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1.
PLoS One ; 19(7): e0306857, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39037987

RESUMEN

OBJECTIVE: Using pediatric anthropomorphic phantoms (APs), we aimed to determine the scanning tube voltage/current combinations that could achieve optimal image quality and avoid excessive radiation exposure in pediatric patients. MATERIALS AND METHODS: A 64-slice scanner was used to scan a standard test phantom to determine the volume CT dose indices (CTDIvol), and three pediatric anthropomorphic phantoms (APs) with highly accurate anatomy and tissue-equivalent materials were studied. These specialized APs represented the average 1-year-old, 5-year-old, and 10-year-old children, respectively. The physical phantoms were constructed with brain tissue-equivalent materials having a density of ρ = 1.07 g/cm3, comprising 22 numbered 2.54-cm-thick sections for the 1-year-old, 26 sections for the 5-year-old, and 32 sections for the 10-year-old. They were scanned to acquire brain CT images and determine the standard deviations (SDs), effective doses (EDs), and contrast-to noise ratios (CNRs). The APs were scanned by 21 combinations of tube voltages/currents (80, 100, or 120 kVp/10, 40, 80, 120, 150, 200, or 250 mA) and rotation time/pitch settings of 1 s/0.984:1. RESULTS: The optimal tube voltage/current combinations yielding optimal image quality were 80 kVp/80 mA for the 1-year-old AP; 80 kVp/120 mA for the 5-year-old AP; and 80 kVp/150 mA for the 10-year-old AP. Because these scanning tube voltages/currents yielded SDs, respectively, of 12.81, 13.09, and 12.26 HU, along with small EDs of 0.31, 0.34, and 0.31 mSv, these parameters and the induced values were expediently defined as optimal. CONCLUSIONS: The optimal tube voltages/currents that yielded optimal brain image quality, SDs, CNRs, and EDs herein are novel and essentially important. Clinical translation of these optimal values may allow CT diagnosis with low radiation doses to children's heads.


Asunto(s)
Encéfalo , Fantasmas de Imagen , Dosis de Radiación , Tomografía Computarizada por Rayos X , Humanos , Encéfalo/diagnóstico por imagen , Niño , Preescolar , Tomografía Computarizada por Rayos X/métodos , Lactante , Masculino
2.
Adv Sci (Weinh) ; : e2404272, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953411

RESUMEN

The phenomenon of flexoelectricity, wherein mechanical deformation induces alterations in the electron configuration of metal oxides, has emerged as a promising avenue for regulating electron transport. Leveraging this mechanism, stress sensing can be optimized through precise modulation of electron transport. In this study, the electron transport in 2D ultra-smooth In2O3 crystals is modulated via flexoelectricity. By subjecting cubic In2O3 (c-In2O3) crystals to significant strain gradients using an atomic force microscope (AFM) tip, the crystal symmetry is broken, resulting in the separation of positive and negative charge centers. Upon applying nano-scale stress up to 100 nN, the output voltage and power values reach their maximum, e.g. 2.2 mV and 0.2 pW, respectively. The flexoelectric coefficient and flexocoupling coefficient of c-In2O3 are determined as ≈0.49 nC m-1 and 0.4 V, respectively. More importantly, the sensitivity of the nano-stress sensor upon c-In2O3 flexoelectric effect reaches 20 nN, which is four to six orders smaller than that fabricated with other low dimensional materials based on the piezoresistive, capacitive, and piezoelectric effect. Such a deformation-induced polarization modulates the band structure of c-In2O3, significantly reducing the Schottky barrier height (SBH), thereby regulating its electron transport. This finding highlights the potential of flexoelectricity in enabling high-performance nano-stress sensing through precise control of electron transport.

