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1.
Synth Syst Biotechnol ; 10(1): 1-9, 2025.
Article in English | MEDLINE | ID: mdl-39193251

ABSTRACT

Ceramides, formed by the dehydration of long-chain fatty acids with phytosphingosine and its derivatives, are widely used in skincare, cosmetics, and pharmaceuticals. Due to the exceedingly low concentration of phytosphingosine in plant seeds, relying on the extraction method is highly challenging. Currently, the primary method for obtaining phytosphingosine is the deacetylation of tetraacetyl phytosphingosine (TAPS) derived from fermentation. Wickerhamomyces ciferrii, an unconventional yeast from the pods of Dipteryx odorata, is the only known microorganism capable of naturally secreting TAPS, which is of great industrial value. In recent years, research and applications focused on modifying W. ciferrii for TAPS overproduction have increased rapidly. This review first describes the discovery history, applications, microbial synthesis pathway of TAPS. Research progress in using haploid breeding, mutagenesis breeding, and metabolic engineering to improve TAPS production is then summarized. In addition, the future prospects of TAPS production using the W. ciferrii platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future researches are also emphasized.

2.
Acta Crystallogr B Struct Sci Cryst Eng Mater ; 80(Pt 4): 347-359, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39136540

ABSTRACT

In the course of an investigation of the supramolecular behaviour of copper(II) complexes with the 5-phenylimidazole/perchlorate ligand system (`blend') remarkable solvatomorphism has been observed. By employing a variety of crystallization solvents (polar protic, polar/non-polar aprotic), a series of 12 crystalline solvatomorphs with the general formula [Cu(ClO4)2(LH)4]·x(solvent) have been obtained [LH = 5-phenylimidazole, x(solvent) = 3.3(H2O) (1), 2(methanol) (2), 2(ethanol) (3), 2(1-propanol) (4), 2(2-propanol) (5), 2(2-butanol) (6), 2(dimethylformamide) (7), 2(acetone) (8), 2(tetrahydrofurane) (9), 2(1,4-dioxane) (10), 2(ethyl acetate) (11) and 1(diethyl ether) (12)]. The structures have been solved using single-crystal X-ray diffraction and the complexes were characterized by thermal analysis and infrared spectroscopy. The solvatomorphs are isostructural (triclinic, P1), with the exception of compound 9 (monoclinic, P21/n). The supramolecular structures and the role of the various solvents is discussed. All potential hydrogen-bond functionalities, both of the [Cu(ClO4)2(LH)4] units and of the solvents, are utilized in the course of the crystallization process. The supramolecular assembly in all structures is directed by strong recurring Nimidazole-H...Operchlorate motifs leading to robust scaffolds composed of the [Cu(ClO4)2(LH)4] host complexes. The solvents are located in channels and, with the exception of the disordered waters in 1 and the diethyl ether in 12, participate in hydrogen-bonding formation with the [Cu(ClO4)2(LH)4] complexes, serving as both hydrogen-bond acceptors and donors (for the polar protic solvents in 2-6), or solely as hydrogen-bond acceptors (for the polar/non-polar aprotic solvents in 7-11), linking the complexes and contributing to the stability of the crystalline compounds.

3.
Biofabrication ; 16(4)2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39136309

ABSTRACT

Multicellular spheroids such as microtissues and organoids have demonstrated great potential for tissue engineering applications in recent years as these 3D cellular units enable improved cell-cell and cell-matrix interactions. Current bioprinting processes that use multicellular spheroids as building blocks have demonstrated limited control on post printing distribution of cell spheroids or moderate throughput and printing efficiency. In this work, we presented a laser-assisted bioprinting approach able to transfer multicellular spheroids as building blocks for larger tissue structures. Cartilaginous multicellular spheroids formed by human periosteum derived cells (hPDCs) were successfully bioprinted possessing high viability and the capacity to undergo chondrogenic differentiation post printing. Smaller hPDC spheroids with diameters ranging from ∼100 to 150µm were successfully bioprinted through the use of laser-induced forward transfer method (LIFT) however larger spheroids constituted a challenge. For this reason a novel alternative approach was developed termed as laser induced propulsion of mesoscopic objects (LIPMO) whereby we were able to bioprint spheroids of up to 300µm. Moreover, we combined the bioprinting process with computer aided image analysis demonstrating the capacity to 'target and shoot', through automated selection, multiple large spheroids in a single sequence. By taking advantage of target and shoot system, multilayered constructs containing high density cell spheroids were fabricated.


