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1.
Sci Rep ; 14(1): 11506, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769108

RESUMO

The optimal design of groundwater circulation wells (GCWs) is challenging. The key to purifying groundwater using this technique is its proficiency and productivity. However, traditional numerical simulation methods are limited by long modeling times, random optimization schemes, and optimization results that are not comprehensive. To address these issues, this study introduced an innovative approach for the optimal design of a GCW using machine learning methods. The FloPy package was used to create and implement the MODFLOW and MODPATH models. Subsequently, the formulated models were employed to calculate the characteristic indicators of the effectiveness of the GCW operation, including the radius of influence (R) and the ratio of particle recovery (Pr). A detailed collection of 3000 datasets, including measures of operational efficiency and key elements in machine learning, was meticulously compiled into documents through model execution. The optimization models were trained and evaluated using multiple linear regression (MLR), artificial neural networks (ANN), and support vector machines (SVM). The models produced by the three approaches exhibited notable correlations between anticipated outcomes and datasets. For the optimal design of circulating well parameters, machine learning methods not only improve the optimization speed, but also expand the scope of parameter optimization. Consequently, these models were applied to optimize the configuration of the GCW at a site in Xi'an. The optimal scheme for R (Q = 293.17 m3/d, a = 6.09 m, L = 7.28 m) and optimal scheme for Pr (Q = 300 m3/d, a = 3.64 m, L = 1 m) were obtained. The combination of numerical simulations and machine learning is an effective tool for optimizing and predicting the GCW remediation effect.

2.
BMC Biol ; 22(1): 113, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750524

RESUMO

BACKGROUND: Protein posttranslational modifications (PTMs) are fast and early responses to environmental changes, including pathogen infection. Jujube witches' broom (JWB) is a phytoplasma disease causing great economic loss in jujube production. After phytoplasma infection, the transcriptional, translational, and metabolic levels in jujube were activated, enabling it to survive during phytoplasma invasion. However, no study has yet reported on PTMs in jujube. Lysine crotonylation (Kcr) and lysine succinylation (Ksu) have been popular studies in recent years and their function in plant phytoplasma-stress responses remains unclear. RESULTS: Here, 1656 crotonylated and 282 succinylated jujube proteins were first identified under phytoplasma-stress, of which 198 were simultaneously crotonylated and succinylated. Comparative analysis revealed that 656 proteins, 137 crotonylated and 43 succinylated proteins in jujube were regulated by phytoplasma infection, suggesting that Kcr was more universal than Ksu. Kcr differentially expressed proteins (DEPs) were related to ribosomes, photosynthetic and carbon metabolism, while Ksu DEPs were mainly involved in carbon metabolism, the TCA cycle and secondary metabolite biosynthesis. The crosstalk network among proteome, crotonylome and succinylome showed that DEPs related to ribosomal, peroxidases and glutathione redox were enriched. Among them, ZjPOD51 and ZjPHGPX2 significantly increased at the protein and Kcr level under phytoplasma-stress. Notably, 7 Kcr sites were identified in ZjPHGPX2, a unique antioxidant enzyme. After inhibitor nicotinamide (NAM) treatment, GPX enzyme activity in jujube seedlings was reduced. Further, site-directed mutagenesis of key Kcr modification sites K130 and/or K135 in ZjPHGPX2 significantly reduced its activity. CONCLUSIONS: This study firstly provided large-scale datasets of Kcr and Ksu in phytoplasma-infected jujube and revealed that Kcr modification in ZjPHGPX2 positively regulates its activity.


