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1.
Hum Pathol ; 152: 105650, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39187207

RESUMEN

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is prevalent in the Asian population; however, little is known about its molecular characteristics. In this study, we examined the CD30 expression in ENKTLs and then performed whole exome sequencing on ten CD30+ ENKTL and CD30- ENKTL paired samples. CD30 was positive in 55.74% of the ENKTLs. Single nucleotide and insertion/deletion polymorphism analyses revealed that 53.41% of the somatic mutations in CD30+ ENKTLs were shared with CD30- ENKTLs, including mutations in SERPINA9, MEGF6, MUC6, and KDM5A. Frequently mutated genes were primarily associated with cell proliferation and migration, the tumor microenvironment, energy and metabolism, epigenetic modulators, vascular remodeling, and neurological function. PI3K-AKT, cAMP, cGMP-PKG, and AMPK pathways were enriched in both CD30+ and CD30- ENKTLs. Copy number variation analysis identified a unique set of genes in CD30+ ENKTLs, including T-cell receptor genes (TRBV6-1 and TRBV8), cell cycle-related genes (MYC and CCND3), immune-related genes (GPS2, IFNA14, TTC38, and CTSV), and a large number of ubiquitination-related genes (USP32, TRIM23, TRIM2, DUSP7, and UBE2QL1). BCL10 mutation was identified in 6/10 CD30+ ENKTLs and 7/10 CD30- ENKTLs. Immunohistochemical analysis revealed that the expression pattern of BCL10 in normal lymphoid tissues was similar to that of BCL2; however, its expression in ENKTL cells was significantly higher (67.92% vs. 16.98%), implying the potential application of BCL10 inhibitors for treating ENKTLs. These results provide new insights into the genetic characteristics of CD30+ and CD30- ENKTLs, and could facilitate the clinical development of novel therapies for ENKTL.

2.
Eur J Med Chem ; 277: 116761, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39151276

RESUMEN

The P-glycoprotein (ABCB1)-mediated multidrug resistance (MDR) has emerged as a significant impediment to the efficacy of cancer chemotherapy in clinical therapy, which could promote the development of effective agents for MDR reversal. In this work, we reported the exploration of novel pyrazolo [1,5-a]pyrimidine derivatives as potent reversal agents capable of enhancing the sensitivity of ABCB1-mediated MDR MCF-7/ADR cells to paclitaxel (PTX). Among them, compound 16q remarkably increased the sensitivity of MCF-7/ADR cells to PTX at 5 µM (IC50 = 27.00 nM, RF = 247.40) and 10 µM (IC50 = 10.07 nM, RF = 663.44). Compound 16q could effectively bind and stabilize ABCB1, and does not affect the expression and subcellular localization of ABCB1 in MCF-7/ADR cells. Compound 16q inhibited the function of ABCB1, thereby increasing PTX accumulation, and interrupting the accumulation and efflux of the ABCB1-mediated Rh123, thus resulting in exhibiting good reversal effects. In addition, due to the potent reversal effects of compound 16q, the abilities of PTX to inhibit tubulin depolymerization, and induce cell cycle arrest and apoptosis in MCF-7/ADR cells under low-dose conditions were restored. These results indicate that compound 16q might be a promising potent reversal agent capable of revising ABCB1-mediated MDR, and pyrazolo [1,5-a]pyrimidine might represent a novel scaffold for the discovery of new ABCB1-mediated MDR reversal agents.

3.
Food Chem ; 461: 140009, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-39167943

RESUMEN

A label-free electrochemical immunosensor was developed to rapidly detect tilmicosin (TMC) residues in pork and milk. The immunosensor was constructed by immobilizing a high-affinity monoclonal antibody against TMC on an rGO-PEI-Ag nanocomposite-modified electrode. The rGO-PEI-Ag nanocomposites were prepared by mixing polyethyleneimine (PEI) modified reduced graphene oxide (rGO) with AgNO3 solution. The prepared rGO-PEI-Ag nanocomposites showed good redox activity and conductivity, as characterized by ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), and X-ray diffraction (XRD). During the preparation process, staphylococcal protein A (SPA) was added to targetedly bind the Fc segment of the monoclonal antibody. The immunosensor showed a low detection limit (LOD) of 0.0013 ng/mL, a linear range of 0.01-100 ng/mL, and recoveries ranging from 92.77 to 100.02% in pork and 92.26-101.23% in milk. Furthermore, the immunosensor exhibited good stability, reproducibility, and specificity in detecting TMC in pork and milk real samples.

