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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(7): 730-735, 2024 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-39014950

RESUMO

OBJECTIVES: To study chest computed tomography (CT) manifestations in neonates with chronic granulomatous disease (CGD) to provide clues for early diagnosis of this disease. METHODS: A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital. RESULTS: Nine neonates with CGD were included, with eight presenting respiratory symptoms as the initial sign. Chest CT findings included: consolidation in all 9 cases; nodules in all 9 cases, characterized by multiple, variably sized scattered nodules in both lungs; masses in 4 cases; cavities in 3 cases; abscesses in 6 cases; bronchial stenosis in 2 cases; pleural effusion, interstitial changes, and mediastinal lymphadenopathy each in 1 case. CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement; no signs of pulmonary emphysema, lung calcification, halo signs, crescent signs, bronchiectasis, or scar lesions were observed. There was no evidence of rib or vertebral bone destruction. Fungal infections were present in 8 of the 9 cases, including 6 with Aspergillus infections; three of these involved mixed infections with Aspergillus, with masses most commonly associated with mixed Aspergillus infections (3/4). CONCLUSIONS: The primary manifestations of neonatal CGD on chest CT are consolidation, nodules, and/or masses, with Aspergillus as a common pathogen. These features can serve as early diagnostic clues for neonatal CGD.


Assuntos
Doença Granulomatosa Crônica , Tomografia Computadorizada por Raios X , Humanos , Doença Granulomatosa Crônica/diagnóstico por imagem , Recém-Nascido , Masculino , Feminino , Estudos Retrospectivos , Tórax/diagnóstico por imagem
2.
Mol Phylogenet Evol ; 199: 108140, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38981554

RESUMO

Cryptic diversity abounds in many biological species, posing challenges to our understanding of biological diversity, conservation and management. Taking the common coralline algae, the subfamily Lithophylloideae as an illustration, this study delved into the implications of cryptic diversity through global-level phylogenetic and geographical analysis based upon Lithophylloideae molecular data worldwide, as well as a multi-locus time-calibrated phylogeny to elucidate their possible evolutionary process. The multiscale analysis revealed the polyphyly in current concept of the genus Lithophyllum. Geographic isolation resulting from the Tethys terminal event (TTE) has led to two distinct distribution regions for this so-called cosmopolitan genus: one regionally distributed along European coasts/Mediterranean that should include the taxonomical Lithophyllum; others widely distributed, particularly among pan-tropic waters, suggesting at least five groups to be rediscovered within the subfamily Lithophylloideae. Meanwhile, the cryptic genus Titanoderma, lacking morphological identification features with Lithophyllum, exhibited differences in distribution and evolutionary patterns consistent with their ecological habits, thus supporting their separation. This study provided useful hints for cryptic diversity, which advocated an integrative thinking to investigating global cryptic diversity and exploring the broad linkages between phylogenetic relationships and evolutionary origin, biogeography, morphological and ecological traits to achieve a more comprehensive understanding of biodiversity.

3.
Int J Med Sci ; 21(7): 1250-1256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818475

RESUMO

Background: Recovery time is a crucial factor in ensuring the safety and effectiveness of both patients and endoscopy centers. Propofol is often preferred due to its fast onset and minimal side effects. Remimazolam is a new intravenous sedative agent, characterized by its rapid onset of action, quick recovery and organ-independent metabolism. Importantly, its effect can be specifically antagonized by flumazenil. The primary goal of this study is to compare the recovery time of remimazolam besylate and propofol anesthesia during endoscopic procedures in elderly patients. Methods: 60 patients aged 65-95 years who underwent gastrointestinal endoscopy were randomly and equally assigned to two groups: the remimazolam group (Group R) and the propofol group (Group P). The primary measure was the recovery time, defined as the time from discontinuing remimazolam or propofol until reaching an Observer's Assessment of Alertness and Sedation scale (OAA/S) score of 5 (responds readily to name spoken in normal tone). The time required to achieve an OAA/S score of 3 (responds after name spoken loudly or repeatedly along with glazed marked ptosis) was also recorded and compared. Results: The recovery time for Group R (2.6 ± 1.6 min) was significantly shorter than that for Group P (10.8 ± 3.0 min), with a 95% confidence interval (CI): 6.949-9.431 min, p <0.001. Similarly, the time to attain an OAA/S score of 3 was significantly less in Group R (1.6 ± 0.9 min) compared to Group P (9.6 ± 2.6 min), with a 95% CI: 6.930-8.957 min, p <0.001. Conclusion: Our study demonstrated that remimazolam anesthesia combined with flumazenil antagonism causes a shorter recovery time for elderly patients undergoing gastrointestinal endoscopy compared to propofol. Remimazolam followed by flumazenil antagonism provides a promising alternative to propofol for geriatric patients, particularly during gastrointestinal endoscopy.


