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1.
Nature ; 607(7920): 703-707, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35831496

RESUMEN

Single-molecule imaging with atomic resolution is a notable method to study various molecular behaviours and interactions1-5. Although low-dose electron microscopy has been proved effective in observing small molecules6-13, it has not yet helped us achieve an atomic understanding of the basic physics and chemistry of single molecules in porous materials, such as zeolites14-16. The configurations of small molecules interacting with acid sites determine the wide applications of zeolites in catalysis, adsorption, gas separation and energy storage17-21. Here we report the atomic imaging of single pyridine and thiophene confined in the channel of zeolite ZSM-5 (ref. 22). On the basis of integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM)23-25, we directly observe the adsorption and desorption behaviours of pyridines in ZSM-5 under the in situ atmosphere. The adsorption configuration of single pyridine is atomically resolved and the S atoms in thiophenes are located after comparing imaging results with calculations. The strong interactions between molecules and acid sites can be visually studied in real-space images. This work provides a general strategy to directly observe these molecular structures and interactions in both the static image and the in situ experiment, expanding the applications of electron microscopy to the further study of various single-molecule behaviours with high resolution.

2.
Nature ; 592(7855): 541-544, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33883731

RESUMEN

Single-molecule imaging is challenging but highly beneficial for investigating intermolecular interactions at the molecular level1-6. Van der Waals interactions at the sub-nanometre scale strongly influence various molecular behaviours under confinement conditions7-11. Inspired by the traditional compass12, here we use a para-xylene molecule as a rotating pointer to detect the host-guest van der Waals interactions in the straight channel of the MFI-type zeolite framework. We use integrated differential phase contrast scanning transmission electron microscopy13-15 to achieve real-space imaging of a single para-xylene molecule in each channel. A good correlation between the orientation of the single-molecule pointer and the atomic structure of the channel is established by combining the results of calculations and imaging studies. The orientations of para-xylene help us to identify changes in the van der Waals interactions, which are related to the channel geometry in both spatial and temporal dimensions. This work not only provides a visible and sensitive means to investigate host-guest van der Waals interactions in porous materials at the molecular level, but also encourages the further study of other single-molecule behaviours using electron microscopy techniques.

3.
J Am Chem Soc ; 146(7): 4327-4332, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38277433

RESUMEN

The structural exploration of three-dimensional covalent organic frameworks (3D COFs) is of great significance to the development of COF materials. Different from structurally diverse MOFs, which have a variety of connectivity (3-24), now the valency of 3D COFs is limited to only 4, 6, and 8. Therefore, the exploration of organic building blocks with higher connectivity is a necessary path to broaden the scope of 3D COF structures. Herein, for the first time, we have designed and synthesized a 12-connected triptycene-based precursor (triptycene-12-CHO) with 12 symmetrical distributions of aldehyde groups, which is also the highest valency reported until now. Based on this unique 12-connected structure, we have successfully prepared a novel 3D COF with lnj topology (termed 3D-lnj-COF). The as-synthesized 3D COF exhibits honeycomb main pores and permanent porosity with a Brunauer-Emmett-Teller surface area of 1159.6 m2 g-1. This work not only provides a strategy for synthesizing precursors with a high connectivity but also provides inspiration for enriching the variety of 3D COFs.

4.
Int J Cancer ; 155(2): 193-202, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38554117

RESUMEN

Tissue-resident memory T cells (TRM) are a specialized subset of T cells that reside in tissues and provide long-term protective immunity against pathogens that enter the body through that specific tissue. TRM cells have specific phenotype and reside preferentially in barrier tissues. Recent studies have revealed that TRM cells are the main target of immune checkpoint inhibitor immunotherapy since their role in cancer immunosurveillance. Furthermore, TRM cells also play a crucial part in pathogenesis of immune-related adverse events (irAEs). Here, we provide a concise review of biological characteristics of TRM cells, and the major advances and recent findings regarding their involvement in immune checkpoint inhibitor immunotherapy and the corresponding irAEs.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Células T de Memoria , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Células T de Memoria/inmunología , Memoria Inmunológica/inmunología , Animales
5.
New Phytol ; 241(2): 764-778, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37904576

