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1.
ACS Omega ; 9(30): 33239-33250, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39100329

RESUMEN

Bioassay-guided fractionation of P. quinquefolium and P. ginseng root extracts afforded six compounds. Among these, two bioactive compounds ginsenoside Re (1) and (20S)-ginsenoside Rg2 (5) exhibiting significant relaxation in rabbit corpus cavernosum with EC50 values of 95.1 and 114.7 µM, respectively. In addition, the phytochemical composition of the water extract of the roots of P. quinquefolium was investigated, and thirty-one compounds were characterized, including four undescribed compounds panajaponol B (18) and panaxjapynes D-F (21-23). Moreover, the spectral characteristics and biosynthetic pathway of Panax triterpene saponins were discussed according to our results and some previous reports.

2.
IDCases ; 37: e02022, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100729

RESUMEN

Cryptococcus neoformans is a global invasive mycosis that is known to cause significant morbidity and mortality. It is commonly observed that individuals with compromised immune systems are more prone to developing cryptococcal meningitis. Although ocular involvement is rare, previous studies have indicated that ocular lesions precede symptomatic meningitis in only 27 % of patients with central nervous system involvement. Intraocular infections typically manifest as chorioretinopathy and vitreous inflammation, often leading to severe vision loss. In this case, we present the clinical details of a 57-year-old immunocompetent woman who visited the ophthalmology department of West China Hospital of Sichuan University with a progressive loss of vision in her right eye. After a thorough evaluation, she was diagnosed with fungal endophthalmitis, and subsequently initiated on appropriate induction anti-fungal therapy for cryptococcal meningoencephalitis. This case highlights the importance of early recognition and treatment, which can potentially improve the prognosis for patients.

3.
Neural Regen Res ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39104165

RESUMEN

Ferroptosis, a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation, is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury. Thus, in this study, bulk RNA sequencing data (GSE47681 and GSE5296) and single-cell RNA sequencing data (GSE162610) were acquired from gene expression databases. We then conducted differential analysis and immune infiltration analysis. Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms. Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes. Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells, confirming the high expression of Atf3 and Piezo1 in these cells. Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide. In a mouse model of T8 spinal cord injury, low-dose cycloheximide treatment was found to improve neurological function, decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase, and increase levels of the anti-inflammatory cytokine arginase 1. Correspondingly, the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia, while the expression of Acsl4 decreased. Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury, identify the key cell types and genes involved in ferroptosis after spinal cord injury, and validate the efficacy of potential drug therapies, pointing to new directions in the treatment of spinal cord injury.

4.
Blood Press Monit ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39105269

RESUMEN

The aim of this study was to evaluate the accuracy of the JAMR upper-arm blood pressure monitor B23 in the general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2 : 2018/AMD 1 : 2020). The study recruited participants who met the criteria of the AAMI/ESH/ISO Universal Standard in terms of their number, sex, age, limb size, and blood pressure (BP) distribution. The study involved measuring BP, including both SBP and DBP, using both the test device and a standard mercury sphygmomanometer in sequential measurements. Of 90 participants, 85 qualified participants were analyzed. A total of 255 sets of comparison data (three sets for each subject) were obtained and analyzed. For the validation criterion 1, the mean ±â€…SD of the differences between the JAMR B23 and mercury sphygmomanometer BP readings was -0.24 ±â€…6.52/-2.67 ±â€…5.6 mmHg (SBP/DBP). For criterion 2, the SD of the averaged BP (SBP/DBP) differences between the JAMR B23 and reference BP (SBP/DBP) per participant was 5.61/5.13 mmHg (the requirement was ≤6.95/6.43 mmHg by calculation). The JAMR B23 passed all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2 : 2018/AMD 1 : 2020) and can be recommended for clinical and self/home use in the general population.

5.
Bioact Mater ; 41: 61-82, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39104774

RESUMEN

Despite numerous studies on chondrogenesis, the repair of cartilage-particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-ß3 (TGF-ß3) into mesoporous silica nanoparticles (MSNs). Then, TGF-ß3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@µS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-ß3 amplified chondrogenesis and matrix formation. µS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.

