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1.
J Nanobiotechnology ; 22(1): 193, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643134

RESUMEN

Pyroptosis, a novel type of programmed cell death (PCD), which provides a feasible therapeutic option for the treatment of tumors. However, due to the hypermethylation of the promoter, the critical protein Gasdermin E (GSDME) is lacking in the majority of cancer cells, which cannot start the pyroptosis process and leads to dissatisfactory therapeutic effects. Additionally, the quick clearance, systemic side effects, and low concentration at the tumor site of conventional pyroptosis reagents restrict their use in clinical cancer therapy. Here, we described a combination therapy that induces tumor cell pyroptosis via the use of ultrasound-targeted microbubble destruction (UTMD) in combination with DNA demethylation. The combined application of UTMD and hydralazine-loaded nanodroplets (HYD-NDs) can lead to the rapid release of HYD (a demethylation drug), which can cause the up-regulation of GSDME expression, and produce reactive oxygen species (ROS) by UTMD to cleave up-regulated GSDME, thereby inducing pyroptosis. HYD-NDs combined with ultrasound (US) group had the strongest tumor inhibition effect, and the tumor inhibition rate was 87.15% (HYD-NDs group: 51.41 ± 3.61%, NDs + US group: 32.73%±7.72%), indicating that the strategy had a more significant synergistic anti-tumor effect. In addition, as a new drug delivery carrier, HYD-NDs have great biosafety, tumor targeting, and ultrasound imaging performance. According to the results, the combined therapy reasonably regulated the process of tumor cell pyroptosis, which offered a new strategy for optimizing the therapy of GSDME-silenced solid tumors.


Asunto(s)
Neoplasias , Piroptosis , Humanos , Piroptosis/fisiología , Microburbujas , Neoplasias/tratamiento farmacológico , Apoptosis , Hidralazina/farmacología , Hidralazina/uso terapéutico
2.
Open Life Sci ; 19(1): 20220838, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38585639

RESUMEN

To enhance our understanding of Aspergillus cristatus, an important functional microorganism, the characteristics of its mitochondrial genome were analyzed and compared with related species. The mitochondrial genome of A. cristatus was determined to be 77,649 bp in length, with 15 protein-coding regions. Notably, its length surpassed that of the other species, primarily attributable to the intron length. Gene order exhibited significant variations, with greater conservation observed in the genus Penicillium compared to Aspergillus. Phylogenetic tree analyses indicated that the genera Aspergillus and Penicillium are closely related but monophyletic. Furthermore, the phylogenetic tree constructed based on protein-coding genes effectively distinguished all strains with high branching confidence. This approach provides a robust reflection of the evolutionary relationship between A. cristatus and its related species, offering potential for the development of molecular markers suitable for Aspergillus and Penicillium.

3.
ACS Synth Biol ; 13(4): 1059-1076, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38546129

RESUMEN

Triterpenoids possess a range of biological activities and are extensively utilized in the pharmaceutical, food, cosmetic, and chemical industries. Traditionally, they are acquired through chemical synthesis and plant extraction. However, these methods have drawbacks, including high energy consumption, environmental pollution, and being time-consuming. Recently, the de novo synthesis of triterpenoids in microbial cell factories has been achieved. This represents a promising and environmentally friendly alternative to traditional supply methods. Saccharomyces cerevisiae, known for its robustness, safety, and ample precursor supply, stands out as an ideal candidate for triterpenoid biosynthesis. However, challenges persist in industrial production and economic feasibility of triterpenoid biosynthesis. Consequently, metabolic engineering approaches have been applied to improve the triterpenoid yield, leading to substantial progress. This review explores triterpenoids biosynthesis mechanisms in S. cerevisiae and strategies for efficient production. Finally, the review also discusses current challenges and proposes potential solutions, offering insights for future engineering.


Asunto(s)
Saccharomyces cerevisiae , Triterpenos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Triterpenos/metabolismo , Plantas/metabolismo , Ingeniería Metabólica
4.
Adv Sci (Weinh) ; : e2310159, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38514904

