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1.
Autophagy ; : 1-18, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38705724

RESUMO

The endoplasmic reticulum (ER) serves as a hub for various cellular processes, and maintaining ER homeostasis is essential for cell function. Reticulophagy is a selective process that removes impaired ER subdomains through autophagy-mediatedlysosomal degradation. While the involvement of ubiquitination in autophagy regulation is well-established, its role in reticulophagy remains unclear. In this study, we screened deubiquitinating enzymes (DUBs) involved in reticulophagy and identified USP20 (ubiquitin specific peptidase 20) as a key regulator of reticulophagy under starvation conditions. USP20 specifically cleaves K48- and K63-linked ubiquitin chains on the reticulophagy receptor RETREG1/FAM134B (reticulophagy regulator 1), thereby stabilizing the substrate and promoting reticulophagy. Remarkably, despite lacking a transmembrane domain, USP20 is recruited to the ER through its interaction with VAPs (VAMP associated proteins). VAPs facilitate the recruitment of early autophagy proteins, including WIPI2 (WD repeat domain, phosphoinositide interacting 2), to specific ER subdomains, where USP20 and RETREG1 are enriched. The recruitment of WIPI2 and other proteins in this process plays a crucial role in facilitating RETREG1-mediated reticulophagy in response to nutrient deprivation. These findings highlight the critical role of USP20 in maintaining ER homeostasis by deubiquitinating and stabilizing RETREG1 at distinct ER subdomains, where USP20 further recruits VAPs and promotes efficient reticulophagy.Abbreviations: ACTB actin beta; ADRB2 adrenoceptor beta 2; AMFR/gp78 autocrine motility factor receptor; ATG autophagy related; ATL3 atlastin GTPase 3; BafA1 bafilomycin A1; BECN1 beclin 1; CALCOCO1 calcium binding and coiled-coil domain 1; CCPG1 cell cycle progression 1; DAPI 4',6-diamidino-2-phenylindole; DTT dithiothreitol; DUB deubiquitinating enzyme; EBSS Earle's Balanced Salt Solution; FFAT two phenylalanines (FF) in an acidic tract; GABARAP GABA type A receptor-associated protein; GFP green fluorescent protein; HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase; IL1B interleukin 1 beta; LIR LC3-interacting region; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; PIK3C3/Vps34 phosphatidylinositol 3-kinase catalytic subunit type 3; RB1CC1/FIP200 RB1 inducible coiled-coil 1; RETREG1/FAM134B reticulophagy regulator 1; RFP red fluorescent protein; RHD reticulon homology domain; RIPK1 receptor interacting serine/threonine kinase 1; RTN3L reticulon 3 long isoform; SEC61B SEC61 translocon subunit beta; SEC62 SEC62 homolog, preprotein translocation factor; SIM super-resolution structured illumination microscopy; SNAI2 snail family transcriptional repressor 2; SQSTM1/p62 sequestosome 1; STING1/MITA stimulator of interferon response cGAMP interactor 1; STX17 syntaxin 17; TEX264 testis expressed 264, ER-phagy receptor; TNF tumor necrosis factor; UB ubiquitin; ULK1 unc-51 like autophagy activating kinase 1; USP20 ubiquitin specific peptidase 20; USP33 ubiquitin specific peptidase 33; VAMP8 vesicle associated membrane protein 8; VAPs VAMP associated proteins; VMP1 vacuole membrane protein 1; WIPI2 WD repeat domain, phosphoinositide interacting 2; ZFYVE1/DFCP1 zinc finger FYVE-type containing 1.

