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1.
Angew Chem Int Ed Engl ; : e202410710, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949854

RESUMEN

Metallo-supramolecular cages have garnered tremendous attention for their diverse yet molecular-level precision structures. However, physical properties of these supramolecular ensembles, which are of potential significance in molecular electronics, remain largely unexplored. We herein constructed a series of octahedral metallo-cages and cage-fullerene complexes with notably enhanced structural stability. As such, we could systematically evaluate the electrical conductivity of these ensembles at both single-molecule level and aggregated bulk state (as well-defined films). Our findings reveal that counteranions and fullerene guests play a pivotal role in determining the electrical conductivity of aggregated state, while such effects are less significant for single-molecule conductance. Both counteranions and fullerenes effectively tune the electronic structures and packing density of metallo-supramolecular assemblies, and facilitate efficient charge transfer between the cage hosts and fullerenes, resulting in a notable one order of magnitude increase in electrical conductivity of the aggregated state.

2.
Cell Rep ; 43(7): 114391, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38923459

RESUMEN

Inhibition of nucleic acid targets is mediated by Argonaute (Ago) proteins guided by RNA or DNA. Although the mechanisms underpinning the functions of eukaryotic and "long" prokaryotic Ago proteins (pAgos) are well understood, those for short pAgos remain enigmatic. Here, we determine two cryoelectron microscopy structures of short pAgos in association with the NADase-domain-containing protein Sir2-APAZ from Geobacter sulfurreducens (GsSir2/Ago): the guide RNA-target DNA-loaded GsSir2/Ago quaternary complex (2.58 Å) and the dimer of the quaternary complex (2.93Å). These structures show that the nucleic acid binding causes profound conformational changes that result in disorder or partial dissociation of the Sir2 domain, suggesting that it adopts a NADase-active conformation. Subsequently, two RNA-/DNA-loaded GsSir2/Ago complexes form a dimer through their MID domains, further enhancing NADase activity through synergistic effects. The findings provide a structural basis for short-pAgo-mediated defense against invading nucleic acids.

3.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38888405

RESUMEN

Addressing the challenge of limited accuracy and real-time performance in intelligent guided vehicle (IGV) image recognition and detection, typically reliant on traditional feature extraction approaches. This study delves into a visual navigation detection method using an improved You Only Look Once (YOLO) model-simplified YOLOv2 (SYOLOv2) to satisfy the complex operating conditions of the port and the limitations of IGV hardware computing. The convolutional neural network structure of YOLOv2 is refined to ensure adaptability to varying weather conditions using a single image. Preprocessing of images involves Contrast Limited Adaptive Histogram Equalization (CLAHE), while an adaptive image resolution detection model, contingent upon vehicle speed, is proposed to enhance the detection performance. The comparative experiments conducted on image datasets reflective of actual road conditions and weather conditions demonstrate notable enhancements in accuracy and frames transmitted per second compared to conventional methods. These improvements signify the efficacy of the proposed approach in meeting the stringent requirements for real-time detection on IGV platforms.

4.
Imeta ; 3(2): e166, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38882497

RESUMEN

Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

6.
J Anesth ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829406

RESUMEN

PURPOSE: Thoracic epidural anesthesia (TEA) is often used for analgesia after thoracic surgery. Erector spinae plane block (ESPB) has been proposed to provide adequate analgesia. We hypothesized that ESPB would be noninferior to TEA as a part of multimodal analgesia in pediatric patients undergoing the Nuss procedure. METHODS: Patients aged 7-18 years and scheduled for the Nuss procedure were randomly allocated to receive bilateral single-shot ESPB or TEA and a multimodal analgesic regimen including parent-controlled intravenous analgesia (PCIA). At 6 h, 12 h, 18 h, and 24 h postoperatively, pain was evaluated using the numeric rating scale (NRS) and opioid consumption was assessed by counting the number of PCIA boluses. The joint primary outcomes were the average pain score and opioid consumption at 24 h after surgery. The secondary outcomes were the NRS scores and the number of opioid boluses administered at different postoperative time points, adverse events, and recovery quality. RESULTS: Three hundred patients underwent randomization, and 286 received ESPB (147 patients) or TEA (139 patients). At 24 h postoperatively, ESPB was noninferior to TEA in terms of the average NRS score (mean difference, - 0.1, 95% confidence interval [CI], - 0.3-0.1, margin = 1, P for noninferiority < 0.001) and the number of opioid boluses administered (mean difference, - 1.1, 95% CI, - 2.8-0.6, margin = 7, P for noninferiority < 0.001). Adverse events and patient recovery were comparable between groups. CONCLUSIONS: The results demonstrate that combined with a multimodal analgesia, ESPB provides noninferior analgesia compared to TEA with respect to pain score and opioid consumption among pediatric patients undergoing the Nuss procedure.

