efficiency and accuracy for inhibitor screening but also eliminated the occurrence of false positive results in the past. The emodin, with a notable inhibitory effect on α-glucosidase, was successfully screened from five traditional Chinese medicines using this method. The molecular docking results also demonstrated that emodin was well embedded into the active pocket of α-glucosidase. In summary, the strategy provided an efficient method for developing new enzyme inhibitors from natural products.


Assuntos
Emodina , Inibidores de Glicosídeo Hidrolases , Humanos , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , Cromatografia de Afinidade , Extratos Vegetais/química
5.
Environ Pollut ; 347: 123743, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38462195

RESUMO

Newly synthesized chemicals are being introduced into the environment without undergoing proper toxicological evaluation, particularly in terms of their effects on the vulnerable neurodevelopment. Thus, it is important to carefully assess the developmental neurotoxicity of these novel environmental contaminants using methods that are closely relevant to human physiology. This study comparatively evaluated the potential developmental neurotoxicity of 19 prevalent environmental chemicals including neonicotinoids (NEOs), organophosphate esters (OPEs), and synthetic phenolic antioxidants (SPAs) at environment-relevant doses (100 nM and 1 µM), using three commonly employed in vitro neurotoxicity models: human neural stem cells (NSCs), as well as the SK-N-SH and PC12 cell lines. Our results showed that NSCs were more sensitive than SK-N-SH and PC12 cell lines. Among all the chemicals tested, the two NEOs imidaclothiz (IMZ) and cycloxaprid (CYC), as well as the OPE tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), generated the most noticeable perturbation by impairing NSC maintenance and neuronal differentiation, as well as promoting the epithelial-mesenchymal transition process, likely via activating NF-κB signaling. Our data indicate that novel NEOs and OPEs, particularly IMZ, CYC, and TDCIPP, may not be safe alternatives as they can affect NSC maintenance and differentiation, potentially leading to neural tube defects and neuronal differentiation dysplasia in fetuses.


Assuntos
Retardadores de Chama , Humanos , Retardadores de Chama/análise , Organofosfatos/toxicidade , Fosfatos/análise , Diferenciação Celular , Ésteres , Monitoramento Ambiental
6.
J Hazard Mater ; 469: 133932, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38484659

RESUMO

The extensive use of aluminum (Al) poses an escalating ecological risk to aquatic ecosystems. The epiphytic biofilm on submerged plant leaves plays a crucial role in the regulation nutrient cycling and energy flow within aquatic environments. Here, we conducted a mesocosm experiment aimed at elucidating the impact of different Al concentrations (0, 0.6, 1.2, 2.0 mg/L) on microbial communities in epiphytic biofilms on Vallisneria natans. At 1.2 mg/L, the highest biofilms thickness (101.94 µm) was observed. Al treatment at 2.0 mg/L significantly reduced bacterial diversity, while micro-eukaryotic diversity increased. Pseudomonadota and Bacteroidota decreased, whereas Cyanobacteriota increased at 1.2 mg/L and 2.0 mg/L. At 1.2 and 2.0 mg/L. Furthermore, Al at concentrations of 1.2 and 2.0 mg/L enhanced the bacterial network complexity, while micro-eukaryotic networks showed reduced complexity. An increase in positive correlations among microbial co-occurrence patterns from 49.51% (CK) to 57.05% (2.0 mg/L) was indicative of augmented microbial cooperation under Al stress. The shift in keystone taxa with increasing Al concentration pointed to alterations in the functional dynamics of microbial communities. Additionally, Al treatments induced antioxidant responses in V. natans, elevating leaf reactive oxygen species (ROS) content. This study highlights the critical need to control appropriate concentration Al concentrations to preserve microbial diversity, sustain ecological functions, and enhance lake remediation in aquatic ecosystems.