Assuntos
Período de Recuperação da Anestesia , Benzodiazepinas , Endoscopia Gastrointestinal , Hipnóticos e Sedativos , Propofol , Humanos , Idoso , Propofol/administração & dosagem , Masculino , Feminino , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal/métodos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Benzodiazepinas/uso terapêutico
5.
Front Med (Lausanne) ; 11: 1331103, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741769

RESUMO

Background: Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia, characterised by rapid onset of action, quick recovery, and organ-independent metabolism. Older patients tend to sustain more treatment-emergent adverse events (TEAEs) and worse perioperative prognoses after receiving remimazolam. However, few studies have investigated the appropriate dose of remimazolam for loss of consciousness (LOC) in geriatric patients. We designed this study to provide evidence for dose references and elucidate the relationship between age and remimazolam requirement for inducing LOC during anaesthesia induction. Methods: Exactly 120 patients scheduled for general surgery under general anaesthesia were included and divided into two groups: Group A (60 patients, 18-64 years) and Group B (60 patients, ≥ 65 years). LOC, defined as a Modified Observer's Assessment of Alertness and Sedation score at 1 had been reached, emerged after all participants received a continuous infusion of remimazolam at a rate of 0.05 mg/kg/min. Results: The remimazolam required for inducing LOC was 0.26 and 0.19 mg/kg in groups A and B, respectively, and the remimazolam dose in group B decreased by 26.9% compared to group A. According to the bivariate linear correlation analysis, remimazolam requirement was negatively correlated with age. Multivariable linear regression models and further adjustments for potential impact factors indicated that age was an independent factor for the remimazolam dose required for LOC. Conclusion: This study demonstrated that age was significantly and independently correlated with the remimazolam requirement for inducing LOC. To obtain haemodynamic stability during the induction of general anaesthesia, appropriately reducing the remimazolam dose is recommended for geriatric patients.

6.
Phys Rev Lett ; 132(12): 121601, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38579220

RESUMO

We derive model-independent quantization conditions on the axion couplings (sometimes known as the anomaly coefficients) to the standard model gauge group [SU(3)×SU(2)×U(1)_{Y}]/Z_{q} with q=1, 2, 3, 6. Using these quantization conditions, we prove that any QCD axion model to the right of the E/N=8/3 line on the |g_{aγγ}|-m_{a} plot must necessarily face the axion domain wall problem in a postinflationary scenario. We further demonstrate the higher-group and noninvertible global symmetries in the standard model coupled to a single axion. These generalized global symmetries lead to universal bounds on the axion string tension and the monopole mass. If the axion were discovered in the future, our quantization conditions could be used to constrain the global form of the standard model gauge group.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124199, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38555822

RESUMO

A series of "turn off" pH fluorescence probes with chalcone skeleton for basic system have been developed. The molecules emitted bright yellow fluorescence under acidic condition, resulting AIE coupled ESIPT characteristic and ICT process. What's more, the compounds exhibited excellent sensitivity and selectivity for detecting pH as a facile "On-Off" fluorescence probe, and the fluorescence of them were quenched with the ESIPT process interrupted under alkaline condition. Theoretical calculation for the related compounds also performed to verify the electron effect on photophysical properties and confirm the rational speculation on the mechanism.