6.
Small ; : e2403967, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39106223

RESUMEN

Platinum-Ruthenium (PtRu) bimetallic nanoparticles are promising catalysts for methanol oxidation reaction (MOR) required by direct methanol fuel cells. However, existing catalyst synthesis methods have difficulty controlling their composition and structures. Here, a direct Joule heating method to yield highly active and stable PtRu catalysts for MOR is shown. The optimized Joule heating condition at 1000 °C over 50 microseconds produces uniform PtRu nanoparticles (6.32 wt.% Pt and 2.97 wt% Ru) with an average size of 2.0 ± 0.5 nanometers supported on carbon black substrates. They have a large electrochemically active surface area (ECSA) of 239 m2 g-1 and a high ECSA normalized specific activity of 0.295 mA cm-2. They demonstrate a peak mass activity of 705.9 mA mgPt -1 for MOR, 2.8 times that of commercial 20 wt.% platinum/carbon catalysts, and much superior to PtRu catalysts obtained by standard hydrothermal synthesis. Theoretical calculation results indicate that the superior catalytic activity can be attributed to modified Pt sites in PtRu nanoparticles, enabling strong methanol adsorption and weak carbon monoxide binding. Further, the PtRu catalyst demonstrates excellent stability in two-electrode methanol fuel cell tests with 85.3% current density retention and minimum Pt surface oxidation after 24 h.

7.
ACS Nano ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39106490

RESUMEN

Spinel cobalt oxides (Co3O4) have emerged as a promising class of catalysts for the electrochemical nitrate reduction reaction (eNO3RR) to ammonia, offering advantages such as low cost, high activity, and selectivity. However, the specific role of crystallographic facets in determining the catalysts' performance remains elusive, impeding the development of efficient catalysts. In this study, we have synthesized various Co3O4 nanostructures with exposed facets of {100}, {111}, {110}, and {112}, aiming to investigate the dependence of the eNO3RR activity on the crystallographic facets. Among the catalysts tested, Co3O4 {111} shows the best performance, achieving an ammonia Faradaic efficiency of 99.1 ± 1.8% with a yield rate of 35.2 ± 0.6 mg h-1 cm-2 at -0.6 V vs RHE. Experimental and theoretical results reveal a transformation process in which the active phases evolve from Co3O4 to Co3O4-x with oxygen vacancy (Ov), followed by a Co3O4-x-Ov/Co(OH)2 hybrid, and finally Co(OH)2. This process is observed for all facets, but the formation of Ov and Co(OH)2 is the most rapid on the (111) surface. The presence of Ov significantly reduces the free energy of the *NH2 intermediate formation from 1.81 to -0.53 eV, and plentiful active sites on the densely reconstructed Co(OH)2 make Co3O4 {111} an ideal catalyst for ammonia synthesis via eNO3RR. This work provides insights into the understanding of the realistic active components, offers a strategy for developing highly efficient Co-based spinel catalysts for ammonia synthesis through tuning the exposed facets, and helps further advance the design and optimization of catalysts in the field of eNO3RR.

8.
Angew Chem Int Ed Engl ; : e202412740, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107257

RESUMEN

The production of ammonia (NH3) from nitrogen sources involves competitive adsorption of different intermediates and multiple electron and proton transfers, presenting grand challenges in catalyst design. In nature nitrogenases reduce dinitrogen to NH3 using two component proteins, in which electrons and protons are delivered from Fe protein to the active site in MoFe protein for transfer to the bound N2. We draw inspiration from this structural enzymology, and design a two-component metal-sulfur-carbon (M-S-C) catalyst composed of sulfur-doped carbon-supported ruthenium (Ru) single atoms (SAs) and nanoparticles (NPs) for the electrochemical reduction of nitrate (NO3-) to NH3. The catalyst demonstrates a remarkable NH3 yield rate of ~37 mg L-1 h-1 and a Faradaic efficiency of ~97% for over 200 hours, outperforming those consisting solely of SAs or NPs, and even surpassing most reported electrocatalysts. Our experimental and theoretical investigations reveal the critical role of Ru SAs with the coordination of S in promoting the formation of the HONO intermediate and the subsequent reduction reaction over the NP-surface nearby. This study proves a better understanding of how M-S-Cs act as a synthetic nitrogenase mimic during ammonia synthesis, and contributes to the future mechanism-based catalyst design.