2.
Sci Rep ; 14(1): 10643, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724634

RESUMO

Heterojunctions play a crucial role in improving the absorption of visible light and performance of photocatalysts for organic contaminants degradation in water. In this work, a novel type-II-II Ag2CO3/Bi2WO6 (AB) heterojunction was synthesized by hydrothermal reaction and in situ-precipitation methods. The mechanisms of charge transfer and carrier separation at the interface of heterojunctions and the influence on the photocatalytic activity were investigated. The degradation of levofloxacin (LEV) under visible light irradiation was employed to evaluate the photocatalytic performance of AB. The results showed that 85.4% LEV was degraded by AB, which was 1.38 and 1.39 times higher than that of Bi2WO6 and Ag2CO3, respectively. The work functions of the different crystal planes in the AB heterojunction, which was calculated by density functional theory, are a significant difference. The Fermi energy (Ef) of Ag2CO3 (- 6.005 eV) is lower than Bi2WO6 (- 3.659 eV), but the conduction band (CB) is higher. Therefore, using AB heterojunctions as an example, the research explored the mechanism of type-II-II which CB and Ef of one semiconductor cannot simultaneously surpass those of another material, based on the built-in electric field theory. Through this analysis, a deeper understanding of type-II heterojunctions was achieved, and providing valuable insights into the behavior of this specific heterojunction system.

3.
Chem Commun (Camb) ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726591

RESUMO

Developing an intermediate-temperature solid oxide fuel cell (IT-SOFC) is one of the most promising ways of achieving carbon neutrality, but its air-electrode is restricted by the conflict between the sluggish catalytic activity and durability. Herein, an A-site high-entropy perovskite composite La0.2Ba0.2Sr0.2Ca0.2Ce0.2-xCoO3-δ-xCeO2 (LBSCCC-CeO2) air-electrode material is fabricated via a one-step self-constructing strategy, which shows excellent oxygen reduction activity and stability due to the high-entropy structure and the synergy effect between LBSCCC and interfacial CeO2. This work provides a new way of fabricating high-performance air-electrodes in IT-SOFCs.

4.
Neural Netw ; 177: 106366, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38744112

RESUMO

Image super-resolution (ISR) is designed to recover lost detail information from low-resolution images, resulting in high-quality and high-definition high-resolution images. In the existing single ISR (SISR) methods based on convolutional neural networks (CNN), however, most of the models cannot effectively combine global and local information and are also easy to ignore the correlation between different hierarchical feature information. To address these problems, this study proposes a multi-level feature interactive image super-resolution network, which is constructed by the convolutional units inspired by nonlinear spiking mechanism in nonlinear spiking neural P systems, including shallow feature processing, deep feature extraction and fusion, and reconstruction modules. The different omni domain self-attention blocks are introduced to extract global information in the deep feature extraction and fusion stage and formed a feature enhancement module having a Transformer structure using a novel convolutional unit for extracting local information. Furthermore, to adaptively fuse features between different hierarchies, we design a multi-level feature fusion module, which not only can adaptively fuse features between different hierarchies, but also can better interact with contextual information. The proposed model is compared with 16 state-of-the-art or baseline models on five benchmark datasets. The experimental results show that the proposed model not only achieves good reconstruction performance, but also strikes a good balance between model parameters and performance.

5.
Fitoterapia ; : 106007, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38744384

RESUMO

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

6.
Nat Commun ; 15(1): 4013, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740778

RESUMO

Elucidating the neural basis of fear allows for more effective treatments for maladaptive fear often observed in psychiatric disorders. Although the basal forebrain (BF) has an essential role in fear learning, its function in fear expression and the underlying neuronal and circuit substrates are much less understood. Here we report that BF glutamatergic neurons are robustly activated by social stimulus following social fear conditioning in male mice. And cell-type-specific inhibition of those excitatory neurons largely reduces social fear expression. At the circuit level, BF glutamatergic neurons make functional contacts with the lateral habenula (LHb) neurons and these connections are potentiated in conditioned mice. Moreover, optogenetic inhibition of BF-LHb glutamatergic pathway significantly reduces social fear responses. These data unravel an important function of the BF in fear expression via its glutamatergic projection onto the LHb, and suggest that selective targeting BF-LHb excitatory circuitry could alleviate maladaptive fear in relevant disorders.


