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Cancer antigen 125 (CA125) is the gold standard biomarker for clinical diagnosis of ovarian cancer, with a threshold value of 35 U/mL in serum. In this paper, a disposable ultrasensitive immunosensor based on Ti3C2Tx-MXene/amino-functionalized carbon nanotube (NH2-CNT) modified screen-printed carbon electrode (SPCE) was constructed for the detection of the ovarian cancer antigen CA125. By optimizing the mass ratio of Ti3C2Tx to NH2-CNT, Ti3C2Tx/NH2-CNT composite with excellent electrochemical properties was prepared, which is beneficial for amplifying the initial electrochemical signal. The positively charged NH2-CNT effectively alleviated the stacking problem of Ti3C2Tx, and its amino group also facilitated the covalent immobilization of the capture antibody. Meanwhile, chitosan (CS) with excellent film-forming ability was also used to successfully enhance the adsorption of electrode material, thus improving the stability of the sensor. In addition, CS could further enhance the current signal. The prepared immunosensor exhibited excellent performance in CA125 detection with a wide linear range from 1 mU/mL to 500 U/mL, and good selectivity, reproducibility and lomg-term stability. Furthermore, the immunosensor showed satisfactory results for the detection of CA125 in clinical serum samples, which is promising for the clinical screening, early diagnosis and prognostic examination of ovarian cancer.
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Técnicas Biossensoriais , Antígeno Ca-125 , Eletrodos , Nanotubos de Carbono , Neoplasias Ovarianas , Antígeno Ca-125/sangue , Humanos , Nanotubos de Carbono/química , Feminino , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Técnicas Eletroquímicas/métodos , Titânio/química , Limite de Detecção , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Proteínas de MembranaRESUMO
Heterostructures endow electrochemical hybrids with promising energy storage properties owing to synergistic effects and interfacial interaction. However, developing a facile but effective approach to maximize interface effects is crucial but challenging. Herein, a bimetallic sulfide/carbon heterostructure is realized in a confined carbon network via a high-throughput template-assisted strategy to induce highly active and stable electrode architecture. The designed heterostructures not only yield abundant interconnected Co9S8/MoS2/N-doped carbon (Co9S8/MoS2/NC) heterojunctions with continuous channels for ion/electron transfer but maintain excellent conversion reversibility. Serving as anode for sodium storage, the Co9S8/MoS2/NC framework displayed excellent sodium storage properties (reversible capacity of 480 mAh/g after 100 cycles at 0.2 A/g and 286.2 mAh/g after 500 cycles at 2 A/g). Given this, this study can guide future design protocols for interface engineering by forming dynamic channels of conversion reaction kinetics for potential applications in high-performance electrodes.
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Quantum state tomography (QST) via local measurements on reduced density matrices (LQST) is a promising approach but becomes impractical for large systems. To tackle this challenge, we developed an efficient quantum state tomography method inspired by quantum overlapping tomography [Phys. Rev. Lett. 124, 100401 (2020)PRLTAO0031-900710.1103/PhysRevLett.124.100401], which utilizes parallel measurements (PQST). In contrast to LQST, PQST significantly reduces the number of measurements and offers more robustness against shot noise. Experimentally, we demonstrate the feasibility of PQST in a treelike superconducting qubit chip by designing high-efficiency circuits, preparing W states, ground states of Hamiltonians, and random states, and then reconstructing these density matrices using full quantum state tomography (FQST), LQST, and PQST. Our results show that PQST reduces measurement cost, achieving fidelities of 98.68% and 95.07% after measuring 75 and 99 observables for six-qubit and nine-qubit W states, respectively. Furthermore, the reconstruction of the largest density matrix of the 12-qubit W state is achieved with the similarity of 89.23% after just measuring 243 parallel observables, while 3^{12}=531 441 complete observables are needed for FQST. Consequently, PQST will be a useful tool for future tasks such as the reconstruction, characterization, benchmarking, and properties learning of states.
