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1.
Eur J Med Chem ; 275: 116622, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38959727

RESUMEN

Blockade of the programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is an attractive strategy for immunotherapy, but the clinical application of small molecule PD-1/PD-L1 inhibitors remains unclear. In this work, based on BMS-202 and our previous work YLW-106, a series of compounds with benzo[d]isothiazol structure as scaffold were designed and synthesized. Their inhibitory activity against PD-1/PD-L1 interaction was evaluated by a homogeneous time-resolved fluorescence (HTRF) assay. Among them, LLW-018 (27c) exhibited the most potent inhibitory activity with an IC50 value of 2.61 nM. The cellular level assays demonstrated that LLW-018 exhibited low cytotoxicity against Jurkat T and MDA-MB-231. Further cell-based PD-1/PD-L1 blockade bioassays based on PD-1 NFAT-Luc Jurkat cells and PD-L1 TCR Activator CHO cells indicated that LLW-018 could interrupt PD-1/PD-L1 interaction with an IC50 value of 0.88 µM. Multi-computational methods, including molecular docking, molecular dynamics, MM/GBSA, MM/PBSA, Metadynamics, and QM/MM MD were utilized on PD-L1 dimer complexes, which revealed the binding modes and dissociation process of LLW-018 and C2-symmetric small molecule inhibitor LCH1307. These results suggested that LLW-018 exhibited promising potency as a PD-1/PD-L1 inhibitor for further investigation.


Asunto(s)
Antígeno B7-H1 , Diseño de Fármacos , Receptor de Muerte Celular Programada 1 , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Relación Estructura-Actividad , Estructura Molecular , Relación Dosis-Respuesta a Droga , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/síntesis química , Células Jurkat , Simulación del Acoplamiento Molecular , Tiazoles/farmacología , Tiazoles/química , Tiazoles/síntesis química , Animales , Benzotiazoles/farmacología , Benzotiazoles/química , Benzotiazoles/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química
2.
J Mol Neurosci ; 74(3): 59, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890235

RESUMEN

Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by which is still unclear. Extracellular regulated protein kinases (ERK) maintain neuronal survival, growth, and regulation of synaptic plasticity by phosphorylating specific transcription factors to regulate expression of brain-derived neurotrophic factor (BDNF). Dual-specific phosphatase 1 (DUSP1) and DUSP6 dephosphorylate tyrosine and serine/threonine residues in ERK1/2 to inactivate them. To investigate the molecular mechanism by which alcohol affects memory and emotion, a chronic intermittent alcohol exposure (CIAE) model was established. The results demonstrated that mice in the CIAE group developed short-term recognition memory impairment and anxiety-like behavior; meanwhile, the expression of DUSP1 and DUSP66 in the mPFC was increased, while the levels of p-ERK and BDNF were decreased. Micro-injection of DUSP1/6 inhibitor BCI into the medial prefrontal cortex (mPFC) restored the dendritic morphology by reversing the activity of ERK-BDNF and ultimately improved cognitive and emotional impairment caused by CIAE. These findings indicate that CIAE inhibits ERK-BDNF by increasing DUSP1/6 in the mPFC that may be associated with cognitive and emotional deficits. Consequently, DUSP1 and DUSP6 appear to be potential targets for the treatment of alcoholic brain disorders.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Fosfatasa 1 de Especificidad Dual , Etanol , Ratones Endogámicos C57BL , Corteza Prefrontal , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Ratones , Masculino , Fosfatasa 1 de Especificidad Dual/metabolismo , Fosfatasa 1 de Especificidad Dual/genética , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Etanol/toxicidad , Etanol/farmacología , Fosfatasa 6 de Especificidad Dual/metabolismo , Fosfatasa 6 de Especificidad Dual/genética , Aminoacetonitrilo/análogos & derivados , Aminoacetonitrilo/farmacología , Aminoacetonitrilo/uso terapéutico , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Sistema de Señalización de MAP Quinasas
3.
Am J Clin Nutr ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38942116