Subject(s)
Bioprinting , Cartilage , Lasers , Spheroids, Cellular , Tissue Engineering , Bioprinting/methods , Humans , Spheroids, Cellular/cytology , Tissue Engineering/methods , Cartilage/cytology , Cartilage/physiology , Periosteum/cytology , Printing, Three-Dimensional , Chondrogenesis , Cell Differentiation , Cells, Cultured , Cell Survival
4.
Sci Total Environ ; 951: 175528, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39147048

ABSTRACT

Eco-engineering of coastal infrastructure aims to address the insufficient intertidal habitat provided by coastal development and flood defence. There are numerous ways to enhance coastal infrastructure with habitat features, but a common method involves retrofitting artificial rockpools. Often these are 'bolt-on' units that are fixed to existing coastal infrastructure but there is a paucity of literature on how to optimise their arrangement for biodiversity. In this study, 24 artificial rockpools were installed at three levels between High Water Neaps and Mean Tide Level on a vertical concrete seawall on the south coast of the UK. The species abundance of the rockpools and adjacent seawall were surveyed at low tide for 2 years following rockpool installation and compared. Over the course of the study, sediment had begun to accumulate in some of the rockpools. At the 2-year mark, the sediment was removed and assessed for macrofauna. Algal biomass of the seawall and rockpools was estimated using previously obtained dry weight values for the dominant algae taxa. After 2 years, it was determined that artificial rockpools successfully increase species richness of seawalls, particularly at higher tidal levels where water-retaining refugia are crucial for many species. The rockpools hosted 37 sessile taxa and 9 sessile taxa were recorded on the seawall. Rockpools increased the vertical elevation for brown canopy-forming seaweeds by providing better attachment surfaces. Although the retained sediment only hosted 3 infaunal species, it was observed to provide shelter for shore crabs during surveys. As sea levels and ocean and air temperatures continue to rise, vertical eco-engineering arrangements will play a crucial role in allowing species to migrate up the tidal zone, negating habitat loss and localised extinction.

5.
Int J Biol Macromol ; 278(Pt 2): 134615, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39128743

ABSTRACT

The application of bone grafting materials in bone tissue engineering is paramount for treating severe bone defects. In this comprehensive review, we explore the significance and novelty of utilizing bioactive polymers as grafts for successful bone repair. Unlike metals and ceramics, polymers offer inherent biodegradability and biocompatibility, mimicking the native extracellular matrix of bone. While these polymeric micro-nano materials may face challenges such as mechanical strength, various fabrication techniques are available to overcome these shortcomings. Our study not only investigates diverse biopolymeric materials but also illuminates innovative fabrication methods, highlighting their importance in advancing bone tissue engineering.

6.
J Technol Transf ; 49(4): 1259-1286, 2024.
Article in English | MEDLINE | ID: mdl-39183938

ABSTRACT

The emergence and evolution of engineering biology, and its potential to address multiple global challenges is associated with the rise of biofoundries. These innovation intermediaries are facilities that employ advanced automation and computational analytics to accelerate engineering biology applications. Yet, for biofoundries to fully achieve their promise of generating applications that address grand societal challenges, they need to meet three key challenges: translation of research technology and its commercialization, attention to sustainability, and responsible innovation. Using web content analysis and interviews, this paper explores the functions and capabilities undertaken by existing public biofoundries, the extent to which they address these three challenges, and opportunities and models for enhancement. We also probe the roles undertaken by three other contrasting types of innovation intermediaries to identify practices and opportunities for integration and partnering with public biofoundries. We find that public biofoundries exhibit relatively strong capabilities for research translation, whereas efforts toward sustainability and responsibility are generally less prominent. For biofoundry enhancement, we propose an organisational model based on external partnering where public biofoundries are positioned as intermediaries within regional innovation systems. The framework put forward is reproducible and could be used in other contexts for assessing innovation intermediary organisational functions and capabilities toward meeting societal challenges.

7.
Nano Lett ; 24(34): 10569-10576, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39106059

ABSTRACT

4H-silicon carbide (4H-SiC) possesses a high Baliga figure of merit, making it a promising material for power electronics. However, its applications are limited by low hole mobility. Herein, we found that the hole mobility of 4H-SiC is mainly limited by the strong interband electron-phonon scattering using mode-level first-principles calculations. Our research indicates that applying compressive strain can reverse the sign of crystal-field splitting and change the ordering of electron bands close to the valence band maximum. Therefore, the interband electron-phonon scattering is severely suppressed and the electron group velocity is significantly increased. The out-of-plane hole mobility of 4H-SiC can be greatly enhanced by ∼200% with 2% uniaxial compressive strain applied. This work provides new insights into the electron transport mechanisms in semiconductors and suggests a strategy to improve hole mobility that could be applied to other semiconductors with hexagonal crystalline geometries.