Assuntos
Hydrocharitaceae , Microbiota , Alumínio/toxicidade , Biofilmes , Folhas de Planta , Interações Microbianas
7.
Cont Lens Anterior Eye ; 47(2): 102123, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38246852

RESUMO

OBJECTIVE: To investigate the effects of orthokeratology lenses (OK lenses) on corneal biomechanics in subjects of different ages. METHODS: Fifty subjects with mild to moderate myopia were categorized into three groups (Group I-III) based on their age. Corvis ST was used to collect dynamic corneal response parameters (DCRs) at different follow-up time points. Repeated measures analysis of variance combined with simple effect analysis was used to analyze the changes in DCRs in different groups during the follow-up period. Multiple linear regression analysis was used to analyze the correlations between axial length growth (ALG) at 6 months (ALG-6M) or 12 months (ALG-12M) and sex, baseline spherical equivalent refraction (SER), and DCRs. RESULTS: The DCRs changed in all three groups after wearing OK lenses. Most DCRs showed significant differences between baseline and 6 months after wearing OK lenses, while the differences between DCRs at 6 months and 12 months were not statistically significant. No significant differences in DCRs were observed among the three groups at the same follow-up time point. Additionally, at 6 months post-OK lens wear, ALG-6M was significantly correlated with velocity of the corneal apex at the first applanation (A1V-6M) (P = 0.002), Corvis biomechanical index (CBI-6M) (P = 0.004), the maximum amount of corneal movement (DAM-6M) (P = 0.010), deformation amplitude ratio of 2 mm (DAR2-6M) (P = 0.010), and stress-strain index (SSI-6M) (P = 0.038) in Group I. Furthermore, ALG-12M showed significant correlations with SSI-6M (P = 0.031), peak distance at the DAM (PD)-6M (P = 0.037), baseline Ambrósio Relational Thickness to the horizontal profile (P = 0.013) in Group I. CONCLUSIONS: The majority of DCRs displayed significant changes within the initial 6 months of OK lens wear. Minimal variation in DCRs was observed across different age groups at the same follow-up time point. Certain DCR parameters exhibited correlations with ALG, suggesting their potential in predicting ALG in myopic children undergoing OK lenses correction.


Assuntos
Miopia , Procedimentos Ortoceratológicos , Criança , Humanos , Topografia da Córnea , Córnea , Miopia/terapia , Refração Ocular , China , Comprimento Axial do Olho
8.
Environ Pollut ; 344: 123301, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190873

RESUMO

The widespread application of sulfonamide antibiotics in aquaculture has raised concerns about their adverse environmental impacts. Periphyton plays a crucial role in the aquatic ecosystem. In this study, we examined sulfamethoxazole (SMX) effects on the community structure and interactions of periphyton in simulated aquaculture water. Our findings indicated that the total biomass of periphyton decreased, while the biomass of periphytic algae and the secretion of extracellular polymeric substances (EPS) increased at 0.7 × 10-3 mg/L. Under higher SMX concentrations (5 mg/L and 10 mg/L), periphyton growth was severely inhibited, the microbial community structure of periphyton were sharply altered, characterized by the cyanobacteria growth suppression and decrease in the diversity index of community. Furthermore, elevated SMX concentrations (5 mg/L and 10 mg/L) increased the ratio of negative relationships from 45.4% to 49.4%, which suggested that high SMX concentrations promoted potential competition among microbes and disrupted the microbial food webs in periphyton. The absolute abundance of sul1 and sul2 genes in T2 and T3 groups were 2-3 orders of magnitude higher than those in control group after 30 days of SMX exposure, which elevated the risk of resistance gene enrichment and dissemination in the natural environment. The study contributes to our understanding of the detrimental effects of antibiotic pollution, which can induce changes in the structure and interaction relationship of microbial communities in aquaculture water.


Assuntos
Microbiota , Perifíton , Sulfametoxazol/toxicidade , Biomassa , Água , Antibacterianos/toxicidade , Aquicultura
9.
Clin Neurophysiol ; 158: 43-55, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38176157