3.
Anal Chem ; 96(24): 10056-10063, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38832555

RESUMEN

The identification of single nucleotide polymorphisms (SNPs) is of paramount importance for disease diagnosis and clinical prognostication. In the context of nonsmall cell lung cancer (NSCLC), the emergence of resistance mutations, exemplified by the epidermal growth factor receptor (EGFR) T790 M and C797S, is intricately linked to the therapeutic efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Herein, a highly efficient and specific SNP detection platform for T790 M and C797S mutations has been engineered through the integration of an asymmetric polymerase chain reaction (PCR) and an ingeniously tailored four-way junction (4WJ) probe. Notably, a molecular beacon (MB) probe was judiciously designed to discern the allelic configuration of these mutations. The administration of first- and third-generation EGFR-TKIs demonstrates therapeutic efficacy solely when the mutations are in the trans configuration, characterized by a low fluorescence signal. In contrast, significant fluorescence by the MB probe is indicative of the C797S mutation being in a cis arrangement with T790M, thereby rendering the cells refractory to the therapeutic interventions of both first- and third-generation EGFR-TKIs. The assay is capable of concurrently detecting two point-mutations and ascertaining their allelic positions in a single test within 1.5 h, enhancing both efficiency and simplicity. It also exhibits high accuracy in the identification of clinical samples, offering promising implications for therapeutic guidelines. By enabling tailored treatment plans based on specific genetic profiles, our approach not only advances the precision of NSCLC treatment strategies but also marks a significant contribution to personalized medicine.


Asunto(s)
Alelos , Receptores ErbB , Mutación , Inhibidores de Proteínas Quinasas , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Polimorfismo de Nucleótido Simple , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico
4.
Genomics ; 116(5): 110889, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901654

RESUMEN

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

6.
Nat Commun ; 15(1): 484, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38212331

RESUMEN

Previous studies on the molecular classification of cholangiocarcinoma (CCA) focused on certain anatomical sites, and disregarded tissue contamination biases in transcriptomic profiles. We aim to provide universal molecular classification scheme and prognostic biomarker of CCAs across anatomical locations. Comprehensive bioinformatics analysis is performed on transcriptomic data from 438 CCA cases across various anatomical locations. After excluding CCA tumors showing normal tissue expression patterns, we identify two universal molecular subtypes across anatomical subtypes, explore the molecular, clinical, and microenvironmental features of each class. Subsequently, a 30-gene classifier and a biomarker (called "CORE-37") are developed to predict the molecular subtype of CCA and prognosis, respectively. Two subtypes display distinct molecular characteristics and survival outcomes. Key findings are validated in external cohorts regardless of the stage and anatomical location. Our study provides a CCA classification scheme that complements the conventional anatomy-based classification and presents a promising prognostic biomarker for clinical application.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Transcriptoma , Pronóstico , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Conductos Biliares Intrahepáticos , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología
7.
Cancer Biol Ther ; 24(1): 2256927, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-38032149

RESUMEN

BACKGROUND: PD-1/PD-L1 inhibitors are approved treatments for patients with esophageal squamous cell carcinoma (ESCC). The present investigation aspired to explore the interrelation between molecular phenotype and PD-L1 expression in ESCC. METHODS: PD-L1 testing and targeted next-generation sequencing (NGS) were performed on tumoral tissues from 139 ESCC patients. Tumor-infiltrating lymphocytes (TILs) were scrutinized using a tyramide signal amplification system combined with immunohistochemistry. RESULTS: Among enrolled patients, 36.7% displayed high PD-L1 expression (combined positive score [CPS] ≥10). BRCA1 and NF1 gene mutations were significantly associated with high PD-L1 expression (p < .05) while TGFß pathway alterations were linked to low PD-L1 expression (p = .02). High copy number instability (CNI) and copy number alterations (CNA) were correlated with low PD-L1 expression. Patients with CDKN2A deletion exhibited higher PD-L1 expression. Varying types of TILs were observed across different PD-L1 expression groups. The ratio of CD8+PD-L1+ T cells and CD8+PD-1+ T cells to CD8+ T cells remained comparable in both tumoral and stromal regions, but the ratio of CD68+PD-L1+ macrophages to CD68+ macrophages was higher than the ratio of CD68+PD-1+ macrophages to CD68+ macrophages. CPS was significantly correlated with PD-L1+ lymphocytes and CD68+ macrophages in the tumoral region. CD8+ T cell infiltration was positively correlated with PD-1+ cells in both tumoral and stromal regions. CONCLUSION: In this study, we presented the prevalence rates of PD-L1 expression in Chinese ESCC patients. The association of genetic profiles with PD-L1 expression levels also provide the clue that genomic phenotype may interact with the immunologic phenotype in ESCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Linfocitos T CD8-positivos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Linfocitos Infiltrantes de Tumor , Pronóstico , Receptor de Muerte Celular Programada 1/genética , Microambiente Tumoral
8.
Polymers (Basel) ; 15(18)2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37765574