10.
Mol Cell ; 84(4): 760-775.e7, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38215751

RESUMO

Apart from the canonical serotonin (5-hydroxytryptamine [5-HT])-receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. Here, we report a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) serotonylation system that promotes the glycolytic metabolism and antitumor immune activity of CD8+ T cells. Tissue transglutaminase 2 (TGM2) transfers 5-HT to GAPDH glutamine 262 and catalyzes the serotonylation reaction. Serotonylation supports the cytoplasmic localization of GAPDH, which induces a glycolytic metabolic shift in CD8+ T cells and contributes to antitumor immunity. CD8+ T cells accumulate intracellular 5-HT for serotonylation through both synthesis by tryptophan hydroxylase 1 (TPH1) and uptake from the extracellular compartment via serotonin transporter (SERT). Monoamine oxidase A (MAOA) degrades 5-HT and acts as an intrinsic negative regulator of CD8+ T cells. The adoptive transfer of 5-HT-producing TPH1-overexpressing chimeric antigen receptor T (CAR-T) cells induced a robust antitumor response. Our findings expand the known range of neuroimmune interaction patterns by providing evidence of receptor-independent serotonylation post-translational modification.


Assuntos
Linfócitos T CD8-Positivos , Serotonina , Linfócitos T CD8-Positivos/metabolismo , Serotonina/metabolismo , Serotonina/farmacologia , Processamento de Proteína Pós-Traducional , Transdução de Sinais
11.
Hypertens Res ; 47(5): 1103-1119, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38228750

RESUMO

This comprehensive review offers a thorough exploration of recent advancements in our understanding of the intricate cardiovascular complications associated with Primary Aldosteronism (PA). PA encompasses a spectrum of conditions characterized by hypertension and excessive production of aldosterone operating independently of the renin-angiotensin system. Given its association with an elevated risk of cardiovascular and cerebrovascular complications, as well as a higher incidence of metabolic syndrome in comparison to individuals with essential hypertension (EH), an accurate diagnosis of PA is of paramount importance. This review delves into the intricate interplay between PA and cardiovascular health and focuses on the key pathophysiological mechanisms contributing to adverse cardiac outcomes. The impact of different treatment modalities on cardiovascular health is also examined, offering insights into potential therapeutic approaches. By highlighting the significance of recognizing PA as a significant contributor to cardiovascular morbidity, this review emphasizes the need for improved screening, early diagnosis, and tailored management strategies to both enhance patient care and mitigate the burden of cardiovascular diseases. The findings presented herein underscore the growing importance of PA in the context of cardiovascular medicine and emphasize the potential for translating these insights into targeted interventions to improve patient outcomes.


Assuntos
Doenças Cardiovasculares , Hiperaldosteronismo , Humanos , Doenças Cardiovasculares/etiologia , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiologia , Hiperaldosteronismo/terapia , Aldosterona/metabolismo , Adrenalectomia
12.
Cell Oncol (Dordr) ; 47(1): 81-96, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37606818

RESUMO

BACKGROUND: Reprogramming glucose metabolism, also known as the Warburg effect (aerobic glycolysis), is a hallmark of cancers. Increased tumor glycolysis not only favors rapid cancer cell proliferation but reprograms the immune microenvironment to enable tumor progression. The transcriptional factor ONECUT3 plays key roles in the development of the liver and pancreas, however, limited is known about its oncogenic roles, particularly metabolic reprogramming. METHODS: Immunohistochemistry and Western blotting are applied to determine the expression pattern of ONECUT3 and its clinical relevance in pancreatic ductal adenocarcinoma (PDAC). Knockdown and overexpression strategies are employed to determine the in vitro and in vivo functions of ONECUT3. Chromatin immunoprecipitation, luciferase reporter assay, and gene set enrichment analysis are used to decipher the molecular mechanisms. RESULTS: The glycolytic metabolism is inversely associated with T-cell infiltration in PDAC. ONECUT3 is identified as a key regulator for PDAC glycolysis and CD8+ T-cell infiltration. Genetic silencing of ONECUT3 inhibits cell proliferation, promotes cell apoptosis, and reduces glycolytic metabolism as evidenced by glucose uptake, lactate production, and extracellular acidification rate. Opposite effects of ONECUT3 are observed in overexpression studies. ONECUT3 enhances aerobic glycolysis via transcriptional regulation of PDK1. Targeting ONECUT3 effectively suppresses tumor growth, increases CD8+ T-cell infiltration, and potentiates anti-PD-1 therapy in PDAC. Pharmacological inhibition of PDK1 also shows a synergistic effect with anti-PD-1 therapy. In clinical setting, ONECUT3 is closely associated with PDK1 expression and T-cell infiltration in PDAC and acts as an independent prognostic factor. CONCLUSIONS: Our study reveals a previous unprecedented regulatory role of ONECUT3 in PDAC glycolysis and provides in vivo evidence that increased glycolysis is linked to an immunosuppressive microenvironment. Moreover, targeting ONECUT3-PDK1 axis may serve as a promising therapeutic approach for the treatment of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Linhagem Celular Tumoral , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , Proliferação de Células/genética , Ácido Láctico , Glicólise , Microambiente Tumoral
13.
J Formos Med Assoc ; 123 Suppl 2: S104-S113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37173227

