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1.
Anal Chem ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39298294

RESUMO

Tumor-derived small extracellular vesicle (sEV) microRNAs (miRNAs) are emerging biomarkers for cancer diagnostics. Conventional sEV miRNA detection methods necessitate the lysis of sEVs, rendering them laborious and time-consuming and potentially leading to damage or loss of miRNAs. Membrane fusion-based in situ detection of sEV miRNAs involves the preparation of probe-loaded vesicles (e.g., liposomes or cellular vesicles), which are typically sophisticated and require specialist equipment. Membrane perforation methods employ chemical treatments that can induce severe miRNA degradation or leaks. Inspired by previous studies that loaded nucleic acids into EVs or cells using hydrophobic tethers for therapeutic applications, herein, we repurposed this strategy by conjugating a hydrophobic tether onto molecular beacons to aid their transportation into sEVs, allowing for in situ detection of miRNAs in a fusion-free and multiplexing manner. This method enables simultaneous detection of multiple miRNA species within serum-derived sEVs for the diagnosis of prostate cancer, breast cancer, and gastric cancer with an accuracy of 83.3%, 81.8%, and 100%, respectively, in a cohort of 66 individuals, indicating that it holds a high application potential in clinical diagnostics.

2.
Sci Total Environ ; 952: 175969, 2024 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-39222812

RESUMO

Bisphenols, bisphenol A diglycidyl ether (BADGE), and bisphenol F diglycidyl ether (BFDGE) are commonly used as raw materials or additives in the production of several industrial and consumer products. However, information regarding the occurrence and distribution of these industrial chemicals in freshwater ecosystem is limited. In this study, four bisphenols, six BADGEs, and three BFDGEs were determined in abiotic and biotic samples collected from the Dongjiang River basin in southern China. Among the four bisphenols, BPA was widely present in all samples analyzed including surface water (median: 1.81 ng/L), sediment (3.1 ng/g dw), aquatic plants (3.69 ng/g dw), algae (7.57 ng/g dw), zooplankton (6.17 ng/g dw), and fish muscle (5.28 ng/g dw). Among the nine BADGEs and BFDGEs analyzed, BADGE, BADGE•H2O, BADGE·HCl·H2O and BADGE•2H2O was found in all sample types. Although the median concentration of BADGE•2H2O in surface water was below LOQ, this compound was found at median concentrations of 2.61, 3.59, 1.03, 1.69, and 49.8 ng/g dw in sediment, plants, algae, zooplankton, and fish muscle, respectively. Significant positive linear correlations were found among logarithmic transformed concentrations of BPA, BADGE, BADGE•H2O, BADGE•HCl•H2O, and BADGE•2H2O in sediment. The bioconcentration factor (logBCF) values of BADGE, BADGE•H2O, BADGE•HCl, BADGE•HCl•H2O, BADGE•2H2O, and BADGE•2HCl in fish, plants, algae, and zooplankton were > 3.3 L/kg (wet weight), indicating that these chemicals possess moderate bioaccumulation potential. The estimated daily total intake of bisphenols and BADGEs through fish consumption was 75.1 ng/kg bw/day for urban adult residents. The study provides baseline information on the occurrence of bisphenols, BADGEs, and BFDGEs in a freshwater ecosystem.


Assuntos
Compostos Benzidrílicos , Monitoramento Ambiental , Compostos de Epóxi , Fenóis , Rios , Poluentes Químicos da Água , China , Poluentes Químicos da Água/análise , Compostos Benzidrílicos/análise , Rios/química , Fenóis/análise , Compostos de Epóxi/análise , Humanos , Bioacumulação , Medição de Risco , Animais , Exposição Ambiental/estatística & dados numéricos
3.
Nano Converg ; 11(1): 36, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39249580

