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1.
ACS Appl Electron Mater ; 6(5): 2807-2815, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38828037

RESUMO

The direct, solid state, and reversible conversion between heat and electricity using thermoelectric devices finds numerous potential uses, especially around room temperature. However, the relatively high material processing cost limits their real applications. Silver selenide (Ag2Se) is one of the very few n-type thermoelectric (TE) materials for room-temperature applications. Herein, we report a room temperature, fast, and aqueous-phase synthesis approach to produce Ag2Se, which can be extended to other metal chalcogenides. These materials reach TE figures of merit (zT) of up to 0.76 at 380 K. To improve these values, bismuth sulfide (Bi2S3) particles also prepared in an aqueous solution are incorporated into the Ag2Se matrix. In this way, a series of Ag2Se/Bi2S3 composites with Bi2S3 wt % of 0.5, 1.0, and 1.5 are prepared by solution blending and hot-press sintering. The presence of Bi2S3 significantly improves the Seebeck coefficient and power factor while at the same time decreasing the thermal conductivity with no apparent drop in electrical conductivity. Thus, a maximum zT value of 0.96 is achieved in the composites with 1.0 wt % Bi2S3 at 370 K. Furthermore, a high average zT value (zTave) of 0.93 in the 300-390 K range is demonstrated.

2.
Environ Pollut ; 356: 124351, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878812

RESUMO

Per- and polyfluoroalkyl substances (PFASs) have been widely detected in various food, which has attracted worldwide concern. However, the factors influencing the transfer and bio-accumulation of PFASs from soils to wheat in normal farmland, is still ambiguous. We investigated the PFASs accumulation in agricultural soils and grains from 10 cites, China, and evaluated the health risks of PFASs via wheat consumption. Our results show that ∑PFASs in soils range from 0.34 µg/kg to 1.59 µg/kg with PFOA and PFOS dominating, whilst ∑PFASs in wheats range from 2.74 to 6.01 µg/kg with PFOA, PFBA and PFHxS dominating. The lower pH conditions and high total organic carbon (TOC) could result in the higher accumulation of PFASs in soils and subsequently in wheat grains, whilst the bioaccumulation factors of PFASs increase with increasing pH conditions but not with TOC. The estimated daily intake (EDI) values of PFBA, PFOA, and PFHxS are relatively high, but data supports that ingesting wheat grains does not result in any potential risk to the human beings. Our studies provided more information about PFASs accumulation in wheat grains, and help us understand the current potential risks of PFASs in food.

3.
Clin Exp Med ; 24(1): 117, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833019

RESUMO

To carry out an in-depth analysis of the scientific research on autoimmunity, we performed the first bibliometric analysis focusing on publications in journals dedicated to autoimmunity (JDTA) indexed by science citation index during the period 2004-2023. Using bibliometric analysis, we quantitatively and qualitatively analyzed the country, institution, author, reference and keywords information of publications in JDTA, so as to understand the quantity, publication pattern and publication characteristics of these publications. The co-occurrence networks, clustering map and timeline map were created by CiteSpace and VOSviewer software to visualize the results. The CiteSpace was also used to analyze the strongest citation burst of keywords, which could describe the frequency, intensity and time period of high-frequency keywords, and indicate the research hotspots in the field. A total of 5 710 publications were analyzed, and their annual distribution number was basically stable from 2004 to 2023, fluctuating around 300. The United States and Italy led the way in terms of the number of publications, followed by France and China. For international cooperation, the developed countries represented by the United States cooperate more closely, but the cooperation was localized, reflecting that there was no unified model of autoimmunity among countries. UDICE-French Research Universities had the greatest number of publications. Subsequently, the number of publications decreased slowly with the ranking, and the gradient was not large. Eric Gershwin and Yehuda Shoenfeld stood out among the authors. They had an excellent academic reputation and great influence in the field of autoimmunity. The results of keyword analysis showed that JDTA publications mainly studied a variety of autoimmune diseases, especially SLE and RA. At the same time, JDTA publications also paid special attention to the research of cell function, autoantibody expression, animal experiments, disease activity, pathogenesis and treatment. This study is the first to analyze the publications in JDTA from multiple indicators by bibliometrics, thus providing new insights into the research hotspots and development trends in the field of autoimmunity.


