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1.
J Med Chem ; 67(8): 6292-6312, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38624086

RESUMO

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) are emerging drug targets of small molecules. Despite some mitochondria-selective ligands being reported for drug delivery against cancers, the ligand design is mostly limited to the triphenylphosphonium scaffold. The ligand designed with lipophilic small-sized scaffolds bearing multipositive charges targeting the unique feature of high mitochondrial membrane potential (MMP) is lacking and most mitochondria-selective ligands are not G4-targeting. Herein, we report a new small-sized dicationic lipophilic ligand to target MMP and mitochondrial DNA G4s to enhance drug delivery for anticancer. The ligand showed marked alteration of mitochondrial gene expression and substantial induction of ROS production, mitochondrial dysfunction, DNA damage, cellular senescence, and apoptosis. The ligand also exhibited high anticancer activity against HCT116 cancer cells (IC50, 3.4 µM) and high antitumor efficacy in the HCT116 tumor xenograft mouse model (∼70% tumor weight reduction).


Assuntos
Antineoplásicos , Neoplasias Colorretais , Quadruplex G , Mitocôndrias , Humanos , Quadruplex G/efeitos dos fármacos , Ligantes , Animais , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Camundongos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Camundongos Nus , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Ensaios Antitumorais Modelo de Xenoenxerto , Células HCT116 , DNA Mitocondrial/metabolismo
2.
PLoS One ; 19(4): e0301120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38687753

RESUMO

Determining the exact type of epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation in lung cancer has become important. We found that not all ex20ins mutations reported by cobas EGFR test v2 could be validated by Sanger sequencing even using surgical specimens with high tumor contents. This study aimed to validate the ex20ins results reported by the cobas test and to determine whether there were clinicopathological factors associated with aberrant cobas ex20ins report. In total, 123 cobas-reported cases with ex20ins were retrospectively collected and validated by Sanger sequencing and Idylla assay. Clinicopathological features between ex20ins cobas+/Sanger+ group (n = 71) and cobas+/Sanger- group (n = 52) were compared. The Idylla assay detected ex20ins in 82.6% of cobas+/Sanger+ cases but only in 4.9% of cobas+/Sanger- cases. The cobas+/Sanger- group was significantly associated with higher tumor contents, poorly differentiated patterns, tumor necrosis, and a lower internal control cycle threshold value reported by the Idylla which suggesting the presence of increased EGFR gene copy numbers. EGFR fluorescence in situ hybridization (FISH) revealed the majority of cobas+/Sanger- group had EGFR high copy number gain (16%) or amplification (76%) according to the Colorado criteria. Among cases reported to have concomitant classic EGFR and ex20ins mutations by the cobas, the classic EGFR mutations were all detected by Sanger sequencing and Idylla, while the ex20ins mutations were undetected by Sanger sequencing (0%) or rarely reported by Idylla assay (3%). FISH revealed high EGFR copy number gain (17.9%) and amplification (79.5%) in cases reported having concomitant classic EGFR and ex20ins mutations by the cobas. This study demonstrated an unusually high frequency of EGFR amplification in cases with aberrant cobas ex20ins report which could not be validated by Sanger sequencing or Idylla assay. Ex20ins reported by the cobas test should be validated using other methods especially those reported having concomitant ex20ins and classic EGFR mutations.


Assuntos
Receptores ErbB , Éxons , Neoplasias Pulmonares , Humanos , Receptores ErbB/genética , Masculino , Feminino , Pessoa de Meia-Idade , Éxons/genética , Idoso , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Estudos Retrospectivos , Mutagênese Insercional , Amplificação de Genes , Adulto , Mutação , Idoso de 80 Anos ou mais , Análise Mutacional de DNA/métodos
3.
ACS Sens ; 9(3): 1545-1554, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38450702