RESUMEN

BACKGROUND: Although high ultra-processed food (UPF) consumption has been linked with increased mortality risk in the general population, whether UPFs harm participants with a history of cancer remains unclear. OBJECTIVE: This study aimed to evaluate the association of UPF consumption with mortality among participants with a history of cancer. METHODS: Prospective cohort analysis was conducted on 13640 participants with a history of cancer from the UK Biobank. UPFs were defined by the Nova classification. UPF consumption was calculated as the weight proportion of UPFs in the total food consumption. Cox proportional hazard models were used to assess the association between UPF consumption and mortality among participants with a history of cancer. RESULTS: The median UPF consumption was 29.25% (interquartile range: 19.46%-40.62%) for males and 25.81% (interquartile range: 16.61%-36.35%) for females in the total diet among participants with a history of cancer. During a median follow-up of 10.77 years, 1611 deaths were documented. Multivariable-adjusted hazard ratios (95% confidence intervals) among participants in the highest quartile of UPF consumption relative to the lowest were 1.17 (1.02, 1.35) for all-cause mortality and 1.22 (1.03, 1.44) for cancer mortality. CONCLUSIONS: Higher UPF consumption after the diagnosis among participants with a history of cancer is associated with higher risk of mortality.

4.
Materials (Basel) ; 17(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38930224

RESUMEN

Unforeseen failures in girth welds present a significant challenge for the pipeline industry. This study utilizes 3D Digital Image Correlation (DIC) assisted cross-weld tensile testing to analyze the strain response of high-strength thick-walled pipelines, providing essential insights into the strain migration and fracture mechanisms specific to girth welds. The results reveal that the welding process significantly affects the mechanical distribution within the girth weld. The tested Shielded Metal Arc Welded (SMAW-ed) pipe exhibited undermatched girth welds due to high heat input, while Gas Metal Arc Welding (GMAW) introduced a narrower weld and Heat-Affected Zone (HAZ) with higher hardness than the base metal, indicative of overmatched girth welds. Strain migration, resulting from a combination of metallurgical heterogeneous materials and geometrical reinforcement strengthening, progressed from the softer HAZ to the base metal in the SMAW-ed sample with reinforcement, ultimately leading to fracture in the base metal. In contrast, the GMAW-ed sample shows no strain migration. Reinforcement significantly improves the tensile strength of girth welds and effectively prevents failure in the weld region. Sufficient reinforcement is crucial for minimizing the risk of failure in critical areas such as the weld metal and HAZ, particularly in SMAW-ed pipes.

5.
Mol Biol Rep ; 51(1): 776, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904879

RESUMEN

BACKGROUND: Traumatic hemorrhagic shock (THS) is a complex pathophysiological process resulting in multiple organ failure. Intestinal barrier dysfunction is one of the mechanisms implicated in multiple organ failure. The present study aimed to explore the regulatory role of mitogen-activated protein kinase kinase 3 (MKK3) in THS-induced intestinal injury and to elucidate its potential mechanism. METHODS: Rats were subjected to trauma and hemorrhage to establish a THS animal model. MKK3-targeted lentiviral vectors were injected via the tail vein 72 h before modeling. Twelve hours post-modeling, the mean arterial pressure (MAP) and heart rate (HR) were monitored, and histological injury to the intestine was assessed via H&E staining and transmission electron microscopy. Mitochondrial function and mitochondrial reactive oxygen species (ROS) were evaluated. IEC-6 cells were exposed to hypoxia to mimic intestinal injury following THS in vitro. RESULTS: MKK3 deficiency alleviated intestinal injury and restored mitochondrial function in intestinal tissues from THS-induced rats and hypoxia-treated IEC-6 cells. In addition, MKK3 deficiency promoted Sirt1/PGC-1α-mediated mitochondrial biogenesis and restricted Pink1/Parkin-mediated mitophagy in the injured intestine and IEC-6 cells. Furthermore, the protective effect of MKK3 knockdown against hypoxia-induced mitochondrial damage was strengthened upon simultaneous LC3B/Pink1/Parkin knockdown or weakened upon simultaneous Sirt1 knockdown. CONCLUSION: MKK3 deficiency protected against intestinal injury induced by THS by promoting mitochondrial biogenesis and restricting excessive mitophagy.