RESUMO

The oxide and halide perovskite materials with a ABX3 structure exhibit a number of excellent properties, including a high dielectric constant, electrochemical properties, a wide band gap, and a large absorption coefficient. These properties have led to a range of applications, including renewable energy and optoelectronics, where high-performance catalysts are needed. However, it is difficult for a single structure of perovskite alone to simultaneously fulfill the diverse needs of multiple applications, such as high performance and good stability at the same time. Consequently, perovskite nanocomposites have been developed to address the current limitations and enhance their functionality by combining perovskite with two or more materials to create complementary materials. This review paper categorizes perovskite nanocomposites according to their structural composition and outlines their synthesis methodologies, as well as their applications in various fields. These include fuel cells, electrochemical water splitting, CO2 mitigation, supercapacitors, and optoelectronic devices. Additionally, the review presents a summary of their research status, practical challenges, and future prospects in the fields of renewable energy and electronics.

4.
Sci Total Environ ; 950: 175388, 2024 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-39122050

RESUMO

Although the effects of human-enhanced atmospheric nitrogen (N) deposition are well documented, the response of dryland soils to N deposition remains unclear owing to the divergence in hydrological outputs and soil heterogeneity. We selected a typical desert steppe in western China to simulate the effects of long-term N deposition by applying 0 (CK), 3.5, 7, and 14 g N m-2 yr-1 for 12 consecutive years. We found that, compared with the CK plots, the total N content of the upper (0-10 cm) and lower (10-20 cm) soil layers in fertilized plots increased by 8.3-14.6 % and 2.4-8.2 %, respectively. Correspondingly, the available, NH4+-, and NO3--N contents in the upper soil significantly increased by 25.5-68.3 %. However, in the lower soil, available and NO3--N contents were significantly lower than those in the CK plots, and their variation trend was opposite to that of NH4+-N, implying N turnover and leaching. As a result, the upper and lower soil pH in fertilized plots significantly decreased by 0.36-0.53 and 0.31-0.37 units; however, their CaCO3 content significantly increased by 9.8-22.8 % and 7.2-30.3 %, respectively. The total phosphorus (P) content in the upper and lower soil layers in fertilized plots significantly increased and decreased by 3.6-51.3 % and 16.7-62.5 %, respectively, however, both significantly decreased along the N fertilization gradient. Furthermore, the upper and lower soil organic carbon (SOC) content in the fertilized plots significantly increased by 57.7-78.1 % and 19.2-27.4 %, respectively. Pearson's correlation analysis revealed that available soil P was significantly negatively correlated with plant shoot Mn content (a proxy for rhizosphere carboxylates), whereas dissolved OC, SOC, and CaCO3 were significantly positively correlated, suggesting that Ca cycling is involved in P cycling and SOC sequestration. Our study suggests that long-term N input exacerbates P limitation in desert steppes, however, enhances SOC sequestration.

5.
J Environ Manage ; 368: 122092, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39121624

RESUMO

Integrated reservoir water quantity and quality management is significant for water supply security and river ecosystem health. However, the spatiotemporal heterogeneity of water quality and the nonuniform response of multiple indicators to operation changes make it difficult to determine optimal operation schedules. This study proposes a coupled simulation-surrogate-optimization modeling approach for compromising multiple water quantity and quality targets in reservoir operations. The Environmental Fluid Dynamics Code (EFDC) was used to simulate spatiotemporal reservoir water quality dynamics. Subsequently, an ecological damage assessment method was established, accounting for the spatiotemporal heterogeneity of multiple water quality indicators and the nonlinear relationship between the water quality deterioration and ecological damage. To quickly simulate the ecological damage, a surrogate model was developed using the nonlinear autoregressive network with exogenous inputs (NARX). Finally, the surrogate model was integrated into a reservoir operation optimization model for compromising socioeconomic and ecological targets. By applying the methods to China's Danjiangkou Reservoir as a case, it was shown that more even nutrient distribution in the reservoir increased water eutrophication area while reducing concentration peak values, which helped decrease the ecological damage. Operation changes could lead to opposite effects on in-reservoir and downstream ecological targets, increasing operation optimization complexity. Both ecological and socioeconomic benefits significantly increased (by 9.4%-16.4%) during dry years under the optimized operation scheme, implying that synergies were obtained. This study offers implications and a management tool for reservoir operations to address the multiple tradeoffs among socioeconomic and ecological benefits.