RESUMO

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.


Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Renina , Hidrocortisona , Captopril
14.
Cell Oncol (Dordr) ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38015381

RESUMO

BACKGROUND: Accumulating studies have shown that tumors are regulated by nerves, and there is abundant nerve infiltration in the tumor microenvironment. Many solid tumors including breast cancer (BRCA) have different degrees of perineural invasion (PNI), which is closely related to the tumor occurrence and progression. However, the regulatory mechanism of PNI in BRCA remains largely unexplored. METHODS: PNI-related molecular events are analyzed by the RNAseq data of BRCA samples deposited in The Cancer Genome Atlas (TCGA) database. Extracellular matrix (ECM) components within the tumor microenvironment are analyzed by immunohistochemical staining of α-SMA, Sirius red staining, and Masson trichrome staining. Soft and stiff matrix gels, living cell imaging, and dorsal root ganglion (DRG) coculture assay are used to monitor cancer cell invasiveness towards nerves. Western blotting, qRT-PCR, enzyme-linked immunosorbent assay combined with neutralizing antibody and small molecular inhibitors are employed to decode molecular mechanisms. RESULTS: Comparative analysis that the ECM was significantly associated with PNI status in the TCGA cohort. BRCA samples with higher α-SMA activity, fibrillar collagen, and collagen content had higher frequency of PNI. Compared with soft matrix, BRCA cells cultured in stiff matrix not only displayed higher cell invasiveness to DRG neurons but also had significant neurotrophic effects. Mechanistically, integrin ß1 was identified as a functional receptor to the influence of stiff matrix on BRCA cells. Moreover, stiffened matrix-induced activation of integrin ß1 transduces FAK-YAP signal cascade, which enhances cancer invasiveness and the neurotrophic effects. In clinical setting, PNI-positive BRCA samples had higher expression of ITGB1, phosphorylated FAK, YAP, and NGF compared with PNI-negative BRCA samples. CONCLUSIONS: Our findings suggest that stiff matrix induces expression of pro-metastatic and neurotrophic genes through integrin ß1-FAK-YAP signals, which finally facilitates PNI in BRCA. Thus, our study provides a new mechanism for PNI in BRCA and highlights nerve-based tumor treatment strategies.

15.
Am J Chin Med ; 51(8): 2041-2075, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37957120

RESUMO

Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) is a single species of Cyclocarya paliurus in Juglandaceae. It is a unique rare medicinal plant resource in China that is mainly distributed in the south of China. The leaves of C. paliurus, as a new food ingredient, are processed into tea products in daily life. Triterpenoids are the main active ingredient in C. paliurus. So far, 164 triterpenoid compounds have been isolated and identified from C. paliurus, which are included 3,4-seco-dammaranes, dammaranes, oleanane, ursane, lupinanes, taraxeranes, and norceanothanes. Modern pharmacological studies manifested that these ingredients have a wide range of pharmacological activities both in vitro and in vivo, such as reducing blood sugar, lowering blood lipids, and anti-tumor, anti-inflammatory, anti-oxidant, and other activities. In addition, current results indicate that the pharmacological mechanisms of triterpenoids were closely related to their chemical structure, molecular signaling pathways, and the expression of related proteins. In order to further study C. paliurus based on the current research situation, this review summarizes the prospect and systematic summary of the triterpenes of C. paliurus from the aspects of structural characteristics, quality control, biological activity, and the structure-activity relationship, which provide a reference for further research and application of the triterpenoids from C. paliurus in the field of functional food and medicine.