Asunto(s)
Intestinos , MAP Quinasa Quinasa 3 , Mitocondrias , Especies Reactivas de Oxígeno , Choque Hemorrágico , Animales , Masculino , Ratas , Línea Celular , Modelos Animales de Enfermedad , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Intestinos/patología , MAP Quinasa Quinasa 3/metabolismo , MAP Quinasa Quinasa 3/genética , Mitocondrias/metabolismo , Mitofagia , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Choque Hemorrágico/complicaciones , Choque Hemorrágico/metabolismo , Choque Hemorrágico/genética , Choque Traumático/metabolismo , Choque Traumático/complicaciones , Choque Traumático/genética
6.
J Am Chem Soc ; 146(27): 18556-18564, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38943576

RESUMEN

Manipulating single electrons at the atomic scale is vital for mastering complex surface processes governed by the transfer of individual electrons. Polarons, composed of electrons stabilized by electron-phonon coupling, offer a pivotal medium for such manipulation. Here, using scanning tunneling microscopy and spectroscopy (STM/STS) and density functional theory (DFT) calculations, we report the identification and manipulation of a new type of polaron, dubbed van der Waals (vdW) polaron, within mono- to trilayer ultrathin films composed of Sb2O3 molecules that are bonded via vdW attractions. The Sb2O3 films were grown on a graphene-covered SiC(0001) substrate via molecular beam epitaxy. Unlike prior molecular polarons, STM imaging observed polarons at the interstitial sites of the molecular film, presenting unique electronic states and localized band bending. DFT calculations revealed the lowest conduction band as an intermolecular bonding state, capable of ensnaring an extra electron through locally diminished intermolecular distances, thereby forming an intermolecular vdW polaron. We also demonstrated the ability to generate, move, and erase such vdW polarons using an STM tip. Our work uncovers a new type of polaron stabilized by coupling with intermolecular vibrations where vdW interactions dominate, paving the way for designing atomic-scale electron transfer processes and enabling precise tailoring of electron-related properties and functionalities.

7.
mSystems ; : e0045924, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38934544

RESUMEN

Gut microbiota of the bumblebee is critical as it modulates the health and fitness of the host. However, the mechanisms underlying the formation and maintenance of the diversity of bumblebee gut bacteria over a long period of evolution have yet to be elucidated. In particular, the gut bacterial diversity and community assembly processes of Bombus pyrosoma across the Chinese border remain unclear. In this study, we systematically carried out unprecedented sampling of 513 workers of the species Bombus pyrosoma across the Chinese landscape and used full-length 16S rRNA gene sequencing to examine their gut microbiota diversity and biogeography. The gut microbiota composition and community structure of Bombus pyrosoma from different geographical locations were diverse. On the whole, the gut bacteria Gilliamella and Snodgrassella are dominant in bumblebees, but opportunistic pathogens Serratia and Pseudomonas are dominant in some sampling sites such as Hb15, Gs1, Gs45, Qhs15, and Ssx35. All or part of environmental factors such as latitude, annual mean temperature, elevation, human footprint, population density, and annual precipitation can affect the alpha diversity and community structure of gut bacteria. Further analysis showed that the assembly and shift of bumblebee gut bacterial communities under geographical variation were mainly driven by the stochastic drift of the neutral process rather than by variable selection of niche differentiation. In conclusion, our unprecedented sampling uncovers bumblebee gut microbiome diversity and shifts over evolutionary time. IMPORTANCE: The microbiotas associated with organisms facilitates host health and fitness, and the homeostasis status of gut microbiota also reflects the habitat security faced by the host. In addition, managing gut microbiota is important to improve bumblebee health by understanding the ecological process of the gut microbiome. Thus, we first carried out an runprecedented sampling of 513 workers of the species Bombus pyrosoma across the Chinese landscape and used full-length 16S rRNA gene sequencing to uncover their gut microbiota diversity and biogeography. Our study provides new insights into the understanding of gut microbiome diversity and shifts for Chinese Bumblebee over evolutionary time.