Assuntos
Rios , Qualidade da Água , Abastecimento de Água , Modelos Teóricos , Ecossistema , China , Monitoramento Ambiental , Eutrofização , Ecologia
6.
J Cell Biol ; 223(10)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39133213

RESUMO

Mitochondrial functions can be regulated by membrane contact sites with the endoplasmic reticulum (ER). These mitochondria-ER contact sites (MERCs) are functionally heterogeneous and maintained by various tethers. Here, we found that REEP5, an ER tubule-shaping protein, interacts with Mitofusins 1/2 to mediate mitochondrial distribution throughout the cytosol by a new transport mechanism, mitochondrial "hitchhiking" with tubular ER on microtubules. REEP5 depletion led to reduced tethering and increased perinuclear localization of mitochondria. Conversely, increasing REEP5 expression facilitated mitochondrial distribution throughout the cytoplasm. Rapamycin-induced irreversible REEP5-MFN1/2 interaction led to mitochondrial hyperfusion, implying that the dynamic release of mitochondria from tethering is necessary for normal mitochondrial distribution and dynamics. Functionally, disruption of MFN2-REEP5 interaction dynamics by forced dimerization or silencing REEP5 modulated the production of mitochondrial reactive oxygen species (ROS). Overall, our results indicate that dynamic REEP5-MFN1/2 interaction mediates cytosolic distribution and connectivity of the mitochondrial network by "hitchhiking" and this process regulates mitochondrial ROS, which is vital for multiple physiological functions.


Assuntos
Retículo Endoplasmático , GTP Fosfo-Hidrolases , Mitocôndrias , Espécies Reativas de Oxigênio , Retículo Endoplasmático/metabolismo , Mitocôndrias/metabolismo , Humanos , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética , Espécies Reativas de Oxigênio/metabolismo , Células HeLa , Microtúbulos/metabolismo , Células HEK293 , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Ligação Proteica , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Citosol/metabolismo , Dinâmica Mitocondrial
7.
Cell Biol Int ; 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39099163

RESUMO

Telocytes (TCs), a novel type of mesenchymal or interstitial cell with specific, very long and thin cellular prolongations, have been found in various mammalian organs and have potential biological functions. However, their existence during lung development is poorly understood. This study aimed to investigate the existence, morphological features, and role of CD34+ SCs/TCs in mouse lungs from foetal to postnatal life using primary cell culture, double immunofluorescence, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The immunofluorescence double staining profiles revealed positive expression of CD34 and PDGFR-α, Sca-1 or VEGFR-3, and the expression of these markers differed among the age groups during lung development. Intriguingly, in the E18.5 stage of development, along with the CD34+ SCs/TCs, haematopoietic stem cells and angiogenic factors were also significantly increased in number compared with those in the E14.5, E16.5, P0 and P7. Subsequently, TEM confirmed that CD34+ SCs/TCs consisted of a small cell body with long telopodes (Tps) that projected from the cytoplasm. Tps consisted of alternating thin and thick segments known as podomers and podoms. TCs contain abundant endoplasmic reticulum, mitochondria and secretory vesicles and establish close connections with neighbouring cells. Furthermore, SEM revealed characteristic features, including triangular, oval, spherical, or fusiform cell bodies with extensive cellular prolongations, depending on the number of Tps. Our findings provide evidence for the existence of CD34+ SCs/TCs, which contribute to vasculogenesis, the formation of the air‒blood barrier, tissue organization during lung development and homoeostasis.