9.
Biomed Pharmacother ; 178: 117268, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39116780

RESUMEN

Gastric precancerous lesion (GPL) is a crucial stage in the development of gastric cancer, characterized by incomplete intestinal epithelial chemotaxis and heterogeneous hyperplasia with high malignant potential. Early intervention in GPL is vital for preventing gastric cancer. Additionally, there are shared risk factors and pathogenesis between tumors and coronary heart disease (CHD), with an increasing number of tumor patients GPL complicated with CHD due to improved survival rates. Reperfusion therapy in CHD can result in myocardial ischemia-reperfusion injury (MIRI). Traditional Chinese medicine (TCM) has demonstrated unique advantages in treating GPL and MIRI by promoting blood circulation and removing blood stasis. Panax ginseng total saponin (PNS), a component of TCM known for its blood circulation benefits, has shown positive effects in inhibiting tumor growth and improving myocardial ischemia. This study utilized a GPL-MIRI mouse model to investigate the effects of PNS in treatment. Results indicated that PNS significantly improved typical GPL lesions in mice, such as incomplete intestinal epithelialization and heteroplasia, and also reduced myocardial infarction. At the molecular level, PNS exhibited a bidirectional regulatory role in the GPL-MIRI model. It enhanced the autophagic process in gastric mucosal cells by inhibiting the PI3K/Akt/mTOR signaling pathway, while suppressed excessive autophagy in cardiomyocytes. These findings offer new insights and treatment strategies for managing GPL and MIRI using the TCM compound PNS.

10.
Sci Total Environ ; : 175346, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39117201

RESUMEN

Nitrite is a common nitrogen-containing compound that possesses high biological toxicity, thereby posing a serious threat to aquatic organisms. Therefore, it is imperative to develop a rapid and quantitative determination approach for nitrite. In this study, the aim was to prepare a novel electrochemical sensor to determine nitrite. This was achieved by synthesizing Au/Zn dendritic complexes on a carbon cloth self-supported electrode after plasma treated by a stepwise strategy of electrodeposition and in-situ corrosion. In accordance with the optimal experimental conditions, the electrode exhibited remarkable catalytic activity for the electrooxidation of nitrite ions (pH = 8.0), accompanied by a considerable enhancement in peak anodic current in comparison to the unmodified electrode. The sensor exhibited a wide linear range (1-833 µM, 833-8330 µM), high sensitivity (3506 µA mM-1 cm-2, 538 µA mM-1 cm-2), a low detection limit (0.43 µM), and excellent selectivity, reproducibility, and stability for the determination of nitrite. Furthermore, the prepared sensor was successfully applied to the detection of nitrite in tap water, fish holding pond water and duck pond water, demonstrating good recovery and no significant difference from the spectrophotometric results. The results suggest that the electrochemical sensor developed in this study represents a straightforward yet efficacious approach to the development of advanced portable sensors for aquaculture applications.

11.
Cell Chem Biol ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39116881

RESUMEN

We describe a protein proximity inducing therapeutic modality called Regulated Induced Proximity Targeting Chimeras or RIPTACs: heterobifunctional small molecules that elicit a stable ternary complex between a target protein (TP) selectively expressed in tumor cells and a pan-expressed protein essential for cell survival. The resulting co-operative protein-protein interaction (PPI) abrogates the function of the essential protein, thus leading to death selectively in cells expressing the TP. This approach leverages differentially expressed intracellular proteins as novel cancer targets, with the advantage of not requiring the target to be a disease driver. In this chemical biology study, we design RIPTACs that incorporate a ligand against a model TP connected via a linker to effector ligands such as JQ1 (BRD4) or BI2536 (PLK1) or CDK inhibitors such as TMX3013 or dinaciclib. RIPTACs accumulate selectively in cells expressing the HaloTag-FKBP target, form co-operative intracellular ternary complexes, and induce an anti-proliferative response in target-expressing cells.