8.
Opt Express ; 32(11): 18916-18930, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859038

RESUMEN

Ultraviolet micro-LEDs show great potential as a light source for maskless photolithography. However, there are few reports on micro-LED based maskless photolithography systems, and the studies on the effects of system parameters on exposure patterns are still lacking. Hence, we developed a maskless photolithography system that employs micro-LEDs with peak wavelength 375 nm to produce micrometer-sized exposure patterns in photoresists. We also systematically explored the effects of exposure time and current density of micro-LED on static direct writing patterns, as well as the effects of stage velocity and current pulse width on dynamic direct writing patterns. Furthermore, reducing the size of micro-LED pixels enables obtaining high-resolution exposure patterns, but this approach will bring technical challenges and high costs. Therefore, this paper proposes an oblique direct writing method that, instead of reducing the micro-LED pixel size, improves the pattern resolution by changing the tilt angle of the sample. The experimental results show that the linewidths of the exposed lines decreased by 4.0% and 15.2%, respectively, as the sample tilt angle increased from 0° to 15° and 30°, which confirms the feasibility of the proposed method to improve the pattern resolution. This method is also expected to correct the exposure pattern error caused by optical distortion of the lens in the photolithography system. The system and method reported can be applied in various fields such as PCBs, photovoltaics, solar cells, and MEMS.

9.
Trends Mol Med ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38719712

RESUMEN

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research.

10.
Front Plant Sci ; 15: 1296641, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711612

RESUMEN

Introduction: Plastic film mulching (PFM) and deficit irrigation (DI) are vital water-saving approaches in arid agriculture. Cyperus esculentus is a significant crop in dry zones. However, scant data exists on the impacts of these water-saving methods on C. esculentus yield and quality. Method: Using randomized block experiment design. Three irrigation strategies were tested: CK (standard irrigation), RW20 (20% water reduction), and RW40 (40% water reduction). Mulchin treatments included film mulching (FM) and no film mulching (NFM). Results: Results revealed substantial effects of film mulching and drip irrigation on soil nutrients and physical properties, with minor influence on grass, root, and tuber stoichiometry. PF treatment, DI treatments, and their interaction significantly affected C. esculentus forage and tuber yields. Initially, grass and tuber yields increased and then decreased with reduced irrigation. The highest yields were under RW20 (3716.31 and 4758.19 kg/ha). FM increased grass and tuber yield by 17.99% and 8.46%, respectively, over NFM. The water reduction augmented the biomass distribuiton of the leaf and root, while reducing the tuber biomass in NFM. FM significantely impacted grass ether extract content, while reduced water influenced grass and tuber crude protein and tuber ether extract content. Mild water stress increased ether extract, crude protein, and soluble matter in grass and tubers, while excessive RW decreased them. Conclusion: Integrating soil traits, nutrients, yield, and quality, findings indicate C. esculentus yield and quality primarily hinge on soil water content, pond hydrogenase, and electrical conductivity. Based on this results, the recommended strategy is to reduce irrigation by 20% for cultivating C. esculentus in this area.

11.
Angew Chem Int Ed Engl ; 63(30): e202406441, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38742483

RESUMEN

Transition-metal carbides with metallic properties have been extensively used as electrocatalysts due to their excellent conductivity and unique electronic structures. Herein, NbC nanoparticles decorated carbon nanofibers (NbC@CNFs) are proposed as an efficient and robust catalyst for electrochemical synthesis of ammonia from nitrate/nitrite reduction, which achieves a high Faradaic efficiency (FE) of 94.4 % and a large ammonia yield of 30.9 mg h-1 mg-1 cat.. In situ electrochemical tests reveal the nitrite reduction at the catalyst surface follows the *NO pathway and theoretical calculations reveal the formation of NbC@CNFs heterostructure significantly broadens density of states nearby the Fermi energy. Finite element simulations unveil that the current and electric field converge on the NbC nanoparticles along the fiber, suggesting the dispersed carbides are highly active for nitrite reduction.