7.
Front Immunol ; 15: 1407632, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38840913

RESUMEN

Background: Sintilimab plus chemotherapy has proven effective as a combination immunotherapy for patients with advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC). A multi-center study conducted in China revealed a median progression-free survival (PFS) of 7.1 months. However, the prediction of response duration to this immunotherapy has not been thoroughly investigated. Additionally, the potential of baseline laboratory features in predicting PFS remains largely unexplored. Therefore, we developed an interpretable machine learning (ML) framework, iPFS-SC, aimed at predicting PFS using baseline (pre-treatment) laboratory features and providing interpretations of the predictions. Materials and methods: A cohort of 146 patients with advanced GC/GEJC, along with their baseline laboratory features, was included in the iPFS-SC framework. Through a forward feature selection process, predictive baseline features were identified, and four ML algorithms were developed to categorize PFS duration based on a threshold of 7.1 months. Furthermore, we employed explainable artificial intelligence (XAI) methodologies to elucidate the relationship between features and model predictions. Results: The findings demonstrated that LightGBM achieved an accuracy of 0.70 in predicting PFS for advanced GC/GEJC patients. Furthermore, an F1-score of 0.77 was attained for identifying patients with PFS durations shorter than 7.1 months. Through the feature selection process, we identified 11 predictive features. Additionally, our framework facilitated the discovery of relationships between laboratory features and PFS. Conclusion: A ML-based framework was developed to predict Sintilimab plus chemotherapy response duration with high accuracy. The suggested predictive features are easily accessible through routine laboratory tests. Furthermore, XAI techniques offer comprehensive explanations, both at the global and individual level, regarding PFS predictions. This framework enables patients to better understand their treatment plans, while clinicians can customize therapeutic approaches based on the explanations provided by the model.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Unión Esofagogástrica , Aprendizaje Automático , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/inmunología , Masculino , Unión Esofagogástrica/patología , Femenino , Persona de Mediana Edad , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Adenocarcinoma/tratamiento farmacológico , Supervivencia sin Progresión , Resultado del Tratamiento , Anciano de 80 o más Años
8.
PLoS Pathog ; 20(5): e1012034, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38814986

RESUMEN

Ilarviruses are a relatively understudied but important group of plant RNA viruses that includes a number of crop pathogens. Their genomes comprise three RNA segments encoding two replicase subunits, movement protein, coat protein (CP), and (in some ilarvirus subgroups) a protein that suppresses RNA silencing. Here we report that, in many ilarviruses, RNA3 encodes an additional protein (termed CP-RT) as a result of ribosomal readthrough of the CP stop codon into a short downstream readthrough (RT) ORF. Using asparagus virus 2 as a model, we find that CP-RT is expressed in planta where it functions as a weak suppressor of RNA silencing. CP-RT expression is essential for persistent systemic infection in leaves and shoot apical meristem. CP-RT function is dependent on a putative zinc-finger motif within RT. Replacing the asparagus virus 2 RT with the RT of an ilarvirus from a different subgroup restored the ability to establish persistent infection. These findings open up a new avenue for research on ilarvirus silencing suppression, persistent meristem invasion and vertical transmission.