8.
mSphere ; 9(8): e0036724, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39109886

ABSTRACT

Protein production strategies in bacteria are often limited due to the need for cell lysis and complicated purification schemes. To avoid these challenges, researchers have developed bacterial strains capable of secreting heterologous protein products outside the cell, but secretion titers often remain too low for commercial applicability. Improved understanding of the link between secretion system structure and its secretory abilities can help overcome the barrier to engineering higher secretion titers. Here, we investigated this link with the PrgI protein, the monomer of the secretory channel of the type 3 secretion system (T3SS) of Salmonella enterica. Despite detailed knowledge of the PrgI needle's assembly and structure, little is known about how its structure influences its secretory capabilities. To study this, we recently constructed a comprehensive codon mutagenesis library of the PrgI protein utilizing a novel one-pot recombineering approach. We then screened this library for functional T3SS assembly and secretion titer by measuring the secretion of alkaline phosphatase using a high-throughput activity assay. This allowed us to construct a first-of-its-kind secretion fitness landscape to characterize the PrgI needle's mutability at each position as well as the mutations which lead to enhanced T3SS secretion. We discovered new design rules for building a functional T3SS as well as identified hypersecreting mutants. This work can be used to increase understanding of the T3SS's assembly and identify further targets for engineering. This work also provides a blueprint for future efforts to engineer other complex protein assemblies through the construction of fitness landscapes.IMPORTANCEProtein secretion offers a simplified alternative method for protein purification from bacterial hosts. However, the current state-of-the-art methods for protein secretion in bacteria are still hindered by low yields relative to traditional protein purification strategies. Engineers are now seeking strategies to enhance protein secretion titers from bacterial hosts, often through genetic manipulations. In this study, we demonstrate that protein engineering strategies focused on altering the secretion apparatus can be a fruitful avenue toward this goal. Specifically, this study focuses on how changes to the PrgI needle protein from the type 3 secretion system from Salmonella enterica can impact secretion titer. We demonstrate that this complex is amenable to comprehensive mutagenesis studies and that this can yield both PrgI variants with increased secretory capabilities and insight into the normal functioning of the type 3 secretion system.


Subject(s)
Bacterial Proteins , Mutagenesis , Salmonella enterica , Type III Secretion Systems , Type III Secretion Systems/genetics , Type III Secretion Systems/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Salmonella enterica/genetics , Salmonella enterica/metabolism , Gene Library , Salmonella typhimurium/genetics , Salmonella typhimurium/metabolism
9.
J Biomater Sci Polym Ed ; : 1-16, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39185697

ABSTRACT

Three-dimensional (3D) porous scaffolds based on polycaprolactone (PCL)/chitosan (CS)/bioactive glass (BG) nanoparticle composites were fabricated by the freeze-drying technique for bone tissue engineering. The physiochemical properties of the developed PCL/CS/BG scaffolds were studied using FTIR, XRD, EDX and SEM. Furthermore, the swelling degree, porosity, water retention ability, compression strength, in vitro biodegradation, bioactivity and biocompatibility of the scaffolds were examined. The PCL/CS/BG scaffolds with 4 wt. % of BG content presented adequate pore size (106 µm), porosity (156%), water swelling degree (128%), water retention ability (179%), compressive strength (3.7 MPa) and controlled degradation behavior, which could be ideal for bone tissue engineering. The PCL/CS/BG composite scaffolds showed good antimicrobial activity against both test bacteria and fungi. The MTT assay demonstrated the biocompatibility of PCL/CS/BG scaffolds against C3H10T1/2 cell line. The Alizarin red staining assay confirmed the osteogenic activity of the PCL/CS/BG scaffolds.