12.
Int J Biol Macromol ; 278(Pt 1): 134624, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39134191

RESUMEN

The molecular chaperone GroEL, commonly found in various bacterial species, exhibits heightened expression levels in response to high temperatures and increased levels of oxygen free radicals. Limited literature currently exists on the probiotic role of GroEL in invertebrates. This study sought to explore how the surface protein GroEL from Lactobacillus plantarum Ep-M17 impacts the intestinal barrier function of Penaeus vannamei. Through pull-down and immunofluorescence assays, the interaction between GroEL and Act1 in the gastrointestinal tract of P. vannamei was confirmed. Results from bacterial binding assays demonstrated that rGroEL can bind to pathogens like Vibrio parahaemolyticus E1 (V. p-E1). In vitro experiments revealed that the administration of rGroEL significantly decreased the levels of inflammatory cytokines induced by pathogens while preserving the integrity of tight junctions between intestinal epithelial cells and reducing bacteria-induced apoptosis. Additionally, rGroEL notably lessened the intestinal loading of V. p-E1 in P. vannamei, downregulated immune-related gene expression, and upregulated BCL/BAX expression in the intestines following V. p-E1 challenge. Mechanistic investigations further showed that rGroEL treatment effectively suppressed the expression and phosphorylation of proteins involved in the NF-κB and PI3K-AKT-mTOR signalling pathways in the intestines of bacteria-infected P. vannamei. Furthermore, GroEL reinforces protection against bacterial infections by enhancing the phagocytic and anti-apoptotic capabilities of P. vannamei hemocytes. These results suggest that GroEL may impede the interaction between pathogens and the intestinal mucosa through its competitive binding characteristics, ultimately reducing bacterial infections.

13.
Artículo en Inglés | MEDLINE | ID: mdl-39137084

RESUMEN

Automated retinal vessel segmentation is crucial for computer-aided clinical diagnosis and retinopathy screening. However, deep learning faces challenges in extracting complex intertwined structures and subtle small vessels from densely vascularized regions. To address these issues, we propose a novel segmentation model, called Geometry-Knowledge Embedded TransUNet (GKE-TUNet), which incorporates explicit embedding of topological features of retinal vessel anatomy. In the proposed GKE-TUNet model, a skeleton extraction network is pre-trained to extract the anatomical topology of retinal vessels from refined segmentation labels. During vessel segmentation, the dense skeleton graph is sampled as a graph of key-points and connections and is incorporated into the skip connection layer of TransUNet. The graph vertices are used as node features and correspond to positions in the low-level feature maps. The graph attention network (GAT) is used as the graph convolution backbone network to capture the shape semantics of vessels and the interaction of key locations along the topological direction. Finally, the node features obtained by graph convolution are read out as a sparse feature map based on their corresponding spatial coordinates. To address the problem of sparse feature maps, we employ convolution operators to fuse sparse feature maps with low-level dense feature maps. This fusion is weighted and connected to deep feature maps. Experimental results on the DRIVE, CHASE-DB1, and STARE datasets demonstrate the competitiveness of our proposed method compared to existing ones.

14.
J Agric Food Chem ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137321

RESUMEN

Thiazole and phenoxyacetic acid are key moieties in many natural and synthetic biologically active agents. A series of N-(5-(3,5-methoxyphenyl)-(thiazole-2-yl))phenoxyacetamide derivatives 6an-6bd were designed and synthesized, and their structures were confirmed by NMR and HRMS. Most of derivatives exhibited superior inhibition of Echinochloa crusgalli (E.c.) and Lactuca sativa (L.s.) seed germination by the Petri dish bioassay. Indeed, herbicidal bioassays indicated that 6an (2-(2,4-dichlorophenoxy)-N-(5-(3,5-dimethoxyphenyl)-1,3,4-thiadiazol-2-yl)acetamide) had the best inhibition against L.s. (IC50 = 42.7 g/ha, 375 g/ha at field experiments). 6an also had no harmful effect on Zea mays at 2- to 4-fold field usage. Moreover, transcriptomics and metabolomics analysis showed that 6an significantly influenced cell metabolism, including galactose metabolism and ascorbate and aldarate metabolism. These discoveries highlight that 6an shows promise to be developed as a potential herbicide.