Assuntos
Autoimunidade , Bibliometria , Publicações Periódicas como Assunto , Humanos , Pesquisa Biomédica/tendências , Estados Unidos , França , China , Itália
4.
Front Cell Infect Microbiol ; 14: 1394955, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912208

RESUMO

Background: Accumulated evidences indicate that dysbiosis of the urinary microbiota is associated with kidney stone formation. In the present study, we aimed to investigate the urinary microbiota composition and functionality of patients with calcium oxalate stones and compare it with those of healthy individuals. Method: We collected bladder urine samples from 68 adult patients with calcium oxalate stones and 54 age-matched healthy controls by transurethral catheterization. 16S rRNA gene and shotgun sequencing were utilized to characterize the urinary microbiota and functionality associated with calcium oxalate stones. Results: After further exclusion, a total of 100 subjects was finally included and analyzed. The diversity of the urinary microbiota in calcium oxalate stone patients was not significantly different from that of healthy controls. However, the urinary microbiota structure of calcium oxalate stone formers significantly differed from that of healthy controls (PERMANOVA, r = 0.026, P = 0.019). Differential representation of bacteria (e.g., Bifidobacterium) and several enriched functional pathways (e.g., threonine biosynthesis) were identified in the urine of calcium oxalate stone patients. Conclusion: Our results showed significantly different urinary microbiota structure and several enriched functional pathways in calcium oxalate stone patients, which provide new insight into the pathogenesis of calcium oxalate stones.


Assuntos
Bactérias , Oxalato de Cálcio , Microbiota , RNA Ribossômico 16S , Humanos , Oxalato de Cálcio/urina , Oxalato de Cálcio/metabolismo , Masculino , Feminino , RNA Ribossômico 16S/genética , Pessoa de Meia-Idade , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , Cálculos Renais/urina , Cálculos Renais/microbiologia , Urina/microbiologia , Urina/química , Disbiose/microbiologia , Estudos de Casos e Controles , Idoso
6.
Chin J Integr Med ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910191

RESUMO

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

7.
Front Med (Lausanne) ; 11: 1368346, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835791

RESUMO

Objective: Interleukin-6 (IL-6) is a multiple-effect cell factor implicated in the etiopathogenesis of several rheumatologic disorders. The blockade of the IL-6 pathway via IL6R inhibitors effectively treats these disorders. However, the clinical significance of the IL6R blockade for ankylosing spondylitis (AS) therapy remains controversial. With advances in genomics, increasing evidence has revealed the role of heritability in the etiology of disease, and Mendelian randomization (MR) analyses are being used more broadly to infer causation. Therefore, this MR study aims to evaluate the potential therapeutic utility of IL6R-targeted approaches in AS. Methods: The C-reactive protein (CRP) level was used as an exposure factor, and rheumatoid arthritis (RA) was used as a positive control. As-related genome-wide association study (GWAS) data were used as the primary outcome of drug-targeted MR analyses to test the relation between IL6R blockers and AS. Inverse variance weighting (IVW) is the primary analytical approach. Various sensitivity tests were performed to check the robustness and trustworthiness of the causality estimation, including consistency, heterogeneity, and pleiotropy analyses. In addition, repeated analysis was conducted using different GWAS data related to exposures and outcomes to examine the results for stability. Results: According to the IVW results, IL6R inhibitors significantly reduced the risk of AS in ukb-b-18194 (OR: 0.995, 95% CI 0.993-0.996, P = 5.12 × 10-08) and ukb-a-88 (OR: 0.994, 95% CI 0.993-0.996, P = 6.25 × 10-15). Moreover, repeated analyses were performed using different exposure-related GWAS data, yielding similar results, ukb-b-18194 (OR: 0.995, 95% CI 0.993-0.997, P = 1.25 × 10-06) and ukb-a-88 (OR: 0.995, 95% CI 0.994-0.997, P = 7.81 × 10-09). Heterogeneity analyses and pleiotropy analyses indicated no significant heterogeneity or pleiotropy. Conclusion: This MR analysis result further validates that the IL-6 pathway may contribute to the pathogenesis of AS and that the inhibition of IL6R reduces the risk of AS. These findings may guide future studies and provide more favorable drug treatment options for people at high risk of AS.