4.
Int J Numer Method Biomed Eng ; : e3852, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049450

RESUMEN

Needle syringe irrigation is frequently used in root canal therapy, and the flow pattern during irrigation can be efficiently manipulated by means of passive flow control technique, resulting in expected irrigation performance improvement. Therefore, novel needles with composite flow control structures are numerically investigated and optimized in this study. Based on the 30G needle, six single/double side-vented needles with dimple and protrusion are proposed. Two flow rates in line with clinical applications, 5.3 and 8.6 m/s, are used in the analysis. Three performance parameters are investigated. The safety of the irrigation system is evaluated by the root canal apical pressure, whereas the irrigant extension and the flushing efficiency are evaluated by the extending depth and the effective cleaning area, respectively. The results demonstrate that the shear stress of the double-side-vented needle is higher while the irrigant extension is enhanced with a dimple structure. The performance of the double-side-vented needle with a dimple is superior to that of other designs, with up to 33% improvement in extending depth and a 22% increase in effective cleaning area over the prototype. New needles do not raise risk of irrigant extrusion. Furthermore, the effect of dimple depth and outlet angle are investigated. The needle with a dimple of 0.04 mm depth shows the highest extending depth within the confines of the investigation. The effective cleaning area is significantly influenced by the needle outlets, and the effective cleaning area expands with an increase in needle outlet angle, while the extending depth gradually declines.

6.
Antonie Van Leeuwenhoek ; 117(1): 103, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39042225

RESUMEN

Genus Thermus is the main focus of researcher among the thermophiles. Members of this genus are the inhabitants of both natural and artificial thermal environments. We performed phylogenomic analyses and comparative genomic studies to unravel the genomic diversity among the strains belonging to the genus Thermus in geographically different thermal springs. Sixteen Thermus strains were isolated and sequenced from hot springs, Qucai hot springs in Tibet and Tengchong hot springs in Yunnan, China. 16S rRNA gene based phylogeny and phylogenomic analyses based on concatenated set of 971 Orthologous Protein Families (supermatrix and gene content methods) revealed a mixed distribution of the Thermus strains. Whole genome based phylogenetic analysis showed, all 16 Thermus strains belong to five species; Thermus oshimai (YIM QC-2-109, YIM 1640, YIM 1627, 77359, 77923, 77838), Thermus antranikianii (YIM 73052, 77412, 77311, 71206), Thermus brokianus (YIM 73518, 71318, 72351), Thermus hydrothermalis (YIM 730264 and 77927) and one potential novel species 77420 forming clade with Thermus thalpophilus SYSU G00506T. Although the genomes of different strains of Thermus of same species were highly similar in their metabolic pathways, but subtle differences were found. CRISPR loci were detected through genome-wide screening, which showed that Thermus isolates from two different thermal locations had well developed defense system against viruses and adopt similar strategy for survival. Additionally, comparative genome analysis screened competence loci across all the Thermus genomes which could be helpful to acquire DNA from environment. In the present study it was found that Thermus isolates use two mechanism of incomplete denitrification pathway, some Thermus strains produces nitric oxide while others nitrious oxide (dinitrogen oxide), which show the heterotrophic lifestyle of Thermus genus. All isolated organisms encoded complete pathways for glycolysis, tricarboxylic acid and pentose phosphate. Calvin Benson Bassham cycle genes were identified in genomes of T. oshimai and T. antranikianii strains, while genomes of all T. brokianus strains and organism 77420 were lacking. Arsenic, cadmium and cobalt-zinc-cadmium resistant genes were detected in genomes of all sequenced Thermus strains. Strains 77,420, 77,311, 73,518, 77,412 and 72,351 genomes were found harboring genes for siderophores production. Sox gene clusters were identified in all sequenced genomes, except strain YIM 730264, suggesting a mode of chemolithotrophy. Through the comparative genomic analysis, we also identified 77420 as the genome type species and its validity as novel organism was confirmed by whole genome sequences comparison. Although isolate 77420 had 99.0% 16S rRNA gene sequence similarity with T. thalpophilus SYSU G00506T but based on ANI 95.86% (Jspecies) and digital DDH 68.80% (GGDC) values differentiate it as a potential novel species. Similarly, in the phylogenomic tree, the novel isolate 77,420 forming a separate branch with their closest reference type strain T. thalpophilus SYSU G00506T.


