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1.
J Colloid Interface Sci ; 678(Pt B): 95-104, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39241451

RESUMEN

The intercalation of organic molecules is a promising approach to modulate the structure of 2D transition metal borides (MBenes), aiming to enhance charge transport and improve electrochemical performance in energy storage applications. However, key questions remain regarding how organic molecules with diverse functionalities penetrate and align between the MBene layer, as well as the mechanism of charge redistribution during intercalation. Addressing these questions is crucial for guiding the design of Organic-MBene heterostructures. To this end, a comprehensive approach combining theoretical calculations and experimental analyses was employed to explore the self-assembly mechanisms of organic molecules featuring N, O, S and tertiary amine end groups on the MoB-MBene surface. Experimental characterizations confirm that the interaction between MoB and organic compounds depends on the end groups. First principles calculations demonstrate that organic molecules tend to adopt a flat configuration on the MoB surface during molecular assembly. Calculations also reveal that the binding and charge transfer processes from organic molecules to MoB are highly dependent on the specific end groups, consistent with experimental observations. Furthermore, the effect of combining organic molecules with MoB on battery performance was further discussed, offering new insights for advancing the research and development of MBenes in aqueous battery systems.

2.
Phys Med Biol ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284350

RESUMEN

OBJECTIVE: The study aims to reduce the imaging radiation dose in Adaptive Radiotherapy (ART) while maintaining high-quality CT images, critical for effective treatment planning and monitoring. APPROACH: We developed the Prior-aware Learned Primal-Dual Network (pLPD-UNet), which uses prior CT images to enhance reconstructions from low-dose scans. The network was separately trained on thorax and abdomen datasets to accommodate the unique imaging requirements of each anatomical region. MAIN RESULTS: The pLPD-UNet demonstrated improved reconstruction accuracy and robustness in handling sparse data compared to traditional methods. It effectively maintained image quality essential for precise organ delineation and dose calculation, while achieving a significant reduction in radiation exposure. SIGNIFICANCE: This method offers a significant advancement in the practice of ART by integrating prior imaging data, potentially setting a new standard for balancing radiation safety with the need for high-resolution imaging in cancer treatment planning.

3.
Front Pharmacol ; 15: 1446776, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39263572

RESUMEN

Gut microecology,the complex community consisting of microorganisms and their microenvironments in the gastrointestinal tract, plays a vital role in maintaining overall health and regulating various physiological and pathological processes. Recent studies have highlighted the significant impact of gut microecology on the regulation of uric acid metabolism. Natural products, including monomers, extracts, and traditional Chinese medicine formulations derived from natural sources such as plants, animals, and microorganisms, have also been investigated for their potential role in modulating uric acid metabolism. According to research, The stability of gut microecology is a crucial link for natural products to maintain healthy uric acid metabolism and reduce hyperuricemia-related diseases. Herein, we review the recent advanced evidence revealing the bidirectional regulation between gut microecology and uric acid metabolism. And separately summarize the key evidence of natural extracts and herbal formulations in regulating both aspects. In addition,we elucidated the important mechanisms of natural products in regulating uric acid metabolism and secondary diseases through gut microecology, especially by modulating the composition of gut microbiota, gut mucosal barrier, inflammatory response, purine catalyzation, and associated transporters. This review may offer a novel insight into uric acid and its associated disorders management and highlight a perspective for exploring its potential therapeutic drugs from natural products.

4.
J Clin Pediatr Dent ; 48(5): 86-94, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39275824

RESUMEN

To comparatively assess the periodontal condition and oral hygiene of children and adolescents at different ages presenting with different types of orofacial clefts (OFCs). A total of 1608 patients aged 6-18 years who had not previously undergone periodontal treatment were enrolled in this study. Participants were categorized into two age groups: 6-12 years (Group I) and 13-18 years (Group II). Participants in both age groups were further classified into one of the three OFC-type subgroups: cleft lip only (without or with alveolar cleft), cleft lip and cleft palate, and cleft palate only. Periodontal health was determined by evaluating plaque formation and gingival status with reference to the Silness and Loe plaque index (PI), Loe gingival index (GI), and community periodontal index (CPI). Periodontal health and oral hygiene were not significantly different between Groups I and II for cleft type (p > 0.05). A significant difference was not observed in PI for cleft type among the groups (p > 0.05). In Group II, GI and CPI were significantly higher than in Group I (p < 0.05). According to our results, cleft type does not influence periodontal health of children and adolescents with OFCs. Age, however, influences periodontal diseases' prevalence and severity.