RESUMO

OBJECTIVE: This study aimed to explore the effect of catechol-O-methyltransferase (COMT) Val158Met and brain-derived neurotrophic factor (BDNF) Val66Met to post-stroke cognitive impairment (PSCI) and the interaction with transcranial direct current stimulation (tDCS). METHODS: Seventy-six patients with PSCI were randomly assigned to Group (1) (n = 38) to receive anodal tDCS of left dorsolateral prefrontal cortex or Group (2) (n = 38) to receive sham stimulation. The intensity of the tDCS was 2 mA, and the stimulations were applied over the left DLPFC for 10 sessions. The Montreal Cognitive Assessment (MoCA) and backward digit span test (BDST) were assessed before, immediately after, and one month after stimulation. RESULTS: After stimulation, patients in the tDCS group showed better improvement in both MoCA and BDST than those in the sham group. The results of GLMs also supported the main effects of tDCS on general cognitive function and working memory. Then we found that COMT genotype may have a main effect on the improvement of MoCA and BDST, and there may be an interaction between COMT genotype and tDCS in enhancing BDST. In contrast, BDNF genotype showed no significant main or interaction effects on any scales. CONCLUSIONS: These findings demonstrate that tDCS can improve cognition after stroke. Gene polymorphisms of COMT can affect the efficacy of tDCS on PSCI, but BDNF may not. SIGNIFICANCE: This study found that COMT Val158Met has an interaction on the efficacy of prefrontal tDCS in cognitive function, which provides reference for future tDCS research and clinical application.


Assuntos
Disfunção Cognitiva , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Catecol O-Metiltransferase/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Córtex Pré-Frontal/fisiologia , Cognição , Disfunção Cognitiva/genética , Disfunção Cognitiva/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/terapia , Método Duplo-Cego
10.
Sci Total Environ ; 913: 169702, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38163615

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are a class of highly stable chemicals, widely used in everyday products, and widespread in the environment, even in pregnant women. While epidemiological studies have linked prenatal exposure to PFAS with atopic dermatitis in children, little is known about their toxic effects on skin development, especially during the embryonic stage. In this study, we utilized human embryonic stem cells to generate non-neural ectoderm (NNE) cells and exposed them to six PFAS (perfluorooctanoic acid (PFOA), undecafluorohexanoic acid (PFHxA), heptafluorobutyric acid (PFBA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorobutyric acid (PFBS)) during the differentiation process to assess their toxicity to early skin development. Our results showed that PFOS altered the spindle-like morphology of NNE cells to a pebble-like morphology, and disrupted several NNE markers, including KRT16, SMYD1, and WISP1. The six PFAS had a high potential to cause hypohidrotic ectodermal dysplasia (HED) by disrupting the expression levels of HED-relevant genes. Transcriptomic analysis revealed that PFOS treatment produced the highest number (1156) of differentially expressed genes (DEGs) among the six PFAS, including the keratinocyte-related genes KRT6A, KRT17, KRT18, KRT24, KRT40, and KRT81. Additionally, we found that PFOS treatment disturbed several signaling pathways that are involved in regulating skin cell fate decisions and differentiation, including TGF-ß, NOTCH, Hedgehog, and Hippo signaling pathways. Interestingly, we discovered that PFOS inhibited, by partially interfering with the expression of cytoskeleton-related genes, the ciliogenesis of NNE cells, which is crucial for the intercellular transduction of the above-mentioned signaling pathways. Overall, our study suggests that PFAS can inhibit ciliogenesis and hamper the transduction of important signaling pathways, leading potential congenital skin diseases. It sheds light on the underlying mechanisms of early embryonic skin developmental toxicity and provides an explanation for the epidemiological data on PFAS. ENVIRONMENTAL IMPLICATION: We employed a model based on human embryonic stem cells to demonstrate that PFOS has the potential to elevate the risk of hypohidrotic ectodermal dysplasia. This is achieved by targeting cilia, inhibiting ciliogenesis, and subsequently disrupting crucial signaling pathways like TGF-ß, NOTCH, Hedgehog, and Hippo, during the early phases of embryonic skin development. Our study highlights the dangers and potential impacts of six PFAS pollutants on human skin development. Additionally, we emphasize the importance of closely considering PFHxA, PFBA, PFHxS, and PFBS, as they have shown the capacity to modify gene expression levels, albeit to a lesser degree.


Assuntos
Ácidos Alcanossulfônicos , Displasia Ectodérmica Anidrótica Tipo 1 , Poluentes Ambientais , Fluorocarbonos , Criança , Humanos , Feminino , Gravidez , Animais , Ouriços , Ácidos Alcanossulfônicos/toxicidade , Alcanossulfonatos , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , Fator de Crescimento Transformador beta , Microtúbulos
11.
Anim Biosci ; 37(2): 370-384, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38186256