RESUMEN

The thermo-optic effect is a crucial driving mechanism for optical devices. The application of the thermo-optic effect in integrated photonics has received extensive investigation, with continuous progress in the performance and fabrication processes of thermo-optic devices. Due to the high thermo-optic coefficient, polymers have become an excellent candidate for the preparation of high-performance thermo-optic devices. Firstly, this review briefly introduces the principle of the thermo-optic effect and the materials commonly used. In the third section, a brief introduction to the waveguide structure of thermo-optic devices is provided. In addition, three kinds of thermo-optic devices based on polymers, including an optical switch, a variable optical attenuator, and a temperature sensor, are reviewed. In the fourth section, the typical fabrication processes for waveguide devices based on polymers are introduced. Finally, thermo-optic devices play important roles in various applications. Nevertheless, the large-scale integrated applications of polymer-based thermo-optic devices are still worth investigating. Therefore, we propose a future direction for the development of polymers.

9.
Environ Monit Assess ; 195(7): 871, 2023 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-37349560

RESUMEN

Water transfer is an effective way to solve the unequal distribution of water resources to meet the needs of urban residents and industry. Annual wet weight data indicated that there may be algal blooms during water transfer. We explored the ecological risk of water transfer from Xiashan to the Jihongtan reservoir through algae growth potential (AGP) tests. The results showed that the Jihongtan reservoir had certain self-regulation abilities. When the total dissolved phosphorus (TDP) concentration was not more than 0.04 mg/L, the risk of algal bloom was low. When the N/P ratio (by mass) was less than 40, the ecological imbalance of algal growth may be caused. When the N/P ratio was 20, it was the best environment for algal growth. Under the current nutrient condition of the Jihongtan reservoir, the volume of ecological safety threshold in water transfer was 60% of the Jihongtan reservoir's capacity. If the nutrient level was further increased, the water transfer threshold would rise to 75%. In addition, water transfer may cause the homogenization of water quality and accelerate the eutrophication process of reservoirs. Regarding risk assessment, we believe that controlling nitrogen and phosphorus are more consistent with the natural evolution of reservoirs than controlling phosphorus alone for solving the problem of eutrophication.


Asunto(s)
Monitoreo del Ambiente , Eutrofización , Calidad del Agua , Fósforo/análisis , Nitrógeno/análisis , China
10.
Anal Chem ; 95(15): 6433-6440, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37026469

RESUMEN

Although promising in monitoring low-abundance analytes, most of the DNAzyme walker is only responsive to a specific target. Herein, a universal, ready-to-use platform is developed by coupling nicking-enhanced rolling circle amplification and a self-powered DNAzyme walker (NERSD). It addressed the issues that DNAzyme strands need to be specifically designed for different biosensing system, allowing highly sensitive analysis of various targets with the same DNAzyme walker components. It is also specific owing to target-dependent ligation of the padlock probe and precise cleavage of a substrate by a DNAzyme strand. As typically demonstrated, the strategy has an equivalent capacity with the qRT-PCR kit in distinguishing plasma miR-21 levels of breast cancer patients from normal subjects and is able to differentiate intracellular miR-21 and ATP levels by confocal imaging. The approach characteristic of programmability, flexibility, and generality indicated the potential in all kinds of biosensing and imaging platform.


Asunto(s)
ADN Catalítico , Diagnóstico por Imagen , MicroARNs , Humanos , Diagnóstico por Imagen/métodos , Técnicas Biosensibles/métodos , Técnicas de Amplificación de Ácido Nucleico , MicroARNs/análisis
11.
J Ethnopharmacol ; 312: 116506, 2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37086874

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Hypertensive nephropathy (HN) is a complication of hypertension. Taohongsiwu decoction (THSWD) is used clinically but its application in the prevention and treatment of HN remains unelucidated. AIM OF STUDY: This study aims to explore the potential targets and molecular mechanisms of THSWD in the treatment of HN. MATERIALS AND METHODS: A network pharmacology approach was used to predict the components and targets of THSWD for treating HN. Animal experiments were performed to verify the network pharmacology findings. RESULTS: 205 targets were identified and regarded as potential targets of THSWD in HN treatment. Subsequently, we screened 17 hub genes and identified TP53 as the most critical one. KEGG enrichment analysis showed that p53 signaling pathway might play a significant role. In vivo experiments indicated that high-salt diets can lead to high blood pressure, kidney injury, inflammation, and fibrosis. Furthermore, the altered levels of biomarkers (Iron, malondialdehyde, catalase, ferritin, transferrin, Superoxide dismutase and Glutathione Peroxidase 4) provided evidence of ferroptosis. We found that the ferroptosis inhibitor ferrostatin-1 (Fer-1) and THSWD could significantly alleviate HN by suppressing ferroptosis. THSWD and Fer-1 treatment downregulated the protein and mRNA expression of p53, p21, RB, and CTNNB1, which were upregulated by high salt. Meanwhile, THSWD and Fer-1 reversed the downregulation of Nrf2 caused by high-salt diet. CONCLUSIONS: Our results suggested that THSWD attenuate HN induced by a high-salt diet through inhibiting ferroptosis via the p53/Nrf2/p21 pathway.