RESUMO

rRNAs are prevalent in living organisms. They are produced in nucleolus and mitochondria and play essential cellular functions. In addition to the primary biofunction in protein synthesis, rRNAs have been recognized as the emerging signaling molecule and drug target for studies on nucleolus morphology, mitochondrial autophagy, and tumor cell malignancy. Currently, only a few rRNA-selective probes have been developed, and most of them encounter the drawbacks of low water solubility, poor nuclear membrane permeability, short emission wavelength, low stability against photobleaching, and high cytotoxicity. These unfavorable properties of rRNA probes limit their potential applications. In the present study, we reported a new rRNA-selective and near-infrared fluorescent turn-on probe, 4MPS-TO, capable of tracking rRNA in live human cancer cells. The real-time monitoring performance in nucleolus morphology and mitochondrial autophagy is demonstrated in HeLa cells. The probe shows great application potential for being used as a rRNA-selective, sensitive, and photostable imaging tool in chemical biology study and drug screening.


Assuntos
Mitofagia , Neoplasias , Humanos , Células HeLa , Corantes Fluorescentes/química , Imagem Óptica/métodos , Autofagia
4.
J Control Release ; 368: 650-662, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490374

RESUMO

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.


Assuntos
Glioblastoma , Nanopartículas , Neoplasias , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Fototerapia/métodos , Encéfalo , Barreira Hematoencefálica , Corantes , Nanomedicina Teranóstica/métodos , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral
5.
Zool Res ; 45(2): 367-380, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485506

RESUMO

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.


Assuntos
Osteoporose , Doenças dos Roedores , Humanos , Camundongos , Animais , Peixe-Zebra , Espermina/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/prevenção & controle , Osteoporose/veterinária , Prednisolona/efeitos adversos , Glucocorticoides , Doenças dos Roedores/induzido quimicamente , Doenças dos Roedores/tratamento farmacológico
6.
Plant Methods ; 20(1): 23, 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311750

RESUMO

BACKGROUND: Camellia oleifera, an essential woody oil tree in China, propagates through grafting. However, in production, it has been found that the interaction between rootstocks and scions may affect fruit characteristics. Therefore, it is necessary to predict fruit characteristics after grafting to identify suitable rootstock types. METHODS: This study used Deep Neural Network (DNN) methods to analyze the impact of 106 6-year-old grafting combinations on the characteristics of C.oleifera, including fruit and seed characteristics, and fatty acids. The prediction of characteristics changes after grafting was explored to provide technical support for the cultivation and screening of specialized rootstocks. After determining the unsaturated fat acids, palmitoleic acid C16:1, cis-11 eicosenoic acid C20:1, oleic acid C18:1, linoleic acid C18:2, linolenic acid C18:3, kernel oil content, fruit height, fruit diameter, fresh fruit weight, pericarp thickness, fresh seed weight, and the number of fresh seeds, the DNN method was used to calculate and analyze the model. The model was screened using the comprehensive evaluation index of Mean Absolute Error (MAPE), determinate correlation R2 and and time consumption. RESULTS: When using 36 neurons in 3 hidden layers, the deep neural network model had a MAPE of less than or equal to 16.39% on the verification set and less than or equal to 13.40% on the test set. Compared with traditional machine learning methods such as support vector machines and random forests, the DNN method demonstrated more accurate predictions for fruit phenotypic characteristics, with MAPE improvement rates of 7.27 and 3.28 for the 12 characteristics on the test set and maximum R2 improvement values of 0.19 and 0.33. In conclusion, the DNN method developed in this study can effectively predict the oil content and fruit phenotypic characteristics of C. oleifera, providing a valuable tool for predicting the impact of grafting combinations on the fruit of C. oleifera.