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Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell-derived sarcomas that are sporadic or associated with Neurofibromatosis 1 (NF1) gene mutations. Traditional therapies are usually ineffective for treating MPNSTs, so new targets need to be identified for the treatment of MPNSTs. In the present study, the role of the mitochondrial translocator protein (TSPO) in the regulation of cell proliferation and the cell cycle in MPNSTs was investigated. TSPO expression was lower in MPNSTs than in NFs. Loss-of-function experiments revealed that TSPO deficiency promoted MPNST cell growth, migration, and invasion and influenced the cell cycle in vitro and in vivo. In addition, TSPO depletion suppressed cell apoptosis by downregulating the expression of caspase-3, caspase-8, HSP60, p27, p53, and BCL-2 and suppressed the cell cycle by upregulating CDK1, CDK2, CCNB1 and CCNA2. Furthermore, CDK1 was determined to be an upstream target of TSPO-mediated regulation via RNA-seq, qPCR, and Western blotting. Specifically, depletion of CDK1 weakened the effect of TSPO deficiency on cell proliferation and migration. More importantly, CDK1 knockdown induced significant cell cycle arrest in the G2/M phase. In summary, TSPO deficiency regulates the cell cycle in MPNSTs by targeting CDK1, which may be an effective molecular target for prognosis evaluation and treatment.
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Proteína Quinase CDC2 , Movimento Celular , Proliferação de Células , Receptores de GABA , Humanos , Proteína Quinase CDC2/metabolismo , Proteína Quinase CDC2/genética , Receptores de GABA/metabolismo , Receptores de GABA/genética , Camundongos , Animais , Movimento Celular/genética , Linhagem Celular Tumoral , Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Progressão da Doença , Masculino , Feminino , Neoplasias de Bainha Neural/genética , Neoplasias de Bainha Neural/patologia , Neoplasias de Bainha Neural/metabolismo , Camundongos NusRESUMO
Organic material polyimides (PI) are widely used in secondary batteries due to green safety, renewables, and structural designability. However, problems such as low conductivity and structural damage of polyimide electrode materials seriously limit its practical application. Herein, an innovative in situ modification method with CaCl2 is used to construct pure Al metal-based artificial SEI film on the surface of PI to improve the electrochemical performance of organic dual-ion batteries. Compared with the pure PI material, it has a noticeable improvement in cycle performance. Importantly, characterization results of the physicochemical analysis show that the pure Al metal-based artificial SEI film formed in situ on the surface of the PI material plays a key role in isolating and improving the electrochemical performance of PI anode materials. The innovative approach offers an efficacious strategy to construct pure metal-based artificial SEI films for the practical implementation of organic batteries.
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Cerium and lanthanum dialkyl complexes [η5-1,2,4-(Me3C)3C5H2]Ln(CH2C6H4-o-NMe2)2 (Ln = Ce 1 and La 2), supported by a tri-tert-butylcyclopentadienyl ligand, have been successfully synthesized. Studies demonstrate that these complexes possess diverse reactivity toward various small molecules. For example, the reaction of complexes 1 and 2 with diphenyl dichalcogenides PhEEPh (E = S, Se) results in the formation of lanthanide thiolates [(η5-1,2,4-(Me3C)3C5H2)Ln(SPh)(µ-SPh)]2 (Ln = Ce 3 and La 4) and selenolates [(η5-1,2,4-(Me3C)3C5H2)Ln(SePh)(µ-SePh)]2 (Ln = Ce 5 and La 6), concomitantly releasing PhE(CH2C6H4-o-NMe2). Furthermore, complexes 1 and 2, upon reaction with dibenzyl disulfide, yield tetranuclear rare-earth metallomacrocyclic compounds {[(η5-1,2,4-(Me3C)3C5H2)Ln(µ-SCH2C6H5)]2(µ-η3:η3-SCHC6H5)}2 (Ln = Ce 7 and La 8). This reaction may involve a process of σ-bond metathesis and C-H