Asunto(s)
Ferroptosis , Hipertensión , Animales , Factor 2 Relacionado con NF-E2/genética , Farmacología en Red , Proteína p53 Supresora de Tumor/genética
12.
Front Endocrinol (Lausanne) ; 13: 967822, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36213291

RESUMEN

Dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), is a new type of oral hypoglycemic drugs which can promote glucose excretion in the kidney. Studies have shown that dapagliflozin has renoprotective effect in the treatment of type 2 diabetes. However, the underlying mechanism remains unclear. Here, we combined integrated RNA sequencing and network pharmacology approach to investigate the molecular mechanism of dapagliflozin for diabetic nephropathy (DN). Dapagliflozin significantly relieved glucose intolerance, urinary albumin/creatinine ratio (UACR) and renal pathological injuries of db/db mice. The LncRNA and mRNA expression in kidney tissues from control group (CR), db/db group (DN) and dapagliflozin group (DG) were assessed by RNA sequencing. We identified 7 LncRNAs and 64 mRNAs common differentially expressed in CR vs DN and DN vs DG, which were used to construct co-expression network to reveal significantly correlated expression patterns in DN. In addition, network pharmacology was used to predict the therapeutic targets of dapagliflozin and we constructed component-target-pathway network according to the results of RNA sequencing and network pharmacology. We found that SMAD9, PPARG, CD36, CYP4A12A, CYP4A12B, CASP3, H2-DMB2, MAPK1, MAPK3, C3 and IL-10 might be the pivotal targets of dapagliflozin for treating DN and these genes were mainly enriched in pathways including TGF-ß signaling pathway, PPAR signaling pathway, Chemokine signaling pathway, etc. Our results have important implication and provide novel insights into the protective mechanism of dapagliflozin for treating DN.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , ARN Largo no Codificante , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Albúminas/genética , Albúminas/metabolismo , Albúminas/uso terapéutico , Animales , Compuestos de Bencidrilo , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 3/uso terapéutico , Quimiocinas/metabolismo , Creatinina , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Glucosa/metabolismo , Glucósidos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-10/uso terapéutico , Ratones , Farmacología en Red , PPAR gamma/metabolismo , ARN Largo no Codificante/genética , ARN Mensajero/genética , Análisis de Secuencia de ARN , Sodio/metabolismo , Transportador 2 de Sodio-Glucosa/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Factor de Crecimiento Transformador beta
13.
Langmuir ; 38(43): 13150-13157, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36269326

RESUMEN

As we all know, chopsticks can hold food, so can we use this method to carry Newtonian fluids such as droplets? This paper studies the process of this transfer and uses this method to realize the manipulation of open microfluidics by robots. To realize this transfer operation, we first analyzed the force of droplets in this chopstick-like structure and found that the bidirectional movement of droplets in this structure can be achieved by changing the structural parameters. Afterward, the whole process of the transfer of droplets using the chopstick-like structure was analyzed, and the parameter requirements for realizing this transfer were determined. The research in this paper provides a theoretical basis for the controllable manipulation of droplets which can be widely used in unmanned laboratories.


Asunto(s)
Robótica , Movimiento , Microfluídica/métodos
14.
Langmuir ; 38(44): 13522-13531, 2022 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-36288502

RESUMEN

Droplet controllable operation has wide applications in microfluidics, biomedicine, microreactors, and other fields. Droplets can spontaneously transfer from a high-energy state to a low-energy state, but how to reverse transfer the droplets is a difficult task. In this article, we use a special hydrophilic-hydrophobic interphase structure (HHIS) to achieve this reverse transfer. We specifically study the critical conditions under which droplet transfer can be achieved. The length of the hydrophilic surface in this structure and the hydrophilic/hydrophobic properties of the surface must be in the appropriate range. Based on this, an optimized structure used to transfer droplets was designed. Finally, we carried out research on biological applications and successfully achieved the transfer of droplets from zebrafish eggs and zebrafish larvae. This unique method is low-cost, biofriendly, and highly applicable to various surfaces, illustrating the great potential in chemical and biological analysis.