Asunto(s)
Labio Leporino , Fisura del Paladar , Índice de Placa Dental , Higiene Bucal , Enfermedades Periodontales , Índice Periodontal , Humanos , Labio Leporino/complicaciones , Fisura del Paladar/complicaciones , Adolescente , Niño , Masculino , China/epidemiología , Femenino , Factores de Edad , Placa Dental
5.
Eur J Med Chem ; 278: 116794, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39226707

RESUMEN

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1-8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9-30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC50 value of 0.49 µM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aß42 aggregation. Moreover, the selected nuclide [18F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment.


Asunto(s)
Acetofenonas , Enfermedad de Alzheimer , Diseño de Fármacos , Imidazoles , Fármacos Neuroprotectores , Oximas , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Oximas/química , Oximas/farmacología , Oximas/síntesis química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/síntesis química , Animales , Relación Estructura-Actividad , Imidazoles/farmacología , Imidazoles/química , Imidazoles/síntesis química , Acetofenonas/química , Acetofenonas/farmacología , Acetofenonas/síntesis química , Estructura Molecular , Humanos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/antagonistas & inhibidores , Acetilcolinesterasa/metabolismo , Relación Dosis-Respuesta a Droga , Ratas , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química
6.
Front Endocrinol (Lausanne) ; 15: 1390035, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257905

RESUMEN

Background: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Research has identified a close relationship between fibroblast growth factor 21 (FGF21) and DR. FGF21 is a member of the FGF subfamily, which is activated by the Klotho coenzyme involved in the occurrence of DR. However, the association between FGF21, Klotho, and DR remains controversial. Aim: To assess FGF21 and Klotho levels in patients with DR. Methods: A literature search of the Web of Science, Wiley Online Library, PubMed, China National Knowledge Infrastructure and Wanfang databases was performed. The title or abstract search terms "diabetic retinopathy" and "DR" were used in combination with "fibroblast growth factor 21", "FGF21", and "Klotho". Meta-analysis results are presented as standardized mean difference (SMD) with corresponding 95% confidence interval (CI). Results: Fifteen studies were included in this meta-analysis. FGF21 levels in patients with DR were significantly higher than in non-DR patients with diabetes (SMD: 2.12, 95% CI [1.40, 2.84]). Klotho levels in patients with DR were significantly lower than in non-DR patients with diabetes (SMD: -0.63, 95% CI [-1.22, - 0.04]). Conclusions: This systematic review is the first to evaluate the relationship between FGF21, Klotho levels, and DR. FGF21 levels were significantly higher in patients with DR. Fully elucidating the role of FGF21 will significantly contribute to the treatment of DR.


Asunto(s)
Retinopatía Diabética , Factores de Crecimiento de Fibroblastos , Proteínas Klotho , Humanos , Proteínas Klotho/sangre , Factores de Crecimiento de Fibroblastos/sangre , Retinopatía Diabética/sangre , Retinopatía Diabética/metabolismo , Glucuronidasa/sangre
7.
Food Chem ; 463(Pt 1): 141149, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39255703

RESUMEN

Replacing animal fat with vegetable oil occurred extensively in the meat products, but whether these replacements will affect the nutrition of meat protein was seldom revealed. Effect of substitution of back fat (BF) by vegetable oils or their oleogels in emulsion-type sausage on the digestion process of meat protein was investigated. Replacement of BF with vegetable oils and their oleogels decreased the G'/G" values of meat paste, and oleogels largely weakened the structure of sausages. The substitution significantly reduced the liberation of -NH2 during the initial gastric and intestinal digestion, and resulted in bigger digests in CLSM images. The reduced gastric digestibility induced by substitution was shown to be related to the reduced stability of gastric digests, which can be attributed to the larger particle size and reduced viscosity of digests. These results highlighted stability of digests as a key point changing the digestion process of meat protein.