8.
Nature ; 632(8024): 280-286, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39112621

RESUMO

Optical computing promises to improve the speed and energy efficiency of machine learning applications1-6. However, current approaches to efficiently train these models are limited by in silico emulation on digital computers. Here we develop a method called fully forward mode (FFM) learning, which implements the compute-intensive training process on the physical system. The majority of the machine learning operations are thus efficiently conducted in parallel on site, alleviating numerical modelling constraints. In free-space and integrated photonics, we experimentally demonstrate optical systems with state-of-the-art performances for a given network size. FFM learning shows training the deepest optical neural networks with millions of parameters achieves accuracy equivalent to the ideal model. It supports all-optical focusing through scattering media with a resolution of the diffraction limit; it can also image in parallel the objects hidden outside the direct line of sight at over a kilohertz frame rate and can conduct all-optical processing with light intensity as weak as subphoton per pixel (5.40 × 1018- operations-per-second-per-watt energy efficiency) at room temperature. Furthermore, we prove that FFM learning can automatically search non-Hermitian exceptional points without an analytical model. FFM learning not only facilitates orders-of-magnitude-faster learning processes, but can also advance applied and theoretical fields such as deep neural networks, ultrasensitive perception and topological photonics.

9.
Int J Infect Dis ; : 107225, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39197743

RESUMO

BACKGROUND: Spondylitis is a spinal infection which has been increasing in susceptible populations globally. This disease is caused by various microorganisms. Fungal spondylitis is rare in clinical practice and is strongly associated with immunosuppression and diabetes. Here, we report a case of suspected ca Melampsora spondylitis. CASE PRESENTATION: A patient was suspected with Melampsora spondylitis at the L3-S1 level. The patient received two surgical operations and antifungal treatments. The Next-generation sequencing (NGS) analysis of the tissue specimen obtained during the two surgical procedures confirmed the diagnosis of Melampsora spondylitis. The patient was successfully treated with voriconazole, vancomycin, and meropenem following surgical debridement with pedicle screw internal fixation. CONCLUSION: The diagnosis of fungal spondylitis is often delayed or missed. Physicians should consider fungal spondylitis in the differential diagnosis of neck pain to facilitate early treatment and prevent spinal cord injury and disability. Although fungal infections often occur in immunocompromised patients, fungal spondylitis has also been reported in immunocompetent patients in recent years. In addition, Candida albicans is usually considered a common bacterium in fungal spondylitis. This case underscores the need to develop more advanced diagnostic and therapeutic techniques to identify the pathogenic bacteria associated with fungal spondylitis besides Candida albicans.

10.
Bioelectrochemistry ; 160: 108792, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39126818

RESUMO

CYP2C19*3 enzyme plays a pivotal role in drug metabolism and is tightly regulated by the CYP2C19*3 gene. Therefore, quantification of CYP2C19*3 gene holds paramount importance for achieving personalized medication guidance in precision medicine. In this project, the magnetic electrochemical biosensors were constructed for the ultra-sensitive detection of CYP2C19*3 gene. Employing magnetic α-Fe2O3/Fe3O4@Au as the matrixes for signal amplification, CYP2C19*3 complementary chains (c-ssDNA) were bound to their surfaces through gold-sulfur bonds with subsequent specific sites blockade by bovine serum albumin (BSA) to form the α-Fe2O3/Fe3O4@Au/c-ssDNA/BSA biosensors. This design enabled efficient biosensors separation, target gene capture, and self-assembly on the electrode surface, enhancing the response signal. The biosensors exhibited excellent capture capabilities with a wide linear range (1 pM-1 µM), a low detection limit of 0.2710 pM, a quantitation limit of 0.9033 pM, reproducibility with an RSD value of 1.26 %, and stable storage for at least one week. The RSD value of CYP2C19*3 in serum samples consistently remained below 4.5 %, with a recovery rate ranging 95.52 % from 102.71 %. Moreover, the target gene could be accurately identified and captured in a mixed system of multiple nucleotide mutants of the CYP2C19*3 gene, suggesting a promising applicability and popularization.