Asunto(s)
Genoma Bacteriano , Genómica , Manantiales de Aguas Termales , Filogenia , ARN Ribosómico 16S , Thermus , Thermus/genética , Thermus/clasificación , Thermus/aislamiento & purificación , Manantiales de Aguas Termales/microbiología , ARN Ribosómico 16S/genética , Tibet , China , ADN Bacteriano/genética , Análisis de Secuencia de ADN
7.
Adv Mater ; : e2404659, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38870958

RESUMEN

Single-atom electrocatalysts (SACs) are a class of promising materials for driving electrochemical energy conversion reactions due to their intrinsic advantages, including maximum metal utilization, well-defined active structures, and strong interface effects. However, SACs have not reached full commercialization for broad industrial applications. This review summarizes recent research achievements in the design of SACs for crucial electrocatalytic reactions on their active sites, coordination, and substrates, as well as the synthesis methods. The key challenges facing SACs in activity, selectivity, stability, and scalability, are highlighted. Furthermore, it is pointed out the new strategies to address these challenges including increasing intrinsic activity of metal sites, enhancing the utilization of metal sites, improving the stability, optimizing the local environment, developing new fabrication techniques, leveraging insights from theoretical studies, and expanding potential applications. Finally, the views are offered on the future direction of single-atom electrocatalysis toward commercialization.

8.
Materials (Basel) ; 17(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38894036

RESUMEN

This paper presents a comprehensive investigation into the thermal stability of superlattice-like (SLL) thin films fabricated by varying the sputtering sequences of the SLL [Ge8Sb92(25nm)/GeTe(25nm)]1 and SLL [GeTe(25nm)/Ge8Sb92(25nm)]1 configurations. Our results reveal significantly enhanced ten-year data retention (Tten) for both thin films measured at 124.3 °C and 151.9 °C, respectively. These values surpass the Tten of Ge2Sb2Te5 (85 °C), clearly demonstrating the superior thermal stability of the studied SLL configurations. Interestingly, we also observe a distinct difference in the thermal stability between the two SLL configurations. The superior thermal stability of SLL [GeTe(25nm)/Ge8Sb92(25nm)]1 is attributed to the diffusion of the Sb precipitated phase from Ge8Sb92 to GeTe. This diffusion process effectively reduces the impact of the Sb phase on the thermal stability of the thin film. In contrast, in the case of SLL [Ge8Sb92(25nm)/GeTe(25nm)]1, the presence of the Sb precipitated phase in Ge8Sb92 facilitates the crystallization of GeTe, leading to reduced thermal stability. These findings underscore the significant influence of the sputtering sequence on the atomic behavior and thermal properties of superlattice-like phase change materials. Such insights provide a robust foundation for the design and exploration of novel phase change materials with improved thermal performance.

9.
Dalton Trans ; 53(25): 10434-10445, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38713392

RESUMEN

Potassium borate glass has great potential as an ion transport material. The ion transport rate is closely related to the microstructure of the glass. However, the disorder and variations in boron and oxygen atom types in the glass structure pose challenges in the analysis of this complex glass structure. In this work, the structure of potassium borate glass was unveiled through the neutron diffraction method and ab initio molecular dynamics (AIMD) simulations. The B-O, K-O, and O-O atomic interactions, bond lengths, coordination numbers, cavity distribution, ring structure distributions and other detailed information in the microstructure of potassium borate glass were obtained. By comparing the structure and properties of potassium borate glass with those of crystals of similar components, it is found that the bond lengths of 3B-BO (BO, bridging oxygen), 4B-BO and 3B-NBO (NBO, non-bridging oxygen) are longer than those of corresponding crystals, so the structure of the boron-oxygen network is looser and the density is smaller than that of similar crystals. Moreover, we found a rule that in both borate glass and crystal, the increase of NBO shortened the length of the B-O bond, and the increase of 4B increased the length of the B-O bond. The key structures affecting the transport rate of K+ were NBO, chain structure units and cavities. This work will provide reference data for designing and developing electrically conductive amorphous materials with faster potassium-ion transport rates.