activation. While the reaction of 1 and 2 with dibenzyl diselenide in the presence of LiCH2C6H4-o-NMe2 leads to the formation of lanthanide-lithium selenido clusters [(η5-1,2,4-(Me3C)3C5H2)La(µ-SeCH2C6H5)]3(µ3-Se)[µ3-SeLi(THF)3] (Ln = Ce 9 and La 10). Meanwhile, lanthanide selenido clusters [(η5-1,2,4-(Me3C)3C5H2)La(µ-SeCH2C6H4-o-NMe2)]4(µ3-Se)2 (Ln = Ce 11 and La 12) can be obtained by treating 1 and 2 with elemental selenium in a 1:2 molar ratio. Additionally, the treatment of 1 and 2 with benzoxazole generates ring-opening/C-C coupling/C-N coupling products {(η5-1,2,4-(Me3C)3C5H2)La[µ-OC6H4-o-NâCHN(CH(CH2C6H4-o-NMe2)2C6H4-o-O]}2 (Ln = Ce 13 and La 14). All new compounds were characterized by various spectroscopic methods, and their solid-state structures were confirmed by single-crystal X-ray diffraction analyses.
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BACKGROUND: Lung cancer (LC) is the leading cause of malignancy-related mortalities globally, and the existing treatment interventions are associated with harmful side effects. In the current study, we evaluated the anti-tumor efficiency of nerolidol (NRD) on human non-small cell lung cancer (NSCLC) cells. OBJECTIVES: Nerolidol is a sesquiterpene alcohol extracted from the essential oils of aromatic flora with known anti-cancer activities. MATERIAL AND METHODS: The latent action of NRD on antiproliferative and apoptotic effects in A549 cells is uncertain. Thus, our work is designed to explore the antiproliferative and apoptotic actions of NRD (20 and 25 µM/mL) against A549 cells. The activity of NRD on A549 cell cytotoxicity, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis, anti-apoptotic proteins, and MAPK/TAT3/NF-κB and P13K/AKT signaling pathways were assessed using MTT tests, dichlorodihydrofluorescein diacetate (DCFH-DA), dual acridine orange/ethidium bromide (AO/EB), DAPI, Rh-123, reverse transciption polymerase chain reaction (RT-PCR), and western blot analyses. RESULTS: We found that NRD could inhibit NSCLC cell viability through elevated intracellular ROS and MMP loss and elicited apoptosis in a quantity-dependent manner. Similarly, NRD can reduce inflammatory cytokines and anti-apoptotic elements, as well as trigger apoptotic signaling pathways. CONCLUSIONS: Our data established that NRD decreases A549 cell proliferation through ROS-mediated apoptosis, triggering the MAPK/STAT3/NF-κB and P13K/AKT pathways, suggesting that NRD is a possible protective remedy for NSCLC.
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Molecular cloning and functional characterization of Nemopilema nomurai venom metalloproteinases have provided deeper insights into the pathogenesis of jellyfish dermatitis. This study reports a new cDNA clone from N. nomurai tentacle venom (Transcript sequence: ID469) encoding 362 amino acid residues, belonged to astacin family and capable of disrupting the cell matrix. The N. nomurai metalloproteinase 469 (NnM469) comprises a signal peptide and propeptide, followed by metalloproteinase domain containing a zinc-binding motif, and two ShKT domains. Notably, NnM469 features a zinc-binding motif (HEXXH) at the active site, within an extended sequence of HEXXHXXGFXHE, which is unique to astacin. Immunocytochemistry revealed that NnM469 is located in the stab tube and envelope of jellyfish nematocysts. Western blot and LC-MS/MS analysis confirmed that the NnM469 protein was successfully expressed using the Pichia pastoris expression system. The recombinant NnM469 could degrade the cell matrix, resulting in the death of HaCaT cells with an IC50 of 26.34 µg/mL. Finally, I-TASSER-generated structure and function predictions indicated that conserved Asp53, His168, His172, His178, and Tyr227 serve as key amino acid residues for the Zn2+ ion binding in the catalytic center. In summary, the study of the molecular characteristics and function of NnM469 presents an opportunity to develop therapeutic interventions for jellyfish venom-induced dermatitis.