RESUMEN

Bioactive triterpenes feature complex fused-ring structures, primarily shaped by the first-committed enzyme, 2,3-oxidosqualene cyclases (OSCs) in plant triterpene biosynthesis. Triterpenes with B,C-ring-opened skeletons are extremely rare with unknown formation mechanisms, harbouring unchartered chemistry and biology. Here, through mining the genome of Chenopodium quinoa followed by functional characterization, we identified a stress-responsive and neofunctionalized OSC capable of generating B,C-ring-opened triterpenes, including camelliol A and B and the novel (-)-quinoxide A as wax components of the specialized epidermal bladder cells, namely the quinoxide synthase (CqQS). Protein structure analysis followed by site-directed mutagenesis identified key variable amino acid sites underlying functional interconversion between pentacyclic ß-amyrin synthase (CqbAS1) and B,C-ring-opened triterpene synthase CqQS. Mutation of one key residue (N612K) in even evolutionarily distant Arabidopsis ß-amyrin synthase could generate quinoxides, indicating a conserved mechanism for B,C-ring-opened triterpene formation in plants. Quantum computation combined with docking experiments further suggests that conformations of conserved W613 and F413 of CqQS might be key to selectively stabilizing intermediate carbocations towards B,C-ring-opened triterpene formation. Our findings shed light on quinoa triterpene skeletal diversity and mechanisms underlying B,C-ring-opened triterpene biosynthesis, opening avenues towards accessing their chemistry and biology and paving the way for quinoa trait engineering and quality improvement.


Asunto(s)
Chenopodium quinoa , Transferasas Intramoleculares , Triterpenos , Chenopodium quinoa/metabolismo , Triterpenos/metabolismo , Transferasas Intramoleculares/genética , Transferasas Intramoleculares/metabolismo
6.
Opt Express ; 32(7): 12763-12773, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571106

RESUMEN

Terahertz (THz) microcavities have garnered considerable attention for their ability to localize and confine THz waves, allowing for strong coupling to remarkably enhance the light-matter interaction. These properties hold great promise for advancing THz science and technology, particularly for high-speed integrated THz chips where transient interaction between THz waves and matter is critical. However, experimental study of these transient time-domain processes requires high temporal and spatial resolution since these processes, such as THz strong coupling, occur in several picoseconds and microns. Thus, most literature studies rarely cover temporal and spatial processes at the same time. In this work, we thoroughly investigate the transient cavity-cavity strong-coupling phenomena at THz frequency and find a Rabi-like oscillation in the microcavities, manifested by direct observation of a periodic energy exchange process via a phase-contrast time-resolved imaging system. Our explanation, based on the Jaynes-Cummings model, provides theoretical insight into this transient strong-coupling process. This work provides an opportunity to deeply understand the transient strong-coupling process between THz microcavities, which sheds light on the potential of THz microcavities for high-speed THz sensor and THz chip design.

7.
Opt Lett ; 49(3): 758-761, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300108

RESUMEN

We propose a scheme to achieve nonreciprocal magnon blockade via the Barnett effect in a magnon-based hybrid system. Due to the rotating yttrium iron garnet (YIG) sphere, the Barnett shift induced by the Barnett effect can be tuned from positive to negative via controlling magnetic field direction, leading to nonreciprocity. We show that a nonreciprocal unconventional magnon blockade (UMB) can emerge only from one magnetic field direction but not from the other side. Particularly, by further tuning system parameters, we simultaneously observe a nonreciprocal conventional magnon blockade (CMB) and a nonreciprocal UMB. This result achieves a switch between efficiency (UMB) and purity (CMB) of a single-magnon blockade. Interestingly, stronger UMB can be reached under stronger qubit-magnon coupling, even the strong coupling regime. Moreover, the nonreciprocity of the magnon blockade is sensitive to temperature. This work opens up a way for achieving quantum nonreciprocal magnetic devices and chiral magnon communications.