Assuntos
Técnicas Biossensoriais , Citocromo P-450 CYP2C19 , Técnicas Eletroquímicas , Limite de Detecção , Nanotubos , Técnicas Biossensoriais/métodos , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Técnicas Eletroquímicas/métodos , Humanos , Nanotubos/química , Compostos Férricos/química , DNA/química , DNA/genética , Ouro/química
11.
J Biol Chem ; 300(8): 107563, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39002680

RESUMO

CD8+ T cell immunity, mediated by human leukocyte antigen (HLA) and T cell receptor (TCR), plays a critical role in conferring immune memory and protection against viral pathogens. The emergence of SARS-CoV-2 variants poses a serious challenge to the efficacy of current vaccines. Whereas numerous SARS-CoV-2 mutations associated with immune escape from CD8+ T cells have been documented, the molecular effects of most mutations on epitope-specific TCR recognition remain largely unexplored. Here, we studied an HLA-A24-restricted NYN epitope (Spike448-456) that elicits broad CD8+ T cell responses in COVID-19 patients characterized by a common TCR repertoire. Four natural mutations, N450K, L452Q, L452R, and Y453F, arose within the NYN epitope and have been transmitted in certain viral lineages. Our findings indicate that these mutations have minimal impact on the epitope's presentation by cell surface HLA, yet they diminish the affinities of their respective peptide-HLA complexes (pHLAs) for NYN peptide-specific TCRs, particularly L452R and Y453F. Furthermore, we determined the crystal structure of HLA-A24 loaded with the Y453F peptide (NYNYLFRLF), and subsequently a ternary structure of the public TCRNYN-I complexed to the original NYN-HLA-A24 (NYNYLYRLF). Our structural analysis unveiled that despite competent presentation by HLA, the mutant Y453F peptide failed to establish a stable TCR-pHLA ternary complex due to reduced peptide: TCR contacts. This study supports the idea that cellular immunity restriction is an important driving force behind viral evolution.


Assuntos
Epitopos de Linfócito T , Evasão da Resposta Imune , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , SARS-CoV-2/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , COVID-19/virologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/química , Mutação , Cristalografia por Raios X
12.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38980133

RESUMO

In this paper, a long-stroke parallel compliant tip-tilt-piston micropositioning stage driven by voice coil motors (VCMs) is proposed. The stage is equipped with three sets of driving arms, which include a spherical hinge, VCM, and parallelogram guide mechanism, evenly spaced at 120° intervals. The spherical hinge is composed of orthogonal leaf-spring beams, and the VCM is embedded into the parallelogram mechanism to form a compact design. The compliance matrix method and the geometric method facilitated the determination of compliance in all six degree-of-freedom directions of the spherical hinge and the derivation of kinematic equations for decoupling the motion of the stage. In addition, finite element analysis was utilized to determine the maximum stroke and stress of the stage. To validate the proposed design, a stage prototype was constructed and subjected to experimental testing. Furthermore, a feedback controller was designed, integrating proportional integral controller, notch filter, and sliding mode controller feedforward. The experimental results indicate that the stage can achieve a long stroke of ±50.75 mrad × ±44.2 mrad × ±4.425 mm, with the natural frequencies in the three-axis direction of 22.3 × 25.5 × 25.5 Hz3. In addition, the maximum relative tracking error was maintained below 5.25%, highlighting the effectiveness of the control technique in achieving a high tracking performance.

13.
Biosens Bioelectron ; 260: 116460, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38843769

RESUMO

Neutrophils need to migrate through tight tissue spaces to eliminate pathogens, but their movement is often hindered by their large and stiff nuclei. Neutrophil migration is impaired in sepsis patients, but it is unclear whether this defect is related to the deformability of their nuclei. Herein, we designed microfluidic devices with micron-scale narrow slits to simulate biological barriers. This setup allowed us to observe and record neutrophil movement and nuclear deformation in real-time. We also developed a method for morphological analysis to quantify nucleus deformation in numerous individual cells. Our studies showed that neutrophils from healthy individuals could adjust their nuclear shape to squeeze through these constrictions, whereas those from sepsis patients demonstrated less flexibility. Neutrophils with rigid nuclei struggled to pass through narrow gaps and were more likely to rupture under pressure. These findings suggest that the migration defects of neutrophils observed in sepsis may be attributed to the inability of neutrophils to deform their nuclei, highlighting the crucial role of microfluidic technologies in offering new insights into migration defects under pathological conditions.