7.
Environ Res ; 249: 118431, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38346481

RESUMO

Plant uptake, accumulation, and transformation of organophosphate esters (OPEs) play vital roles in their geochemical cycles and exposure risks. Here we reviewed the recent research advances in OPEs in plants. The mean OPE concentrations based on dry/wet/lipid weight varied in 4.80-3,620/0.287-26.8/12,000-315,000 ng g-1 in field plants, and generally showed positive correlations with those in plant habitats. OPEs with short-chain substituents and high hydrophilicity, particularly the commonly used chlorinated OPEs, showed dominance in most plant samples, whereas some tree barks, fruits, seeds, and roots demonstrated dominance of hydrophobic OPEs. Both hydrophilic and hydrophobic OPEs can enter plants via root and foliar uptake, and the former pathway is mainly passively mediated by various membrane proteins. After entry, different OPEs undergo diverse subcellular distributions and acropetal/basipetal/intergenerational translocations, depending on their physicochemical properties. Hydrophilic OPEs mainly exist in cell sap and show strong transferability, hydrophobic OPEs demonstrate dominant distributions in cell wall and limited migrations owing to the interception of Casparian strips and cell wall. Additionally, plant species, transpiration capacity, growth stages, commensal microorganisms, and habitats also affect OPE uptake and transfer in plants. OPE metabolites derived from various Phase I transformations and Phase II conjugations are increasingly identified in plants, and hydrolysis and hydroxylation are the most common metabolic processes. The metabolisms and products of OPEs are closely associated with their structures and degradation resistance and plant species. In contrast, plant-derived food consumption contributes considerably to the total dietary intakes of OPEs by human, particularly the cereals, and merits specifical attention. Based on the current research limitations, we proposed the research perspectives regarding OPEs in plants, with the emphases on their behavior and fate in field plants, interactions with plant-related microorganisms, multiple uptake pathways and mechanisms, and comprehensive screening analysis and risk evaluation.


Assuntos
Plantas , Humanos , Plantas/metabolismo , Ésteres/metabolismo , Organofosfatos/metabolismo , Poluentes Ambientais/metabolismo
8.
ACS Appl Mater Interfaces ; 16(4): 4854-4862, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38252590

RESUMO

In halide perovskite solar cells (PSCs), moderate lead iodide (PbI2) can enhance device efficiency by providing some passivation effects, but extremely active PbI2 leads to the current density-voltage hysteresis effect and device instability. In addition, defects distributed on the buried interface of tin oxide (SnO2)/perovskite will lead to the photogenerated carrier recombination. Here, rubidium chloride (RbCl) is introduced at the buried SnO2/perovskite interface, which not only acts as an interfacial passivator to interact with the uncoordinated tin ions (Sn4+) and fill the oxygen vacancy on the SnO2 surface but also converts PbI2 into an inactive (PbI2)2RbCl compound to stabilize the perovskite phase via a bottom-up evolution effect. These synergistic effects deliver a champion PCE of 22.13% with suppressed hysteresis for the W RbCl PSCs, in combination with enhanced environmental and thermal stability. This work demonstrates that the interfacial defect passivation and bottom-up excess PbI2 management using RbCl modifiers are promising strategies to address the outstanding challenges associated with PSCs.

9.
Tree Physiol ; 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38281184

RESUMO

Stomata are pivotal in modulating water and carbon processes within plants. However, our understanding of the temporal dynamics of water- and carbon-related traits, as influenced by stomatal behavior, remains limited. Here, we explore how stomatal regulation behavior and water- and carbon-related traits vary with changing environments by examining the seasonal variations in these traits of the native tree species Schima superba in low subtropical China. In February, April, and July of 2022, a series of water- and carbon-related traits were measured in the leaves and stems. The results showed that S. superba exhibited isohydric behavior in February when the soil dried out and vapor pressure deficit (VPD) was lower but anisohydric behavior in April and July when the soil was wetter and VPD was higher. In February, NSC and their components increased, and a relatively large contribution of soluble sugars to the change in NSC was observed. In the branches and phloem, NSC and their components displayed a relatively high monthly variability, suggesting their role in maintaining carbon balance within the trees. Conversely, the NSC in the leaves demonstrated minimal monthly variability. The specific leaf area, as well as the concentration of nitrogen (N) and phosphorus (P) per unit mass in leaves and the cumulative stem water release, exhibited a decrease with a reduction in soil water potential. Interestingly, the hydraulic conductivity remained consistent throughout this process. Furthermore, the relatively low monthly growth rate observed in February could suggest a carbon sink limitation. In conclusion, the increased NSC and decreased water status of S. superba under relatively stressed soil conditions indicated a trade-off between water and carbon storage. Our findings enhance our comprehension of the dynamics and regulation of water and carbon status in forests, thereby advancing the development of plant carbon and water process models under climate change scenarios.