Assuntos
Phytoplasma , Doenças das Plantas , Proteínas de Plantas , Ziziphus , Ziziphus/microbiologia , Ziziphus/metabolismo , Phytoplasma/fisiologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Doenças das Plantas/microbiologia , Processamento de Proteína Pós-Traducional , Estresse Fisiológico , Lisina/metabolismo
3.
Toxicol Appl Pharmacol ; 487: 116958, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38735591

RESUMO

Acute lung injury (ALI) remains a significant clinical challenge due to the absence of effective treatment alternatives. This study presents a new method that employs a screening platform focusing on MyD88 affinity, anti-inflammatory properties, and toxicity. This platform was used to evaluate a 300-compound library known for its anti-inflammatory potential. Among the screened compounds, Bicyclol emerged as a standout, exhibiting MyD88 binding and a significant reduction in LPS-stimulated pro-inflammatory factors production in mouse primary peritoneal macrophages. By targeting MyD88, Bicyclol disrupts the MyD88/TLR4 complex and MyD88 polymer formation, thereby mitigating the MAPKs and NF-κB signaling pathways. In vivo experiments further confirmed Bicyclol's efficacy, demonstrating alleviated ALI symptoms, decreased inflammatory cytokines level, and reduced inflammatory cells presence in lung tissues. These findings were associated with a decrease in mortality in LPS-challenged mice. Overall, Bicyclol represents a promising treatment option for ALI by specifically targeting MyD88 and limiting inflammatory responses.

4.
Heliyon ; 10(9): e30276, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38711667

RESUMO

Investigating oat tissue microflora during its different developmental stages is necessary for understanding its growth and anti-disease mechanism. In this study, 16S rDNA and ITS (Internally Transcribed Spacer) high-throughput sequencing technology were used to explore the microflora diversity of oat tissue. Twenty-seven samples of leaves, stems, and roots from three developmental stages, namely the seedling stage (SS), jointing stage (JS), and maturity stage (MS), underwent sequencing analysis. The analysis showed that 6480 operational taxonomic units (OTUs) were identified in the examined samples, of which 1698 were fungal and 4782 were bacterial. Furthermore, 126 OTUs were shared by fungi, mainly Ascomycota, Basidiomycota, and Mucoromycota at the phylum level, and 39 OTUs were shared by bacteria, mainly Actinobacteriota and Proteobacteria at the phylum level. The microbial diversity of oat tissue in the three developmental stages showed differences, and the α-diversity of the bacteria and ß-diversity of the bacteria and fungi in the roots were higher than those of the stems and leaves. Among the bacteria species, Thiiopseudomonas, Rikenellaceae RC9 gut group, and Brevibacterium were predominant in the leaves, MND1 was predominant in the roots, and Lactobacillus was predominant in the stems. Moreover, Brevibacterium maintained a stable state at all growth stages. In the fungal species, Phomatospora was dominant in the leaves, Kondoa was dominant in the roots, and Pyrenophora was dominant in the stems. All species with a high abundance were related to the growth process of oats and antagonistic bacteria. Furthermore, connection modules were denser in bacterial than in fungal populations. The samples were treated with superoxide dismutase and peroxidase. There were 42 strains associated with SOD (Superoxide dismutase), 60 strains associated with POD (Peroxidase), and 38 strains in total, which much higher than fungi. The network analysis showed that bacteria might have more dense connection modules than fungi, The number of bacterial connections to enzymes were much higher than that of fungi. Furthermore, these results provide a basis for further mechanistic research.