RESUMEN

Vacuolar malic acid accumulation largely determines fruit acidity, a key trait for the taste and flavor of apple and other fleshy fruits. Aluminum-activated malate transporter 9 (ALMT9/Ma1) underlies a major genetic locus, Ma, for fruit acidity in apple, but how the protein transports malate across the tonoplast is unclear. Here, it is shown that overexpression of the coding sequence of Ma1 (Ma1α) drastically decreases fruit acidity in "Royal Gala" apple, leading to uncovering alternative splicing underpins Ma1's function. Alternative splicing generates two isoforms: Ma1ß is 68 amino acids shorter with much lower expression than the full-length protein Ma1α. Ma1ß does not transport malate itself but interacts with the functional Ma1α to form heterodimers, creating synergy with Ma1α for malate transport in a threshold manner (When Ma1ß/Ma1α ≥ 1/8). Overexpression of Ma1α triggers feedback inhibition on the native Ma1 expression via transcription factor MYB73, decreasing the Ma1ß level well below the threshold that leads to significant reductions in Ma1 function and malic acid accumulation in fruit. Overexpression of Ma1α and Ma1ß or genomic Ma1 increases both isoforms proportionally and enhances fruit malic acid accumulation. These findings reveal an essential role of alternative splicing in ALMT9-mediated malate transport underlying apple fruit acidity.

5.
J Invertebr Pathol ; 203: 108072, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38341022

RESUMEN

Pathogenic microorganism of silkworm are important factors that threaten the high-quality development of sericulture. Among them, Bombyx mori nucleopolyhedrovirus (BmNPV) caused diseases often lead to frequent outbreaks and high mortality, resulting in huge losses to sericultural industry. Current molecular detection methods for BmNPV require expensive equipment and sikilled technical personnel. As a result, the most commonly detection method for silkworm egg production enterprises involves observing the presence of polyhedra under a microscope. However, this method has low accuracy and sensitivity. There is an urgent need to develop a new detection technology with high sensitivity, high specificity, and applicability for silkworm farms, silkworm egg production enterprises and quarantine departments. In this study, we successfully established the CRISPR/Cas13a BmNPV visualized detection technology by combining Recombinase Polymerase Amplification (RPA) technology and CRISPR/Cas13a system. This technology is based on microplate lateral, flow test strips and portable fluorescence detector. The detection sensitivity can reach up to 1 copies/µL for positive standard plasmid and 1 fg/µL for BmNPV genome in 30-45 min, demonstrating high sensitivity. By detecting silkworm tissues infected with different pathogens, we determined that CRISPR/Cas13a detection technology has good specificity. In summary, the newly established nucleic acid detection technology for BmNPV is characterized by high sensitivity, high specificity, low cost and convenience for visualization. It can be applied in field detection and silkworm egg quality monitory system.


Asunto(s)
Bombyx , Nucleopoliedrovirus , Animales , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Nucleopoliedrovirus/genética , Sensibilidad y Especificidad
6.
J Control Release ; 367: 45-60, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38246204

RESUMEN

PD-1/PD-L1-based immune checkpoint blockade therapy has shown limited benefits in tumor patients, partially attributed to the inadequate infiltration of immune effector cells within tumors. Here, we established a nanoplatform named DPPA/IL-15 NPs to target PD-L1 for the tumor delivery of IL-15 messenger RNA (mRNA). DPPA/IL-15 NPs were endowed with ultrasound responsiveness and contrast-enhanced ultrasound (CEUS) imaging performance. They effectively protected IL-15 mRNA from degradation and specifically transfected it into tumor cells through the utilization of ultrasound-targeted microbubble destruction (UTMD). This resulted in the activation of IL-15-related immune effector cells while blocking the PD-1/PD-L1 pathway. In addition, UTMD could generate reactive oxygen species (ROS) that induce endoplasmic reticulum (ER) stress-driven immunogenic cell death (ICD), initiating anti-tumor immunity. In vitro and in vivo studies revealed that this combination therapy could induce a robust systemic immune response and enhance anti-tumor efficacy. Thus, this combination therapy has the potential for clinical translation through enhanced immunotherapy and provides real-time ultrasound imaging guidance.


Asunto(s)
Antígeno B7-H1 , Neoplasias , Humanos , Microburbujas , Receptor de Muerte Celular Programada 1/metabolismo , Interleucina-15/genética , Neoplasias/terapia , Inmunoterapia/métodos , Microambiente Tumoral , Línea Celular Tumoral
7.
J Clin Neurosci ; 119: 70-75, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37988975