10.
Sci Rep ; 14(1): 74, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168759

RESUMO

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that can cause gastrointestinal ulcers by affecting dopamine levels. Therefore, MPTP has been considered a toxic substance that causes gastric ulcer disease in experimental animals. In this study, tree shrews were used as the animal model of gastric mucosa injury, and MPTP was intraperitoneally injected at a lower MPTP dosage 2 mg/kg/day for 13 weeks, while tree shrews were not injected as the control group. Under the light microscope, local congestion or diffuse bleeding points of gastric mucosa and multiple redness and swelling bleeding symptoms on the inner wall were observed in the treatment group, as well as immune cell infiltration was found in HE staining, but no such phenomenon was observed in the control group. In order to explore the molecular basis of changes in MPTP induced gastric mucosa injury, the transcriptome and proteome data of gastric mucosa were analyzed. We observed significant differences in mRNA and protein expression levels under the influence of MPTP. The changes in mRNA and proteins are related to increased immune infiltration, cellular processes and angiogenesis. More differentially expressed genes play a role in immune function, especially the candidate genes RPL4 and ANXA1 with significant signal and core role. There are also differentially expressed genes that play a role in mucosal injury and shedding, especially candidate genes GAST and DDC with certain signaling and corresponding functions. Understanding the factors and molecular basis that affect the expression of related genes is crucial for coping with Emotionality gastric mucosa injury disease and developing new treatment methods to establish the ability to resist disease.


Assuntos
Tupaia , Tupaiidae , Animais , Tupaia/genética , Musaranhos/genética , Proteômica , Análise de Sequência de RNA , RNA Mensageiro , China , Estômago
11.
Huan Jing Ke Xue ; 45(1): 489-495, 2024 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-38216498

RESUMO

The environmental effects of microplastics, which are considered a type of emerging contaminants, have attracted increasing concern due to their small size, large specific surface area, strong adsorption capacity, and low degradability. Microplastics can change soil properties and affect the migration ability of nutrients and pollutants in soil, but their effects on the leaching of soil nutrients and heavy metals have not been sufficiently studied. A soil column leaching experiment was conducted to explore the effects of polystyrene (PS) and polylactic acid (PLA) microplastics at different mass fractions (0%, 0.2%, and 2%) on the leaching of nutrients and cadmium under simulated rainfall scenarios. The results showed that increasing rainfall intensity enhanced the leaching of nutrients and cadmium from soil. During downpour conditions, 2% PS significantly increased the leaching of total nitrogen and the content of available phosphorus in soil and reduced the leaching of inorganic phosphorus and the content of ammonium nitrogen in the soil, whereas it increased the content of available potassium during heavy rain. By comparison, 2% PLA reduced the leaching of nitrate nitrogen during heavy rain and intense rainfall and decreased the content of ammonium nitrogen in soil during intense rainfall and downpour conditions and the content of total nitrogen in soil during downpours. In addition, 0.2% PLA significantly increased cadmium leaching during downpours. To conclude, the effects of microplastics on the leaching of nutrients and cadmium were dependent on the type and concentration of microplastics, as well as the rainfall level. Our findings showed that the microplastics derived from both nondegradable PS and biodegradable PLA could affect the leaching of nutrients and heavy metals from soil.

12.
Environ Pollut ; 341: 122933, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37977360

RESUMO

Owing to their dominant wastewater origin, bioavailability, and toxicity, the occurrence and behavior of organophosphate esters (OPEs) in aquatic systems have attracted considerable attention over the past two decades. Aquatic plants can accumulate and metabolize OPEs in water, thereby playing an important role in their behavior and fate in waterbodies. However, their uptake, translocation and transformation mechanisms in plants remain incompletely characterized. We investigated the accumulation and transformation of OPEs in water hyacinth (Eichhornia crassipes) through a series of hydroponic experiments using three representative OPEs, tris(2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPP). These OPEs can not only be adsorbed onto and enter plant roots via passive diffusion pathways, which are facilitated by anion channels and/or aquaporins, but also can return to the solution when concentration gradients exist. After entry, hydrophilic TCEP showed a dominant distribution in the cell sap, strong acropetal transportability, and rapid translocation rate, whereas hydrophobic TPP was mostly retained in the root cell wall and therefore demonstrated weak acropetal transportability; TBEP with moderate hydrophilicity remained in the middle. All these OPEs can be transformed into diesters, which presented higher proportions in the cell sap and therefore have stronger acropetal transferability than their parent OPEs. TCEP exhibits the lowest biodegradability, followed by TPP and TBEP. These OPEs exerted apparent effects on plant growth, photosynthesis, and the diversity and composition of the rhizosphere microbial community.