10.
Adv Mater ; : e2407927, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39185788

ABSTRACT

The combination of nanoparticles and tumor-targeting bacteria for cancer immunotherapy can overcome the shortcomings of poor nanoparticle accumulation, limited penetration, and restricted distribution. However, it remains a great challenge for the hybrid system to improve therapeutic efficacy through the simultaneous and controllable regulation of immune cells and tumor cells. Herein, a hybrid therapeutic platform is rationally designed to achieve immune cascade-augmented cancer immunotherapy. To construct the hybrids, photothermal nanoparticles responsive to light in the second near-infrared (NIR-II) region are conjugated onto the surface of engineered bacteria through pH-responsive Schiff base bonds. Taking advantage of the hypoxia targeting and deep penetration characteristics of the bacteria, the hybrids can accumulate at tumor sites. Then nanoparticles detach from the bacteria to realize genetic engineering of tumor cells, which induces tumor cell apoptosis and down-regulate the expression of programmed cell death ligand 1 to alleviate immunosuppressive tumor microenvironment. The mild photothermal heating can not only induce tumor-associated antigen release, but also trigger sustainable expression of cytokine interleukin-2. Notably, a synergistic antitumor effect is achieved between the process of p53 transfection and NIR-II light-activated genetic engineering of bacteria. This work proposes a facile strategy for the construction of hybrid system to achieve cascade-augmented cancer immunotherapy.

11.
Sci Total Environ ; 950: 175231, 2024 Nov 10.
Article in English | MEDLINE | ID: mdl-39098417

ABSTRACT

Accurate prediction of instantaneous high lake water levels and flood flows (flood stages) from micro-catchments to big river basins are critical for flood forecasting. Lake Carl Blackwell, a small-watershed reservoir in the south-central USA, served as a primary case study due to its rich historical dataset. Bearing knowledge that both current and previous rainfall contributes to the reservoirs' water body, a series of hourly rainfall features were created to maximize predicting power, which include total rainfall amounts in the current hour, the past 2 h, 3 h, …, 600 h in addition to previous-day lake levels. Notedly, the rainfall features are the accumulated rainfall amounts from present to previous hours rather than the rainfall amount in any specific hour. Random Forest Regression (RFR) was used to score the features' importance and predict the flood stages along with Neural Network - Multi-layer Perceptron Regression (NN-MLP), Support Vector Regression (SVR), Extreme Gradient Boosting (XGBoost), and the ordinary multi-variant linear regression (MLR) together with dimension reduced linear models of Principal Component Regression (PCR) and Partial Least Square Regression (PLSR). The prediction accuracy for the lake flood stages can be as high as 0.95 in R2, 0.11 ft. in mean absolute error (MAE), and 0.21 ft. in root mean square error (RMSE) for the testing dataset by the RFR (NN-MLP performed equally well), with small accuracy decreases by the other two non-linear algorithms of XGBoost and SVR. The linear regressions with dimension reductions had the lowest accuracy. Furthermore, our approach demonstrated high accuracy and broad applicability for surface runoff and streamflow predictions across three different-sized watersheds from micro-catchment to big river basins in the region, with increases of predicting power from earlier rainfall for larger watersheds and vice versa.

12.
Article in English | MEDLINE | ID: mdl-39099339

ABSTRACT

Significance: Release of extracellular vesicles (EVs) by various cell types has been shown to mediate the delivery of biologically active payloads from donor cells to recipient cells; however, it remains unclear what cell types these EVs come from. With a focus on fluorescent reporters to monitor the release of EVs, especially those under the control of cell type-specific promoters, we address the translational relevance of genetic tools in cultured cells, normal tissues, and in models of development, injury, cancer, and wound healing. Recent Advances: It is well established that EVs are released by many cell types in the body via fusion and release processes at the plasma membrane. Since there remains debate about what fraction of EVs are released through regulated endosomal trafficking pathways versus nonspecific mechanisms, the development and validation of novel molecular tools are important to address the cellular source of EVs. Critical Issues: There is a need to develop and characterize new cell type-specific reporter mouse models that build upon the examples detailed here to identify the cellular source of EVs with genetic approaches being useful in addressing these critical limitations. Future Directions: Advances in reporter systems will drive a better understanding of EV subsets to identify compartment-specific EV localization to guide the development of more translationally relevant models for the wound healing field.

13.
Bioresour Technol ; 409: 131187, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39094965

ABSTRACT

Metabolic engineering provides a powerful approach to efficiently produce valuable compounds, with the aid of emerging gene editing tools and diverse metabolic regulation strategies. However, apart from the current known biochemical pathway information, a variety of unclear constraints commonly limited the optimization space of cell phenotype. Hydroxytyrosol is an important phenolic compound that serves various industries with prominent health-beneficial properties. In this study, the inverse metabolic engineering based on metabolome analysis was customized and implemented to disclose the hidden rate-limiting steps and thus to improve hydroxytyrosol production in Saccharomyces cerevisiae (S. cerevisiae). The potential rate-limiting steps involved three modules that were eliminated individually via reinforcing and balancing metabolic flow, optimizing cofactor supply, and weakening the competitive pathways. Ultimately, a 118.53 % improvement in hydroxytyrosol production (639.84 mg/L) was achieved by inverse metabolic engineering.