5.
Plant Physiol Biochem ; 211: 108679, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38714127

RESUMO

Cold stress is a limiting stress factor that limits plant distribution and development; however, polyploid plants have specific characteristics such as higher resistance to abiotic stress, especially cold stress, that allow them to overcome this challenge. The cultivated cultivar Ziziphus jujuba Mill. 'Yueguang' (YG) and its autotetraploid counterpart 'Hongguang' (HG) exhibit differential cold tolerance. However, the underlying molecular mechanism and methods to enhance their cold tolerance remain unknown. Anatomical structure and physiological analysis indicated YG had a higher wood bark ratio, and xylem ratio under cold treatment compared to HG. However, the half-lethal temperature (LT50), cortex ratio, and malondialdehyde (MDA) content were significantly decreased in YG than HG, which indicated YG was cold tolerant than HG. Transcriptome analysis showed that 2084, 1725, 2888, and 2934 differentially expressed genes (DEGs) were identified in HC vs YC, H20 vs Y20, Y20 vs YC, and H20 vs HC treatment, respectively. Meanwhile, KEGG enrichment analysis of DEGs showed that several metabolic pathways, primarily plant hormone signal transduction and the MAPK signaling pathway, were involved in the differential regulation of cold tolerance between YG and HG. Furthermore, exogenous abscisic acid (ABA) and brassinolide (BR) treatments could improve their cold tolerance through increased SOD and POD activities, decreased relative electrical conductivity, and MDA content. All of these findings suggested that plant hormone signal transduction, particularly ABA and BR, might have an important role in the regulation of differential cold tolerance between YG and HG, laying the foundation for further improving cold tolerance in jujube and examining the molecular mechanisms underlying differences in cold tolerance among different ploidy cultivars.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38713298

RESUMO

PURPOSE: The unsatisfactory efficacy of PD-L1 antibodies in glioblastoma (GBM) is largely due to the temporal and spatial heterogeneity of PD-L1 expression. Molecular imaging can enhance understanding of the tumor immune microenvironment and guide immunotherapy. However, highly sensitive imaging agents capable of effectively visualizing PD-L1 heterogeneity are limited. This study introduces a novel PET tracer, offering improved imaging of PD-L1 heterogeneity in GBM xenografts, with a comparative analysis to [18F]AlF-NOTA-WL12. METHODS: [18F]AlF-NOTA-PCP2 was synthesized with high purity and its affinity for PD-L1 was characterized using surface plasmon resonance (SPR) and cell binding assays. Its specificity for PD-L1 was evaluated both in vitro using various cell lines and in vivo with GBM xenograft models in NOD/SCID mice. PET/CT imaging was conducted to evaluate the tracer's biodistribution, pharmacokinetics, and ability to quantify tumoral spatial heterogeneity of PD-L1 expression. A focused comparative analysis between [18F]AlF-NOTA-PCP2 and [18F]AlF-NOTA-WL12 was conducted, examining binding affinity, biodistribution, pharmacokinetics, and imaging effectiveness in GBM xenografts. Additionally, human radiation dosimetry estimates compared the safety profiles of both tracers. RESULTS: [18F]AlF-NOTA-PCP2 demonstrated high radiochemical purity (> 95%) and a strong affinity for PD-L1, comparable to [18F]AlF-NOTA-WL12. In vitro and in vivo studies confirmed its specificity for PD-L1, with increased uptake in PD-L1 expressing cells and tumors. Toxicological profiles indicated no significant abnormalities in serum biochemical indicators or major organ tissues. MicroPET/CT imaging showed [18F]AlF-NOTA-PCP2's effectiveness in visualizing PD-L1 expression levels and spatial heterogeneity in GBM xenografts. Comparative studies revealed [18F]AlF-NOTA-PCP2's improved pharmacokinetic properties, including higher tumor-to-blood ratios and lower nonspecific liver uptake, as well as reduced radiation exposure compared to [18F]AlF-NOTA-WL12. CONCLUSION: [18F]AlF-NOTA-PCP2 distinguishes itself as an exceptionally sensitive PET/CT tracer, adept at non-invasively and accurately quantifying PD-L1 expression and its spatial heterogeneity in tumors, especially in GBM. Its favorable pharmacokinetic properties, safety profile, and high affinity for PD-L1 highlight its potential for enhancing the precision of cancer immunotherapy and guiding individualized treatment strategies. While promising, its clinical translation, especially in brain imaging, necessitates further validation in clinical trials.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38727094