Asunto(s)
Ilarvirus , Enfermedades de las Plantas , Interferencia de ARN , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Codón de Terminación/genética , Ilarvirus/genética , Nicotiana/virología , Nicotiana/genética , Nicotiana/metabolismo , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , ARN Viral/genética , ARN Viral/metabolismo , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Proteínas Virales/genética , Proteínas Virales/metabolismo
9.
Sci Data ; 11(1): 493, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744841

RESUMEN

With the development of Non-Intrusive Load Monitoring (NILM), it has become feasible to perform device identification, energy consumption decomposition, and load switching detection using Deep Learning (DL) methods. Similar to other machine learning problems, the research and validation of NILM necessitate substantial data support. Moreover, different regions exhibit distinct characteristics in their electricity environments. Therefore, there is a need to provide open datasets tailored to different regions. In this paper, we introduce the Transient Dataset of Household Appliances with Intensive Switching Events (TDHA25). This dataset comprises switch instantaneous data from 10 typical household appliances in China. The TDHA dataset features a high sampling rate, accurate labelling, and realistic representation of actual appliance start-up waveforms. Additionally, appliance switching is achieved through precise control of relay switches, thus mitigating interference caused by mechanical switches. By furnishing such a dataset, we aim not only to enhance the recognition accuracy of existing NILM algorithms but also to facilitate the application of NILM algorithms in regions sharing similar electricity consumption characteristics to those of China.

10.
Biosens Bioelectron ; 256: 116278, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38608497

RESUMEN

The DNA-based logic circuit, constructed to mimic biochemical reaction networks, is highly significant in detecting biomarkers at the molecular level. The differences in the expression levels of microRNAs (miRNAs) within different types of cells provide hope for distinguishing cell subtypes. However, reliance on a single miRNA often leads to unreliable results. Herein, we constructed an enzyme-triggered cascade logic circuit based on the AND gate, which is capable of generating corresponding fluorescence signals in the presence of target miRNAs. The introduction of apurinic/apyrimidinic (AP) sites effectively reduces the likelihood of false signal generation. Amplification of the fluorescence signal relies on the catalytic hairpin assembly and the repetitive reuse of the multicomponent nucleic acid enzyme (MNAzyme). We demonstrated that the logic circuit can not only distinguish cancer cells from normal cells but also identify different types of cancer cells. The programmability of the logic circuits and the simplicity of the assay system allow us to modify the functional sequences to recognize different types of biomarkers, thus providing a reference for the identification of various cell subtypes.


Asunto(s)
Técnicas Biosensibles , ADN , MicroARNs , Humanos , Técnicas Biosensibles/métodos , MicroARNs/genética , ADN/genética , ADN/química , Neoplasias/genética , Computadores Moleculares , Línea Celular Tumoral , Biomarcadores de Tumor/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética
11.
Int J Mol Med ; 53(6)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38606498

RESUMEN

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Figs. 2C and 4B were strikingly similar to data appearing in different form in a paper by different authors at a different research institute that had already been submitted for publication. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 2078­2088, 2020; DOI: 10.3892/ijmm.2020.4749].

12.
Theor Appl Genet ; 137(5): 113, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38678511

RESUMEN

KEY MESSAGE: The rust resistance genes Lr53 and Yr35 were introgressed into bread wheat from Aegilops longissima or Aegilops sharonensis or their S-genome containing species and mapped to the telomeric region of chromosome arm 6BS. Wheat leaf and stripe rusts are damaging fungal diseases of wheat worldwide. Breeding for resistance is a sustainable approach to control these two foliar diseases. In this study, we used SNP analysis, sequence comparisons, and cytogenetic assays to determine that the chromosomal segment carrying Lr53 and Yr35 was originated from Ae.longissima or Ae. sharonensis or their derived species. In seedling tests, Lr53 conferred strong resistance against all five Chinese Pt races tested, and Yr35 showed effectiveness against Pst race CYR34 but susceptibility to race CYR32. Using a large population (3892 recombinant gametes) derived from plants homozygous for the ph1b mutation obtained from the cross 98M71 × CSph1b, both Lr53 and Yr35 were successfully mapped to a 6.03-Mb telomeric region of chromosome arm 6BS in the Chinese Spring reference genome v1.1. Co-segregation between Lr53 and Yr35 was observed within this large mapping population. Within the candidate region, several nucleotide-binding leucine-rich repeat genes and protein kinases were identified as candidate genes. Marker pku6B3127 was completely linked to both genes and accurately predicted the absence or presence of alien segment harboring Lr53 and Yr35 in 87 tetraploid and 149 hexaploid wheat genotypes tested. We developed a line with a smaller alien segment (< 6.03 Mb) to reduce any potential linkage drag and demonstrated that it conferred resistance levels similar to those of the original donor parent 98M71. The newly developed introgression line and closely linked PCR markers will accelerate the deployment of Lr53 and Yr35 in wheat breeding programs.