Asunto(s)
Microfluídica , Pez Cebra , Animales , Interacciones Hidrofóbicas e Hidrofílicas , Microfluídica/métodos
15.
Artículo en Inglés | MEDLINE | ID: mdl-36091599

RESUMEN

Objective: QiDan DiHuang decoction (QDD) has been proven to have good efficacy in decreasing albuminuria levels, improving renal function, and inhibiting renal fibrosis in diabetic nephropathy (DN). However, the potential mechanism remains unclear. The purpose of this study was to explore the underlying mechanism of QDD for treating DN in vitro and in vivo. Methods: Db/db mice were treated with QDD or saline intragastrically for 12 weeks. Non-diabetic db/m mice were used as controls. Rat renal tubular epithelial cells (NRK-52E) were cultured in high glucose conditions. ATF4 siRNA was transfected into NRK-52E cells. Different indicators were detected via UPLC, RT-PCR, western blotting, cell viability assays and apoptosis, transmission electron microscopy, histology, and immunofluorescence staining. Results: Db/db mice experienced severe kidney damage and fibrosis, increased levels of PERK, eIF2α, and ATF4, and suppression of renal autophagy compared with db/m mice. The results showed a significant improvement in glucose intolerance, blood urea nitrogen, urine albumin, serum creatinine, and renal fibrosis in db/db mice with QDD treatment. Meanwhile, the application of QDD resulted in the downregulation of PERK, eIF2α, and ATF4 and the upregulation of autophagy in diabetic kidneys. In vitro, the exposure of NRK-52E cells to high glucose resulted in downregulation of the ratio of LC3-II/LC3-I and upregulation of P62, a reduction in the number of autophagosomes and upregulation of fibronectin (FN), collagen IV and TGF-ß1 protein, which was reversed by QDD treatment through inhibiting ATF4 expression. Conclusions: Taken together, our results suggest that QDD effectively alleviates diabetic renal injuries and fibrosis by inhibiting the PERK-eIF2α-ATF4 pathway and promoting autophagy in diabetic nephropathy.

16.
Front Genet ; 13: 850290, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35646096

RESUMEN

Background: The feasibility and value of pericardial effusion as a liquid biopsy sample for actionable alteration detection in patients with non-small cell lung cancer (NSCLC) has not been adequately investigated. Here, we aim to reveal genomic alterations between pericardial effusion and paired tumor tissue, plasma (plasma cfDNA), and pleural effusion supernatant (PE-cfDNA) based on second-generation sequencing technology. Material and methods: A total of 26 advanced NSCLC patients were retrospectively studied. The following samples were collected and sequenced using two targeted next-generation sequencing panels: pericardial effusion (n = 26), matched tumor tissue (n = 6), plasma (n = 16), and pleural effusion supernatant (n = 5). Results: A total of 10 actionable alterations were identified in pericardial effusion of the NSCLC patients, including MET amplification, EGFR L858R, EGFR T790M, EGFR exon 19 deletion, EGFR L861Q, KRAS G12C, EML4-ALK (exon 18: exon 20) fusion, EML4-ALK (exon 20: exon 20) fusion, EML4-ALK (exon 6: exon 20) fusion, and ERBB2 exon 20 insertion. All these actionable alterations harbored multiple drug-sensitive targets as well as several drug-resistant targets, such as EGFR T790M. Compared to plasma cfDNA of 16 patients, paired pericardial effusion had higher number of actionable alterations (p = 0.08) as well as higher percentage of the population with actionable alterations (p = 0.16). Moreover, 8 out of 10 actionable alterations with single nucleotide variations (SNVs) or insertions/deletions (indels) had a higher variant allele frequency (VAF) in pericardial effusion than plasma cfDNA. In addition, we identified two actionable alterations in paired pericardial effusion, which were absence in PE-cfDNA. Clearly, 2 out of 3 actionable alterations with SNVs/indels in pericardial effusion had a higher VAF than those in PE-cfDNA. Our finding suggested the importance of pericardial effusion in the optimal selection of patients for targeted therapy. Conclusion: Among liquid biopsy specimens from the advanced NSCLC patients, pericardial effusion may be a better candidate for genomic profiling than plasma cfDNA, while it could serve as a supplement to PE-cfDNA in detecting actionable alterations. Therefore, pericardial effusion might provide a new alternative for selection of patients for better treatment management.