Assuntos
Antineoplásicos , Juglandaceae , Triterpenos , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade , Triterpenos/química , Antineoplásicos/farmacologia , Juglandaceae/química , Controle de Qualidade , Folhas de Planta/química
16.
J Transl Med ; 21(1): 615, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697300

RESUMO

BACKGROUND: IFN-λ has been shown to have a dual function in cancer, with its tumor-suppressive roles being well-established. However, the potential existence of a negative ''tumor-promoting'' effect of endogenous IFN-λ is still not fully understood. METHODS: We conducted a comprehensive review and analysis of the perturbation of IFN-λ genes across various cancer types. Correlation coefficients were utilized to examine the relationship between endogenous IFN-λ expression and clinical factors, immune cell infiltration, tumor microenvironment, and response to immunotherapy. Genes working together with IFN-λ were obtained by constructing the correlation-based network related to IFN-λ and the gene interaction network in the KEGG pathway and IFN-λ-related genes obtained from the networks were integrated as candidate markers for the prognosis model. We then applied univariate and multivariate COX regression models to select cancer-specific independent prognostic markers associated with IFN-λ and to investigate risk factors for these genes by survival analysis. Additionally, computational methods were used to analyze the transcriptome, copy number variations, genetic mutations, and methylation of IFN-λ-related patient groups. RESULT: Endogenous expression of IFN-λ has been linked to poor prognosis in cancer patients, with the genes IFN-λ2 and IFN-λ3 serving as independent prognostic markers. IFN-λ acts in conjunction with related genes such as STAT1, STAT2, and STAT3 to affect the JAK-STAT signaling pathway, which promotes tumor progression. Abnormalities in IFN-λ genes are associated with changes in immune checkpoints and immune cell infiltration, which in turn affects cancer- and immune-related pathways. While there is increased immune cell infiltration in patients with IFN-λ expression, this does not improve survival prognosis, as T-cell dysfunction and an inflammatory environment are also present. The amplification of IFNL2 and IFNL3 copy number variants drives specific endogenous expression of IFN-λ in patients, and those with this specific expression have been found to have more mutations in the TP53 gene and lower levels of DNA methylation. CONCLUSION: Our study integrated multi-omics data to provide a comprehensive insight into the dark side of endogenous IFN-λ, providing a fundamental resource for further discovery and therapeutic exploration in cancer.


Assuntos
Interferon lambda , Neoplasias , Humanos , Variações do Número de Cópias de DNA/genética , Neoplasias/genética , Citocinas , Metilação de DNA/genética , Microambiente Tumoral
17.
Membranes (Basel) ; 13(8)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37623754

RESUMO

Polyamide (PA) nanofiltration (NF) membranes suffer from biofouling, which will deteriorate their separation performance. In this study, we proposed a strategy to incorporate silver nanoparticles (Ag NPs) into PA NF membranes in situ, in order to simultaneously enhance water permeability and antibacterial performance. The chloride-doped carbon quantum dots (Cl-CQDs) with photocatalytic performance were pre-embedded in the PA selective layer. Under visible light irradiation, the photogenerated charge carriers generated by Cl-CQDs rapidly transported to silver ions (Ag+ ions), resulting in the in situ formation of Ag NPs. The proposed strategy avoided the problem of aggregating Ag NPs, and the amount of Ag NPs on the membrane surfaces could be easily tuned by changing silver nitrate (AgNO3) concentrations and immersion times. These uniformly dispersed Ag NPs increased membrane hydrophilicity. Thus, the obtained thin film nanocomposite Ag NPs (TFN-Ag) membrane exhibited an improved water flux (31.74 L m-2 h-1), which was ~2.98 times that of the pristine PA membrane; meanwhile, the sodium sulfate (Na2SO4) rejection rate was 96.11%. The sterilization rates of the TFN-Ag membrane against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were 99.55% and 99.52%, respectively. Thus, this facile strategy simultaneously improved the permeability and antibacterial property of PA NF membranes.