8.
Int Med Case Rep J ; 17: 719-723, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100686

RESUMEN

Transcatheter aortic valve replacement (TAVR) has been recently indicated for the treatment of patients with severe aortic stenosis in all risk profiles. At present, TAVR has become mature at home and abroad, but the relevant experience is deficient in the treatment of aortic valve stenosis with outflow tract stenosis. One case of a high-risk surgical patient was included in this paper who suffered from severe aortic valve stenosis with left ventricular outflow tract (LVOT) stenosis. In this case, TAVR was performed with deep implantation of a new valve and both aortic valve stenosis and LVOT stenosis were treated through a single TAVR procedure. This case highlights the vital role of such treatment in dealing with both aortic valve stenosis and LVOT stenosis through a single TAVR procedure, thus providing valuable information for similar cases.

9.
Front Neurol ; 15: 1395764, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114532

RESUMEN

Background: This study examines whether clot patterns at large artery occlusion sites, as observed using digital subtraction angiography (DSA) and computed tomography angiography (CTA), can reliably indicate intracranial atherosclerotic stenosis (ICAS) in acute ischemic stroke (AIS) patients. Methods: We conducted a retrospective analysis of patients treated with stent retriever thrombectomy for intracranial occlusions at our institute since 2017, with follow-up assessments conducted at 3 months. The patients were grouped based on the initial angiography clot topographies (i.e., cut-off or tapered signs). We assessed the potential of these topographies in predicting ICAS, including a clinical outcome analysis based on clot pattern, age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and onset-to-door time. Results: Among 131 patients (with a mean age of 66.6 years), the clot pattern emerged as a significant predictor of ICAS. The DSA-based model had a predictive area under the curve (AUC) of 0.745, with 55.1% sensitivity and 94.0% specificity. A multivariate model including age, onset-to-door time, TOAST classification as large artery atherosclerosis (LAA), and the presence of the tapered sign in clot patterns had an AUC of 0.916. In patients over 65 years of age with an onset-to-door time of >5 h and exhibiting a tapered sign in the clot pattern, the AUC reached 0.897. The predictive ability of the tapered sign was similar in DSA and CTA, showing 73.4% agreement between modalities. Conclusion: The clot pattern with the tapered sign as observed using DSA is significantly associated with ICAS. Incorporating this clot pattern with age, TOAST classification as LAA, and onset-to-door time enhances the prediction of ICAS. The clot pattern identified by CTA is also a reliable predictor, highlighting the importance of assessing clot patterns in ICAS identification.

10.
Cancer Lett ; : 217194, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39168299

RESUMEN

Chemoresistance remains the main obstacle limiting the treatment of osteosarcoma, seriously affecting the prognosis of adolescent patients with osteosarcoma. Recently, long non-coding RNAs (lncRNAs) were reported to be involved in chemoresistance, while the mechanisms of lncRNAs underlying osteosarcoma resistance to chemotherapy remain elusive. Here, LINC00520 was identified as a novel cisplatin resistance-related lncRNA in osteosarcoma, and its high expression was associated with poor prognosis of osteosarcoma patients. Functionally, LINC00520 could potentiate osteosarcoma resistance to cisplatin in vitro and in vivo. Mechanistically, LINC00520 bound to ENO1 and upregulated ENO1 protein expression by blocking FBXW7-mediated ENO1 ubiquitination and proteasomal degradation, thereby promoting glycolysis and ultimately inducing cisplatin resistance in osteosarcoma. Furthermore, METTL3 could stabilize and upregulate LINC00520 in an m6A-YTHDF2-dependent manner in osteosarcoma. This study proposes a novel lncRNA-driven mechanism for cisplatin resistance in osteosarcoma, and offers a promising therapeutic strategy for reversing chemoresistance in osteosarcoma by targeting the METTL3/LINC00520/ENO1/glycolysis axis.

11.
Environ Sci Technol ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138130

RESUMEN

The synthesis of polycyclic aromatic hydrocarbon (PAH) data allows us to quantify and gain insights into the spatiotemporal dynamics of PAH contamination in marine bays. Here, a data synthesis framework was developed to understand data-driven insights into the spatiotemporal levels, compositional profiles, and potential sources of PAHs in water and sediment of marine bays. PAHs were detected in 69 bays worldwide, with contamination hotspots located in Asian bays. PAH concentrations in pre-2000 were significantly lower than those in the 2000s and post-2010, while the dominant species in water and sediment were 2-3 ring and 4-6 ring PAHs, respectively. The composition patterns of PAHs included 2-3 ring, 3-5 ring, and 4-5 ring dominant categories, but no significant distance decay relationship was found in the composition similarity due to international energy trade. Temporal dynamic patterns of concentrations included Descending-, Ascending-, and Inverted V-type, whereas over longer time spans, the pattern is more similar to the Inverted V-type owing to the reductions in emission intensity. PAHs were derived from both petrogenic and pyrolytic sources, with combustion from both coal and petroleum being the dominant source. These data-driven discoveries provide quantitative insights into the spatiotemporal patterns in the concentration and composition of PAHs, contributing to the mitigation of PAH contamination.