12.
Reprod Biol ; 24(2): 100893, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38754347

RESUMEN

Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. As a critical regulator of the Hippo pathway, the phosphorylation status of Yes-associated protein 1 (YAP1), mainly at S127, is critical for its oncogenic function. Herein, we aim to investigate the precise molecular mechanism between long noncoding RNA HOX transcript antisense RNA (HOTAIR) and YAP1 phosphorylation in regulating tumor migration and invasion. In this study, we showed that inhibition of HOTAIR significantly decreased the migration and invasion of cancer cells both in vitro and in vivo through elevating the phosphorylation level of YAP1 on serine 127, demonstrating a tumor suppressive role of YAP1 S127 phosphorylation. Through bisulfite sequencing PCR (BSP), we found that inhibition of HOTAIR dramatically increased Large Tumor Suppressor Kinase 1 (LATS1) expression by regulating LATS1 methylation via DNA methyltransferase 3ß (DNMT3B). In accordance with this observation, DNMT3B just only altered the distribution of YAP1 in the cytoplasm and the nucleus by inhibiting its phosphorylation, but did not change its total expression. Mechanistically, we discovered that HOTAIR suppressed YAP1 S127 phosphorylation by regulating the methylation of LATS1 via DNMT3B, the consequence of which is the translocation of YAP1 into the nucleus, reinforcing its coactivating transcriptional function, which in turn promotes the migration and invasion of cancer cells. Collectively, our data reveal that the phosphorylation of YAP1 S127 plays a vital role in the function of HOTAIR in tumorigenicity, and should be taken into consideration in future therapeutic strategies for cervical cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Movimiento Celular , ADN (Citosina-5-)-Metiltransferasas , ADN Metiltransferasa 3B , Invasividad Neoplásica , Proteínas Serina-Treonina Quinasas , ARN Largo no Codificante , Factores de Transcripción , Neoplasias del Cuello Uterino , Proteínas Señalizadoras YAP , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , Humanos , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/genética , Femenino , Proteínas Señalizadoras YAP/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Línea Celular Tumoral , Ratones , Animales , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Fosforilación , Metilación de ADN , Ratones Endogámicos BALB C
13.
Prev Med ; 185: 108021, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38821420

RESUMEN

OBJECTIVE: Lifestyle factors after cancer diagnosis could influence cancer survival. This study aimed to investigate the joint effects of smoking, physical activity, alcohol consumption, diet and sleep duration on all-cause, cancer and non-cancer mortality of cancer survivors in UK biobank. METHODS: The follow-up period concluded in December 2021, with post-diagnostic lifestyle factors assessed at baseline. A lifestyle score ranging from 0 to 5 was assigned based on adherence to the selected lifestyle factors. The study employed Cox regression models for hazard ratios (HRs) and Kaplan-Meier for survival rates, with stratified and sensitivity analyses to assess the robustness of our findings under various assumptions. RESULTS: During a median follow-up of 12.7 years, 5652 deaths were documented from 34,184 cancer survivors. Compared to scoring 0-1, the HRs (95% CIs) for all-cause mortality with lifestyle scores of 2, 3, 4, and 5 were 0.70 (95% CI: 0.64, 0.76), 0.57 (0.52, 0.62), 0.50 (0.45, 0.54) and 0.43 (0.38, 0.48), respectively. Specific cancer types, particularly digestive, breast, female reproductive, non-solid, and skin cancers, showed notable benefits from adherence to healthy lifestyle, with the HRs of 0.55 (0.39, 0.79), 0.54 (0.42, 0.70), 0.32 (0.19, 0.53), 0.58 (0.39, 0.86), and 0.36 (0.28, 0.46) for lifestyle score of 5, respectively. Stratified analyses indicated the association was particularly significant among those with normal/lower BMI and higher Townsend Deprivation Index (Pinteraction = 0.001 and < 0.001, respectively). CONCLUSIONS: Healthier lifestyles were significantly linked with reduced mortality among cancer survivors. These findings highlight the need for adherence to healthy lifestyle habits to improve survival.