Assuntos
Prosencéfalo Basal , Medo , Habenula , Neurônios , Animais , Habenula/fisiologia , Masculino , Medo/fisiologia , Prosencéfalo Basal/fisiologia , Prosencéfalo Basal/metabolismo , Camundongos , Neurônios/fisiologia , Neurônios/metabolismo , Optogenética , Camundongos Endogâmicos C57BL , Comportamento Social , Comportamento Animal/fisiologia , Vias Neurais/fisiologia , Ácido Glutâmico/metabolismo , Condicionamento Clássico/fisiologia
7.
JMIR Form Res ; 8: e49276, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38723251

RESUMO

BACKGROUND: Open-system electronic cigarette (EC) product features, such as battery capacity, maximum output wattage, and so forth, are major components that drive product costs and may influence use patterns. Moreover, continued innovation and monitoring of product features and prices will provide critical information for designing appropriate taxation policies and product regulations. OBJECTIVE: This study will examine how product features are associated with the prices of devices sold in web-based vape shops. METHODS: We draw samples from 5 popular, US-based, web-based vape shops from April to August 2022 to examine starter kits, device-only products, and e-liquid container-only products. We implemented a linear regression model with a store-fixed effect to examine the association between device attributes and prices. RESULTS: EC starter kits or devices vary significantly by type, with mod prices being much higher than pod and vape pen prices. The prices of mod starter kits were even lower than those of mod devices, suggesting that mod starter kits are discounted in web-based vape shops. The price of mod kits, mod device-only products, and pod kits increased as the battery capacity and output wattage increased. For vape pens, the price was positively associated with the volume size of the e-liquid container. On the other hand, the price of pod kits was positively associated with the number of containers. CONCLUSIONS: A unit-based specific tax, therefore, will impose a higher tax burden on lower-priced devices such as vape pens or pod systems and a lower tax burden on mod devices. A volume- or capacity-based specific tax on devices will impose a higher tax burden on vape pens with a larger container size. Meanwhile, ad valorem taxes pegged to wholesale or retail prices would apply evenly across device types, meaning those with advanced features such as higher battery capacities and output wattage would face higher rates. Therefore, policy makers could manipulate tax rates by device type to discourage the use of certain device products.

8.
Stem Cell Rev Rep ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703310

RESUMO

BACKGROUND: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have demonstrated efficacy in repairing uterine scars, although the underlying mechanisms remain unclear. METHODS: Uterine injury was surgically induced in a rat model, followed by immediate transplantation of 5 × 10 ^ 5 hUC-MSCs to each side of the uterus. Uterine morphology was evaluated at days 14 and 30 using HE and Masson staining. Immunohistochemistry assessed macrophage polarization, angiogenesis and endometrial receptivity in the endometrium. Additionally, the regulatory effects of hUC-MSCs on macrophage polarization were explored through coculture. qRT-PCR quantified the expression of anti-inflammatory (IL10 and Arg1) and pro-inflammatory (iNOS and TNF-α) factors. Western blotting evaluated CD163 expression. RESULTS: Transplantation of hUC-MSCs promoted the healing of uterine injuries and tissue regeneration while inhibiting tissue fibrosis. Immunohistochemistry at days 14 and 30 post-transplantation demonstrated the polarization of macrophages toward the M2 phenotype in the uterine injury area in the presence of hUC-MSCs. Furthermore, hUC-MSC transplantation improved angiogenesis and endometrial receptivity in the uterine injury rat model, associated with increased IL10 expression. hUC-MSC-induced angiogenesis can be resisted by depleted macrophages. In vitro coculture experiments further demonstrated that hUC-MSCs promoted IL10 expression in macrophages while suppressing TNF-α and iNOS expression. Western blotting showed enhanced CD163 expression in macrophages following hUC-MSC treatment. CONCLUSIONS: hUC-MSCs contribute to the healing of uterine injuries by targeting macrophages to promote angiogenesis and the expression of anti-inflammatory factors.