Asunto(s)
Aegilops , Mapeo Cromosómico , Resistencia a la Enfermedad , Genes de Plantas , Puccinia , Aegilops/genética , Aegilops/microbiología , Cromosomas de las Plantas/genética , Resistencia a la Enfermedad/genética , Introgresión Genética , Ligamiento Genético , Marcadores Genéticos , Fitomejoramiento , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Polimorfismo de Nucleótido Simple , Puccinia/fisiología , Triticum/genética , Triticum/microbiología
13.
Anal Chem ; 96(10): 4213-4223, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38427460

RESUMEN

The accurate quantification of cancer-derived exosomes, which are emerging as promising noninvasive biomarkers for liquid biopsies in the early diagnosis of cancer, is becoming increasingly imperative. In our work, we developed a magnetically controlled photothermal, colorimetric, and fluorescence trimode aptasensor for human gastric cancer cell (SGC-7901)-derived exosomes. This sensor relied on CP/Mn-PBA DSNBs nanocomposites, created by decorating copper peroxide (CP) nanodots on polyethyleneimine-modified manganese-containing Prussian blue analogues double-shelled nanoboxes (PEI-Mn-PBA DSNBs). Through self-assembly, we attached CD63 aptamer-labeled CP/Mn-PBA DSNBs (Apt-CP/Mn-PBA DSNBs) to complementary DNA-labeled magnetic beads (cDNA-MB). During exosome incubation, these aptamers preferentially formed complexes with exosomes, and we efficiently removed the released CP/Mn-PBA DSNBs by using magnetic separation. The CP/Mn-PBA DSNBs exhibited high photoreactivity and photothermal conversion efficiency under near-infrared (NIR) light, leading to temperature variations under 808 nm irradiation, correlating with different exosome concentrations. Additionally, colorimetric detection was achieved by monitoring the color change in a 3,3',5,5'-tetramethylbenzidine (TMB) system, facilitated by PEI modification, NIR-enhanced peroxidase-like activity of CP/Mn-PBA DSNBs and their capacity to generate Cu2+ and H2O2 under acidic conditions. Moreover, in the presence of Cu2+ and ascorbic acid (AA), DNA sequences could form dsDNA-templated copper nanoparticles (CuNPs), which emitted strong fluorescence at around 575 nm. Increasing exosome concentrations correlated with decreases in temperature, absorbance, and fluorescence intensity. This trimode biosensor demonstrated satisfactory ability in differentiating gastric cancer patients from healthy individuals using human serum samples.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Exosomas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Cobre , Peróxidos , Peróxido de Hidrógeno , Colorimetría
14.
J Am Chem Soc ; 146(12): 8528-8535, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38497738

RESUMEN

Surface waves are known for their mechanical role in coastal processes that influence the weather and climate. However, their chemical impact, particularly on the transformation of pyrogenic carbon, is poorly understood. Pyrogenic carbon is generally assumed to show negligible postformational alteration of its stable carbon isotope composition. Here we present an electrochemical interaction of pyrogenic carbon with the sprayed seawater microdroplets resulting from wave breaking, driven by the galvanic coupling between the microdroplet water-carbon interfaces and the microdroplet water-vapor interfaces. This enables refractory pyrogenic carbon to rapidly degrade via the oxygenation and mineralization reaction, which makes it ∼2.6‰ enriched in 13C, far exceeding the generally assumed postformation alteration values (<0.5‰) of pyrogenic carbon. The unique chemical dynamics of seawater microdroplets provide new insights into the discrepancy in carbon isotope signatures between riverine and marine black carbon, emphasizing the potential of coastal oceans for carbon sequestration in the global carbon cycle.