RESUMO

Commercial nickel foam (NF), which is composed of numerous interconnected ligaments and hundred-micron pores, is widely acknowledged as a current collector/electrode material for catalysis, sensing, and energy storage applications. However, the commonly used NF often does not work satisfactorily due to its smooth surface and hollow structure of the ligaments. Herein, a gas-phase-induced engineering, two-step gaseous oxidation-reduction (GOR) is presented to directly transform the thin-walled hollow ligament of NF into a three-dimensional (3D) nanoporous prism structure, resulting in the fabrication of a unique hierarchical porous nickel foam (HPNF). This 3D nanoporous architecture is achieved by utilizing the spontaneous reconstruction of nickel atoms during volume expansion and contraction in the GOR process. The process avoids the involution of acid-base corrosion and sacrificial components, which are facile, environmentally friendly, and suitable for large-scale fabrication. Furthermore, MnO2 is electrochemically deposited on the HPNF to form a supercapacitor electrode (HPNF/MnO2). Because of the fully open structure for ion transport, superhydrophilic properties, and the increased contact area between MnO2 and the current collector, the HPNF/MnO2 electrode exhibits a high specific capacitance of 997.5 F g-1 at 3 A g-1 and remarkable cycling stability with 99.6% capacitance retention after 20000 cycles in 0.1 M Na2SO4 electrolyte, outperforming most MnO2-based supercapacitor electrodes.

9.
PLoS Biol ; 22(3): e3002515, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38512963

RESUMO

The signaling environment, or niche, often governs the initial difference in behavior of an adult stem cell and a derivative that initiates a path towards differentiation. The transition between an instructive stem cell niche and differentiation niche must generally have single-cell resolution, suggesting that multiple mechanisms might be necessary to sharpen the transition. Here, we examined the Drosophila ovary and found that Cap cells, which are key constituents of the germline stem cell (GSC) niche, express a conserved microRNA (miR-124). Surprisingly, loss of miR-124 activity in Cap cells leads to a defect in differentiation of GSC derivatives. We present evidence that the direct functional target of miR-124 in Cap cells is the epidermal growth factor receptor (EGFR) and that failure to limit EGFR expression leads to the ectopic expression of a key anti-differentiation BMP signal in neighboring somatic escort cells (ECs), which constitute a differentiation niche. We further found that Notch signaling connects EFGR activity in Cap cells to BMP expression in ECs. We deduce that the stem cell niche communicates with the differentiation niche through a mechanism that begins with the selective expression of a specific microRNA and culminates in the suppression of the major anti-differentiation signal in neighboring cells, with the functionally important overall role of sharpening the spatial distinction between self-renewal and differentiation environments.


Assuntos
Proteínas de Drosophila , MicroRNAs , Animais , Feminino , Drosophila/genética , Drosophila/metabolismo , Ovário/metabolismo , Proteínas de Drosophila/metabolismo , Nicho de Células-Tronco/genética , Diferenciação Celular/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Células-Tronco/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Comunicação , Drosophila melanogaster/metabolismo , Células Germinativas/metabolismo
10.
J Agric Food Chem ; 72(13): 7244-7255, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38517372

RESUMO

The instability of curcumin's structure and the toxic side effects of piperlongumine have limited their potential applications in cancer treatment. To overcome these challenges, we designed and synthesized a novel curcumin-piperlongumine hybrid molecule, 3-[(E)-4-hydroxy-3-methoxybenzylidene]-1-[(E)-3-(3,4,5-trimethoxyphenyl)acryloyl]piperidin-2-one (CP), using a molecular hybridization strategy. CP exhibited enhanced structural stability and safety compared with its parent compounds. Through in vitro and in vivo biological activity screenings, CP effectively inhibited cell proliferation, caused cell cycle arrest in the G2/M phase, and induced apoptosis. Mechanistically, CP-induced apoptosis was partially mediated by cell cycle arrest. Furthermore, we discovered that CP induces cell cycle arrest and apoptosis through the regulation of JNK signaling. These findings highlight the potential of CP as a promising therapeutic agent for lung cancer treatment.