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The treatment-induced activation level within the perivascular tumor microenvironment (TME) that supports T-cell trafficking and optimal T-cell differentiation is unknown. We investigated the mechanisms by which inflammatory responses generated by tumor-specific T cells delivered to ovarian tumor-bearing mice alone or after oncolytic vaccinia virus-driven immunogenic cancer cell death affect antitumor efficacy. Analyses of the perivascular TME by spatially resolved omics technologies revealed reduced immunosuppression and increased tumoricidal T-cell trafficking and function after moderate inflammatory responses driven by a CXCR4 antagonist-armed oncolytic virus. Neither weak nor high inflammation created a permissive TME for T-cell trafficking. Notably, treatment-mediated differences in T-cell effector programs acquired within the perivascular TME contrasted with comparable antigenic priming in the tumor-draining lymph nodes regardless of the activation mode of antigen-presenting cells. These findings provide new insights into combinatorial treatment strategies that enable tumor-specific T cells to overcome multiple barriers for enhanced trafficking and control of tumor growth.
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OBJECTIVES: This study aimed to evaluate the diagnostic significance of computed tomography (CT) detected ascites in gastric cancer (GC) with peritoneal metastasis (PM) and investigate its association with systemic inflammatory response. METHODS: This retrospective study included 111 GCs with ascites (PM: n = 51; No PM: n = 60). Systemic inflammatory indexes, tumor markers, and the CT-assessed characteristics of ascites were collected. The differences in parameters between the two groups were analyzed. Diagnostic performance was obtained by receiver operating characteristic curve analysis. The association between the volume of ascites and clinical characteristics was evaluated with correlation analysis. RESULTS: In this study, over half of GCs with ascites were not involved with PM. The systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), five tumor markers, and the characteristics of ascites showed significant differences between the two groups (all p < 0.05). Among them, SII, NLR, PLR, and the volume of ascites achieved the areas under the curve of 0.700, 0.698, 0.704, and 0.903, respectively. Moreover, the volumes of ascites showed positive correlations with SII, NLR, and PLR in GCs with PM, and the volumes of ascites detected in the upper abdomen were more strongly correlated with CA125 level (all p < 0.05). CONCLUSION: Many GCs with CT-detected ascites did not occur with synchronous PM. The presence of upper abdominal ascites had certain clinical significance for diagnosing PM in GCs. Systemic inflammatory indexes were elevated and positively correlated with the volume of ascites in GCs with PM, which might suggest the enhanced systemic inflammatory response. CRITICAL RELEVANCE STATEMENT: CT-detected ascites in the upper abdomen played an indicative role in identifying synchronous PM in GCs, and the systemic inflammatory response was enhanced in GCs with PM, which might be helpful for clinical evaluation. KEY POINTS: Many GCs with CT-detected ascites did not occur with synchronous PM. CT-detected ascites in the upper abdomen help in identifying PM in GCs. GCs with PM showed elevated systemic inflammatory indexes and enhanced systemic inflammatory response.
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The exacerbation of wildfires caused by global warming poses a significant threat to human health and environmental integrity. This review examines the particulate matter (PM) and gaseous pollutants resulting from fire incidents and their impacts on individual health, with a specific focus on the occupational hazards faced by firefighters. Of particular concern is the release of carbon-containing gases and fine particulate matter (PM2.5) from forest fires and urban conflagrations, which exceed the recommended limits and pose severe health risks. Firefighters exposed to these pollutants demonstrate an elevated risk of developing pulmonary and cardiovascular diseases and cancer compared to the general population, indicating an urgent need for enhanced protective measures and health management strategies for firefighters. Through a meticulous analysis of the current research findings, this review delineates future research directions, focusing on the composition and properties of these pollutants, the impacts of fire-emitted pollutants on human health, and the development of novel protective technologies.