8.
BMC Cancer ; 24(1): 531, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671390

RESUMEN

OBJECTIVE: In the pathogenesis of myeloproliferative neoplasms (MPN), inflammation plays an important role. However, it is unclear whether there is a causal link between inflammation and MPNs. We used a bidirectional, two-sample Mendelian randomization (MR) approach to investigate the causal relationship between systemic inflammatory cytokines and myeloproliferative neoplasms. METHODS: A genome-wide association study (GWAS) of 8293 European participants identified genetic instrumental variables for circulating cytokines and growth factors. Summary statistics of MPN were obtained from a GWAS including 1086 cases and 407,155 controls of European ancestry. The inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). RESULTS: Our results showed that higher Interleukin-2 receptor, alpha subunit (IL-2rα) levels, and higher Interferon gamma-induced protein 10 (IP-10) levels were associated with an increased risk of MPN (OR = 1.36,95%CI = 1.03-1.81, P = 0.032; OR = 1.55,95%CI = 1.09-2.22, P = 0.015; respectively).In addition, Genetically predicted MPN promotes expression of the inflammatory cytokines interleukin-10 (IL-10) (BETA = 0.033, 95% CI = 0.003 ~ 0.064, P = 0.032) and monokine induced by interferon-gamma (MIG) (BETA = 0.052, 95% CI = 0.002-0.102, P = 0.043) and, on activation, normal T cells express and secrete RANTES (BETA = 0.055, 95% CI = 0.0090.1, P = 0.018). CONCLUSION: Our findings suggest that cytokines are essential to the pathophysiology of MPN. More research is required if these biomarkers can be used to prevent and treat MPN.


Asunto(s)
Citocinas , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Mieloproliferativos , Humanos , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/sangre , Citocinas/sangre , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Masculino , Predisposición Genética a la Enfermedad , Femenino , Estudios de Casos y Controles , Inflamación/genética , Inflamación/sangre
9.
Theor Appl Genet ; 137(3): 74, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38451289

RESUMEN

KEY MESSAGE: Eight selected hotspots related to ear traits were identified from two maize-teosinte populations. Throughout the history of maize cultivation, ear-related traits have been selected. However, little is known about the specific genes involved in shaping these traits from their origins in the wild progenitor, teosinte, to the characteristics observed in modern maize. In this study, five ear traits (kernel row number [KRN], ear length [EL], kernel number per row [KNR], cob diameter [CD], and ear diameter [ED]) were investigated, and eight quantitative trait loci (QTL) hotspots were identified in two maize-teosinte populations. Notably, our findings revealed a significant enrichment of genes showing a selection signature and expressed in the ear in qbdCD1.1, qbdCD5.1, qbpCD2.1, qbdED1.1, qbpEL1.1, qbpEL5.1, qbdKNR1.1, and qbdKNR10.1, suggesting that these eight QTL are selected hotspots involved in shaping the maize ear. By combining the results of the QTL analysis with data from previous genome-wide association study (GWAS) involving two natural panels, we identified eight candidate selected genes related to KRN, KNR, CD, and ED. Among these, considering their expression pattern and sequence variation, Zm00001d025111, encoding a WD40/YVTN protein, was proposed as a positive regulator of KNR. This study presents a framework for understanding the genomic distribution of selected loci crucial in determining ear-related traits.


Asunto(s)
Estudio de Asociación del Genoma Completo , Zea mays , Zea mays/genética , Genómica , Fenotipo , Sitios de Carácter Cuantitativo
10.
Bioorg Chem ; 144: 107111, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38218068

RESUMEN

To mine fascinating molecules from the rhizomes of Atractylodes chinensis, the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D-S (1-16) including three unprecedented carbon skeletons (1-5) and eleven new oxygen-bridged hybrids (6-16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1, 4, 8, and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1-5 were also discussed.