Assuntos
Benzodioxóis , Curcumina , Neoplasias Pulmonares , Humanos , Curcumina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Linhagem Celular Tumoral , Pontos de Checagem do Ciclo Celular , Apoptose , Proliferação de Células , Sistema de Sinalização das MAP Quinases , Ciclo Celular
11.
Int J Biol Macromol ; 264(Pt 1): 130429, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428762

RESUMO

CIPKs are kind of serine/threonine (Ser/Thr) protein kinases which play important roles in response to biotic and abiotic stresses, and in plant growth and development. However, CIPKs in jujube (Ziziphus jujuba Mill.) had limited information, especially regarding their response to cold stress. In the current study, a total of 18 ZjCIPKs were identified in jujube genome which unevenly distributed on seven chromosomes. Conserved motif and gene structural analysis depicted them with conserved DEGLSA and APE motifs and similar structures. Phylogenetic analysis indicated that CIPKs were classified into five subgroups (I-V). In addition, three pairs of ZjCIPKs exhibited tandem duplication while the segmental duplication of ZjCIPKs was not identified. Study on the cis-acting elements indicted that stress or hormone related cis-acting elements were distributed unevenly on ZjCIPKs promoters and most ZjCIPKs were down- or up-regulated by the cold stress. VIGS induced silencing of ZjCIPK5 decreased the cold tolerance of sour jujube. Subcellular location analysis showed ZjCIPK5 located in nucleus. Moreover, transcription factor ZjbHLH74 which was induced at 6 h under cold stress could interact with the promoter of ZjCIPK5 to regulate jujube cold tolerance. These findings provided insights to a molecular basis of CIPK5 in jujube cold tolerance breeding for future.


Assuntos
Ziziphus , Ziziphus/genética , Filogenia , Melhoramento Vegetal , Fatores de Transcrição/genética , Resposta ao Choque Frio/genética , Proteínas de Plantas/química , Regulação da Expressão Gênica de Plantas
12.
PeerJ ; 12: e17009, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38436035

RESUMO

Background: Inflammation and metabolic disorders are important factors in the occurrence and development of obesity complications. In this study, we investigated the protective effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, Cyy-287, on mice fed a high-fat diet (HFD). Methods: The mice were randomly separated into four groups (n ≥ 7): control (regular diet), HFD, HFD with Cyy-287 (5 mg/kg), and HFD with Cyy-287 (20 mg/kg) following HFD feeding for 10 weeks. After a 10-week administration, ALT and AST enzymes, echocardiography, immunohistochemical (IHC), Western blot (WB), Masson and Sirius Red staining were used to evaluate functional and morphological changes to the heart and liver. Microsomes from the mouse liver were extracted to quantify the total amount of CYP450 enzymes after drug treatment. Results: Cyy-287 decreased the levels of serum glucose, LDL, TC, ALT, and AST activities in HFD-treated mice. However, Cyy-287 administration increased ejection fraction (EF) and fractional shortening (FS) index of the heart. Cyy-287 inhibited histopathological changes in the heart and liver; decreased inflammatory activity; significantly diminished p38 mitogen-activated protein kinase (MAPK), the nuclear factor-kappa B (NF-κB) axis, and sterol regulatory element-binding protein-1c (SREBP-1c); and upregulated the AMP-activated protein kinase (AMPK) pathway in HFD-treated mice. Cyy-287 restored the content of hepatic CYP450 enzymes. Conclusion: These findings demonstrated that Cyy-287 protected heart and liver cells from obesity-induced damage by inhibiting inflammation, fibrosis, and lipid synthesis.


Assuntos
Obesidade , Pirimidinas , Animais , Camundongos , Obesidade/complicações , Pirimidinas/farmacologia , Diaminas , Inflamação/tratamento farmacológico , Fibrose , Lipídeos
13.
Acta Pharmacol Sin ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438580

RESUMO

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.