17.
J Org Chem ; 87(12): 7673-7695, 2022 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-35667025

RESUMEN

Benzoquinones can undergo reversible reductions and are attractive candidates for use as active materials in green carbon-based batteries. Related compounds of potential utility include 4,4'-diphenoquinones, which have extended quinonoid structures with two carbonyl groups in different rings. Diphenoquinones are a poorly explored class of compounds, but a wide variety can be synthesized, isolated, crystallized, and fully characterized. Experimental and computational approaches have established that typical 4,4'-diphenoquinones have nearly planar cores in which two cyclohexadienone rings are joined by an unusually long interannular C═C bond. Derivatives unsubstituted at the 3,3',5,5'-positions react readily by hydration, dimerization, and other processes. Association of diphenoquinones in the solid state normally produces chains or sheets held together by multiple C-H···O interactions, giving structures that differ markedly from those of the corresponding 4,4'-dihydroxybiphenyls. Electrochemical studies in solution and in the solid state show that diphenoquinones are reduced rapidly and reversibly at potentials higher than those of analogous benzoquinones. Together, these results help bring diphenoquinones into the mainstream of modern chemistry and provide a foundation for developing redox-active derivatives for use in carbon-based electrochemical devices.


Asunto(s)
Benzoquinonas , Carbono , Benzoquinonas/química , Dimerización , Oxidación-Reducción , Quinonas
18.
Mar Drugs ; 20(2)2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35200639

RESUMEN

Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine, Arca inflata Reeve. The full amino acid sequence and secondary structure of P6 were determined by tandem mass de novo sequencing and circular dichroism spectroscopy, respectively. P6 markedly inhibited cell proliferation and colony formation, and induced apoptosis in CRC cells. Mechanistically, transcriptomics analysis and a serial functional evaluation showed that P6 induced colon cancer cell apoptosis through the activation of the p38-MAPK signaling pathway. Moreover, it was demonstrated that P6 exhibited antitumor effects in a tumor xenograft model, and induced cell cycle arrest in CRC cells in a concentration-dependent mode. These findings provide the first line of indication that P6 could be a potential therapeutic agent for CRC treatment.


Asunto(s)
Antineoplásicos/farmacología , Arcidae/química , Neoplasias Colorrectales/tratamiento farmacológico , Péptidos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dicroismo Circular , Células HT29 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Péptidos/química , Péptidos/aislamiento & purificación , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
19.
IEEE Trans Nanobioscience ; 21(1): 10-20, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34529569

RESUMEN

Flexible printed electronic technology makes it possible to fabricate low-cost digital microfluidic (DMF) chips. Inkjet printing on flexible substrates is one of the most cost-effective fabrication processes for DMF chips. Based on inkjet printing technology and simplified coating methods of dielectric and hydrophobic layers, we fabricated low-cost flexible DMF chips (FDMFCs) on PET sheet and on matte photo paper. The surface quality, conductivity and spatial output resolution of the silver lines under different number of printings, different line widths and line gaps on the two types of FDMFCs were comprehensively analyzed. The traditional square dispensing electrodes were optimized to reduce the volume error of the droplets generated during the repeated dispensing operations. Droplets can be driven to implement all the operations on various configurations of FDMFCs by electrowetting-on-dielectric, including closed configuration, open configuration, hybrid configuration composed of closed and open regions on a single chip, and open curved configuration, which are defined as full-range droplet actuation. The droplet motion between closed and open regions in two position modes of the top plate was deeply studied. Droplet operation experiments prove that the motion performance of droplets can be comparable to that of chips processed by traditional technology, and the rapid prototyping technology of the FDMFCs can make the performance of droplet operation mainly depend on the conductivity of the electrode layer and the electrode gap and greatly weaken the influence of the substrate surface quality on the FDMFCs.


Asunto(s)
Electrohumectación , Microfluídica , Conductividad Eléctrica , Electrodos , Plata
20.
CNS Neurosci Ther ; 28(1): 92-104, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34643338

RESUMEN

AIMS: The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS. METHODS: Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics. RESULTS: Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores. CONCLUSION: STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson/terapia , Sustancia Blanca/patología , Anciano , Encéfalo/patología , Imagen de Difusión Tensora , Femenino , Humanos , Levodopa/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/cirugía , Núcleo Subtalámico/patología
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