Asunto(s)
Atractylodes , Atractylodes/química , Hidroquinonas , Antiinflamatorios , Dicroismo Circular , Estructura Molecular
11.
J Pediatr Hematol Oncol ; 46(2): 96-103, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38315896

RESUMEN

CBFA2T3-GLIS2 is the most frequent chimeric oncogene identified to date in non-Down syndrome acute megakaryocytic leukemia (AMKL), which is associated with extremely poor clinical outcome. The presence of this fusion gene is associated with resistance to high-intensity chemotherapy, including hematopoietic stem cell transplantation (HSCT), and a high cumulative incidence of relapse frequency. The clinical features and clinical effects of China Children's Leukemia Group-acute myeloid leukemia (AML) 2015/2019 regimens and haploidentical HSCT (haplo-HSCT) for treatment of 6 children harboring the CBFA2T3-GLIS2 fusion gene between January 2019 and December 2021 were retrospectively analyzed. The 6 patients included 4 boys and 2 girls with a median disease-onset age of 19.5 months (range: 6-67 mo) who were diagnosed with AMKL. Flow cytometry demonstrated CD41a, CD42b, and CD56 expression and lack of HLA-DR expression in all 6 patients. All the children were negative for common leukemia fusion genes by reverse transcription polymerase chain reaction, but positive for the CBFA2T3-GLIS2 fusion gene by next-generation sequencing and RNA sequencing. All patients received chemotherapy according to China Children's Leukemia Group-AML 2015/2019 regimens, and 4 achieved complete remission. Four children underwent haplo-HSCT with posttransplant cyclophosphamide-based conditioning; 3 had minimal residual disease negative (minimal residual disease <0.1%) confirmed by flow cytometry at the end of the follow-up, with the remaining patient experiencing relapse at 12 months after transplantation. Transcriptome RNA sequencing is required for the detection of the CBFA2T3-GLIS2 fusion gene and for proper risk-based allocation of pediatric patients with AML in future clinical strategies. Haplo-HSCT with posttransplant cyclophosphamide-based conditioning may improve survival in children with AMKL harboring the fusion gene.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Megacarioblástica Aguda , Leucemia Mieloide Aguda , Masculino , Femenino , Niño , Humanos , Lactante , Preescolar , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/terapia , Leucemia Megacarioblástica Aguda/diagnóstico , Estudios Retrospectivos , Neoplasia Residual , Leucemia Mieloide Aguda/terapia , Ciclofosfamida , Recurrencia , Proteínas Represoras , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo
12.
Mol Ther ; 31(9): 2575-2590, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37408308

RESUMEN

Tertiary lymphoid structures (TLSs) in tumor tissues facilitate immune cell trafficking and cytotoxicity, which benefits survival and favorable responses in immune therapy. Here, we observed a high correlation of tumor necrosis factor superfamily member 14 (LIGHT) expression with TLS signature genes, which are all markers for immune cell accumulation and better prognosis, through retrieving RNA sequencing (RNA-seq) data from patients with cancer, suggesting the potential of LIGHT in reconstituting a high immune-infiltrated tumor microenvironment. Accordingly, LIGHT co-expressed chimeric antigen receptor T (LIGHT CAR-T) cells not only showed enhanced cytotoxicity and cytokine production but also improved CCL19 and CCL21 expression by surrounding cells. And the supernatant of LIGHT CAR-T cells promoted T cell migration in a paracrine manner. Furthermore, LIGHT CAR-T cells showed superior anti-tumor efficacy and improved infiltration in comparison with conventional CAR-T cells in immunodeficient NSG mice. Accordingly, murine LIGHT-OT-1 T cells normalized tumor blood vessels and enforced intratumoral lymphoid structures in C57BL/6 syngeneic tumor mouse models, implying the potential of LIGHT CAR-T in clinical application. Taken together, our data revealed a straightforward strategy to optimize trafficking and cytotoxicity of CAR-T cells by redirecting TLSs through LIGHT expression, which has great potential to expand and optimize the application of CAR-T therapy in solid tumors.