RESUMEN

BACKGROUND: Patients with myasthenia gravis (MG) lose part of their working or living ability due to illness, and bring burden to caregivers. The purpose of this study was to explore the factors related to caregivers' disease family burden for MG patients in Northwest China. METHODS: The study utilized our Myasthenia Gravis database and distributed online questionnaires to both MG patients and their caregivers. The questionnaires included a general data collection form, the Patient Health Questionnaire-9 (PHQ-9) scale, and the Caregivers' Family Burden Scale of Disease (FBSD). Univariate analysis and multivariate linear regression analysis were run, with FBSD as the outcome variable for separate analyses. RESULTS: 178 MG patients were eligible for inclusion in the analysis, of whom 80 patients' caregivers had a positive family burden of MG. The daily activity burden of the family and the economic burden of the family were the heaviest among the six dimensions of the caregivers' family disease burdens. The factors independently associated with FBSD were depression symptom level, MG severity classification and family's monthly per capita income (p < 0.05). CONCLUSIONS: Depression symptom level, MG severity classification and family's monthly per capita income are independent factors related to the caregivers' disease family burden for MG patients.


Asunto(s)
Miastenia Gravis , Calidad de Vida , Humanos , Estudios Transversales , Cuidadores , Costo de Enfermedad , China/epidemiología , Miastenia Gravis/epidemiología , Encuestas y Cuestionarios
8.
Plant Biotechnol J ; 22(1): 98-115, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37688588

RESUMEN

As a multifunctional hormone-like molecule, melatonin exhibits a pleiotropic role in plant salt stress tolerance. While actin cytoskeleton is essential to plant tolerance to salt stress, it is unclear if and how actin cytoskeleton participates in the melatonin-mediated alleviation of plant salt stress. Here, we report that melatonin alleviates salt stress damage in pigeon pea by activating a kinase-like protein, which interacts with an actin-depolymerizing factor. Cajanus cajan Actin-Depolymerizing Factor 9 (CcADF9) has the function of severing actin filaments and is highly expressed under salt stress. The CcADF9 overexpression lines (CcADF9-OE) showed a reduction of transgenic root length and an increased sensitivity to salt stress. By using CcADF9 as a bait to screen an Y2H library, we identified actin depolymerizing factor-related phosphokinase 1 (ARP1), a novel protein kinase that interacts with CcADF9. CcARP1, induced by melatonin, promotes salt resistance of pigeon pea through phosphorylating CcADF9, inhibiting its severing activity. The CcARP1 overexpression lines (CcARP1-OE) displayed an increased transgenic root length and resistance to salt stress, whereas CcARP1 RNA interference lines (CcARP1-RNAi) presented the opposite phenotype. Altogether, our findings reveal that melatonin-induced CcARP1 maintains F-actin dynamics balance by phosphorylating CcADF9, thereby promoting root growth and enhancing salt tolerance.


Asunto(s)
Cajanus , Melatonina , Melatonina/farmacología , Melatonina/metabolismo , Actinas/metabolismo , Cajanus/genética , Destrina/metabolismo , Tolerancia a la Sal/genética , Fosforilación , Citoesqueleto de Actina/metabolismo
9.
Plant Biotechnol J ; 22(1): 181-199, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37776153

RESUMEN

Aluminium (Al) toxicity decreases crop production in acid soils in general, but many crops have evolved complex mechanisms to resist it. However, our current understanding of how plants cope with Al stress and perform Al resistance is still at the initial stage. In this study, the citrate transporter CcMATE35 was identified to be involved in Al stress response. The release of citrate was increased substantially in CcMATE35 over-expression (OE) lines under Al stress, indicating enhanced Al resistance. It was demonstrated that transcription factor CcNFYB3 regulated the expression of CcMATE35, promoting the release of citrate from roots to increase Al resistance in pigeon pea. We also found that a Long noncoding RNA Targeting Citrate Synthase (CcLTCS) is involved in Al resistance in pigeon pea. Compared with controls, overexpression of CcLTCS elevated the expression level of the Citrate Synthase gene (CcCS), leading to increases in root citrate level and citrate release, which forms another module to regulate Al resistance in pigeon pea. Simultaneous overexpression of CcNFYB3 and CcLTCS further increased Al resistance. Taken together, these findings suggest that the two modules, CcNFYB3-CcMATE35 and CcLTCS-CcCS, jointly regulate the efflux and synthesis of citrate and may play an important role in enhancing the resistance of pigeon pea under Al stress.