Subject(s)
Metabolic Engineering , Metabolomics , Phenylethyl Alcohol , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolism , Phenylethyl Alcohol/metabolism , Phenylethyl Alcohol/analogs & derivatives , Metabolic Engineering/methods , Metabolome
14.
J Agric Food Chem ; 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39180741

ABSTRACT

Dihydroquercetin is a vital flavonoid compound with a wide range of physiological activities. However, factors, such as metabolic regulation, limit the heterologous synthesis of dihydroquercetin in microorganisms. In this study, flavanone 3-hydroxylase (F3H) and flavanone 3'-hydroxylase (F3'H) were screened from different plants, and their co-expression in Saccharomyces cerevisiae was optimized. Promoter engineering and redox partner engineering were used to optimize the corresponding expression of genes involved in the dihydroquercetin synthesis pathway. Dihydroquercetin production was further improved through multicopy integration pathway genes and systems metabolic engineering. By increasing NADPH and α-ketoglutarate supply, the catalytic efficiency of F3'H and F3H was improved, thereby effectively increasing dihydroquercetin production (235.1 mg/L). Finally, 873.1 mg/L dihydroquercetin titer was obtained by fed-batch fermentation in a 5-L bioreactor, which is the highest dihydroquercetin production achieved through de novo microbial synthesis. These results established a pivotal groundwork for flavonoids synthesis.

15.
Front Microbiol ; 15: 1444099, 2024.
Article in English | MEDLINE | ID: mdl-39171255

ABSTRACT

Valencene, a sesquiterpene with the odor of sweet and fresh citrus, is widely used in the food, beverage, flavor and fragrance industry. Valencene is traditionally obtained from citrus fruits, which possess low concentrations of this compound. In the past decades, the great market demand for valencene has attracted considerable attention from researchers to develop novel microbial cell factories for more efficient and sustainable production modes. This review initially discusses the biosynthesis of valencene in plants, and summarizes the current knowledge of the key enzyme valencene synthase in detail. In particular, we highlight the heterologous production of valencene in different hosts including bacteria, fungi, microalgae and plants, and focus on describing the engineering strategies used to improve valencene production. Finally, we propose potential engineering directions aiming to further increase the production of valencene in microorganisms.

16.
J Am Stat Assoc ; 119(545): 81-94, 2024.
Article in English | MEDLINE | ID: mdl-39185398

ABSTRACT

In the emerging field of materials informatics, a fundamental task is to identify physicochemically meaningful descriptors, or materials genes, which are engineered from primary features and a set of elementary algebraic operators through compositions. Standard practice directly analyzes the high-dimensional candidate predictor space in a linear model; statistical analyses are then substantially hampered by the daunting challenge posed by the astronomically large number of correlated predictors with limited sample size. We formulate this problem as variable selection with operator-induced structure (OIS) and propose a new method to achieve unconventional dimension reduction by utilizing the geometry embedded in OIS. Although the model remains linear, we iterate nonparametric variable selection for effective dimension reduction. This enables variable selection based on ab initio primary features, leading to a method that is orders of magnitude faster than existing methods, with improved accuracy. To select the nonparametric module, we discuss a desired performance criterion that is uniquely induced by variable selection with OIS; in particular, we propose to employ a Bayesian Additive Regression Trees (BART)-based variable selection method. Numerical studies show superiority of the proposed method, which continues to exhibit robust performance when the input dimension is out of reach of existing methods. Our analysis of single-atom catalysis identifies physical descriptors that explain the binding energy of metal-support pairs with high explanatory power, leading to interpretable insights to guide the prevention of a notorious problem called sintering and aid catalysis design.