Asunto(s)
Receptores Quiméricos de Antígenos , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Animales , Ratones , Línea Celular Tumoral , Inmunoterapia Adoptiva , Ratones Endogámicos C57BL , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T , Microambiente Tumoral/genética
13.
Blood Purif ; 53(6): 493-499, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38228097

RESUMEN

INTRODUCTION: Recently, the incidence of hypertriglyceridemia-associated pancreatitis (HTG-AP) has been increasing. The pathogenesis of lipogenic pancreatitis is not fully understood. This study aimed to retrospectively analyze the laboratory data, clinical manifestations, and prognosis of patients with lipid-derived pancreatitis who received lipid purification, to explore whether lipid purification is a better treatment for acute hyperlipidemic pancreatitis. METHODS: In this study, we enrolled five subjects diagnosed with HTG-AP at the Second Xiangya Hospital of Central South University between 2021 and 2022. We collected demographic data, medical histories, clinical manifestations, and laboratory data. All patients received routine therapy. Blood lipid purification was conducted using the double filtration plasmapheresis (DFPP) method. Plasma was separated from blood cells and purified to remove cholesterol, triglycerides, and low-density lipoprotein (LDL). SPSS was used for statistical analyses. RESULTS: Following a single lipoprotein apheresis (LA) treatment, significant improvements in serum lipid levels were observed. Three patients achieved triglyceride levels below 5.65 mmol/L within 24 h, while the remaining 2 patients experienced reductions of 82% and 78%, respectively. The average triglyceride level decreased from 36.82 to 7.27 mmol/L, representing an 80% reduction from baseline. Total cholesterol decreased by 59% on average, and LDL levels decreased by 69%. Statistically significant differences were observed in triglyceride and cholesterol levels before and after treatment. Four patients exhibited increased HDL levels posttreatment, while 1 patient showed a decrease. The average HDL/TC level was 21% higher after treatment. CONCLUSION: LA in HTG-AP effectively improves clinical symptoms, rapidly lowers lipid levels, and achieves good therapeutic outcomes.


Asunto(s)
Eliminación de Componentes Sanguíneos , Pancreatitis , Humanos , Masculino , Femenino , Pancreatitis/terapia , Pancreatitis/sangre , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Eliminación de Componentes Sanguíneos/métodos , Hipertrigliceridemia/terapia , Hipertrigliceridemia/sangre , Hipertrigliceridemia/complicaciones , Triglicéridos/sangre , Lípidos/sangre , Plasmaféresis/métodos , Enfermedad Aguda
14.
Sensors (Basel) ; 24(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38931568

RESUMEN

Accurate determination of the number and location of immature small yellow peaches is crucial for bagging, thinning, and estimating yield in modern orchards. However, traditional methods have faced challenges in accurately distinguishing immature yellow peaches due to their resemblance to leaves and susceptibility to variations in shooting angles and distance. To address these issues, we proposed an improved target-detection model (EMA-YOLO) based on YOLOv8. Firstly, the sample space was enhanced algorithmically to improve the diversity of samples. Secondly, an EMA attention-mechanism module was introduced to encode global information; this module could further aggregate pixel-level features through dimensional interaction and strengthen small-target-detection capability by incorporating a 160 × 160 detection head. Finally, EIoU was utilized as a loss function to reduce the incidence of missed detections and false detections of the target small yellow peaches under the condition of high density of yellow peaches. Experimental results show that compared with the original YOLOv8n model, the EMA-YOLO model improves mAP by 4.2%, Furthermore, compared with SDD, Objectbox, YOLOv5n, and YOLOv7n, this model's mAP was improved by 30.1%, 14.2%,15.6%, and 7.2%, respectively. In addition, the EMA-YOLO model achieved good results under different conditions of illumination and shooting distance and significantly reduced the number of missed detections. Therefore, this method can provide technical support for smart management of yellow-peach orchards.