8.
Immunotargets Ther ; 13: 273-286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881648

RESUMO

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

9.
Eur J Med Res ; 29(1): 334, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38880878

RESUMO

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.


Assuntos
Cognição , Genótipo , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Cognição/fisiologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Apolipoproteínas E/genética , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética
10.
J Geriatr Cardiol ; 21(4): 421-430, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38800549

RESUMO

BACKGROUND: Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI) are available. METHODS: We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months (interquartile range: 26-73 months) follow-up period were compared between patients with the low prealbumin level (< 170 mg/L) and those with the high prealbumin level (≥ 170 mg/L). RESULTS: A total of 114 patients (4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class III (9.9% vs. 4.4%, P = 0.034), cardiovascular death (8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events (19.2% vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level (< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events (odds ratio = 1.918, 95% CI: 1.250-2.942, P = 0.003). The cut-off value of prealbumin level for predicting in-hospital death was 170 mg/L (area under the curve = 0.703, 95% CI: 0.651-0.754, P < 0.001; sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level (170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results. CONCLUSIONS: Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardiovascular mortality in STEMI patients.

11.
Anal Bioanal Chem ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38802680

RESUMO

Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe3O4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H2O2) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H2O2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level.

12.
J Colloid Interface Sci ; 670: 61-72, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759269

RESUMO

Lithium-sulfur batteries (LSBs) hold great potential as future energy storage technology, but their widespread application is hampered by the slow polysulfide conversion kinetics and the sulfur loss during cycling. In this study, we detail a one-step approach to growing tungsten phosphide (WP) nanoparticles on the surface of nitrogen and phosphorus co-doped carbon nanosheets (WP@NPC). We further demonstrate that this material provides outstanding performance as a multifunctional separator in LSBs, enabling higher sulfur utilization and exceptional rate performance. These excellent properties are associated with the abundance of lithium polysulfide (LiPS) adsorption and catalytic conversion sites and rapid ion transport capabilities. Experimental data and density functional theory calculations demonstrate tungsten to have a sulfophilic character while nitrogen and phosphorus provide lithiophilic sites that prevent the loss of LiPSs. Furthermore, WP regulates the LiPS catalytic conversion, accelerating the Li-S redox kinetics. As a result, LSBs containing a polypropylene separator coated with a WP@NPC layer show capacities close to 1500 mAh/g at 0.1C and coulombic efficiencies above 99.5 % at 3C. Batteries with high sulfur loading, 4.9 mg cm-2, are further produced to validate their superior cycling stability. Overall, this work demonstrates the use of multifunctional separators as an effective strategy to promote LSB performance.

13.
J Ethnopharmacol ; 331: 118279, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38705425

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt (L. japonicus, Chinese motherwort), known as Yi Mu Cao which means "good for women", has long been widely used in China and other Asian countries to alleviate gynecological disorders, often characterized by estrogen dysregulation. It has been used for the treatment of polycystic ovary syndrome (PCOS), a common endocrine disorder in women but the underlying mechanism remains unknown. AIM OF THE STUDY: The present study was designed to investigate the effect and mechanism of flavonoid luteolin and its analog luteolin-7-methylether contained in L. japonicus on aromatase, a rate-limiting enzyme that catalyzes the conversion of androgens to estrogens and a drug target to induce ovulation in PCOS patients. MATERIALS AND METHODS: Estrogen biosynthesis in human ovarian granulosa cells was examined using ELISA. Western blots were used to explore the signaling pathways in the regulation of aromatase expression. Transcriptomic analysis was conducted to elucidate the potential mechanisms of action of compounds. Finally, animal models were used to assess the therapeutic potential of these compounds in PCOS. RESULTS: Luteolin potently inhibited estrogen biosynthesis in human ovarian granulosa cells stimulated by follicle-stimulating hormone. This effect was achieved by decreasing cAMP response element-binding protein (CREB)-mediated expression of aromatase. Mechanistically, luteolin and luteolin-7-methylether targeted tumor progression locus 2 (TPL2) to suppress mitogen-activated protein kinase 3/6 (MKK3/6)-p38 MAPK-CREB pathway signaling. Transcriptional analysis showed that these compounds regulated the expression of different genes, with the MAPK signaling pathway being the most significantly affected. Furthermore, luteolin and luteolin-7-methylether effectively alleviated the symptoms of PCOS in mice. CONCLUSIONS: This study demonstrates a previously unrecognized role of TPL2 in estrogen biosynthesis and suggests that luteolin and luteolin-7-methylether have potential as novel therapeutic agents for the treatment of PCOS. The results provide a foundation for further development of these compounds as effective and safe therapies for women with PCOS.