RESUMO

Rumen microbiota play a central role in the digestive process of ruminants. Their remarkable ability to break down complex plant fibers and proteins, converting them into essential organic compounds that provide animals with energy and nutrition. Research on rumen microbiota not only contributes to improving animal production performance and enhancing feed utilization efficiency but also holds the potential to reduce methane emissions and environmental impact. Nevertheless, studies on rumen microbiota face numerous challenges, including complexity, difficulties in cultivation, and obstacles in functional analysis. This review provides an overview of microbial species involved in the degradation of macromolecules, the fermentation processes, and methane production in the rumen, all based on cultivation methods. Additionally, the review introduces the applications, advantages, and limitations of emerging omics technologies such as metagenomics, metatranscriptomics, metaproteomics, and metabolomics, in investigating the functionality of rumen microbiota. Finally, the article offers a forward-looking perspective on the new horizons and technologies in the field of rumen microbiota functional research. These emerging technologies, with continuous refinement and mutual complementation, have deepened our understanding of rumen microbiota functionality, thereby enabling effective manipulation of the rumen microbial community.

13.
J Hazard Mater ; 465: 133028, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38006857

RESUMO

Recent studies have highlighted the presence of potentially harmful chemicals, such as neonicotinoids (NEOs) and organophosphate esters (OPEs), in everyday items. Despite their potential threats to human health, these dangers are often overlooked. In a previous study, we discovered that NEOs and OPEs can negatively impact development, but liver metabolism can help mitigate their harmful effects. In our current research, our objective was to investigate the toxicity mechanisms associated with NEOs, OPEs, and their liver metabolites using a human embryonic stem cell-based differentiation model that mimics early embryonic development. Our transcriptomics data revealed that NEOs and OPEs significantly influenced the expression of hundreds of genes, disrupted around 100 biological processes, and affected two signaling pathways. Notably, the BMP4 signaling pathway emerged as a key player in the disruption caused by exposure to these pollutants. Both NEOs and OPEs activated BMP4 signaling, potentially impacting early embryonic development. Interestingly, we observed that treatment with a human liver S9 fraction, which mimics liver metabolism, effectively reduced the toxic effects of these pollutants. Most importantly, it reversed the adverse effects dependent on the BMP4 pathway. These findings suggest that normal liver function plays a crucial role in detoxifying environmental pollutants and provides valuable experimental insights for addressing this issue.


Assuntos
Poluentes Ambientais , Retardadores de Chama , Gravidez , Feminino , Humanos , Ésteres/toxicidade , Organofosfatos/toxicidade , Fígado/metabolismo , Retardadores de Chama/análise , China , Monitoramento Ambiental , Neonicotinoides , Proteína Morfogenética Óssea 4
14.
Front Biosci (Landmark Ed) ; 28(11): 295, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-38062812

RESUMO

BACKGROUND: Patients with type 2 diabetes mellitus have a higher susceptibility for colorectal cancer and poorer prognosis, but the mechanism is still unknown. Here, we investigated the effect of ADP-ribosyltransferase 1 (ART1) on the growth of colorectal cancer in an animal model of diabetes with high norepinephrine status, as well as the potential mechanism. METHODS: We evaluated the size and weight of transplanted CT26 cell tumors with different ART1 expression levels in a mouse model of diabetes, as well as the survival time. CCK8 and flow cytometry were used to evaluate the growth of CT26 cells in vitro. Western blot was performed to analyze differentially expressed proteins in the ART1-modulated pathway. RESULTS: High levels of norepinephrine and ART1 favored the proliferation of CT26 cells in vitro and in vivo. Moreover, inhibition of norepinephrine-dependent proliferation was observed in ART1-silenced CT26 cells compared to those with normal ART1 expression. Following reduction of the serum norepinephrine level by surgery, the size and weight of transplanted CT26 cell tumors was significantly reduced compared to non-operated and sham-operated mice. Furthermore, the expression of ART1, mTOR, STAT3, and p-AKT protein in the tumor tissue of diabetic mice was higher than in non-diabetic mice. Following reduction of the norepinephrine level by renal denervation (RD), expression of the proliferation-related proteins mTOR, STAT3, p-AKT protein decreased, but no change was seen for ART1 expression. At the same concentration of norepinephrine, ART1 induced the expression of p-AKT, mTOR, STAT3, CyclinD1 and c-myc in CT26 cells in vitro. CONCLUSIONS: We conclude that faster growth of colorectal cancer in high norepinephrine conditions requires the expression of ART1, and that high ART1 expression may be a novel target for the treatment of diabetes-associated colorectal cancer.