12.
Glob Chang Biol ; 30(8): e17466, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39152655

RESUMEN

Global patterns in soil microbiomes are driven by non-linear environmental thresholds. Fertilization is known to shape the soil microbiome of terrestrial ecosystems worldwide. Yet, whether fertilization influences global thresholds in soil microbiomes remains virtually unknown. Here, utilizing optimized machine learning models with Shapley additive explanations on a dataset of 10,907 soil samples from 24 countries, we discovered that the microbial community response to fertilization is highly dependent on environmental contexts. Furthermore, the interactions among nitrogen (N) addition, pH, and mean annual temperature contribute to non-linear patterns in soil bacterial diversity. Specifically, we observed positive responses within a soil pH range of 5.2-6.6, with the influence of higher temperature (>15°C) on bacterial diversity being positive within this pH range but reversed in more acidic or alkaline soils. Additionally, we revealed the threshold effect of soil organic carbon and total nitrogen, demonstrating how temperature and N addition amount interacted with microbial communities within specific edaphic concentration ranges. Our findings underscore how complex environmental interactions control soil bacterial diversity under fertilization.


Asunto(s)
Bacterias , Fertilizantes , Microbiota , Nitrógeno , Microbiología del Suelo , Suelo , Temperatura , Nitrógeno/análisis , Nitrógeno/metabolismo , Fertilizantes/análisis , Concentración de Iones de Hidrógeno , Suelo/química , Carbono/análisis , Carbono/metabolismo , Aprendizaje Automático , Biodiversidad
13.
J Adv Nurs ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164061

RESUMEN

AIMS: To systematically evaluate and analyse literature concerning the factors influencing the implementation of clinical practice guidelines related to enteral nutrition in the adult intensive care unit. BACKGROUND: Guidelines serve as crucial tools for guiding clinical practice. However, a significant gap persists between current clinical practice and guidelines pertaining to enteral nutrition. It is essential to identify the reasons behind this disparity to foster clinical transformation. METHODS: A mixed-methods systematic review. DATA SOURCES: A systematic search was conducted across PubMed, Embase, Medline, Cochrane, PsycINFO and CNKI databases to identify impediments and facilitators to the implementation of ICU clinical practice guidelines related to enteral nutrition. The types of studies included quantitative, qualitative and mixed-methods studies. The search spanned from January 2003 to January 2024 and was updated in May 2024. The quality assessment of the included literature was conducted using the Mixed-Methods Study Evaluation Tool (MMAT). Data analysis was performed using a data-based convergent integration approach. The protocol for this study was prospectively registered (PROSPERO2023, CRD42023483287). RESULTS: Twenty papers were finally included, and 65 findings were extracted, integrating a total of three categories, Category 1: healthcare provider factors, including three sub-themes: knowledge of guideline-related knowledge and awareness of guideline application; social/professional roles and identity domains; beliefs, attitudes and self-efficacy; collaboration, Category 2: practice environments, including two sub-themes: environmental factors and resource areas; systems and behavioural norms, Category 3: patient values and nutritional support preferences including two sub-themes: patient disease status and value orientation. CONCLUSION: Healthcare professionals should analyse obstacles and facilitators to guideline implementation from multiple perspectives, strengthen healthcare collaboration, improve education and training systems, correct misperceptions and increase awareness of evidence-based practice.

14.
Mar Drugs ; 22(8)2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39195447

RESUMEN

Two new compounds, macrolactin XY (1) and (5R, 9S, 10S)-5-(hydroxymethyl)-1,3,7-decatriene-9,10-diol (2), together with nine known compounds (3-11) were isolated from the marine Bacillus subtilis sp. 18 by the OSMAC strategy. These compounds were evaluated for antibacterial activity against six tested microorganisms. Compounds 1-5 and 7-10 showed varied antibacterial activity, with the minimum inhibitory concentration (MIC) ranging from 3 to 12 µg/mL. Macrolactin XY (1) was found to possess superior antibacterial activity, especially exhibiting significant effectiveness against Enterococcus faecalis. The antibacterial activity mechanism against E. faecalis was investigated. The mechanism may disrupt bacterial cell membrane integrity and permeability, and also inhibit the expression of genes associated with bacterial energy metabolism, as established by the experiments concerning cell membrane potential, SDS-PAGE electrophoresis, cell membrane integrity, and key gene expressions. This study offers valuable insights and serves as a theoretical foundation for the future development of macrolactins as antibacterial precursors.