9.
Biomater Res ; 28: 0023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694229

RESUMO

CRISPR/Cas9 gene editing technology is characterized by high specificity and efficiency, and has been applied to the treatment of human diseases, especially tumors involving multiple genetic modifications. However, the clinical application of CRISPR/Cas9 still faces some major challenges, the most urgent of which is the development of optimized delivery vectors. Biomaterials are currently the best choice for use in CRISPR/Cas9 delivery vectors owing to their tunability, biocompatibility, and efficiency. As research on biomaterial vectors continues to progress, hope for the application of the CRISPR/Cas9 system for clinical oncology therapy builds. In this review, we first detail the CRISPR/Cas9 system and its potential applications in tumor therapy. Then, we introduce the different delivery forms and compare the physical, viral, and non-viral vectors. In addition, we analyze the characteristics of different types of biomaterial vectors. We further review recent research progress in the use of biomaterials as vectors for CRISPR/Cas9 delivery to treat specific tumors. Finally, we summarize the shortcomings and prospects of biomaterial-based CRISPR/Cas9 delivery systems.

10.
Angew Chem Int Ed Engl ; : e202402946, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696279

RESUMO

Electrolytes with anion-dominated solvation are promising candidates to achieve dendrite-free and high-voltage potassium metal batteries. However, it's challenging to form anion-reinforced solvates at low salt concentrations. Herein, we construct an anion-reinforced solvation structure at a moderate concentration of 1.5 M with weakly coordinated cosolvent ethylene glycol dibutyl ether. The unique solvation structure accelerates the desolvation of K+, strengthens the oxidative stability to 4.94 V and facilitates the formation of inorganic-rich and stable electrode-electrolyte interface. These enable stable plating/stripping of K metal anode over 2200 h, high capacity retention of 83.0% after 150 cycles with a high cut-off voltage of 4.5 V in K0.67MnO2//K cells, and even 91.5% after 30 cycles under 4.7 V. This work provides insight into weakly coordinated cosolvent and opens new avenues for designing ether-based high-voltage electrolytes.

11.
BJPsych Open ; 10(3): e99, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38699891

RESUMO

BACKGROUND: Psychotic symptoms and elevated fasting blood glucose (FBG) are frequently observed in people with major depressive disorder (MDD), but there is a lack of research into this relationship within this cohort. AIMS: This study aimed to preliminarily explore the prevalence of psychotic symptoms and their predictors among patients with MDD and elevated FBG. METHOD: This study enrolled 1718 patients with first-episode and drug-naïve (FEDN) MDD. Sociodemographic data and physical and biochemical indicators were collected. Clinical symptoms were assessed with tools such as the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression (HRSD) and Positive and Negative Syndrome Scale positive subscale. RESULTS: The odds ratio for psychotic symptoms in those with MDD and elevated FBG (18.7%) was 2.33 times higher than those with MDD without elevated FBG. Presence of psychotic symptoms was significantly correlated with HRSD score, suicide attempts, and total cholesterol and thyroid-stimulating hormone levels. The combination of HRSD score, suicide attempts and thyroid-stimulating hormone levels among patients with MDD and elevated FBG effectively distinguished between individuals with and without psychotic symptoms, achieving an area under the curve of 0.87. CONCLUSIONS: Psychotic symptoms are frequently observed among FEDN MDD patients with elevated FBG, and depressive symptoms, suicide attempts and thyroid-stimulating hormone levels are related to psychotic symptoms in this cohort.

12.
Anal Chem ; 96(19): 7747-7755, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38691774

RESUMO

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTDAND-AND) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTDOR-AND) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND-AND and MTDOR-AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.