10.
Chem Sci ; 15(15): 5581-5588, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38638210

RESUMEN

Exploring novel electrochemiluminescence (ECL) molecules with high efficiency and good stability in aqueous solutions is crucial for achieving highly sensitive detection of analytes. However, developing chiral luminophores with efficient ECL performance is still a challenge. Herein, we first uncover that artemisinin (ART), a well-known chiral antimalarial drug, features a strong ECL emission at 726 nm with the assistance of a co-reactant potassium persulfate (K2S2O8), and an ECL efficiency of 195.3%, compared to that of standard Ru(bpy)3Cl2/K2S2O8. Mechanistic studies indicate that the strong ECL signal of ART is generated when the excited state formed by the reduction of ART peroxide bonds and combination with persulfate returns to the ground state. Significantly, we found that the ECL sensor based on chiral ART could efficiently identify and detect chiral cysteine (Cys) through ECL signals, with a lower limit of detection of 3.7 nM for l-Cys. Density functional theory calculations and scanning electrochemical microscopy technology further confirm that the disparity in the ECL signals is attributed to the different affinity between chiral ART and d/l-Cys, resulting in distinct electron transfer rates. The study demonstrates a new role of ART in ECL investigation and for the first time, achieves the development of ART for the enantioselective recognition and sensitive detection of chiral substances. This will be of vital significance for ECL and chirality research.

11.
Anal Chem ; 96(18): 7304-7310, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38651947

RESUMEN

Radicals can feature theoretically 100% light utilization owing to their nonelectron spin-forbidden transition and represent the most advanced luminescent materials at present. 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO) acts as a typically stable radical with very broad applications. However, their luminescent properties have not been discovered to date. In the present work, we observed the bright electrochemiluminescence (ECL) emission of TEMPO with a higher efficiency (72.3%) via the electrochemistry and coreactant strategies for the first time. Moreover, the radical-based ECL achieved high detection toward boron acid with a lower limit of detection (LOD) of 1.9 nM. This study offers a new approach to generate emissions for some unconventional luminophores and makes a major breakthrough in the field of new luminescent materials as well.

12.
ACS Appl Mater Interfaces ; 16(14): 17778-17786, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38534114

RESUMEN

The pressing need for data storage in the era of big data has driven the development of new storage technologies. As a prominent contender for next-generation memory, phase-change memory can effectively increase storage density through multilevel cell operation and can be applied to neuromorphic and in-memory computing. Herein, the structure and properties of Ta-doped MnTe thin films and their inherent correlations are systematically investigated. Amorphous MnTe thin films sequentially precipitated cubic MnTe2 and hexagonal Te phases with increasing temperature, causing resistance changes. Ta doping inhibited phase segregation in the films and improved their thermal stability in the amorphous state. A phase-change memory cell based on a Ta2.8%-MnTe thin film exhibited three stable resistive states with low resistive drift coefficients. The study findings reveal the possibility of regulating the two-step phase-change process in Ta-MnTe thin films, providing insight into the design of multilevel phase-change memory.

13.
EMBO J ; 43(8): 1499-1518, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38528181

RESUMEN

The intestinal pathogen Salmonella enterica rapidly enters the bloodstream after the invasion of intestinal epithelial cells, but how Salmonella breaks through the gut-vascular barrier is largely unknown. Here, we report that Salmonella enters the bloodstream through intestinal CX3CR1+ macrophages during early infection. Mechanistically, Salmonella induces the migration/invasion properties of macrophages in a manner dependent on host cell actin and on the pathogen effector SteC. SteC recruits host myosin light chain protein Myl12a and phosphorylates its Ser19 and Thr20 residues. Myl12a phosphorylation results in actin rearrangement, and enhanced migration and invasion of macrophages. SteC is able to utilize a wide range of NTPs other than ATP to phosphorylate Myl12a. We further solved the crystal structure of SteC, which suggests an atypical dimerization-mediated catalytic mechanism. Finally, in vivo data show that SteC-mediated cytoskeleton manipulation is crucial for Salmonella breaching the gut vascular barrier and spreading to target organs.