17.
Int J Biol Macromol ; 278(Pt 2): 134774, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39154681

ABSTRACT

Controlling biomolecular-cell interactions is crucial for the design of scaffolds for tissue engineering (TE). Regenerated silk fibroin (RSF) has been extensively used as TE scaffolds, however, RSF showed poor attachment of neuronal cells, such as rat pheochromocytoma (PC12) cells. In this work, amphiphilic peptides containing a hydrophobic isoleucine tail (I3) and laminin or fibronectin derived peptides (IKVAV, PDSGR, YIGSR, RGDS and PHSRN) were designed for promoting scaffold-cell interaction. Three of them (I3KVAV, I3RGDS and I3YIGSR) can self-assemble into nanofibers, therefore, were used to enhance the application of RSF in neuron TE. Live / dead assays revealed that the peptides exhibited negligible cytotoxicity against PC12 cells. The specific interaction between PC12 cells and the peptides were investigate using atomic force microscopy (AFM). The results indicated a synergistic effect in the designed peptides, promoting cellular attachment, proliferation and morphology changes. In addition, AFM results showed that co-assembling peptides I3KVAV and I3YIGSR possesses the best regulation of proliferation and attachment of PC12 cells, consistent with immunofluorescence staining results. Moreover, cell culture with hydrogels revealed that a mixture of peptides I3KVAV and I3YIGSR can also promote 3D neurites outgrowth. The approach of combining two different self-assembling peptides shows great potential for nerve regeneration applications.

18.
iScience ; 27(8): 110561, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39165845

ABSTRACT

Rime optimization algorithm (RIME) encounters issues such as an imbalance between exploitation and exploration, susceptibility to local optima, and low convergence accuracy when handling problems. This paper introduces a variant of RIME called IRIME to address these drawbacks. IRIME integrates the soft besiege (SB) and composite mutation strategy (CMS) and restart strategy (RS). To comprehensively validate IRIME's performance, IEEE CEC 2017 benchmark tests were conducted, comparing it against many advanced algorithms. The results indicate that the performance of IRIME is the best. In addition, applying IRIME in four engineering problems reflects the performance of IRIME in solving practical problems. Finally, the paper proposes a binary version, bIRIME, that can be applied to feature selection problems. bIRIMR performs well on 12 low-dimensional datasets and 24 high-dimensional datasets. It outperforms other advanced algorithms in terms of the number of feature subsets and classification accuracy. In conclusion, bIRIME has great potential in feature selection.

19.
Regen Biomater ; 11: rbae089, 2024.
Article in English | MEDLINE | ID: mdl-39165884

ABSTRACT

Percutaneous coronary interventional is the main treatment for coronary atherosclerosis. At present, most studies focus on blood components and smooth muscle cells to achieve anticoagulation or anti-proliferation effects, while the mediated effects of materials on macrophages are also the focus of attention. Macrophage foam cells loaded with elevated cholesterol is a prominent feature of atherosclerotic plaque. Activation of liver X receptor (LXR) to regulate cholesterol efflux and efferocytosis and reduce the number of macrophage foam cells in plaque is feasible for the regression of atherosclerosis. However, cholesterol efflux promotion remains confined to targeted therapies. Herein, LXR agonists (GW3965) were introduced on the surface of the material and delivered in situ to atherogenic macrophages to improve drug utilization for anti-atherogenic therapy and plaque regression. LXR agonists act as plaque inhibition mediated by multichannel regulation macrophages, including lipid metabolism (ABCA1, ABCG1 and low-density lipoprotein receptor), macrophage migration (CCR7) and efferocytosis (MerTK). Material loaded with LXR agonists significantly reduced plaque burden in atherosclerotic model rats, most importantly, it did not cause hepatotoxicity and adverse reactions such as restenosis and thrombosis after material implantation. Both in vivo and in vitro evaluations confirmed its anti-atherosclerotic capability and safety. Overall, multi-functional LXR agonist-loaded materials with pathological microenvironment regulation effect are expected to be promising candidates for anti-atherosclerosis and have potential applications in cardiovascular devices surface engineering.

20.
Heliyon ; 10(15): e35167, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39166039

ABSTRACT

In developing countries, smart grids are nonexistent, and electricity theft significantly hampers power supply. This research introduces a lightweight deep-learning model using monthly customer readings as input data. By employing careful direct and indirect feature engineering techniques, including Principal Component Analysis (PCA), t-distributed Stochastic Neighbor Embedding (t-SNE), UMAP (Uniform Manifold Approximation and Projection), and resampling methods such as Random-Under-Sampler (RUS), Synthetic Minority Over-sampling Technique (SMOTE), and Random-Over-Sampler (ROS), an effective solution is proposed. Previous studies indicate that models achieve high precision, recall, and F1 score for the non-theft (0) class, but perform poorly, even achieving 0 %, for the theft (1) class. Through parameter tuning and employing Random-Over-Sampler (ROS), significant improvements in accuracy, precision (89 %), recall (94 %), and F1 score (91 %) for the theft (1) class are achieved. The results demonstrate that the proposed model outperforms existing methods, showcasing its efficacy in detecting electricity theft in non-smart grid environments.

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