Assuntos
Eichhornia , Retardadores de Chama , Hidroponia , Ésteres/metabolismo , Organofosfatos/metabolismo
13.
Chemistry ; 30(13): e202303424, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38116816

RESUMO

High-efficacy recycling of spent lithium cobalt oxide (LiCoO2 ) batteries is one of the key tasks in realizing a global resource security strategy due to the rareness of lithium (Li) and cobalt (Co) resources. However, it is of great significance to develop the innovative recycle methods for spent LiCoO2 , simultaneously realizing the efficient recovery of valuable elements and the regeneration of high-performance LiCoO2 . Herein, a novel strategy of regenerating LiCoO2 cathode is proposed, which involves the preparation of micro-spherical aluminum (Al)-doped lithium-lacked precursor (Li2x Co1-x-y Al2/3y CO3, remarked as "PLCAC") via ammonium bicarbonate coprecipitation. The comprehensive conditions affecting particle growth kinetics, morphology and particle size the has been investigated in detail by physical characterizations and electrochemical measurements. And the optimized Al-doped LiCoO2 materials with high-density sphericity (LiCo1-z Alz O2 , remarked as "LCAO") shows a high initial specific capacity of 161 mAh g-1 at 0.1 C and excellent capacity retention of 99.5 % within 100 cycles at 1 C in the voltage range of 2.8 to 4.3 V. Our work provides valuable insights into the featured design of LiCoO2 precursors and cathode materials from spent LiCoO2 batteries, potentially guaranteeing the high-efficacy recycling and utilization of strategic resources.

14.
Water Res ; 249: 120982, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101048

RESUMO

Two-pass reverse osmosis (RO) process is prevailing in seawater desalination, but each process must consume considerable amounts of chemicals to secure product water quality. Caustic soda is used to raise the pH of the first-pass RO permeate (also the second-pass RO feed) to ensure adequate removal of boron in the subsequent second-pass RO, while antiscalants and disinfectants such as hypochlorite are added in the feed seawater for scaling and biofouling control of the first-pass RO membranes. Here, we report for the first time a flow-through electrochemically assisted reverse osmosis (FT-EARO) module system used in the first-pass RO, aiming to dramatically reduce or even eliminate chemical usage for the current RO desalination. This novel system integrated an electroconductive permeate carrier as cathode and an electroconductive feed spacer as anode on each side of the first-pass RO membrane. Upon applying an extremely low-energy (< 0.005 kWh/m3) electrical field, the FT-EARO module could (1) produce a permeate with pH >10 with no alkali dosage, ensuring sufficient boron removal in the second-pass RO, and (2) generate protons and low-concentration free chlorine near the membrane surface, potentially discouraging membrane scaling and biofouling while maintaining satisfactory desalination performance. The current study further elucidated the high scalability of this novel electrified high-pressure RO module design. The low-chemical manner of FT-EARO presents an attractive practical option towards green and sustainable seawater desalination.