15.
Angew Chem Int Ed Engl ; 63(6): e202318459, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38105412

RESUMEN

Intravital fluorescence imaging of functional osteoclasts within their intact disease context provides valuable insights into the intricate biology at the microscopic level, facilitating the development of therapeutic approaches for osteoclast-associated bone diseases. However, there is a lack of studies investigating osteoclast activity within deep-seated bone lesions using appropriate fluorescent probes, despite the advantages offered by the multi-photon excitation system in enhancing deep tissue imaging resolution. In this study, we report on the intravital tracking of osteoclast activity in three distinct murine bone disease models. We utilized a cathepsin K (CatK)-responsive two-photon fluorogenic probe (CatKP1), which exhibited a notable fluorescence turn-on response in the presence of active CatK. By utilizing CatKP1, we successfully monitored a significant increase in osteoclast activity in hindlimb long bones and its attenuation through pharmacological intervention without sacrificing mice. Thus, our findings highlight the efficacy of CatKP1 as a valuable tool for unraveling pathological osteoclast behavior and exploring novel therapeutic strategies.


Asunto(s)
Enfermedades Óseas , Osteoclastos , Animales , Ratones , Osteoclastos/patología , Catepsina K , Huesos , Enfermedades Óseas/patología , Diagnóstico por Imagen
16.
Plant J ; 112(6): 1364-1376, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36305873

RESUMEN

Lateral organ boundaries domain (LBD) proteins are plant-specific transcription factors. Class-I LBD genes have been widely demonstrated to play pivotal roles in organ development; however, knowledge on class-II genes remains limited. Here, we report that ZmLBD5, a class-II LBD gene, is involved in the regulation of maize (Zea mays) growth and the drought response by affecting gibberellin (GA) and abscisic acid (ABA) synthesis. ZmLBD5 is mainly involved in regulation of the TPS-KS-GA2ox gene module, which is comprised of key enzyme-encoding genes involved in GA and ABA biosynthesis. ABA insufficiency increases stomatal density and aperture in overexpression plants and causes a drought-sensitive phenotype by promoting water transpiration. Increased GA1 levels promotes seedling growth in overexpression plants. Accordingly, CRISPR/Cas9 knockout lbd5 seedlings are dwarf but drought-tolerant. Moreover, lbd5 has a higher grain yield under drought stress conditions and shows no penalty in well-watered conditions compared to the wild type. On the whole, ZmLBD5 is a negative regulator of maize drought tolerance, and it is a potentially useful target for drought resistance breeding.


Asunto(s)
Ácido Abscísico , Resistencia a la Sequía , Ácido Abscísico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estomas de Plantas/fisiología , Plantas Modificadas Genéticamente/metabolismo , Fitomejoramiento , Agua/metabolismo , Sequías , Regulación de la Expresión Génica de las Plantas/genética , Estrés Fisiológico/genética
17.
Small ; : e2308599, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38054626

RESUMEN

The occurrence of osteoarthritis (OA) is highly associated with the inflammatory hypoxic microenvironment. Yet currently no attention has been paid to fabricating hypoxia-responsive platforms for OA treatment. Herein, an injectable hydrogel microsphere system (HAM-SA@HCQ) focusing on the hypoxic inflamed joint is prepared with methacrylate-modified sulfonated azocalix[4]arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and dithiol-terminated matrix metalloproteinase 13 (MMP-13) sensitive peptide via a microfluidic device and photo crosslinking technique, followed by encapsulation of the anti-inflammatory drug hydroxychloroquine (HCQ) through host-guest interaction. Owing to the hydrophobic deep cavity, phenolic units, and azo bonds of SAC4A-MA, the hydrogel microspheres show strong drug loading capacity, prominent reactive oxygen species (ROS) scavenging capability, and specific hypoxia-responsive drug release ability. In the OA tissue microenvironment, the hydrogel microspheres undergo degradation by excessive MMP-13 and release HCQ under the hypoxia condition, which synergizes with the ROS-scavenging calixarene to inhibit the inflammatory response of macrophages. After being injected into the OA-inflamed joint, the HAM-SA@HCQ can significantly attenuate the oxidative stress, downregulate the expression of hypoxia-induced factor-1α and inflammatory cytokines, and prevent the cartilage from being destroyed.