15.
J Agric Food Chem ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137390

RESUMEN

Geranylgeranyl diphosphate synthase (GGPPS) is the crucial bottleneck in carotenoid biosynthesis. However, low activity limits the broad application of GGPPS. In this study, OsGGPPS1 in rice was engineered based on ancestral sequence reconstruction (ASR) and semirational design to improve the catalytic performances of existing GGPPS. The better mutant of A22R/A26P with improved enzyme activity was generated based on ASR. Additionally, the improved enzyme activity of mutants as V162A/M218S/F227Y was designed using a semirational design. The combinatorial assembly of the d-OsGGPPS1 mutant (A22R/A26P/V162A/M218S/F227Y) exhibited higher conversion of IPP and each cosubstrate of DMAPP for 9.8-fold in GPP production, GPP for 6.4-fold in FPP production, and FPP for 1.4-fold in GGPP production relative to wild-type OsGGPPS1 at 25 °C, which showed higher conversion than wild-type OsGGPPS1 at temperatures as high as 50 °C. The successful design of OsGGPPS1 was representative of protein engineering, which will shed new light on GGPPS engineering and active plant pigment resource utilization.

16.
Sci Rep ; 14(1): 18625, 2024 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-39128903

RESUMEN

The COVID-19 pandemic has imposed significant challenges on global health, emphasizing the persistent threat of large-scale infectious diseases in the future. This study addresses the need to enhance pooled testing efficiency for large populations. The common approach in pooled testing involves consolidating multiple test samples into a single tube to efficiently detect positivity at a lower cost. However, what is the optimal number of samples to be grouped together in order to minimize costs? i.e. allocating ten individuals per group may not be the most cost-effective strategy. In response, this paper introduces the hierarchical quotient space, an extension of fuzzy equivalence relations, as a method to optimize group allocations. In this study, we propose a cost-sensitive multi-granularity intelligent decision model to further minimize testing costs. This model considers both testing and collection costs, aiming to achieve the lowest total cost through optimal grouping at a single layer. Building upon this foundation, two multi-granularity models are proposed, exploring hierarchical group optimization. The experimental simulations were conducted using MATLAB R2022a on a desktop with Intel i5-10500 CPU and 8G RAM, considering scenarios with a fixed number of individuals and fixed positive probability. The main findings from our simulations demonstrate that the proposed models significantly enhance the efficiency and reduce the overall costs associated with pooled testing. For example, testing costs were reduced by nearly half when the optimal grouping strategy was applied, compared to the traditional method of grouping ten individuals. Additionally, the multi-granularity approach further optimized the hierarchical groupings, leading to substantial cost savings and improved testing efficiency.


Asunto(s)
COVID-19 , Análisis Costo-Beneficio , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , COVID-19/economía , COVID-19/virología , SARS-CoV-2/aislamiento & purificación , Prueba de COVID-19/métodos , Prueba de COVID-19/economía , Pandemias/economía , Técnicas de Apoyo para la Decisión
17.
Angew Chem Int Ed Engl ; : e202411542, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39132837

RESUMEN

Electrooxidation of biomass-derived glycerol which is regarded as a main byproduct of industrial biodiesel production, is an innovative strategy to produce value-added chemicals, but currently showcases slow kinetics, limited Faraday efficiency, and unclear catalytic mechanism. Herein, we report high-efficiency electrooxidation of glycerol into formate via a Cu doped NiCo alloy catalyst supported on nickel foam (Cu-NiCo/NF) in a coupled system paired with nitrate reduction. The designed Cu-NiCo/NF delivers only 1.23 V vs. RHE at 10 mA cm-2, and a record Faraday efficiency of formate of 93.8%. The superior performance is ascribed to the rapid generation of NiIII-OOH and CoIII-OOH and favorable coupling of surface *O with reactive intermediates. Using Cu-NiCo/NF as a bifunctional catalyst, the coupled system synchronously produces NH3 and formate, showing 290 mV lower than the coupling of hydrogen evolution reaction, together with excellent long-term stability for up to 144 h. This work lays out new guidelines and reliable strategies from catalyst design to system coupling for biomass-derived electrochemical refinery.