14.
Animals (Basel) ; 14(10)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38791655

RESUMEN

The two existing clades of Galloanseres, orders Galliformes (landfowl) and Anseriformes (waterfowl), exhibit dramatically different evolutionary trends. Mitochondria serve as primary sites for energy production in organisms, and numerous studies have revealed their role in biological evolution and ecological adaptation. We assembled the complete mitogenome sequences of two species of the genus Aythya within Anseriformes: Aythya baeri and Aythya marila. A phylogenetic tree was constructed for 142 species within Galloanseres, and their divergence times were inferred. The divergence between Galliformes and Anseriformes occurred ~79.62 million years ago (Mya), followed by rapid evolution and diversification after the Middle Miocene (~13.82 Mya). The analysis of selective pressure indicated that the mitochondrial protein-coding genes (PCGs) of Galloanseres species have predominantly undergone purifying selection. The free-ratio model revealed that the evolutionary rates of COX1 and COX3 were lower than those of the other PCGs, whereas ND2 and ND6 had faster evolutionary rates. The CmC model also indicated that most PCGs in Anseriformes exhibited stronger selective constraints. Our study suggests that the distinct evolutionary trends and energy requirements of Galliformes and Anseriformes drive different evolutionary patterns in the mitogenome.

15.
Micromachines (Basel) ; 15(5)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38793181

RESUMEN

Herein, we investigate the temperature compensation for a dual-mass MEMS gyroscope. After introducing and simulating the dual-mass MEMS gyroscope's working modes, we propose a hybrid algorithm for temperature compensation relying on improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN), sample entropy, time-frequency peak filtering, non-dominated sorting genetic algorithm-II (NSGA II) and extreme learning machine. Firstly, we use ICEEMDAN to decompose the gyroscope's output signal, and then we use sample entropy to classify the decomposed signals. For noise segments and mixed segments with different levels of noise, we use time-frequency peak filtering with different window lengths to achieve a trade-off between noise removal and signal retention. For the feature segment with temperature drift, we build a compensation model using extreme learning machine. To improve the compensation accuracy, NSGA II is used to optimize extreme learning machine, with the prediction error and the 2-norm of the output-layer connection weight as the optimization objectives. Enormous simulation experiments prove the excellent performance of our proposed scheme, which can achieve trade-offs in signal decomposition, classification, denoising and compensation. The improvement in the compensated gyroscope's output signal is analyzed based on Allen variance; its angle random walk is decreased from 0.531076°/h/√Hz to 6.65894 × 10-3°/h/√Hz and its bias stability is decreased from 32.7364°/h to 0.259247°/h.

16.
ISA Trans ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38772803

RESUMEN

This paper addresses robust fault detection observer design for a class of discrete-time Takagi-Sugeno nonlinear systems. A novel design method is presented based on finite-frequency H-/H∞ indices and peak-to-peak analysis. The finite-frequency H- and H∞ indices are utilized to characterize fault sensitivity and disturbance robustness, respectively. The peak-to-peak analysis is used to derive a dynamic threshold. An iterative algorithm is further developed to reduce conservatism. Theoretical proof shows that the performance of the proposed method is not worse than some existing works. Simulation results demonstrate the validity and viability of the proposed method.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38771516

RESUMEN

PURPOSE: Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications. METHOD: A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [64Cu]Cu-CB-TE2A-iPA-NRA ([64Cu]Cu-4a-c, i = 1, 2, 3), [64Cu]Cu-NOTA-2PA-NRA ([64Cu]Cu-4d), [64Cu]Cu-DOTA-2PA-NRA ([64Cu]Cu-4e, also known as [64Cu]Cu-3BP-227), and [64Cu]Cu-DOTA-VS-2PA-NRA ([64Cu]Cu-4f). The series of small animal PET/CT were conducted in H1299 lung cancer model. The expression profile of NTSR1 was also confirmed by IHC using patient tissue samples. RESULTS: For most of the compounds studied, PET/CT showed prominent tumor uptake and high tumor-to-background contrast, but the tumor retention was strongly influenced by the chelators used. For previously reported 4e, [64Cu]Cu-labeled derivative showed initial high tumor uptake accompanied by rapid tumor washout at 24 h. The newly developed [64Cu]Cu-4d and [64Cu]Cu-4f demonstrated good tumor uptake and tumor-to-background contrast at early time points, but were less promising in tumor retention. In contrast, our lead compound [64Cu]Cu-4b demonstrated 9.57 ± 1.35, 9.44 ± 2.38 and 9.72 ± 4.89%ID/g tumor uptake at 4, 24, and 48 h p.i., respectively. Moderate liver uptake (11.97 ± 3.85, 9.80 ± 3.63, and 7.72 ± 4.68%ID/g at 4, 24, and 48 h p.i.) was observed with low uptake in most other organs. The PA linker was found to have a significant effect on drug distribution. Compared to [64Cu]Cu-4b, [64Cu]Cu-4a had a lower background, including a greatly reduced liver uptake, while the tumor uptake was only moderately reduced. Meanwhile, [64Cu]Cu-4c showed increased uptake in both the tumor and the liver. The clinical relevance of NTSR1 was also demonstrated by the elevated tumor expression in patient tissue samples. CONCLUSIONS: Through the side-by-side comparison, [64Cu]Cu-4b was identified as the lead agent for further evaluation based on its high and sustained tumor uptake and moderate liver uptake. It can not only be used to efficiently detect NTSR1 expression in lung cancer (for diagnosis, patient screening, and treatment monitoring), but also has the great potential to treat NTSR-positive lesions once chelating to the beta emitter 67Cu.