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Squalene epoxidase plays a pivotal role in the biosynthesis of ergosterol, its derivatives, and other triterpenoid compounds by catalyzing the transformation of squalene into 2,3-oxidosqualene. However, its low catalytic efficiency remains a primary bottleneck for the microbial synthesis of triterpenoids. In this study, the catalytic activity of the squalene epoxidase from Saccharomyces cerevisiae was significantly improved by reshaping its substrate tunnel, resulting in a marked increase in the yield of the final product, ergosterol. First, the amino acid in the catalytic pocket of squalene epoxidase was replaced with alanine (Ala), effectively reducing the steric hindrance, and thus, enhancing the affinity of the enzyme with its substrate. Then, the V249H/L343A mutant was obtained by redesigning the substrate tunnel of dominant mutant L343A, thus, increasing the titer of ergosterol. The study also elucidated the mechanism behind the increased catalytic activity of the V249H/L343A mutant through substrate tunnel parameter analysis and molecular dynamics simulations. Finally, a titer of 3345 mg/L of ergosterol was achieved by strains containing V249H/L343A in a 5 L bioreactor, with a specific yield of 84 mg/g dry cell weight (DCW), marking a 64% increase compared with the titer achieved by wild type strains. This study established a strong foundation for improving the synthetic efficiency of ergosterol and other triterpenoid compounds.
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Immunotherapy has emerged as a highly effective therapeutic strategy for cancer treatment. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway activation facilitates tumor-associated macrophage (TAM) polarization toward M1 phenotype, and Mn2+ are effective agents for this pathway activation. However, the high in vivo degradation rate and toxicity of Mn2+ hamper clinical application of immunotherapy. Here, this work has newly synthesized and screened manganese porphyrins for Mn2+ transport, referred to as photo-STING agonists (PSAs), and further encapsulate them into core-shell nanoparticles named Rm@PP-GA with dual specificity for tumor tissue and TAMs. Not only do PSAs achieve higher Mn2+ delivery efficiency compared to Mn2+, but they also generate reactive oxygen species under light exposure, promoting mitochondrial DNA release for cGAS-STING pathway activation. In Rm@PP-GA, globin and red blood cell membranes (Rm) are used for erythrocyte efferocytosis-mimicking delivery. Rm can effectively prolong the in vivo circulation period while globin enables PSAs to be taken up by TAMs via CD163 receptors. After Rm rupture mediated by perfluorohexane in nanoparticles under ultrasonication, drugs are specifically released for TAM repolarization. Further, dendritic cells mature, as well as T lymphocyte infiltrate, both of which favor tumor eradication. Therefore, cancer immunotherapy is optimized by novel PSAs delivered by erythrocyte efferocytosis-mimicking delivery pattern.
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White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting and doubly robust methods, were used to evaluate the impact of AL on WM BAG adjusting for age, sex, socioeconomic, and lifestyle behaviors. We found increasing one AL score unit significantly increased WM BAG by 0.29 years in association analysis and by 0.33 years in Mendelian analysis. The age- and sex-stratified analysis showed consistent results among participants 45-54 and 55-64 years old, with no significant sex difference. This study demonstrated that higher chronic stress was significantly associated with accelerated brain aging, highlighting the importance of stress management in reducing dementia and neurodegenerative disease risks.
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Secondary amines are widely used as robust catalysts for the enantioselective functionalization of aldehydes, yet they are rarely employed as Lewis bases or hydrogen-bonding catalysts for alkene activation. In this study, we present a decarboxylative [4 + 2] cycloaddition of vinyl benzoxazinanones with nitroolefins to construct tetrahydroquinolines through cascade catalysis. A single chiral morpholine catalyst sequentially functions as both a Lewis base and a hydrogen-bonding catalyst. These activation modes effectively drive the cascade process and control the stereochemistry.