Asunto(s)
Antibacterianos , Bacillus subtilis , Macrólidos , Pruebas de Sensibilidad Microbiana , Bacillus subtilis/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/química , Macrólidos/farmacología , Macrólidos/aislamiento & purificación , Macrólidos/química , Enterococcus faecalis/efectos de los fármacos , Organismos Acuáticos , Membrana Celular/efectos de los fármacos
15.
ACS Appl Mater Interfaces ; 16(34): 45207-45213, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39138122

RESUMEN

This study proposes an innovative paradigm for metaverse-based synthesis experiments, aiming to enhance experimental optimization efficiency through human-guided parameter tuning in the metaverse and augmented artificial intelligence (AI) with human expertise. By integration of the metaverse experimental system with automated synthesis techniques, our goal is to profoundly extend the efficiency and advancement of materials chemistry. Leveraging advanced software algorithms and simulation techniques within the metaverse, we dynamically adjust synthesis parameters in real time, thereby minimizing the conventional trial-and-error methods inherent in laboratory experiments. In comparison fully AI-driven adjustments, this human-intervened approach to metaverse parameter tuning achieves desired results more rapidly. Coupled with automated synthesis techniques, experiments in the metaverse system can be swiftly realized. We validate the high synthesis efficiency and precision of this system through NaYF4:Yb/Tm nanocrystal synthesis experiments, highlighting its immense potential in nanomaterial studies. This pioneering approach not only simplifies the process of nanocrystal preparation but also paves the way for novel methodologies, laying the foundation for future breakthroughs in materials science and nanotechnology.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39116929

RESUMEN

PURPOSE: Parkinson's disease (PD) involves pathological alterations that include cortical impairments at levels of region and network. However, its microstructural abnormalities remain to be further elucidated via an appropriate diffusion neuroimaging approach. This study aimed to comprehensively demonstrate the microstructural patterns of PD as mapped by diffusion kurtosis imaging (DKI). METHODS: The microstructure of grey matter in both the PD group and the matched healthy control group was quantified by a DKI metric (mean kurtosis). The intergroup difference and classification performance of global microstructural complexity were analyzed in a voxelwise manner and via a machine learning approach, respectively. The patterns of information flows were explored in terms of structural connectivity, network covariance and modular connectivity. RESULTS: Patients with PD exhibited global microstructural impairments that served as an efficient diagnostic indicator. Disrupted structural connections between the striatum and cortices as well as between the thalamus and cortices were widely distributed in the PD group. Aberrant covariance of the striatocortical circuitry and thalamocortical circuitry was observed in patients with PD, who also showed disrupted modular connectivity within the striatum and thalamus as well as across structures of the cortex, striatum and thalamus. CONCLUSION: These findings verified the potential clinical application of DKI for the exploration of microstructural patterns in PD, contributing complementary imaging features that offer a deeper insight into the neurodegenerative process.


Asunto(s)
Corteza Cerebral , Vías Nerviosas , Enfermedad de Parkinson , Tálamo , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tálamo/diagnóstico por imagen , Tálamo/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Vías Nerviosas/patología , Vías Nerviosas/diagnóstico por imagen , Cuerpo Estriado/patología , Cuerpo Estriado/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen , Aprendizaje Automático
17.
Chem Sci ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39144458

RESUMEN

Diphenyl ethers (DPEs) are produced by filamentous fungi using polyketide synthases (PKSs) directly, or via Cu oxidase-catalyzed oxidative rearrangements of benzophenone intermediates. Here, we use heterologous expression to reveal a third route towards DPEs in Preussia isomera that relies on an oxidative multienzyme cascade to convert a PKS-generated, ester-linked didepside to depsidones and further to DPEs, and apply comparative genomics to identify conserved biosynthetic gene clusters for this pathway in multiple fungi. The distribution of DPE products is modulated by the expression chassis upon pathway reconstitution. Among the post-PKS enzymes, the DpeH tyrosinase shows considerable substrate promiscuity towards synthetic DPE analogues. By creating hybrid enzymes with a DpeH orthologue from Aspergillus nidulans, we identify the C-terminal region of DpeH to alter substrate recognition. Our work highlights an evolutionarily conserved way to produce DPEs, and provides enzymatic tools to generate DPE analogues with broad spectrum antibiotic activity against multidrug-resistant human pathogens.