Asunto(s)
Cadenas Ligeras de Miosina , Salmonella enterica , Cadenas Ligeras de Miosina/genética , Cadenas Ligeras de Miosina/metabolismo , Actinas/metabolismo , Células Epiteliales/metabolismo , Macrófagos/metabolismo
14.
J Comput Chem ; 45(17): 1456-1469, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38471809

RESUMEN

B 6 O 7 OH 6 2 - is a highly polymerized borate anion of three six-membered rings. Limited research on the B 6 O 7 OH 6 2 - hydrolysis mechanism under neutral solution conditions exists. Calculations based on density functional theory show that B 6 O 7 OH 6 2 - undergoes five steps of hydrolysis to form H3BO3 and B OH 4 - . At the same time, there are a small number of borate ions with different degrees of polymerization during the hydrolysis process, such as triborate, tetraborate, and pentaborate anions. The structure of the borate anion and the coordination environment of the bridging oxygen atoms control the hydrolysis process. Finally, this work explains that in existing experimental studies, the reason for the low B 6 O 7 OH 6 2 - content in solution environments with low total boron concentrations is that it depolymerizes into other types of borate ions and clarifies the borate species. The conversion relationship provides a basis for identifying the possibility of various borate ions existing in the solution. This work also provides a certain degree of theoretical support for the cause of the "dilution to salt" phenomenon.

15.
Virulence ; 15(1): 2331265, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38532247

RESUMEN

Flagella play a crucial role in the invasion process of Salmonella and function as a significant antigen that triggers host pyroptosis. Regulation of flagellar biogenesis is essential for both pathogenicity and immune escape of Salmonella. We identified the conserved and unknown function protein STM0435 as a new flagellar regulator. The ∆stm0435 strain exhibited higher pathogenicity in both cellular and animal infection experiments than the wild-type Salmonella. Proteomic and transcriptomic analyses demonstrated dramatic increases in almost all flagellar genes in the ∆stm0435 strain compared to wild-type Salmonella. In a surface plasmon resonance assay, purified STM0435 protein-bound c-di-GMP had an affinity of ~8.383 µM. The crystal structures of apo-STM0435 and STM0435&c-di-GMP complex were determined. Structural analysis revealed that R33, R137, and D138 of STM0435 were essential for c-di-GMP binding. A Salmonella with STM1987 (GGDEF protein) or STM4264 (EAL protein) overexpression exhibits completely different motility behaviours, indicating that the binding of c-di-GMP to STM0435 promotes its inhibitory effect on Salmonella flagellar biogenesis.


Asunto(s)
Proteínas Bacterianas , GMP Cíclico/análogos & derivados , Proteómica , Animales , Virulencia , Proteínas Bacterianas/genética , Biopelículas , Salmonella/metabolismo , GMP Cíclico/análisis , GMP Cíclico/metabolismo , Regulación Bacteriana de la Expresión Génica
16.
Int Dent J ; 74(1): 71-80, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37833209

RESUMEN

OBJECTIVES: The aim of this research was to investigate the functions of Piezo channels in dentin defect, including mechanical signalling and odontoblast responses. METHODS: Rat dentin-defect models were constructed, and spatiotemporal expression of Piezo proteins was detected in the pulpo-dentinal complex. Real-time polymerase chain reaction (rtPCR) was used to investigate the functional expression pattern of Piezo channels in odontoblasts. Moreover, RNA interference technology was employed to uncover the underlying mechanisms of the Piezo-driven inflammatory response and repair under fluid shear stress (FSS) conditions in vitro. RESULTS: Piezo1 and Piezo2 were found to be widely expressed in the odontoblast layer and dental pulp in the rat dentin-defect model during the end stage of reparative dentin formation. The expression levels of the Piezo1 and Piezo2 genes in MDPC-23 cells were high in the initial stage under FSS loading and then decreased over time. Moreover, the expression trends of inflammatory, odontogenic, and mineralisation genes were generally contrary to those of Piezo1 and Piezo2 over time. After silencing of Piezo1/Piezo2, FSS stimulation resulted in significantly higher expression of inflammatory, odontogenesis, and mineralisation genes in MDPC-23 cells. Finally, the expression of genes involved in the integrin ß1/ERK1 and Wnt5b/ß-catenin signalling pathways was changed in response to RNA silencing of Piezo1 and Piezo2. CONCLUSIONS: Piezo1 and Piezo2 may be involved in regulating the expression of inflammatory and odontogenic genes in odontoblasts stimulated by FSS.