19.
Sci Adv ; 10(16): eadl2063, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38640232

RESUMEN

All-perovskite tandem solar cells (TSCs) have exhibited higher efficiencies than single-junction perovskite solar cells (PSCs) but still suffer from the unsatisfactory performance of low-bandgap (LBG) tin-lead (Sn-Pb) subcells. The inherent properties of PEDOT:PSS are crucial to high-performance Sn-Pb perovskite films and devices; however, the underlying mechanism has not been fully explored and revealed. Here, we report a facile oxalic acid treatment of PEDOT:PSS (OA-PEDOT:PSS) to precisely regulate its work function and surface morphology. OA-PEDOT:PSS shows a larger work function and an ordered reorientation and fiber-shaped film morphology with efficient hole transport pathways, leading to the formation of more ideal hole-selective contact with Sn-Pb perovskite for suppressing interfacial nonradiative recombination losses. Moreover, OA-PEDOT:PSS induces (100) preferred orientation growth of perovskite for higher-quality Sn-Pb films. Last, the OA-PEDOT:PSS-tailored LBG PSC yields an impressive efficiency of up to 22.56% (certified 21.88%), enabling 27.81% efficient all-perovskite TSC with enhanced operational stability.

20.
Front Microbiol ; 15: 1361756, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38591034

RESUMEN

Phyllosphere microbes residing on plant leaf surfaces for maintaining plant health have gained increasing recognition. However, in desert ecosystems, knowledge about the variety, composition, and coexistence patterns of microbial communities in the phyllosphere remains limited. This study, conducted across three basins (Turpan-TLF, Tarim-CL, and Dzungaria-MSW) and three seasons (spring, summer, and autumn) in Xinjiang, China, aimed to explore the diversity and composition of microbial communities in the phyllosphere, encompassing both bacteria and fungi in Alhagi sparsifolia. We also investigated the co-occurrence patterns, influencing factors, and underlying mechanisms driving these dynamics. Results indicate that phyllosphere bacteria exhibited lower diversity indices (ACE, Shannon, Simpson, Fisher phylogenetic diversity, and Richness) in spring compared to summer and autumn, while the Goods Coverage Index (GCI) was higher in spring. Conversely, diversity indices and GCI of phyllosphere fungi showed an opposite trend. Interestingly, the lowest level of multi-functionality and niche width in phyllosphere bacteria occurred in spring, while the highest level was observed in phyllosphere fungi. Furthermore, the study revealed that no significant differences in multi-functionality were found among the regions (CL, MSW, and TLF). Network analysis highlighted that during spring, phyllosphere bacteria exhibited the lowest number of nodes, edges, and average degree, while phyllosphere fungi had the highest. Surprisingly, the multi-functionality of both phyllosphere bacteria and fungi showed no significant correlation with climatic and environmental factors but displayed a significant association with the morphological characteristics and physicochemical properties of leaves. Structural Equation Model indicated that the morphological characteristics of leaves significantly influenced the multi-functionality of phyllosphere bacteria and fungi. However, the indirect and total effects of climate on multi-functionality were greater than the effects of physicochemical properties and morphological characteristics of leaves. These findings offer new insights into leaf phyllosphere microbial community structure, laying a theoretical foundation for vegetation restoration and rational plant resource utilization in desert ecosystems.

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