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Immuno-oncology has transformed the treatment of cancer, with several immunotherapies becoming the standard treatment across histologies. Despite these advancements, the majority of patients do not experience durable clinical benefits, highlighting the imperative for ongoing advancement in immuno-oncology. Computational immuno-oncology emerges as a forefront discipline that draws on biomedical data science and intersects with oncology, immunology, and clinical research, with the overarching goal to accelerate the development of effective and safe immuno-oncology treatments from the laboratory to the clinic. In this review, we outline 10 critical challenges and opportunities in computational immuno-oncology, emphasizing the importance of robust computational strategies and interdisciplinary collaborations amid the constantly evolving interplay between clinical needs and technological innovation.
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Imunoterapia , Oncologia , Neoplasias , Humanos , Imunoterapia/métodos , Oncologia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Biologia Computacional/métodosRESUMO
Objective: To explore the clinical features, surgical treatment, and effectiveness of neurofibromas associated with neurofibromatosis type 1 (NF1). Methods: A clinical data of 41 patients with NF1 admitted between December 2018 and April 2024 was retrospectively analyzed. There were 15 males and 26 females, with an average age of 27.5 years (range, 5-61 years). Only one type of neurofibroma existed in 3 patients and the rest of the patients had more than two types of neurofibromas. Fourteen patients had total resection of multiple cutaneous neurofibromas (CNF). Eighteen patients of diffuse neurofibromas underwent total, near-total, or subtotal resection. Among the 13 patients of localized nodular neurofibromas, 9 of benign tumors underwent total sub-capsular resection and 4 of malignant peripheral nerve sheath tumor (MPNST) underwent maginal resection, and only 1 underwent postoperative radiotherapy and chemotherapy. Among the 15 patients of plexiform neurofibromas (PNF), 5 patients underwent both superficial and deep PNF resection, 2 underwent the superficial PNF resection, and 8 underwent the large nodular lesions in the deep PNF resection. There were 8 MPNST, of which 7 cases underwent total sub-capsular resection and large tumor capsule resection under neurophysiological monitoring, and 1 case with the tumor located on the top of the head underwent wide resection and skin grafting. One patient underwent proton knife therapy after surgery, 2 patients did not receive radiotherapy, and the remaining patients received conventional radiotherapy. Results: All patients were followed up after surgery, and the follow-up time was 3-66 months, with an average of 25.0 months. Patients with CNF recovered satisfactorily after surgery, and there was no recurrence during follow-up. Patients with diffuse neurofibromas relieved preoperative symptoms after surgery. Three patients with diffuse neurofibromas located in the head and face recurred during follow-up. The patients with benign localized nodular neurofibromas recovered well after surgery, and only 1 patient had transient regional neuralgia after surgery. Among the patients with MPNST, 2 patients died of recurrence and lung metastasis, while the remaining 2 patients had no recurrence and metastasis during follow-up. All preoperative symptoms disappeared in patients with benign PNF, and no tumor recurrence was observed during follow-up. Two patients with PNF located in the brachial plexus had difficulty in shoulder abduction after surgery, 1 patient with PNF located in vagus developed hoarseness after surgery. Among the 8 patients with MPNST in PNF, 1 died of lung metastases and 1 died of systemic failure. The remaining 6 patients were in stable condition during follow-up, and no tumor recurrence or metastasis was observed. Conclusion: According to the clinical features of neurofibromas in patients with NF1, choosing appropriate surgical approaches can obtain good effectiveness. Because of the difficulty of completely resection, diffuse neurofibromas, especially those located in the head and face, are prone to recurrence after surgery. MPNST has the worst prognosis, high incidence of recurrence/metastasis, and short survival period. Total resection combined with radiotherapy can decrease local recurrence.