Assuntos
ADP Ribose Transferases , Neoplasias Colorretais , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Norepinefrina , Animais , Camundongos , ADP Ribose Transferases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Diabetes Mellitus Tipo 2/complicações , Norepinefrina/farmacologia , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR
15.
ACS Nano ; 17(23): 24290-24298, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38084421

RESUMO

All-solid-state batteries (ASSBs) with a Li metal anode are expected to be one of the most promising energy storage systems to achieve high energy density. However, the interfacial instability between the Li metal anode and solid-state electrolyte (SSE) limits the rate capability and cycling stability of ASSBs. The main issue is the formation of voids at the Li/SSE interface during Li stripping due to the slow diffusion of Li within the bulk Li metal, then increasing internal cell resistance and inducing the formation of lithium dendrites. To address these issues, a composite Li anode (LAO) composed by Li-Ag alloy and Li2O is constructed by mixing the stoichiometric metal Li and Ag2O directly. LAO anode is capable of improving bulk Li diffusion kinetics and inhibiting the formation of interfacial voids effectively, achieving a high critical current density over 1.5 mA cm-2 and long stable cycling over 1000 h at 1 mA cm-2. The ASSBs, employing LAO as the anode, Li6PS5Cl as the SSE, and LiCoO2 as the cathode, exhibit superior rate capability and stable cycling over 4000 cycles at 5 C. Moreover, ASSBs can operate stably with a high LiCoO2 loading of 17.8 mg cm-2 for more than 100 cycles at 0.2 C.

16.
Nat Commun ; 14(1): 7683, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001113

RESUMO

Dietary restriction is an effective anti-ageing intervention across species. However, the molecular mechanisms from the metabolic aspects of view are still underexplored. Here we show ACS-20 as a key mediator of dietary restriction on healthy ageing from a genetic screen of the C. elegans acyl-CoA synthetase family. ACS-20 functions in the epidermis during development to regulate dietary restriction-induced longevity. Functional transcriptomics studies reveal that elevated expression of PTR-8/Patched is responsible for the proteostasis and lifespan defects of acs-20. Furthermore, the conserved NHR-23 nuclear receptor serves as a transcriptional repressor of ptr-8 and a key regulator of dietary restriction-induced longevity. Mechanistically, a specific region in the ptr-8 promoter plays a key role in mediating the transcription regulation and lifespan extension under dietary restriction. Altogether, these findings identify a highly conserved lipid metabolism enzyme as a key mediator of dietary restriction-induced lifespan and healthspan extension and reveal the downstream transcriptional regulation mechanisms.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Restrição Calórica , Envelhecimento/genética , Fatores de Transcrição/metabolismo , Longevidade/fisiologia , Proteínas de Transporte/metabolismo
17.
Zhonghua Nan Ke Xue ; 29(2): 131-137, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-37847084

RESUMO

OBJECTIVE: To evaluate the effect of transurethral plasmakinetic enucleation of the prostate (PKEP) with complete preservation of the urethral mucosa in the 11-1 o'clock position on urinary continence and erectile function in BPH patients. METHODS: We retrospectively analyzed the clinical data on 84 cases of BPH treated by traditional PKEP (group A, n = 48) or modified PKEP with complete preservation of the urethral mucosa in the 11-1 o'clock position (group B, n = 36) from January 2017 to December 2021. All the patients had sexual activities within three months preoperatively. We followed up the patients for 12 months after surgery and compared the baseline, surgery-related and follow-up data between the two groups of patients. RESULTS: There were no statistically significant differences between the two groups of patients in age, disease duration, prostate volume, preoperative postvoid residual urine (PVR), preoperative maximum urinary flow rate (Qmax), IPSS, PSA level, QOL scores or IIEF-5 scores, nor in the operation time, intraoperative hemoglobin decrease, volume of resected tissue, bladder flushing time, postoperative hospital stay, or postoperative improvement of Qmax and IPSS. The rate of urinary continence was significantly higher in group B than in A at 1 month postoperatively (66.67% ï¼»24/36ï¼½ vs 43.25% ï¼»20/48ï¼½, P = 0.025) and so were IIEF-5 scores at 6 months (16.69 ± 3.21 vs 15.27 ± 2.74, P = 0.032) and 12 months (18.04 ± 2.04 vs 16.96 ± 2.54, P = 0.039), while the incidence rate of retrograde ejaculation markedly lower in the former than in the latter group at 6 months (33.33% ï¼»12/36ï¼½ vs 56.25% ï¼»28/48ï¼½, P = 0.018) and 12 months (25% ï¼»9/36ï¼½ vs 47.92% ï¼»23/48ï¼½, P = 0.027). At 1, 3, 6 and 12 months after surgery, the patients in group B also showed remarkably higher QOL scores than those in group B (2.61 ± 0.81 vs 2.12 ± 0.69, P = 0.005; 2.24 ± 0.66 vs 1.94 ± 0.51,P = 0.026; 2.12 ± 0.83 vs 1.80 ± 0.53,P = 0.047; and 1.94 ± 0.65 vs 1.72 ± 0.58, P = 0.038). CONCLUSION: Modified PKEP with complete preservation of the urethral mucosa in the 11-1 o'clock position can improve urinary continence, protect erectile function and ameliorate QOL in patients with BPH.