Assuntos
Aromatase , Estrogênios , Células da Granulosa , Leonurus , Luteolina , Síndrome do Ovário Policístico , Feminino , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Luteolina/farmacologia , Luteolina/isolamento & purificação , Animais , Humanos , Aromatase/metabolismo , Aromatase/genética , Leonurus/química , Estrogênios/farmacologia , Estrogênios/biossíntese , Camundongos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/isolamento & purificação
14.
PLoS One ; 19(5): e0295350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38748674

RESUMO

BACKGROUND: Talar fractures often require osteotomy during surgery to achieve reduction and screw fixation of the fractured fragments due to limited visualization and operating space of the talar articular surface. The objective of this study was to evaluate the horizontal approach to the medial malleolus facet by maximizing exposure through dorsiflexion and plantarflexion positions. METHODS: In dorsiflexion, plantarflexion, and functional foot positions, we respectively obtained the anterior and posterior edge lines of the projection of the medial malleolus on the medial malleolar facet. The talar model from Mimics was imported into Geomagic software for image refinement. Then Solidworks software was used to segment the medial surface of the talus and extend the edge lines from the three positions to project them onto the "semicircular" base for 2D projection. The exposed area in different positions, the percentage of total area it represents, and the anatomic location of the insertion point at the groove between the anteroposternal protrusions of the medial malleolus were calculated. RESULTS: The mean total area of the "semicircular" region on the medial malleolus surface of the talus was 542.10 ± 80.05 mm2. In the functional position, the exposed mean area of the medial malleolar facet around the medial malleolus both anteriorly and posteriorly was 141.22 ± 24.34 mm2, 167.58 ± 22.36mm2, respectively. In dorsiflexion, the mean area of the posterior aspect of the medial malleolar facet was 366.28 ± 48.12 mm2. In plantarflexion, the mean of the anterior aspect of the medial malleolar facet was 222.70 ± 35.32 mm2. The mean overlap area of unexposed area in both dorsiflexion and plantarflexion was 23.32 ± 5.94 mm2. The mean percentage of the increased exposure area in dorsiflexion and plantarflexion were 36.71 ± 3.25% and 15.13 ± 2.83%. The mean distance from the insertion point to the top of the talar dome was 10.69 ± 1.24 mm, to the medial malleolus facet border of the talar trochlea was 5.61 ± 0.96 mm, and to the tuberosity of the posterior tibiotalar portion of the deltoid ligament complex was 4.53 ± 0.64 mm. CONCLUSIONS: Within the 3D model, we measured the exposed area of the medial malleolus facet in different positions and the anatomic location of the insertion point at the medial malleolus groove. When the foot is in plantarflexion or dorsiflexion, a sufficiently large area and operating space can be exposed during surgery. The data regarding the exposed visualization area and virtual screws need to be combined with clinical experience for safer reduction and fixation of fracture fragments. Further validation of its intraoperative feasibility will require additional clinical research.


Assuntos
Tálus , Humanos , Masculino , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Feminino , Adulto , Parafusos Ósseos , Fraturas do Tornozelo/cirurgia , Fraturas do Tornozelo/diagnóstico por imagem
16.
Chem Sci ; 15(20): 7651-7658, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38784745

RESUMO

Synaptic plasticity is the ability of synapses to modulate synaptic strength in response to dynamic changes within, as well as environmental changes. Although there is a considerable body of knowledge on protein expression and receptor migration in different categories of synaptic plasticity, the contribution and impact of presynaptic vesicle release and neurotransmitter levels towards plasticity remain largely unclear. Herein, nanoelectrochemistry using carbon fiber nanoelectrodes with excellent spatio-temporal resolution was applied for real-time monitoring of presynaptic vesicle release of dopamine inside single synapses of dopaminergic neurons, and exocytotic variations in quantity and kinetics under repetitive electrical stimuli. We found that the presynaptic terminal tends to maintain synaptic strength by rapidly recruiting vesicles, changing the dynamics of exocytosis, and maintaining sufficient neurotransmitter release in following stimuli. Except for small clear synaptic vesicles, dense core vesicles are involved in exocytosis to sustain the neurotransmitter level in later periods of repetitive stimuli. These data indicate that vesicles use a potential regulatory mechanism to establish short-term plasticity, and provide new directions for exploring the synaptic mechanisms in connection and plasticity.