14.
Curr Issues Mol Biol ; 46(3): 1886-1903, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38534739

RESUMO

Kidney renal papillary cell carcinoma (KIRP) is a highly heterogeneous type of kidney cancer, resulting in limited effective prognostic targets for KIRP patients. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the regulation of ferroptosis and iron metabolism, making them potential targets for the treatment and prognosis of KIRP. In this study, we constructed a ferroptosis-related lncRNA risk score model (FRM) based on the TCGA-KIRP dataset, which represents a novel subtype of KIRP not previously reported. The model demonstrated promising diagnostic accuracy and holds potential for clinical translation. We observed significant differences in metabolic activities, immune microenvironment, mutation landscape, ferroptosis sensitivity, and drug sensitivity between different risk groups. The high-risk groups exhibit significantly higher fractions of cancer-associated fibroblasts (CAFs), hematopoietic stem cells (HSC), and pericytes. Drugs (IC50) analysis provided a range of medication options based on different FRM typing. Additionally, we employed single-cell transcriptomics to further analyze the impact of immune invasion on the occurrence and development of KIRP. Overall, we have developed an accurate prognostic model based on the expression patterns of ferroptosis-related lncRNAs for KIRP. This model has the potential to contribute to the evaluation of patient prognosis, molecular characteristics, and treatment modalities, and can be further translated into clinical applications.

15.
Front Microbiol ; 15: 1320845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38314436

RESUMO

Objective: Human brucellosis causes serious public health concerns in Ningxia, China. Methods: This study employed epidemiological, bacteriological, and multiple-locus variable-number tandem repeat analysis (MLVA) methods to conduct an epidemiological investigation, which is necessary for devising tailored control strategies. Results: Between 1958 and 2022, 29,892 cases were reported, with an average annual number of cases and incidence of 467 and 7.1/100,000, respectively. The epidemic situation gradually worsened, with cases escalating from 26 cases in 2005 to 6,292 in 2022, with the incidence rate rising from 0.441 in 2005 to 86.83 in 2022. Geographically, the disease spread from a single affected county in 2004 to encompass all 22 counties in 2022. Yanchi County had the highest incidence, followed by the Hongsibao and Tongxin counties. These data suggest that Brucella infection has become a rampant regional concern in human brucellosis. Between 1958 and 2019, a total of 230 Brucella strains were identified across four studied hosts. These strains comprised four species with 12 biovars, including B. melitensis bv. 1, bv. 2, bv. 3, B. abortus bv. 1, bv. 3, bv. 4, bv. 5, bv. 6, bv. 7, B. suis bv. 1 and bv. 3, and B. canis. These data highlight the high species/biovars and host diversity of the Brucella population, posing a substantial challenge to brucellosis surveillance. There was an apparent transition from multiple species/biovars historically to the current dominance of a single species, B. melitensis, emphasizing the requirement for strengthening surveillance of B. melitensis. Genotypes 42 and 116, constituting 96.2% of the total number of genotypes, predominated in panel 1 and MLVA-11, indicating that all strains belong to the East Mediterranean lineage. MLVA cluster analysis revealed persistent transmission of dominant circulating genotypes, presenting an epidemic pattern characterized primarily by epidemiologically related cases with a few sporadic cases. Strains in this study exhibited high genetic homogeneity with strains from the Northwest, and those from Kazakhstan and Mongolia. Conclusion: The epidemic situation of human brucellosis has gradually worsened; the rampant epidemic of the disease has become a regional concern. The present study highlights that implementing the of targeted surveillance and intervention strategies is urge.

18.
Mol Pharm ; 21(3): 1515-1525, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38291578

RESUMO

Immune checkpoint inhibitors (ICIs) are a powerful treatment modality for various types of cancer. The effectiveness of ICIs is intimately connected to the binding status of antibodies to receptors. However, validated means to accurately evaluate target specificity and predict antibody efficacy in vivo are lacking. A novel peptide-based probe called Al[18F]F-NOTA-PCP1 was developed and validated for its specificity to PD-L1 in A549, U87MG, GL261, and GL261-iPDL1 cell lines, as well as in xenograft models. Then the probe was used in PET/CT scans to determine the binding status of PD-L1 antibodies (atezolizumab, avelumab, and durvalumab) in U87MG xenograft model mice. Moreover, Al[18F]F-NOTA-PCP1 was used to evaluate the impact of different treatment times and doses. Al[18F]F-NOTA-PCP1 PET/CT can be used to evaluate the interaction between PD-L1 and antibodies to determine the effectiveness of immunotherapy. By quantifying target engagement, the probe has the potential to predict the efficacy of immunotherapy and optimize the dose and treatment schedules for PD-L1 immunotherapy. This imaging agent could be a valuable tool in guiding personalized treatment strategies and improving cancer patient outcomes.