Assuntos
DNA , Molécula de Adesão da Célula Epitelial , MicroRNAs , Humanos , Molécula de Adesão da Célula Epitelial/metabolismo , DNA/química , MicroRNAs/análise , MicroRNAs/metabolismo , Mucina-1/metabolismo , Mucina-1/análise , Computadores Moleculares , Células MCF-7 , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Membrana Celular/metabolismo , Membrana Celular/química , Células Hep G2
13.
Int Immunopharmacol ; 133: 112095, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38678668

RESUMO

BACKGROUND: Adenosine A3 receptor (A3R) exerts analgesic, anti-inflammatory, and anti-nociceptive effects. In this study, we determined the analgesic mechanism of manual acupuncture (MA) in rats with complete Freund's adjuvant (CFA)-induced arthritis and explored whether MA ameliorates inflammation in these rats by upregulating A3R. METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into the following groups: Control, CFA, CFA + MA, CFA + sham MA, CFA + MA + DMSO, CFA + MA + IB-MECA, and CFA + MA + Reversine groups. The arthritis rat model was induced by injecting CFA into the left ankle joints. Thereafter, the rats were subjected to MA (ST36 acupoint) for 3 days. The clinical indicators paw withdrawal latency (PWL), paw withdrawal threshold (PWT), and open field test (OFT) were used to determine the analgesic effect of MA. In addition, to explore the effect of A3R on inflammation after subjecting arthritis rats to MA, IB-MECA (A3R agonist) and Reversine (A3R antagonist) were injected into ST36 before MA. RESULTS: MA ameliorated the pathological symptoms of CFA-induced arthritis, including the pain indicators PWL and PWT, number of rearing, total ambulatory distance, and activity trajectory. Furthermore, after MA, the mRNA and protein expression of A3R was upregulated in CFA-induced arthritis rats. In contrast, the protein levels of TNF-α, IL-1ß, Rap1, and p-p65 were downregulated after MA. Interestingly, the A3R agonist and antagonist further downregulated and upregulated inflammatory cytokine expression, respectively, after MA. Furthermore, the A3R antagonist increased the degree of ankle swelling after MA. CONCLUSION: MA can alleviate inflammatory pain by inhibiting the NF-κB signaling pathway via upregulating A3R expression of the superficial fascia of the ST36 acupoint site in CFA-induced arthritis rats.


Assuntos
Terapia por Acupuntura , Artrite Experimental , Adjuvante de Freund , Ratos Sprague-Dawley , Receptor A3 de Adenosina , Regulação para Cima , Animais , Receptor A3 de Adenosina/metabolismo , Receptor A3 de Adenosina/genética , Artrite Experimental/terapia , Ratos , Masculino , Inflamação , Dor/tratamento farmacológico , Pontos de Acupuntura , Manejo da Dor/métodos
14.
Toxicon ; 243: 107720, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38614244

RESUMO

AIM: This study proposed to assess the synergistic effects of Forskolin and Metformin (alone and in combination) on glucose, hematological, liver serum, and oxidative stress parameters in diabetic, healthy, and hepatocellular carcinoma (HCC) induced rats. MATERIALS AND METHODS: Eighty male Wistar rats were divided into 10 experimental groups (8 rats for each group), including 1) healthy group, 2) diabetic group, 3) HCC group, 4) diabet + Metformin (300 mg/kg), 5) diabet + Forskolin (100 mg/kg), 6) diabet + Metformin (300 mg/kg) & Forskolin (100 mg/kg), 7) HCC + Metformin (300 mg/kg), 8) HCC + Forskolin (100 mg/kg), 9) HCC + Metformin (300 mg/kg) & Forskolin (100 mg/kg), and 10) healthy group + Metformin (300 mg/kg) & Forskolin (100 mg/kg). The rats were administrated Forskolin/Metformin daily for 8 weeks. Glucose, hematological, and liver serum parameters were measured and compared among the groups. The levels of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as 8-hydroxydeoxyguanosine (8 OHdG) levels, were also measured. RESULTS: The average blood glucose reduction in diabetic rats with the Forskolin, Metformin, and Forskolin + Metformin treatments was 43.5%, 47.1%, and 53.9%, respectively. These reduction values for HCC rats after the treatments were 21.0%, 16.2%, and 23.7%, respectively. For all the diabetic and HCC rats treated with Forskolin/Metformin, the MDA, SOD, and GPx levels showed significant improvement compared with the diabetic and HCC groups (P < 0.05). Although the rats treated with Forskolin + Metformin experienced a higher reduction in oxidative stress of blood and urine samples compared to the Forskolin group, the differences between this group and rats treated with Metformin were not significant for all parameters. CONCLUSION: Metformin and Forskolin reduced oxidative stress in diabetic and HCC-induced rats. The results indicated that the combination of agents (Metformin & Forskolin) had greater therapeutic effects than Forskolin alone in reducing glucose levels in diabetic rats. However, the ameliorative effects of combining Metformin and Forskolin on blood and urine oxidative stress were not statistically higher than those of Metformin alone.