Asunto(s)
Cajanus , ARN Largo no Codificante , Ácido Cítrico/metabolismo , Cajanus/genética , Aluminio/toxicidad , Aluminio/metabolismo , Citrato (si)-Sintasa , Citratos/metabolismo
10.
Cancer Gene Ther ; 31(3): 454-463, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38135697

RESUMEN

Nasopharyngeal carcinoma (NPC) originates in the epithelial cells of the nasopharynx and is a common malignant tumor in southern China and Southeast Asia. Metastasis of NPC remains the main cause of death for NPC patients even though the tumor is sensitive to radiotherapy and chemotherapy. Here, we found that the transmembrane protein tetraspanin1 (TSPAN1) potently inhibited the in vitro migration and invasion, as well as, the in vivo metastasis of NPC cells via interacting with the IKBB protein. In addition, TSPAN1 was essential in preventing the overactivation of the NF-kB pathway in TSPAN1 overexpressing NPC cells. Furthermore, reduced TSPAN1 expression was associated with NPC metastasis and the poor prognosis of NPC patients. These results uncovered the suppressive role of TSPAN1 against NF-kB signaling in NPC cells for preventing NPC metastasis. Its therapeutic value warrants further investigation.


Asunto(s)
Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , FN-kappa B/genética , FN-kappa B/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Línea Celular Tumoral , Transducción de Señal , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Tetraspaninas/genética , Tetraspaninas/metabolismo
11.
Lasers Med Sci ; 39(1): 16, 2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-38141129

RESUMEN

Pulsed dye laser (PDL) is the most commonly used method for port-wine stain (PWS); however, no studies have reported the safety of PDL. This review aimed to collect and summarize complications reported in relevant literature, assess complication rates in treating PWS with PDL, and explore the relevant influencing factors. A systematic review and meta-analysis were conducted to search for related studies in PubMed, Embase, and the Cochrane Library until August 2022. Two reviewers independently evaluated the risk of bias of included studies. Stata Software version 17.0 was used for the analysis. All complications reported in the literature are divided into acute phase complications and long-term complications. Overall pooled purpura, edema, crusting, blistering, hyperpigmentation, hypopigmentation, and scarring rates were 98.3%, 97.6%, 21.5%, 8.7%, 12.8%, 0.9%, and 0.2%, respectively. Although the acute adverse reactions were found to be common, the long-term permanent complications clearly have a lower frequency, and the occurrence of scarring is much lower than that initially thought. This indicates that effective protective measures after treatment are very important for preventing scar formation. Overall, PDL treatment for PWS shows a high level of safety and low chances of causing long-term complications.


Asunto(s)
Láseres de Colorantes , Mancha Vino de Oporto , Humanos , Mancha Vino de Oporto/radioterapia , Mancha Vino de Oporto/cirugía , Resultado del Tratamiento , Láseres de Colorantes/efectos adversos , Cicatriz , Terapia Combinada
12.
Open Life Sci ; 18(1): 20220772, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38035046

RESUMEN

Most plants belonging to the widely distributed genus Dianthus are used for gardening. Interspecific hybridization of different Dianthus species leads to blurred genetic backgrounds. To obtain more genomic resources and understand the phylogenetic relationships among Dianthus species, the chloroplast genomes of 12 Dianthus species, including nine Dianthus gratianopolitanus varieties, were analyzed. The chloroplast genomes of these 12 species exhibited similar sizes (149,474-149,735 bp), with Dianthus caryophyllus having a chloroplast genome size of 149,604 bp marked by a significant contraction in inverted repeats. In the chloroplast genome of Dianthus, we identified 124-126 annotated genes, including 83-84 protein-coding genes. Notably, D. caryophyllus had 83 protein-coding genes but lacked rpl2. The repeat sequences of the chloroplast genome were consistent among species, and variations in the sequence were limited and not prominent. However, notable gene replacements were observed in the boundary region. Phylogenetic analysis of Dianthus indicated that D. caryophyllus and D. gratianopolitanus were most closely related, suggesting that the degree of variation within nine Dianthus varieties was no less than the variation observed between species. These differences provide a theoretical foundation for a more comprehensive understanding of the diversity within Dianthus species.

13.
Opt Express ; 31(18): 28805-28815, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37710692

RESUMEN

We theoretically explore the conditions for generating optical bistability (OB) in a heterodimer comprised of a semiconductor quantum dot (SQD) and a metallic nanoshell (MNS). The MNS is made of a metallic nanosphere as a core and a dielectric material as a shell. For the specific hybrid system considered, the bistable effect appears only if the frequency of the pump field is equal to (or slightly less than) the exciton frequency for a proper shell thickness. Bistability phase diagrams, when plotted, show that the dipole-induced bistable region can be greatly broadened by changing the shell thickness of the MNS in a strong exciton-plasmon coupling regime. In particular, we demonstrate that the multipole polarization not only narrows the bistable zone but also enlarges the corresponding thresholds for a given intermediate scaled pumping intensity. On the other hand, when the SQD couples strongly with the MNS, the multipole polarization can also significantly broaden the bistable region and induce a great suppression of the FWM (four-wave mixing) signal for a fixed shell thickness. These interesting findings offer a fresh understanding of the bistability conditions in an SQD/MNS heterodimer, and may be useful in the fabrication of high-performance and low-threshold optical bistable nanodevices.