Assuntos
Movimento Celular , Dispositivos Lab-On-A-Chip , Neutrófilos , Sepse , Humanos , Neutrófilos/citologia , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Núcleo Celular
14.
Chembiochem ; 25(13): e202400227, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38700476

RESUMO

Biomarkers are crucial physiological and pathological indicators in the host. Over the years, numerous detection methods have been developed for biomarkers, given their significant potential in various biological and biomedical applications. Among these, the detection system based on functionalized DNA origami has emerged as a promising approach due to its precise control over sensing modules, enabling sensitive, specific, and programmable biomarker detection. We summarize the advancements in biomarker detection using functionalized DNA origami, focusing on strategies for DNA origami functionalization, mechanisms of biomarker recognition, and applications in disease diagnosis and monitoring. These applications are organized into sections based on the type of biomarkers - nucleic acids, proteins, small molecules, and ions - and concludes with a discussion on the advantages and challenges associated with using functionalized DNA origami systems for biomarker detection.


Assuntos
Biomarcadores , DNA , DNA/química , DNA/análise , Biomarcadores/análise , Humanos , Técnicas Biossensoriais , Nanoestruturas/química , Proteínas/análise , Proteínas/química , Conformação de Ácido Nucleico
15.
Mol Cell ; 84(10): 1964-1979.e6, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38759628

RESUMO

The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes cancer cells to GPX4-inactivation-induced ferroptosis. Furthermore, complex I inhibition synergizes with radiotherapy (RT) to selectively suppress the growth of LKB1-deficient tumors by inducing ferroptosis in mouse models. Our data demonstrate a multifaceted role of complex I in regulating ferroptosis and propose a ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.


Assuntos
Proteínas Quinases Ativadas por AMP , Complexo I de Transporte de Elétrons , Ferroptose , Animais , Feminino , Humanos , Camundongos , Quinases Proteína-Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Linhagem Celular Tumoral , Complexo I de Transporte de Elétrons/metabolismo , Complexo I de Transporte de Elétrons/genética , Ferroptose/genética , Ferroptose/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/genética , Mitocôndrias/efeitos dos fármacos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Mol Biol Rep ; 51(1): 680, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796595

RESUMO

Menstrual blood-derived endometrial stem cells (MenSCs) have attracted increasing interest due to their excellent safety, and lack of ethical dilemma as well as their ability to be periodically obtained in a noninvasive manner. However, although preclinical research as shown the therapeutic potential of MenSCs in several diseases, their poor cell survival and low engraftment at disease sites reduce their clinical efficacy. Flotillins (including Flot1 and Flot2) are implicated in various cellular processes, such as vesicular trafficking, signal transduction, cell proliferation, migration and apoptosis. In this study, we aimed to determine the effects of Flotillins on MenSCs survival, proliferation and migration. Our experimental results show that MenSCs were modified to overexpress Flot1 and/or Flot2 without altering their intrinsic characteristics. Flot1 and Flot2 co-overexpression promoted MenSC viability and proliferation capacity. Moreover, Flot1 or Flot2 overexpression significantly promoted the migration and inhibited the apoptosis of MenSCs compared with the negative control group, and these effects were stronger in the Flot1 and Flot2 gene co-overexpression group. However, these effects were significantly reversed after Flot1 and/or Flot2 knockdown. In conclusion, our results indicate that Flot1 and Flot2 overexpression in MenSCs improved their proliferation and migration and inhibited their apoptosis, and this might be an effective approach to improve the efficiency of cell-based therapies.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Proteínas de Membrana , Humanos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Feminino , Endométrio/citologia , Endométrio/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Células Cultivadas , Transdução de Sinais
17.
Mol Biomed ; 5(1): 14, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644450