18.
Transl Cancer Res ; 13(7): 3446-3464, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39145047

RESUMEN

Background: Colorectal cancer (CRC), a prevalent gastrointestinal malignant disease, causes substantial morbidity and mortality. Identification of novel prognostic biomarkers and therapeutic targets is critically needed to improve patient outcomes. Although solute carrier family 12 member 8 (SLC12A8) has high expression in various tumors and affects tumor progression, its role in CRC remains unclear. The aim of this study was to investigate the functions of SLC12A8 in CRC. Methods: SLC12A8 expression and its association with clinical significance in CRC patients were explored via multiple public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Human Protein Atlas (HPA), The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and Kaplan-Meier plotter. The effects of SLC12A8 on the CRC cell apoptosis, epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS) production, and sensitivity to oxaliplatin were verified by in vitro experiments. Results: SLC12A8 expression was upregulated in CRC tissues compared with normal colorectal tissues. Furthermore, high expression of SLC12A8 was associated with poorer prognosis in CRC patients. Pathway enrichment analyses revealed SLC12A8 involvement in oxidative stress and transforming growth factor-beta (TGF-ß) signaling. Experiments in CRC cells showed that SLC12A8 upregulation promoted apoptosis resistance, EMT, and inhibited ROS production. Moreover, SLC12A8 knockdown enhanced the sensitivity of CRC cells to oxaliplatin chemotherapy. Conclusions: Our integrative analyses identify SLC12A8 as a candidate biomarker for CRC progression. Targeting SLC12A8 may improve patient responses to oxaliplatin-based treatment regimens.

19.
Mol Neurobiol ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39207623

RESUMEN

Early brain injury caused by subarachnoid hemorrhage (SAH) is associated with inflammatory response and ferroptosis. Curcumin alleviates neuroinflammation and oxidative stress by as yet unknown neuroprotective mechanisms. The objective of this study was to investigate the impact of curcumin on neuronal ferroptosis and microglia-induced neuroinflammation following SAH. By examining Nrf2/HO-1 expression levels and ferroptosis biomarkers expression both in vitro and in vivo, it was demonstrated that curcumin effectively suppressed ferroptosis in neurons after SAH through modulation of the Nrf2/HO-1 signaling pathway. Furthermore, by analyzing the expression levels of Nrf2, HO-1, p-p65, and inflammation-related genes, it was confirmed that curcumin could prevent the upregulation of pro-inflammatory factors following SAH by regulating the Nrf2/HO-1/NF-κB signaling pathway in microglia. The ability of curcumin to reduce neuronal damage and cerebral edemas after SAH in mice was validated using TUNEL staining, Nissl staining, and measurement of brain tissue water content. Additionally, through implementation of the modified Garcia test, open field test, and Y-maze test, it was established that curcumin ameliorated neurobehavioral impairments in mice post-SAH. Taken together, these data suggest that curcumin may offer a promising therapeutic approach for improving outcomes following SAH by concurrently attenuating neuronal ferroptosis and reducing neuroinflammation.

20.
Chem Biodivers ; : e202401750, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212157

RESUMEN

Polar fungi play a vital role as prolific sources of unique chemical structures and diverse bioactive compounds. Eutypella sp. D-1 is a fungus isolated from the Arctic, and six compounds were extracted from the fermentation broth. Their structures are elucidated from HRESIMS, NMR spectroscopy, and ECD calculations. Compounds 1-5 are newly discovered compounds, with compound 1 possessing a rare peroxide-bridge structure. Compounds 1-4 are categorized as pimarane-type diterpenes, while compounds 5 and 6 belong to the eudesmanolide sesquiterpenes. Compound 4 demonstrates anti-inflammatory activity by inhibiting lipopolysaccharide-induced nitric oxide release in RAW264.7 cells. Compound 4 and 5 show antibacterial activity against Escherichia coli and Staphylococcus aureus.

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