14.
Nat Commun ; 14(1): 5590, 2023 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-37696831

RESUMEN

Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.


Asunto(s)
Neoplasias de la Mama Masculina , Humanos , Femenino , Masculino , Análisis de Expresión Génica de una Sola Célula , Terapia de Inmunosupresión , Metabolismo de los Lípidos/genética , Ácidos Grasos
15.
Drug Dev Res ; 84(7): 1468-1481, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37534761

RESUMEN

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.


Asunto(s)
Neoplasias Nasofaríngeas , Animales , Ratones , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Ratones Desnudos , Línea Celular Tumoral , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Luciferasas , Movimiento Celular , Invasividad Neoplásica , Metástasis de la Neoplasia
16.
Planta ; 258(3): 64, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37555984

RESUMEN

MAIN CONCLUSION: Integrated transcriptome and physiological analysis of apricot leaves after Fusarium solani treatment. In addition, we identified core transcription factors and flavonoid-related synthase genes which may function in apricot disease resistance. Apricot (Prunus armeniaca) is an important economic fruit species, whose yield and quality of fruit are limited owing to its susceptibility to diseases. However, the molecular mechanisms underlying the response of P. armeniaca to diseases is still unknown. In this study, we used physiology and transcriptome analysis to characterize responses of P. armeniaca subjected to Fusarium solani. The results showed increasing malondialdehyde (MDA) content, enhanced peroxidase (POD) and catalase (CAT) activity during F. solani infestation. A large number of differentially expressed genes (DEGs), which included 4281 upregulated DEGs and 3305 downregulated DEGs, were detected in P. armeniaca leaves exposed to F. solani infestation. Changes in expression of transcription factors (TFs), including bHLH, AP2/ERF, and WRKY indicated their role in triggering pathogen-responsive genes in P. armeniaca. During the P. armeniaca response to F. solani infestation, the content of total flavonoid was changed, and we identified enzyme genes associated with flavonoid biosynthesis. Ectopic overexpression of PabHLH15 and PabHLH102 in Nicotiana benthamiana conferred elevated resistance to Fspa_1. Moreover, PabHLH15 and PabHLH102 positively interact with the promoter of flavonoid biosynthesis-related genes. A regulatory network of TFs regulating enzyme genes related to flavonoid synthesis affecting apricot disease resistance was constructed. These results reveal the potential underlying mechanisms of the F. solani response of P. armeniaca, which would help improve the disease resistance of P. armeniaca and may cultivate high-quality disease-resistant varieties in the future.


Asunto(s)
Micosis , Prunus armeniaca , Transcriptoma , Prunus armeniaca/genética , Prunus armeniaca/metabolismo , Resistencia a la Enfermedad/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
17.
J Nanobiotechnology ; 21(1): 214, 2023 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-37420266

RESUMEN

Despite rapid advances in metabolic therapies over the past decade, their efficacy in melanoma has been modest, largely due to the interaction between cancer-associated fibroblasts (CAFs) and cancer cells to promote cancer growth. Altering the tumor microenvironment (TME) is challenging and elusive. CAFs is critical for glutamine deprivation survival in melanoma. In this research, we assembled a CAFs-targeted, controlled-release nanodroplets for the combined delivery of the amino acid transporter ASCT2 (SLC1A5) inhibitor V9302 and GLULsiRNA (siGLUL). The application of ultrasound-targeted microbubble disruption (UTMD) allows for rapid release of V9302 and siGLUL, jointly breaking the glutamine metabolism interaction between CAFs and cancer cells on one hand, on the other hand, blocking activated CAFs and reducing the expression of extracellular matrix (ECM) to facilitate drug penetration. In addition, ultrasound stimulation made siGLUL more accessible to tumor cells and CAFs, downregulating GLUL expression in both cell types. FH-V9302-siGLUL-NDs also serve as contrast-enhanced ultrasound imaging agents for tumor imaging. Our study developed and reported FH-NDs as nanocarriers for V9302 and siGLUL, demonstrating that FH-V9302-siGLUL-NDs have potential bright future applications for integrated diagnostic therapy. Graphical Abstract.