RESUMO

NLRP inflammasomes are a group of cytosolic multiprotein oligomer pattern recognition receptors (PRRs) involved in the recognition of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) produced by infected cells. They regulate innate immunity by triggering a protective inflammatory response. However, despite their protective role, aberrant NLPR inflammasome activation and gain-of-function mutations in NLRP sensor proteins are involved in occurrence and enhancement of non-communicating autoimmune, auto-inflammatory, and neurodegenerative diseases. In the last few years, significant advances have been achieved in the understanding of the NLRP inflammasome physiological functions and their molecular mechanisms of activation, as well as therapeutics that target NLRP inflammasome activity in inflammatory diseases. Here, we provide the latest research progress on NLRP inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRP7, NLRP2, NLRP9, NLRP10, and NLRP12 regarding their structural and assembling features, signaling transduction and molecular activation mechanisms. Importantly, we highlight the mechanisms associated with NLRP inflammasome dysregulation involved in numerous human auto-inflammatory, autoimmune, and neurodegenerative diseases. Overall, we summarize the latest discoveries in NLRP biology, their forming inflammasomes, and their role in health and diseases, and provide therapeutic strategies and perspectives for future studies about NLRP inflammasomes.


Assuntos
Inflamassomos , Proteínas NLR , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Proteínas NLR/metabolismo , Animais , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/metabolismo , Transdução de Sinais/imunologia , Imunidade Inata , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética
18.
Science ; 384(6693): 312-317, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38669572

RESUMO

Electrostatic capacitors are foundational components of advanced electronics and high-power electrical systems owing to their ultrafast charging-discharging capability. Ferroelectric materials offer high maximum polarization, but high remnant polarization has hindered their effective deployment in energy storage applications. Previous methodologies have encountered problems because of the deteriorated crystallinity of the ferroelectric materials. We introduce an approach to control the relaxation time using two-dimensional (2D) materials while minimizing energy loss by using 2D/3D/2D heterostructures and preserving the crystallinity of ferroelectric 3D materials. Using this approach, we were able to achieve an energy density of 191.7 joules per cubic centimeter with an efficiency greater than 90%. This precise control over relaxation time holds promise for a wide array of applications and has the potential to accelerate the development of highly efficient energy storage systems.

19.
Science ; 384(6692): 202-209, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38603505

RESUMO

The pursuit of artificial general intelligence (AGI) continuously demands higher computing performance. Despite the superior processing speed and efficiency of integrated photonic circuits, their capacity and scalability are restricted by unavoidable errors, such that only simple tasks and shallow models are realized. To support modern AGIs, we designed Taichi-large-scale photonic chiplets based on an integrated diffractive-interference hybrid design and a general distributed computing architecture that has millions-of-neurons capability with 160-tera-operations per second per watt (TOPS/W) energy efficiency. Taichi experimentally achieved on-chip 1000-category-level classification (testing at 91.89% accuracy in the 1623-category Omniglot dataset) and high-fidelity artificial intelligence-generated content with up to two orders of magnitude of improvement in efficiency. Taichi paves the way for large-scale photonic computing and advanced tasks, further exploiting the flexibility and potential of photonics for modern AGI.

20.
Chemosphere ; 354: 141649, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458356

RESUMO

To avoid the difficulty of separating solids from liquids when reusing powder photocatalysts, 3D stereoscopic photocatalysts were constructed. In this study, three-dimensional S defect-rich MoS2 hierarchical aerogel was prepared by chemical cross-linking of functional ultrathin 2D MoS2. Its phase, micro-morphology and structure were characterized, and it was used in the study of photocatalytic degradation of organic pollutants. Of the samples tested, MS@CA-3 (i.e., defect-rich 3D MoS2 aerogel with a loading of 30 mg of defect-rich MoS2) exhibited the best photocatalytic activity due to its suitable load, good light transmission, and a degradation rate of up to 91.0% after 3 h. In addition, MS@CA-3 aerogel offers high recyclability and structural stability, and the degradation rate of the organic pollutant methylene blue decreases only 9.8% after more than ten cycles of photocatalytic degradation. It combines the high catalytic performance of S defect-rich 2D MoS2 and the convenient reusability of hierarchical porous aerogel. This study provides valuable data and a reference for the practical promotion and application of photocatalytic technology in the field of environmental remediation.


Assuntos
Poluentes Ambientais , Molibdênio , Porosidade , Catálise , Corantes
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