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Neurofibroma , Neurofibromatose 1 , Humanos , Masculino , Feminino , Neurofibromatose 1/cirurgia , Neurofibromatose 1/complicações , Adulto , Pessoa de Meia-Idade , Criança , Adolescente , Adulto Jovem , Neurofibroma/cirurgia , Pré-Escolar , Neurofibroma Plexiforme/cirurgia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Recidiva Local de Neoplasia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Immune checkpoint therapy has emerged as an effective treatment option for various types of cancers. Key immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and lymphocyte activation gene 3 (LAG-3), have become pivotal targets in cancer immunotherapy. Antibodies designed to inhibit these molecules have demonstrated significant clinical efficacy. Nevertheless, the ability to monitor changes in the immune status of tumors and predict treatment response remains limited. Conventional methods, such as assessing lymphocytes in peripheral blood or conducting tumor biopsies, are inadequate for providing real-time, spatial information about T-cell distributions within heterogeneous tumors. Positron emission tomography (PET) using T-cell specific probes represents a promising and noninvasive approach to monitor both systemic and intratumoral immune changes during treatment. This technique holds substantial clinical significance and potential utility. In this paper, we review the applications of PET probes that target immune cells in molecular imaging.
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Maternal Embryonic Leucine Zipper Kinase (MELK) has been studied intensively in recent years due to its overexpression in multiple cancers. However, the cell biology of MELK remains less characterized despite its well-documented association with mitosis. Here we report a distinctive pattern of human MELK that translocates from the cytoplasm to cell cortex within 3 min of anaphase onset. The cortex association lasts about 30 min till telophase. The spatiotemporal specific localization of MELK depends on the interaction between its Threonine-Proline (TP) rich domain and kinase associated 1 (KA1) domain, which is regulated by CDK1 kinase and PP4 protein phosphatase. KA1 domains are known to regulate kinase activities through various intramolecular interactions. Our results revealed a new role for KA1 domain to control subcellular localization of a protein kinase.
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To explore the relationship between unsaturated fatty acid (UFA) content and parameters for microwave extraction, multimaterial and multiparameter testing was conducted in which five kinds of materials with different UFA contents (potato, wheat, corn, soybean, and peanut) were selected for the experiment. Four factors, namely, extraction temperature (X 1), extraction time (X 2), proportional volume of acetone (X 3), and liquid-to-solid ratio (X 4), were screened for their significant effects by using Prob > |T| values from the Plackett-Burman experiment. A microwave extraction orthogonal experiment with four factors and five levels was designed separately using Design-Expert 8.05 software and them concentrated. Microwave-accelerated methyl esterification was then performed, and the UFA content was determined via gas chromatography (flame ionization detector). The optimal extraction conditions (X 1, X 2, X 3, X 4) and the optimal UFA content of potato were 80.68°C, 10.74 min, 0.80, 3.25 mL × g-1, 1.08%; wheat: 80.81°C, 10.54 min, 0.80, 20.91 mL × g-1, 2.26%; corn: 81.18°C, 9.93 min, 0.80, 50.94 mL × g-1, 6.89%; soybean: 82.07°C, 9.07 min, 0.80, 93.87 mL × g-1, 15.81%; and peanut: 83.12°C, 8.11 min, 0.80, 168.70 mL × g-1, 33.07%. Then, the optimization results for the five kinds of materials were synthesized by Origin 8.0 software, the fitting degree of the cubic model with the four extraction factors was the highest, the determination coefficients were 0.9984, 0.9991, 0.8953, and 0.9989, the residual sums of squares were 0.2888, 0.1587, 0.8265, and 0.1864, and the correlation coefficients are ideal. The stability and accuracy of the model were verified by the orthogonal experiment of UFA extraction from rice, and the correlation coefficient between the predicted value and the actual value of the orthogonal experiment was 0.9998. This study systematically collates the optimal parameters for microwave extraction of UFA content in different crops from the perspective of multimaterial and multiparameter, which can provide a large amount of detailed basic data for microwave extraction technology.