18.
Adv Sci (Weinh) ; : e2404194, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39119933

RESUMEN

Electrochemical conversion of nitrate (NO3 -) to ammonia (NH3) is a potential way to produce green NH3 and remediate the nitrogen cycle. In this paper, an efficient catalyst of spherical CuO made by stacking small particles with oxygen-rich vacancies is reported. The NH3 yield and Faraday efficiency are 15.53 mg h-1 mgcat -1 and 90.69%, respectively, in a neutral electrolyte at a voltage of -0.80 V (vs. reversible hydrogen electrode). The high activity of the electrodes results from changes in the phase and structure during electrochemical reduction. Structurally, there is a shift from a spherical structure with dense accumulation of small particles to a layered network structure with uniform distribution of small particles stacked on top of each other, thus exposing more active sites. Furthermore, in terms of phase, the electrode transitions from CuO to Cu/Cu(OH)2. Density functional theory calculations showed that Cu(OH)2 formation enhances NO3- adsorption. Meanwhile, the Cu(OH)2 can inhibit the competing hydrogen evolution reaction, while the formation of Cu (111) crystal surfaces facilitates the hydrogenation reaction. The synergistic effect between the two promotes the NO3- to NH3. Therefore, this study provides a new idea and direction for Cu-based oxides in electrocatalytic NH3 production.

19.
Mol Biotechnol ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120820

RESUMEN

Tumor-associated macrophages (TAM) are considered as crucial influencing factors of lung adenocarcinoma (LUAD) carcinogenesis and metastasis. Profilin 1 (PFN1) has been proposed as a potent driver of migration and drug resistance in LUAD. The focus of this work was to figure out the functional mechanism of PFN1 in macrophage polarization in LUAD. PFN1 expression and its significance in patients' survival were detected by ENCORI and Kaplan-Meier Plotter. RT-qPCR and western blotting examined PFN1 expression in LUAD cells. CCK-8 assay and colony formation assay detected cell proliferation. Flow cytometry detected cell apoptosis. Relevant assay kit tested caspase3 concentration. Western blotting analyzed the expression of proliferation- and apoptosis-related proteins. RT-qPCR and immunofluorescence staining measured M1 and M2 macrophages markers. Mitophagy was assessed by MitoTracker Red staining, immunofluorescence staining, and western blotting. PFN1 expression was increased in LUAD tissues and cells and correlated with the poor survival rate of LUAD patients. Deficiency of PFN1 hindered the proliferation, whereas facilitated the apoptosis of LUAD cells. Additionally, PFN1 interference impaired M2 macrophage polarization. Moreover, PFN1 knockdown exacerbated the mitophagy in LUAD cells and mitophagy inhibitor mitochondrial division inhibitor 1 (Mdivi-1) notably reversed the effects of PFN1 down-regulation on the proliferation, apoptosis as well as macrophage polarization in LUAD cells. To sum up, activation of mitophagy initiated by PFN1 depletion might obstruct the occurrence and M2 macrophage polarization in LUAD.

20.
Nat Commun ; 15(1): 6754, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39117719

RESUMEN

Superparaelectrics are considered promising candidate materials for achieving superior energy storage capabilities. However, due to the complicated local structural design, simultaneously achieving high recoverable energy density (Wrec) and energy storage efficiency (η) under high electric fields remains a challenge in bulk superparaelectrics. Here, we propose utilizing entropy engineering to disrupt long-range ferroic orders into local polymorphic distortion disorder with multiple BO6 tilt types and diverse heterogeneous polarization configurations. This strategy reduces the switching barriers, thereby facilitating the emergence of superparaelectric behaviors with ideal polarization forms. Furthermore, it enables high polarization response, negligible remnant polarization, delayed polarization saturation, and enhanced breakdown electric fields (Eb) in high-entropy superparaelectrics. Consequently, an extraordinary Wrec of 15.48 J cm-3 and an ultrahigh η of 90.02% are achieved at a high Eb of 710 kV cm-1, surpassing the comprehensive energy storage performance of previously reported bulk superparaelectrics. This work demonstrates that entropy engineering is a viable strategy for designing high-performance superparaelectrics.

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