Asunto(s)
Odontoblastos , Ratas , Humanos , Animales , Odontoblastos/fisiología
17.
J Ultrasound Med ; 43(3): 525-533, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38050787

RESUMEN

OBJECTIVE: The purpose of this study is to explore the application value of two-dimensional ultrasound and shear wave elastography (SWE) in the multidimensional evaluation of diastasis recti abdominis (DRA) during different gestational periods. METHODS: A cohort of 202 gravidas that were examined in our hospital between June 2021 and September 2022 were selected for the purpose of the study, which included 26 cases with <14 weeks of pregnancy, 36 cases in the 14th-27th week of pregnancy, 36 cases in the 28th-34th week of pregnancy, 32 cases in the 35th-38th week of pregnancy, 45 cases at 42 days postpartum, and 27 cases at 3 months postpartum. The inter-rectus distance (IRD) and the thickness in each gestational period were measured, and Young's modulus of the rectus abdominis at different gestational periods was measured using SWE by two sonographers. The differences in IRD, thickness, and elasticity characteristics during different periods, and the correlation between rectus abdominis elasticity and IRD, thickness, body mass index (BMI), neonatal weight, and delivery mode were analyzed and compared. The consistency of SWE parameters obtained by different sonographers was also compared. RESULTS: There were significant differences in IRD, thickness, and Young's modulus during different gestational periods (P = .000, P < .001, P < .001). Early postpartum IRD and Young's modulus did not restore to the level of early pregnancy (P < .001, P < .001), while the thickness of rectus abdominis was not significantly different from that of early pregnancy (P = .211). The Young's modulus of rectus abdominis was negatively correlated with the IRD (r = .515), positively correlated with the thickness of rectus abdominis (r = .408), and weakly negatively correlated with maternal BMI (r = -.296). There was no significant correlation with neonatal weight or delivery mode (P = .147, .648). The Bland-Altman plot showed that the two sonographers had good consistency in evaluating the elasticity of rectus abdominis by SWE. CONCLUSION: The multidimensional evaluation of DRA by ultrasound is feasible and IRD and Young's modulus can be used to evaluate the postpartum recovery of DRA. The combination of the two can objectively reflect the severity of DRA morphology and function.


Asunto(s)
Diástasis Muscular , Diagnóstico por Imagen de Elasticidad , Embarazo , Femenino , Recién Nacido , Humanos , Recto del Abdomen/diagnóstico por imagen , Ultrasonografía , Periodo Posparto , Módulo de Elasticidad
18.
Int J Radiat Oncol Biol Phys ; 119(3): 957-967, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38104869

RESUMEN

PURPOSE: The recently proposed Integrated Physical Optimization Intensity Modulated Proton Therapy (IPO-IMPT) framework allows simultaneous optimization of dose, dose rate, and linear energy transfer (LET) for ultra-high dose rate (FLASH) treatment planning. Finding solutions to IPO-IMPT is difficult because of computational intensiveness. Nevertheless, an inverse solution that simultaneously specifies the geometry of a sparse filter and weights of a proton intensity map is desirable for both clinical and preclinical applications. Such solutions can reduce effective biologic dose to organs at risk in patients with cancer as well as reduce the number of animal irradiations needed to derive extra biologic dose models in preclinical studies. METHODS AND MATERIALS: Unlike the initial forward heuristic, this inverse IPO-IMPT solution includes simultaneous optimization of sparse range compensation, sparse range modulation, and spot intensity. The daunting computational tasks vital to this endeavor were resolved iteratively with a distributed computing framework to enable Simultaneous Intensity and Energy Modulation and Compensation (SIEMAC). SIEMAC was demonstrated on a human patient with central lung cancer and a minipig. RESULTS: SIEMAC simultaneously improves maps of spot intensities and patient-field-specific sparse range compensators and range modulators. For the patient with lung cancer, at our maximum nozzle current of 300 nA, dose rate coverage above 100 Gy/s increased from 57% to 96% in the lung and from 93% to 100% in the heart, and LET coverage above 4 keV/µm dropped from 68% to 9% in the lung and from 26% to <1% in the heart. For a simple minipig plan, the full-width half-maximum of the dose, dose rate, and LET distributions decreased by 30%, 1.6%, and 57%, respectively, again with similar target dose coverage, thus reducing uncertainty in these quantities for preclinical studies. CONCLUSIONS: The inverse solution to IPO-IMPT demonstrated the capability to simultaneously modulate subspot proton energy and intensity distributions for clinical and preclinical studies.