Assuntos
Compostos Heterocíclicos com 1 Anel , Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Animais , Camundongos , Antígeno B7-H1/metabolismo , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Peptídeos
19.
Int J Surg Case Rep ; 115: 109276, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38280344

RESUMO

INTRODUCTION AND IMPORTANCE: Solitary bone plasmacytoma (SBP) is an early-stage plasma cell malignancy. It is an extremely rare condition and its diagnosis may not be straightforward. This report presents a case of maxillary SBP. CASE PRESENTATION: A 48-year old man sought care for persistent swelling and pain in the periapical region of the left maxillary molars. He had been diagnosed with "apical periodontitis" and root canal treatment of teeth #26 and #27 was ineffective. Extra-oral examination revealed swelling at the left maxilla. Intraoral examination revealed a hard, non-fluctuant swollen region in the buccal alveolar mucosa adjacent to the apices of teeth #25-27. Cone-beam computed tomography revealed extensive bone destruction in the left maxilla. The patient underwent partial maxillary resection and radical maxillary sinusotomy. Further testing (positron emission CT scan, histopathological and immunohistochemical examination) confirmed the diagnosis of SBP. The patient had a recurrence two years later, which was managed with left subtotal maxillectomy and radiotherapy. There was no evidence of recurrence during 20 months of follow-up. DISCUSSION: SBP may mimic an odontogenic lesion when found in the jaw bone. To confirm the diagnosis, routine blood test, complete body skeletal survey, metastatic investigations and histopathology should be performed. Radiotherapy is the primary treatment. CONCLUSION: SBP may occur in the maxilla mimicking an odontogenic lesion. Surgery may be part of the diagnostic procedure and an adjunct to definitive radiation. Radiotherapy is the primary treatment.

20.
Talanta ; 270: 125517, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38091744

RESUMO

Hydrogen sulfide (H2S) is a toxic contaminant and has great influence on many physiological processes. Due to various pathophysiological roles and environmental pollution problems, it is necessary to construct and develop simple and portable monitoring sensors for the precise detection of H2S. Herein, we developed a smartphone-adapted dual-mode detection platform by integrating the colorimetric and photothermal imaging analysis into a metal-organic framework-based chip (ZIF-8/Cu). Due to the nanoconfinement effect of ZIF-8, small-sized plasmonic CuS could be in-situ formed during the detection procedure of H2S and endowed the chips with excellent photothermal properties. By constructing a smartphone-adapted photothermal imager, the metal-organic framework-based chip could achieve a portable photothermal imaging analysis of H2S. Moreover, as the formed CuS was a good peroxidase-like nanozyme, the chips could also be used to trigger the enzymic catalytic reaction toward the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2, thus providing another colorimetric sensing mode by using a smartphone App. In this smartphone-adapted visualization platform, the portable chemosensors could simultaneously achieve double detection modes at one electrode, which provided a new pathway for the accurate detection of H2S and circumvented the false-positive or negative errors during the detection process. Besides, by using the finite difference time domain (FDTD) simulation method, the in-depth mechanism, including the plasmonic effect and spatial electromagnetic field distribution, was explored to provide a possible reason for the excellent sensing performance of the dual-mode visualization platform. This work provides a new insight into the construction of the accurate, portable and smart sensing platform in the visual screening of H2S.


Assuntos
Estruturas Metalorgânicas , Smartphone , Peróxido de Hidrogênio , Catálise , Colorimetria
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