Assuntos
Incrustação Biológica , Purificação da Água , Osmose , Boro , Membranas Artificiais , Água do Mar
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123750, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38113557

RESUMO

The simultaneous detection of fractional exhaled nitric oxide (FeNO) and end-tidal carbon dioxide (ETCO2) is of great importance for the distinguishing and diagnosis of asthma and chronic obstructive pulmonary disease (COPD), providing more comprehensive information on respiratory disorders. This work demonstrates a simultaneous ETCO2 and FeNO detection system based on quantum cascade laser absorption spectroscopy (QCLAS) technology was presented. The system employs wavelength modulation spectroscopy (WMS) technology and the Herriott multi-pass cell, achieving a detection limit of 2.82 ppb for nitric oxide (NO) and 0.05 % for carbon dioxide (CO2). Real-time exhalation measurements were performed on volunteers with varying ETCO2 and FeNO levels, and the results of the test can accurately distinguish whether the corresponding volunteer was healthy, had asthma or COPD. The effect of exhalation flow rate on the concentration of the two gases was explored. A range of expiratory flow rates were tested in the flow rate interval from 1 to 4 L/min, and there was always an inverse relationship between expiratory flow rate and FeNO concentration, but flow rate changes did not affect ETCO2 concentration. The results indicate that this detection system can simultaneously and effectively measure ETCO2 and FeNO concentrations in real-time.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Dióxido de Carbono , Teste da Fração de Óxido Nítrico Exalado , Lasers Semicondutores , Testes Respiratórios/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Asma/diagnóstico , Óxido Nítrico , Análise Espectral
16.
J Colloid Interface Sci ; 658: 540-552, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38128197

RESUMO

Design of engineered cells to target and deliver nanodrugs to the hard-to-reach regions has become an exciting research area. However, the limited penetration and retention of cell-based carriers in tumor tissue restricted their therapeutic efficiency. Inspired by the enhanced delivery behavior of mobile micro/nanomotors, herein, urease-powered platelet cell motors (PLT@Au@Urease) capable of active locomotion, tumor targeting, and radiosensitizers delivery were designed for boosting radiosensitization. The engineered platelet cell motors were constructed by in situ synthesis and loading of radiosensitizers gold nanoparticles in platelets, and then conjugation with urease as the engine. Under physiological concentration of urea, thrust around PLT@Au@Urease motors can be generated via the biocatalytic reactions of urease, leading to rapid tumor cell targeting and enhanced cellular uptake of radiosensitizers. Encouragingly, in comparison with engineered PLT without propulsion capability (PLT@Au), the self-propelled PLT@Au@Urease motors could significantly increase intracellular ROS level and exacerbate nuclear DNA damage induced by γ-radiation, resulting in a remarkably high sensitization enhancement rate (1.89) than that of PLT@Au (1.08). In vivo experiments with 4 T1-bearing mice demonstrated that PLT@Au@Urease in combination with radiation therapy possessed good antitumor performance. Such an intelligent cell motor would provide a promising approach to enhance radiosensitization and broaden the applications of cell motor-based delivery systems.


Assuntos
Nanopartículas Metálicas , Neoplasias , Animais , Camundongos , Ouro/farmacologia , Urease , Neoplasias/radioterapia
17.
Exp Ther Med ; 27(1): 15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38125352

RESUMO

The ovary is an essential reproductive organ in the female organism and its development seriously affects the physical and mental health of female patients. Ovarian diseases include ovarian cancer, premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Women should pay attention to the most effective treatments for this condition because it is one of the most prevalent gynecological illnesses at present. Extracellular vesicles (EVs), which are smaller vesicles that mediate the exchange of cellular information, include the three categories of exosomes, microvesicles and apoptotic bodies. They are able to transport proteins, RNA and other substances to adjacent or distal cells, thus allowing cellular and tissue homeostasis to be maintained. Numerous previous studies have revealed that EVs are crucial for the treatment of ovarian diseases. They are known to transport its contents to ovarian cancer cells as well as other ovarian cells such as granulosa cells, affecting the development of ovarian disease processes. Therefore, this extracellular vesicle may be involved as a target in the therapeutic process of ovarian disease and may have great potential in the treatment of ovarian disease. In the present review, the role of EVs in the development of three ovarian diseases, including ovarian cancer, POI and PCOS, was mainly summarizes. It is expected that this will provide some theoretical support for the treatment of ovarian disease.