Asunto(s)
Algoritmos , Transferencia Lineal de Energía , Neoplasias Pulmonares , Órganos en Riesgo , Terapia de Protones , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Terapia de Protones/métodos , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Animales , Neoplasias Pulmonares/radioterapia , Órganos en Riesgo/efectos de la radiación , Radioterapia de Intensidad Modulada/métodos , Porcinos
19.
BMC Plant Biol ; 23(1): 571, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37978426

RESUMEN

BACKGROUND: Astragalus grows mainly in drought areas. Cycloastragenol (CAG) is a tetracyclic triterpenoid allelochemical extracted from traditional Chinese medicine Astragalus root. Phospholipase C (PLC) and Gα-submit of the heterotrimeric G-protein (GPA1) are involved in many biotic or abiotic stresses. Nitric oxide (NO) is a crucial gas signal molecule in plants. RESULTS: In this study, using the seedlings of Arabidopsis thaliana (A. thaliana), the results showed that low concentrations of CAG induced stomatal closure, and high concentrations inhibited stomatal closure. 30 µmol·L-1 CAG significantly increased the relative expression levels of PLC1 and GPA1 and the activities of PLC and GTP hydrolysis. The stomatal aperture of plc1, gpa1, and plc1/gpa1 was higher than that of WT under CAG treatment. CAG increased the fluorescence intensity of NO in guard cells. Exogenous application of c-PTIO to WT significantly induced stomatal aperture under CAG treatment. CAG significantly increased the relative expression levels of NIA1 and NOA1. Mutants of noa1, nia1, and nia2 showed that NO production was mainly from NOA1 and NIA1 by CAG treatment. The fluorescence intensity of NO in guard cells of plc1, gpa1, and plc1/gpa1 was lower than WT, indicating that PLC1 and GPA1 were involved in the NO production in guard cells. There was no significant difference in the gene expression of PLC1 in WT, nia1, and noa1 under CAG treatment. The gene expression levels of NIA1 and NOA1 in plc1, gpa1, and plc1/gpa1 were significantly lower than WT, indicating that PLC1 and GPA1 were positively regulating NO production by regulating the expression of NIA1 and NOA1 under CAG treatment. CONCLUSIONS: These results suggested that the NO accumulation was essential to induce stomatal closure under CAG treatment, and GPA1 and PLC1 acted upstream of NO.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Óxido Nítrico/metabolismo , Transducción de Señal , Estomas de Plantas/fisiología , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP/metabolismo
20.
Angew Chem Int Ed Engl ; 62(41): e202311268, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37615518

RESUMEN

For zinc-ion batteries (ZIBs), the non-uniform Zn plating/stripping results in a high polarization and low Coulombic efficiency (CE), hindering the large-scale application of ZIBs. Here, inspired by biomass seaweed plants, an anionic polyelectrolyte alginate acid (SA) was used to initiate the in situ formation of the high-performance solid electrolyte interphase (SEI) layer on the Zn anode. Attribute to the anionic groups of -COO- , the affinity of Zn2+ ions to alginate acid induces a well-aligned accelerating channel for uniform plating. This SEI regulates the desolvation structure of Zn2+ and facilitates the formation of compact Zn (002) crystal planes. Even under high depth of discharge conditions (DOD), the SA-coated Zn anode still maintains a stable Zn stripping/plating behavior with a low potential difference (0.114 V). According to the classical nucleation theory, the nucleation energy for SA-coated Zn is 97 % less than that of bare Zn, resulting in a faster nucleation rate. The Zn||Cu cell assembled with the SA-coated electrode exhibits an outstanding average CE of 99.8 % over 1,400 cycles. The design is successfully demonstrated in pouch cells, where the SA-coated Zn exhibits capacity retention of 96.9 % compared to 59.1 % for bare Zn anode, even under the high cathode mass loading (>10 mg/cm2 ).

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