Asunto(s)
Fibroblastos Asociados al Cáncer , Melanoma , Neoplasias , Humanos , Fibroblastos Asociados al Cáncer/patología , Glutamina , Microambiente Tumoral/fisiología , Neoplasias/patología , Melanoma/metabolismo , Ultrasonografía , Antígenos de Histocompatibilidad Menor/metabolismo , Sistema de Transporte de Aminoácidos ASC/metabolismo
18.
Front Physiol ; 14: 1166061, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37520832

RESUMEN

Ultrasound (US) is widely used in the clinical diagnosis and treatment of musculoskeletal diseases. However, the low efficiency and non-uniformity of artificial recognition hinder the application and popularization of US for this purpose. Herein, we developed an automatic muscle boundary segmentation tool for US image recognition and tested its accuracy and clinical applicability. Our dataset was constructed from a total of 465 US images of the flexor digitorum superficialis (FDS) from 19 participants (10 men and 9 women, age 27.4 ± 6.3 years). We used the U-net model for US image segmentation. The U-net output often includes several disconnected regions. Anatomically, the target muscle usually only has one connected region. Based on this principle, we designed an algorithm written in C++ to eliminate redundantly connected regions of outputs. The muscle boundary images generated by the tool were compared with those obtained by professionals and junior physicians to analyze their accuracy and clinical applicability. The dataset was divided into five groups for experimentation, and the average Dice coefficient, recall, and accuracy, as well as the intersection over union (IoU) of the prediction set in each group were all about 90%. Furthermore, we propose a new standard to judge the segmentation results. Under this standard, 99% of the total 150 predicted images by U-net are excellent, which is very close to the segmentation result obtained by professional doctors. In this study, we developed an automatic muscle segmentation tool for US-guided muscle injections. The accuracy of the recognition of the muscle boundary was similar to that of manual labeling by a specialist sonographer, providing a reliable auxiliary tool for clinicians to shorten the US learning cycle, reduce the clinical workload, and improve injection safety.

19.
Cancer Control ; 30: 10732748231188261, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37523422

RESUMEN

OBJECTIVES: This retrospective cohort study investigated the association of socioeconomic status with survival outcomes among patients with nasopharyngeal carcinoma in an endemic area of China. METHODS: The primary endpoint was overall survival. Survival outcomes were estimated by the Kaplan-Meier method and compared by the log-rank test, and the multivariate Cox proportional hazards model was used to estimate hazard ratios, 95% CIs, and independent prognostic factors. RESULTS: A total of 11 069 adult patients with NPC were enrolled and included in the analysis. Kaplan-Meier survival analysis revealed that overall survival was significantly different among socioeconomic status. Compared with high socioeconomic status patients, low socioeconomic status patients (HR, 1.190; 95% CI, 1.063-1.333) and medium socioeconomic status patients (HR, 1.111; 95% CI, 1.006-1.226) were associated with increased hazard ratio (HR) of overall survival. CONCLUSION: This analysis highlights patients with nasopharyngeal carcinoma who had high socioeconomic status had better overall survival compared with those who had low and medium socioeconomic status.


Asunto(s)
Neoplasias Nasofaríngeas , Adulto , Humanos , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Estudios Retrospectivos , Disparidades Socioeconómicas en Salud , Modelos de Riesgos Proporcionales , Pronóstico
20.
RSC Adv ; 13(19): 13177-13182, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37124008

RESUMEN

Tungsten oxide is regarded as the most promising electrochromic material owing to its continuously tunable optical properties, low cost, and high coloration efficiency. Further improving its optical modulation, switching speed, and coloration efficiency is important to electrochromic smart windows and related devices. Here, we demonstrate an enhanced electrochromic film composed of a WO3 nanosheet and ITO nanoparticles developed by an all-solution technology. The WO3 nanosheet is fabricated by an acid-assisted hydrothermal process with high product efficiency. The introduction of an ITO into the WO3 nanosheets significantly improved the electrochemical activity and the conductivity of the composite film. Compared with a reported electrochromic film without ITO doping, our synthesized composite WO3 film exhibited optical modulation up to 88% and a high coloration efficiency of 154.16 cm2 C-1. Particularly, our electrochromic film was based on the dispersant solution and spin-coating technology, which may also be realized with nano-spray coating for large scale applications. The results offer an effective way to develop large-area electrochromic film and devices.

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