15.
Anal Chem ; 96(14): 5686-5693, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38551337

RESUMEN

Vacuum ultraviolet photoionization (VUV-PI) is a soft ionization technique that operates under pressures ranging from vacuum to ambient pressure. VUV-PI has played an essential role in direct sampling mass spectrometry. In this study, new ionization processes initiated by photoelectrons have been studied through the inclusion of a radio frequency (RF) electric field at different pressures. After deducting the contribution of single photoionization (SPI), the signal intensity of 1 ppmv toluene (C7H8+) in Ar was approximately 5-fold higher than that in N2. Mixed gases with different ionization energies (IEs) and excitation energies (EEs) were further investigated to reveal that metastable species were involved in the enhancement process. Reactant ions were produced by photoelectron impact ionization (PEI), which further triggered ion-molecule reactions, i.e., chemical ionization (CI). Metastable species were produced by photoelectron impact excitation (PEE), which further triggered Penning ionization (PenI). Analytes with IEs above 10.6 eV, such as CO2 (IE = 13.78 eV) and CHCl3 (IE = 11.37 eV), could be sensitively ionized by PenI with a sensitivity comparable to SPI. Except for the contribution of SPI, the dominant ionization process was switched from PEI-CI to PenI when the pressure was elevated from 50 to 500 Pa, as the electron energy gradually decreased and was only able to produce metastable states based on the kinetic energy balance equation of electrons. The conversion processes and conditions from PEI-CI to PenI will provide novel insights to develop new selective and sensitive VUV-PI sources and understand the ionization mechanism in other discharge ionization sources.

16.
Environ Pollut ; 347: 123742, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38460586

RESUMEN

Di (2-ethylhexyl) phthalate (DEHP), identified as an endocrine-disrupting chemical, is associated with reproductive toxicity. This association is particularly noteworthy in newborns with incompletely developed metabolic functions, as exposure to DEHP can induce enduring damage to the reproductive system, potentially influencing adult reproductive health. In this study, we continuously administered 40 µg/kg and 80 µg/kg DEHP to postnatal day 5 (PD5) mice for ten days to simulate low and high doses of DEHP exposure during infancy. Utilizing single-cell RNA sequencing (scRNA-seq), our analysis revealed that varying concentrations of DEHP exposure during infancy induced distinct DNA damage response characteristics in testicular Undifferentiated spermatogonia (Undiff SPG). Specifically, DNA damage triggered mitochondrial dysfunction, leading to acetyl-CoA content alterations. Subsequently, this disruption caused aberrations in histone acetylation patterns, ultimately resulting in apoptosis of Undiff SPG in the 40 µg/kg DEHP group and autophagy in the 80 µg/kg DEHP group. Furthermore, we found that DEHP exposure impacts the development and functionality of Sertoli and Leydig cells through the focal adhesion and PPAR signaling pathways, respectively. We also revealed that Leydig cells regulate the metabolic environment of Undiff SPG via Ptn-Sdc4 and Mdk-Sdc4 after DEHP exposure. Finally, our study provided pioneering evidence that disruptions in testicular homeostasis induced by DEHP exposure during infancy endure into adulthood. In summary, this study elucidates the molecular mechanisms through which DEHP exposure during infancy influences the development of testicular cell populations.


Asunto(s)
Dietilhexil Ftalato , Ácidos Ftálicos , Espermatogonias , Masculino , Ratones , Animales , Dietilhexil Ftalato/metabolismo , Histonas/metabolismo , Acetilación , Testículo/metabolismo , Homeostasis
17.
J Am Soc Mass Spectrom ; 35(3): 575-581, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321587

RESUMEN

A novel ion optical optimization method for planar multireflection time-of-flight mass spectrometry (MR-TOFMS) is introduced in this paper. The multiparameters of the gridless mirror model, including geometric and voltage parameters, are automatically optimized using a self-made program created in SIMION 8.1. Combining with the hill climbing algorithm and parallel computing technique, this method substantially enhances optimization efficiency and accuracy. The fitting results demonstrated that the ion optical performance of the gridless mirror reached up to fourth-order isochronicity with respect to the energy spread and third-order isochronicity with respect to the spatial and angular spread. As a result, the gridless mirror model achieved an aberration limit resolution of 1.7 million under realistic ion beam conditions. Due to constraints of periodic lenses, the aberration limit resolution of the planar MR-TOFMS was optimized to 600k. These results indicate that the hill climbing algorithm is an effective method to search the optimal solutions in complex ion optical systems.