15.
Nat Sci Sleep ; 16: 347-358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606372

RESUMO

Objective: To investigate the changes in the wavelet entropy during wake and different sleep stages in patients with insomnia disorder. Methods: Sixteen patients with insomnia disorder and sixteen normal controls were enrolled. They underwent scale assessment and two consecutive nights of polysomnography (PSG). Wavelet entropy analysis of electroencephalogram (EEG) signals recorded from all participants in the two groups was performed. The changes in the integral wavelet entropy (En) and individual-scale wavelet entropy (En(a)) during wake and different sleep stages in the two groups were observed, and the differences between the two groups were compared. Results: The insomnia disorder group exhibited lower En during the wake stage, and higher En during the N3 stage compared with the normal control group (all P < 0.001). In terms of En(a), patients with insomnia disorder exhibited lower En(a) in the ß and α frequency bands during the wake stage compared with normal controls (ß band, P < 0.01; α band, P < 0.001), whereas they showed higher En(a) in the ß and α frequency bands during the N3 stage than normal controls (ß band, P < 0.001; α band, P < 0.001). Conclusion: Wavelet entropy can reflect the changes in the complexity of EEG signals during wake and different sleep stages in patients with insomnia disorder, which provides a new method and insights about understanding of pathophysiological mechanisms of insomnia disorder. Wavelet entropy provides an objective indicator for assessing sleep quality.

16.
Beilstein J Org Chem ; 20: 815-822, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655553

RESUMO

Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3ß-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through genome mining and heterologous expression, we identified a cav biosynthetic gene cluster responsible for the biosynthesis of DMTs 2-4, along with a P450, CavA, responsible for introducing the C-2 and C-3 hydroxy groups. Furthermore, the substrate scope of CavA revealed its ability to hydroxylate drimenol analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria.

17.
Mar Environ Res ; : 106524, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38664079

RESUMO

Diatoms and dinoflagellates are two typical functional groups of phytoplankton assemblages, which play a crucial role in the structure and functioning of most marine ecosystems. To date, a novel challenge in ecology and biogeochemistry is to address the influences of environmental changes associated with climate change and human activities on the dynamics of diatoms and dinoflagellates. However, the knowledge of the key environmental factors controlling the diatom-dinoflagellate dynamics remains to be improved, particularly in the coastal ecosystems. Therefore, we conducted four cruises along the Qingdao coastline in spring, summer, autumn, and winter 2022 to explore how diatoms and dinoflagellates varied in response to regional environmental changes. The results showed that the phytoplankton communities were dominated by diatoms and dinoflagellates in terms of abundance and species diversity throughout the year in the study region. Yet, there were significant seasonal variability of diatoms and dinoflagellates across the four seasons. For example, diatom species was the most diverse during autumn, and the higher average abundance was observed in the fall and winter. In contrast, the average abundance of dinoflagellates was maximum during the summer and minimum in the autumn season. Moreover, the abundance and species ratios of diatoms/dinoflagellates (dia/dino) also showed significant seasonal variations in the region. The dia/dino abundance ratio was lowest in summer, while the dia/dino species ratio showed an increasing trend from spring to fall and a slight descending trend during winter. Based on the redundancy analysis, we revealed that diatoms and dinoflagellates responded differently to various environmental variables in different seasons, of which temperature and nutrients (especially dissolved inorganic nitrogen, DIN) had highly significant correlations with both the dia/dino abundance and species ratios. Thus, we suggested that temperature and DIN were the key factors controlling the seasonal dynamics of diatoms and dinoflagellates in the Qingdao coastal area.