18.
Lipids Health Dis ; 22(1): 221, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087267

RESUMO

BACKGROUND: The purpose of this pilot study was to investigate associations between fibrinogen/fibrin degradation products (FDP) to high density lipoprotein-cholesterol (HDL-C) ratio (FHR) of mothers and the risk of delivering large/small for gestational age (LGA/SGA) infants and to evaluate the predictive power of FHR on LGA/SGA. METHODS: This study retrospectively reviewed 11,657 consecutive women whose lipid profiles and FDP levels were investigated at the time of admission for delivery at a specialized hospital. The FHR was calculated, and perinatal outcomes, including clinical parameters, were analyzed. RESULTS: The prevalence of SGA was 9% (n = 1034), and that of LGA was 15% (n = 1806) in this cohort study. FHR was significantly lower in women who delivered SGA infants (4.0 ± 3.2 vs. 4.7 ± 3.3 mg/mmol, P < 0.01) and higher in women who delivered LGA infants (5.7 ± 3.8 vs. 4.7 ± 3.3 mg/mmol, P < 0.01) compared with those who delivered infants of normal size for their gestational age. Women in the top quartile for FHR (> 5.9 mg/mmol) had a 2.9-fold higher risk of delivering LGA infants [adjusted odds ratio (OR) = 2.9, P < 0.01] and a 47% lower risk of delivering SGA infants (adjusted OR = 0.47, P < 0.01) than those in the bottom quartile (< 2.7 mg/mmol). In addition, adding FHR to the conventional models significantly improved the area under the curve for the prediction of delivering LGA (0.725 vs. 0.739, P < 0.01) and SGA (0.717 vs. 0.727, P < 0.01) infants. CONCLUSION: These findings suggest that the FHR calculated in late pregnancy is an innovative predictor of delivering LGA and SGA infants. Combining FHR with perinatal parameters could thus enhance the predictive ability for predicting the delivery of LGA/SGA infants.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Doenças do Recém-Nascido , Recém-Nascido , Humanos , Gravidez , Feminino , HDL-Colesterol , Projetos Piloto , Recém-Nascido Grande para a Idade Gestacional , Idade Gestacional , Estudos de Coortes , Estudos Retrospectivos , Peso ao Nascer
19.
Rev Sci Instrum ; 94(4)2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38081275

RESUMO

Here, we report our recent progress in the design, fluid thermodynamics simulation, and high-power test of the2nd harmonic cavity for the China Spallation Neutron Source Phase II. A high-performance and large-size magnetic alloy (MA) core was developed as the load material for the radiofrequency cavity to achieve a high gradient of 40 kV/m. The water-cooling structure and cooling efficiency were studied and improved through numerical analysis and thermal experiments. The long-term stability of the cavity, especially the waterproofness of the MA cores with high heat load, was verified by high power tests.

20.
J Am Chem Soc ; 145(49): 26863-26870, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38048529

RESUMO

Spin-state transition is a vital factor that dominates catalytic processes, but unveiling its mechanism still faces the great challenge of the lack of catalyst model systems. Herein, we propose that the {Fe-Pt} Hofmann clathrates, whose dynamic spin-state transition of metal centers can be chemically manipulated through iodine treatment, can serve as model systems in the spin-related structural-catalytic relationship study. Taking the photocatalytic synthesis of H2O2 as the basic catalytic reaction, when the spin state of Fe(II) in the clathrate is high spin (HS), sacrificial agents are indispensable to the photosynthesis of H2O2 because only the photocatalytic oxygen reduction reaction (ORR) occurs; when it is low spin (LS), both the ORR and water oxidation reaction (WOR) can take place, enabling a high H2O2 photosynthesis rate of 66 000 µM g-1 h-1 under visible-light irradiation. In situ characterizations combined with density functional theory calculations confirmed that, compared with the HS-state counterpart, the LS state can induce strong charge transfer between the LS Fe(II) and the iodide-coordinating Pt(IV) in the polymer and reduce the energy barriers for both the ORR and WOR processes, dominating the on-off switching upon the photosynthesis of H2O2 in O2-saturated water. What's more, the one-pot tandem reactions were conducted to utilize the synthesized H2O2 for transforming the low-value-added sodium alkenesulfonates into value-added bromohydrin products with decent conversion rates. This work provides a pioneering investigation into on-off switching the photocatalytic overall reaction through manipulating the metallic spin-state transition in spin-crossover systems.

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