18.
Heliyon ; 10(3): e25675, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38356598

RESUMEN

How to use appropriate policy measures to intervene industrial symbiosis is valuable in theory but still lacks exploration. This paper discusses the effect of environmental taxation on industrial symbiosis networks. Firstly, the formation mechanism of industrial symbiotic network is analysed with the idea of agent-based modelling. Then, a simulation model was built to simulate the emergence process of industrial symbiosis networks. On this basis, the influence of environmental taxation on the structure and performance of the industrial symbiosis networks is explored. The results show that when the intensity of environmental tax is low, the industrial symbiotic network has the structural characteristics of random network. With the increase of environmental tax intensity, the cyclic ordering of network structure is gradually enhanced. The collection of environmental tax will not only reduce pollution, but also reduce the economic output of the network and reduce enterprise income to a greater extent. Finally, some relevant suggestions for the government to formulate environmental tax policy are provided based on the results.

19.
Anal Chem ; 96(10): 4120-4128, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38412037

RESUMEN

Efficient and accurate acquisition of cellular biomolecular information is crucial for exploring cell fate, achieving early diagnosis, and the effective treatment of various diseases. However, current DNA biosensors are mostly limited to single-target detection, with few complex logic circuits for comprehensive analysis of three or more targets. Herein, we designed a sea anemone-like DNA nanomachine based on DNA strand displacement composed of three logic gates (YES-AND-YES) and delivered into the cells using gold nano bipyramid carriers. The AND gate activation depends on the trigger chain released by upstream DNA strand displacement reactions, while the output signal relies on the downstream DNAzyme structure. Under the influence of diverse inputs (including enzymes, miRNA, and metal ions), the interconnected logic gates simultaneously perform logical analysis on multiple targets, generating a unique output signal in the YES/NO format. This sensor can successfully distinguish healthy cells from tumor cells and can be further used for the diagnosis of different tumor cells, providing a promising platform for accurate cell-type identification.


Asunto(s)
ADN Catalítico , Anémonas de Mar , Animales , Anémonas de Mar/genética , ADN/química , ADN Catalítico/química , Lógica , Oro , Computadores Moleculares
20.
Eur J Pharmacol ; 965: 176331, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38220140

RESUMEN

Inflammatory bowel disease (IBD) is a condition characterized by inflammation in the gastrointestinal tract. Reducing intestinal inflammation is a promising approach for treating IBD. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, a critical component of the innate immune system, is implicated in the pathogenesis of IBD. Therefore, inhibiting NLRP3 inflammasome activation is a potential therapeutic strategy for IBD. In this study, we investigated the effects of the interleukin-5 (IL-5) receptor antagonist YM-90709 on dextran sulfate sodium-induced experimental colitis in mice. We found that YM-90709 reduced the expressions of IL-1ß and caspase-1 p20 in the colon and ameliorated colitis. Furthermore, we identified YM-90709 as an effective agent for inhibiting NLRP3 inflammasome activation. Knockdown of IL-5 receptor or using an inhibitor of STAT5, a key transcription factor downstream of the IL-5/IL-5 receptor signal pathway, also reduced NLRP3 inflammasome-dependent IL-1ß release and ASC speck formation. Our study is the first to demonstrate that the NLRP3 inflammasome may be a downstream signal of IL-5/IL-5 receptor and that YM-90709 protects against IBD by inhibiting IL-5 receptor. These findings suggest a new strategy for regulating intestinal inflammation and managing IBD.


Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sulfato de Dextran/toxicidad , Receptores de Interleucina-5 , Interleucina-5/efectos adversos , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Inflamación , Caspasa 1/metabolismo , Interleucina-1beta/metabolismo , Ratones Endogámicos C57BL
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