18.
J Nutr Educ Behav ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38647517

RESUMO

OBJECTIVE: The primary objective of this study was to develop and validate a Social Cognitive Theory-based instrument to identify psychosocial factors that influence diet and physical activity among Chinese children aged 10-12 years. DESIGN: This is a cross-sectional study, with data collected from questionnaires. SETTING: Two elementary schools in Beijing, China. PARTICIPANTS: Fourth to sixth-grade students (N = 1,486) aged 10-12 years were recruited. VARIABLES MEASURED: Gender, height, weight, nation, and grade were collected. Energy-balanced eating behaviors and their related sociopsychological factors were surveyed. ANALYSIS: Confirmatory factor analysis, Pearson correlations, Cronbach α index, and mediation analysis were used. RESULTS: (1) Confirmatory factor analysis revealed a 6-factor solution (51 items) and all factor loadings > 0.32, indicating that the model fitness was acceptable. (2) All correlation coefficients are statistically significant. All of the Cronbach α indexes were > 0.65, indicating acceptable reliability. (3) The mediating effect of goal intention and outcome expectations between self-efficacy and habit strength was statistically significant (P < 0.01), verifying the theory structure. CONCLUSIONS AND IMPLICATIONS: This questionnaire exhibits good internal consistency, reliability, and structural validity. It can be effectively employed to investigate energy-balanced eating behaviors related to the Social Cognitive Theory in Chinese children.

20.
J Ovarian Res ; 17(1): 80, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622725

RESUMO

BACKGROUND: Chemotherapy exposure has become a main cause of premature ovarian insufficiency (POI). This study aimed to evaluate the role and molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ovarian function protection after chemotherapy. METHODS: hUMSC-Exos were applied to cyclophosphamide-induced premature ovarian insufficiency mice and human ovarian granulosa tumor cells (KGN) to determine their effects on follicular development and granulosa cell apoptosis. Evaluation was done for iron ion and reactive oxygen species (ROS) production, lipid peroxidation levels, and changes in iron death-related molecules (nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Glutathione Peroxidase enzyme 4 (GPX4), and Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT)). Furthermore, rescue experiments using an Nrf2 inhibitor were performed to assess the therapeutic effects of hUMSC-Exos on granulosa cells. RESULTS: hUMSC-Exos promoted ovarian hormone levels and primary follicle development in POI mice and reduced granulosa cell apoptosis. After hUMSC-Exos treatment, the ROS production, free iron ions and lipid peroxidation levels of granulosa cells decreased, and the iron death marker proteins Nrf2, xCT and GPX4 also decreased. Furthermore, the Nrf2 inhibitor ML385 significantly attenuated the effects of hUMSC-Exos on granulosa cells. CONCLUSION: hUMSC-Exos inhibit ferroptosis and protect against CTX-induced ovarian damage and granulosa cell apoptosis through the Nrf2/GPX4 signaling pathway, revealing a novel mechanism of hUMSC-Exos in POI therapy.


Assuntos
Antineoplásicos , Exossomos , Ferroptose , Menopausa Precoce , Células-Tronco Mesenquimais , Insuficiência Ovariana Primária , Feminino , Humanos , Animais , Camundongos , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/terapia , Ferro
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