18.
Opt Express ; 31(4): 5492-5506, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36823828

RESUMEN

Nonreciprocal sideband responses in a spinning microwave magnomechanical system consists of a spinning resonator coupled with a yttrium iron garnet sphere are proposed. We show that the efficiency of sideband generation can be enhanced in one driving direction but restrained in the opposite. This nonreciprocity results from Sagnac effect induced by the spinning resonator, leading to asymmetric magnonic responses in two different driving directions. Beyond the conventional linearized description, the properties of nonreciprocal two-color second-order sideband are demonstrated. By adjusting Sagnac-Fizeau shift and the power of control field, the degree of asymmetric magnonic responses can be strengthened, therefore causing stronger nonreciprocity of sideband. Especially, for the case of strong Sagnac-Fizeau shift and the control field, high level of efficiency and isolation ratio of sideband are achieved simultaneously and the operational bandwidth of strong nonreciprocity can be expanded. Our proposal provides an effective avenue for the manipulation of the nonreciprocity of sideband and has potentially practical applications in on-chip microwave isolation devices and magnon-based precision measurement.

19.
Opt Express ; 31(26): 44375-44384, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38178510

RESUMEN

Tunable terahertz (THz) microcavities are crucial for the compact on-chip THz devices, aiming to future cloud-based computing, and artificial-intelligence technologies. However, the solutions to effectively modulate THz microcavities remain elusive. Strong coupling has been widely demonstrated in many configurations at different ambient conditions to date and may serve as a promising tool to modulate THz microcavities. Here, we schematically design a microcavity-plasmon hybrid system, and propose an effective approach to modulating the resonant frequencies of THz microcavities by the microcavity-resonator strong coupling. In this case, we observed the strongly coupling states, where the resultant two-polariton branches exhibit an anti-crossing splitting in the frequency domain, experimentally exhibiting a ∼6.2% frequency modulation to the microcavity compared to the uncoupled case. This work provides an efficient approach to modulating chip-scale THz microcavities, thereby facilitating the development and application of compact THz integrated devices, further empowering the evolution of future information processing and intelligent computing system.

20.
Pediatr Blood Cancer ; 70(11): e30659, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37669234

RESUMEN

BACKGROUND: Post-transplant cyclophosphamide (PTCy) has been recommended for prevention of graft-versus-host disease (GvHD) following haploidentical hematopoietic cell transplantation (haplo-HCT) for treatment of malignant blood diseases, but disease relapse remains a problem. Although donor lymphocyte infusion (DLI) is reported to be effective for treating post-transplantation relapse, the efficacy and safety of prophylactic-DLI (pro-DLI) post haplo-HCT, and PTCy in pediatric patients with hematological malignancies is unknown. METHODS: We retrospectively analyzed the outcomes of 54 pediatric patients with high-risk myeloid neoplasms who received a PTCy regimen for GvHD prophylaxis and pro-DLI after haploidentical peripheral blood stem cell transplantation. The high-risk myeloid neoplasms in this cohort included acute myeloid leukemia (n = 46) and myelodysplastic syndromes (n = 8). RESULTS: Median follow-up was for 19.7 (range: 3.4-46.6) months. The cumulative incidences of grade II-IV and III-IV acute GvHD were 37.0% (95% CI: 22.7%-48.7%) and 16.7% (95% CI: 6.1%-26.0%), respectively. There were no graft-failure events, and the 2-year rate of moderate/severe chronic GvHD was 8.1% (95% CI: 0%-16.7%). The 2-year non-relapse mortality, relapse, disease-free survival, GvHD-free relapse-free survival, and overall survival rates were 5.1% (95% CI: 0%-11.7%), 16.6% (95% CI: 5.3%-26.6%), 78.9% (95% CI: 68.0%-91.6%), 62.2% (95% CI: 49.4%-78.3%), and 87.3% (95% CI: 78.3%-97.4%), respectively. CONCLUSIONS: Prophylactic donor lymphocyte infusion in the setting of haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide appears to be effective and safe in pediatric patients with high-risk myeloid neoplasms.


Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Niño , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Recurrencia , Linfocitos
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