18.
Biomater Sci ; 11(16): 5674-5679, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37439102

RESUMO

Moderate oxygen (O2) supply and uneven distribution of oxygen at the tumor site usually hinder the therapeutic efficacy of hypoxia-activated prodrugs. In this report, we designed a ferrocene-containing supramolecular nanomedicine (PFC/GOD-TPZ) with the PEG corona and disulfide-bond cross-linked core to co-encapsulate 4-di-N-oxide tirapazamine (TPZ) and glucose oxidase (GOD). The PEG corona of PFC/GOD-TPZ could be weakly acidic tumor pH-responsively detached for an enhanced cellular internalization, while the disulfide-bond cross-linked core could be cleavaged by intracellular glutathione (GSH) to present a GSH-triggered drug-release behavior. Subsequently, the cascade reactions, including catalytic reactions among the released GOD, glucose, and O2 to generate H2O2 and the subsequent Fenton reaction between ferrocene and H2O2, occurred. With the depletion of O2, the non-toxic TPZ was activated and converted into the cytotoxic therapeutic agent benzotriazinyl (BTZ) radical under the exacerbated hypoxic microenvironment. Collectively, the PFC/GOD-TPZ provides a promising strategy for effective combination therapy of GOD-mediated starvation therapy, chemodynamic therapy (CDT), and hypoxia-activated chemotherapy (CT).


Assuntos
Antineoplásicos , Neoplasias , Humanos , Nanomedicina , Metalocenos/farmacologia , Metalocenos/uso terapêutico , Peróxido de Hidrogênio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Tirapazamina/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oxigênio , Hipóxia/tratamento farmacológico , Glutationa , Dissulfetos/farmacologia , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Microambiente Tumoral
19.
ACS Cent Sci ; 9(7): 1419-1426, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37521783

RESUMO

X-ray scintillators are widely used in medical imaging, industrial flaw detection, security inspection, and space exploration. However, traditional commercial scintillators are usually associated with a high use cost because of their substantial toxicity and easy deliquescence. In this work, an atomically precise Au-Cu cluster scintillator (1) with a thermally activated delayed fluorescence (TADF) property was facilely synthesized, which is environmentally friendly and highly stable to water and oxygen. The TADF property of 1 endows it with an ultrahigh exciton utilization rate. Combined with the effective absorption of X-ray caused by the heavy-atom effect and a limited nonradiative transition caused by close packing in the crystal state, 1 exhibits an excellent radioluminescence property. Moreover, 1 has good processability for fabricating a large, flexible thin-film device (10 cm × 10 cm) for high-resolution X-ray imaging, which can reach 40 µm (12.5 LP mm-1). The properties mentioned earlier make the coinage metal cluster promising for use as a substitute for traditional commercial scintillators.

20.
Front Genet ; 14: 1061364, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152984

RESUMO

Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we first analyzed the differences in clinical characteristics among the primary tumor, recurrent tumor, and metastatic tumor in different stages of cancer, which may be caused by the molecular level. Moreover, the importance of predicting early cancer recurrence and metastasis is emphasized by survival analyses. Next, we used a multi-omics approach to identify key molecular changes associated with early cancer recurrence and metastasis and discovered that early metastasis in cancer demonstrated a high degree of genomic and cellular heterogeneity. We performed statistical comparisons for each level of omics data including gene expression, mutation, copy number variation, immune cell infiltration, and cell status. Then, various analytical techniques, such as proportional hazard model and Fisher's exact test, were used to identify specific genes or immune characteristics associated with early cancer recurrence and metastasis. For example, we observed that the overexpression of BPIFB1 and high initial B-cell infiltration levels are linked to early cancer recurrence, while the overexpression or amplification of ANKRD22 and LIPM, mutation of IGHA1 and MUC16, high fibroblast infiltration level, M1 polarization of macrophages, cellular status of DNA repair are all linked to early cancer metastasis. These findings have led us to construct classifiers, and the average area under the curve (AUC) of these classifiers was greater than 0.75 in The Cancer Genome Atlas (TCGA) cancer patients, confirming that the features we identified could be biomarkers for predicting recurrence and metastasis of early cancer. Finally, we identified specific early sensitive targets for targeted therapy and immune checkpoint inhibitor therapy. Once the biomarkers we identified changed, treatment-sensitive targets can be treated accordingly. Our study has comprehensively characterized the multi-omics characteristics and identified a panel of biomarkers of early cancer recurrence and metastasis. Overall, it provides a valuable resource for cancer recurrence and metastasis research and improves our understanding of the underlying mechanisms driving early cancer recurrence and metastasis.

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