Assuntos
Disfunção Erétil , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Disfunção Erétil/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Mucosa , Resultado do Tratamento
18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(5): 582-586, 2023 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-37753902

RESUMO

In recent years, with the rapid development of Chinese domestic surgical robot technology and the expansion of the application market, the "industry-university-research-medicine" collaborative innovation transformation mode has gradually developed and formed. Medical institutions play an important role in multi-party cooperation with enterprises, universities, and research institutes, as well as in product planning, technology research and development, achievement transformation, and personnel training. On the basis of reviewing the current situation of the development of the "industry-university-research-medicine" collaborative innovation transformation mode of domestic surgical robots, this study explores the multiple roles played by medical institutions in this mode and challenges, further putting forward corresponding recommendations.


Assuntos
Medicina , Robótica , Humanos , Universidades , Indústrias , Tecnologia
19.
Chem Commun (Camb) ; 59(82): 12286-12289, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37752883

RESUMO

Ga-modified CuFeO2 used as an efficient catalyst for CO2 hydrogenation to heavy olefins (C=5+) can achieve a high heavy olefin selectivity of 53.5%, which lies at a high level among reported catalysts, at a single pass CO2 conversion of 41.5%. It also displays an excellent long-term stability over 100 h, exhibiting its promising potential for industrial applications.

20.
Pain Res Manag ; 2023: 2028379, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693681

RESUMO

Purpose: Deficits in voluntary activation of the core stabilizing muscles are consistently observed in patients with chronic low back pain (CLBP); however, the underlying neural mechanism remains unclear. This cross-sectional study aimed at testing the hypothesis that the impaired voluntary activation of core stabilizing muscles is associated with structural and functional alterations in the basal ganglia, thalamus, and cortex in patients with CLBP. Methods: We obtained structural and resting-state functional magnetic resonance imaging (rs-fMRI) data from 53 patients with CLBP and 67 healthy controls and estimated the alterations in grey matter volume (GMV) and functional and effective connectivity (EC) of regions with altered GMV via whole brain analysis. The voluntary activation of the multifidus (MF) and transversus abdominis (TrA) was evaluated by ultrasound imaging in these patients. Results: Compared with the HCs, they displayed a significant decrease in GMV in the bilateral thalamus and caudate nucleus, a significant increase in GMV in the left middle frontal gyrus, and increased resting-state functional connectivity between the right caudate nucleus and the bilateral precuneus (voxel-level p < 0.005, Gaussian random field-corrected p < 0.05). The patients also showed increased EC from the right caudate nucleus to the bilateral precuneus, which was significantly correlated with voluntary activation of the bilateral MF and TrA (all p < 0.050). Conclusions: Grey matter alterations may be confined to regions responsible for perception, motor control, and emotion regulation in patients with CLBP. The interrupted EC from the basal ganglia to the default mode network might be involved in the impairment of voluntary activation of the core stabilizing muscles.


Assuntos
Dor Lombar , Humanos , Dor Lombar/diagnóstico por imagem , Estudos Transversais , Gânglios da Base/diagnóstico por imagem , Músculos Abdominais/diagnóstico por imagem , Encéfalo
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