17.
Cell Mol Life Sci ; 81(1): 196, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658440

RESUMO

Telomeres as the protective ends of linear chromosomes, are synthesized by the enzyme telomerase (TERT). Critically short telomeres essentially contribute to aging-related diseases and are associated with a broad spectrum of disorders known as telomeropathies. In cardiomyocytes, telomere length is strongly correlated with cardiomyopathies but it remains ambiguous whether short telomeres are the cause or the result of the disease. In this study, we employed an inducible CRISPRi human induced pluripotent stem cell (hiPSC) line to silence TERT expression enabling the generation of hiPSCs and hiPSC-derived cardiomyocytes with long and short telomeres. Reduced telomerase activity and shorter telomere lengths of hiPSCs induced global transcriptomic changes associated with cardiac developmental pathways. Consequently, the differentiation potential towards cardiomyocytes was strongly impaired and single cell RNA sequencing revealed a shift towards a more smooth muscle cell like identity in the cells with the shortest telomeres. Poor cardiomyocyte function and increased sensitivity to stress directly correlated with the extent of telomere shortening. Collectively our data demonstrates a TERT dependent cardiomyogenic differentiation defect, highlighting the CRISPRi TERT hiPSCs model as a powerful platform to study the mechanisms and consequences of short telomeres in the heart and also in the context of telomeropathies.


Assuntos
Diferenciação Celular , Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Telomerase , Telômero , Telomerase/metabolismo , Telomerase/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Telômero/metabolismo , Encurtamento do Telômero , Linhagem Celular
18.
Fitoterapia ; 175: 105960, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38621426

RESUMO

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.


Assuntos
Compostos Fitoquímicos , Raízes de Plantas , Rehmannia , Raízes de Plantas/química , Estrutura Molecular , Rehmannia/química , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Espécies Reativas de Oxigênio/metabolismo , China , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos Policíclicos/química
19.
Phytochemistry ; 222: 114098, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38648960

RESUMO

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.


Assuntos
Peptídeos beta-Amiloides , Apoptose , Microglia , Simulação de Acoplamento Molecular , Fragmentos de Peptídeos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Lentinula/química , Linhagem Celular
20.
Environ Int ; 187: 108688, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685158

RESUMO

The phyllosphere, particularly the leaf surface of plants, harbors a diverse range of microbiomes that play a vital role in the functioning of terrestrial ecosystems. However, our understanding of microbial successions and their impact on functional genes during plant community development is limited. In this study, considering core and satellite microbial taxa, we characterized the phyllosphere microbiome and functional genes in various microhabitats (i.e., leaf litter, moss and plant leaves) across the succession of a plant community in a low-altitude glacier foreland. Our findings indicate that phyllosphere microbiomes and associated ecosystem stability increase during the succession of the plant community. The abundance of core taxa increased with plant community succession and was primarily governed by deterministic processes. In contrast, satellite taxa abundance decreased during plant community succession and was mainly governed by stochastic processes. The abundance of microbial functional genes (such as C, N, and P hydrolysis and fixation) in plant leaves generally increased during the plant community succession. However, in leaf litter and moss leaves, only a subset of functional genes (e.g., C fixation and degradation, and P mineralization) showed a tendency to increase with plant community succession. Ultimately, the community of both core and satellite taxa collaboratively influenced the characteristics of phyllosphere nutrient-cycling genes, leading to the diverse profiles and fluctuating abundance of various functional genes during plant community succession. These findings offer valuable insights into the phyllosphere microbiome and plant-microbe interactions during plant community development, advancing our understanding of the succession and functional significance of the phyllosphere microbial community.


Assuntos
Microbiota , Folhas de Planta , Folhas de Planta/microbiologia , Ecossistema , Plantas/microbiologia , Desenvolvimento Vegetal
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