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1.
iScience ; 25(1): 103645, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35005567

RESUMO

Deciphering the regulatory network for human naive and primed pluripotency is of fundamental theoretical and applicable significance. Here, by combining quantitative proteomics, phosphoproteomics, and acetylproteomics analyses, we revealed RNA processing and translation as the most differentially regulated processes between naive and primed human embryonic stem cells (hESCs). Although glycolytic primed hESCs rely predominantly on the eukaryotic initiation factor 4E (eIF4E)-mediated cap-dependent pathway for protein translation, naive hESCs with reduced mammalian target of rapamycin complex (mTORC1) activity are more tolerant to eIF4E inhibition, and their bivalent metabolism allows for translating selective mRNAs via both eIF4E-dependent and eIF4E-independent/eIF4A2-dependent pathways to form a more compact naive proteome. Globally up-regulated proteostasis and down-regulated post-translational modifications help to further refine the naive proteome that is compatible with the more rapid cycling of naive hESCs, where CDK1 plays an indispensable coordinative role. These findings may assist in better understanding the unrestricted lineage potential of naive hESCs and in further optimizing conditions for future clinical applications.

2.
Chemosphere ; 286(Pt 3): 131852, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34416594

RESUMO

Two representative DNA adducts from acrylamide exposure, N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl) adenine (N3-GA-Ade), are important long-term exposure biomarkers for evaluating genotoxicity of acrylamide. Catechins as natural antioxidants present in tea possess multiple health benefits, and may also have the potential to protect against acrylamide-induced DNA damage. The current study developed an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous analysis of N7-GA-Gua and N3-GA-Ade in tissues and urine. The validated UHPLC-MS/MS method showed high sensitivity, with limit of detection and limit of quantification ranging 0.2-0.8 and 0.5-1.5 ng/mL, respectively, and achieved qualified precision (RSD<14.0%) and spiking recovery (87.2%-110.0%) with elution within 6 min, which was suitable for the analysis of the two DNA adducts in different matrices. The levels of N7-GA-Gua and N3-GA-Ade ranged 0.9-11.9 and 0.6-3.5 µg/g creatinine in human urine samples, respectively. To investigate the interventional effects of catechins on the two DNA adducts from acrylamide exposure, rats were supplemented with three types of catechins (tea polyphenols, epigallocatechin gallate, and epicatechin) 30 min before administration with acrylamide. Our results showed that catechins effectively inhibited the formation of DNA adducts from acrylamide exposure in both urine and tissues of rats. Among three catechins, epicatechin performed the best inhibitory effect. The current study provided evidence for the chemo-preventive effect of catechins, indicating that dietary supplement of catechins may contribute to health protection against exposure to acrylamide.


Assuntos
Catequina , Adutos de DNA , Acrilamida/toxicidade , Animais , Biomarcadores , Catequina/farmacologia , Ratos , Espectrometria de Massas em Tandem
3.
J Org Chem ; 87(2): 1056-1064, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-34964353

RESUMO

An electrochemical cross-dehydrogenative coupling of indoles with xanthenes has been established at room temperature. This coupling reaction could proceed in the absence of any catalyst or external oxidant, and generate the indole derivatives in moderate yields. Mechanistic experiments support that a radical pathway maybe involved in this reaction system.

4.
Front Oncol ; 11: 740762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868936

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is a high-grade malignant disease with unfavorable prognosis, and although surgical therapy is necessary, not all patients with HCC are suitable candidates for surgery. Downstaging as preoperative therapeutic strategy, which can convert unresectable HCC into resectable HCC, intends to increase the resection rate and improve prognosis. Methods: We searched multiple databases updated to December 30, 2020, for studies on transcatheter arterial chemoembolization (TACE), Yttrium 90 microsphere selective internal radiation (SIR)/transcatheter radioembolization (TARE), hepatic arterial infusion (HAI), and systemic treatment as downstaging treatment before resection for patients with unresectable HCC. Results: A total of 20 comparative and non-comparative studies were finally included in the meta-analysis. The pooled downstaging rate of hepatic resection (HR) was 14% [95% confidence interval (CI) 0.10-0.17] with significant heterogeneity (I 2 = 94.51%). The chemotherapy, combination, and non-cirrhosis groups exhibit higher rates of downstaging, but these differences were not significant. For comparative studies, the overall survival (OS) rates of resection after downstaging were far better than those inpatients who received locoregional therapy (LRT) or systemic treatment alone at 1 year (RR 1.87, 95% CI 1.48-2.38), 3 years (RR 5.56, 95% CI 2.55-12.10), and 5 years (RR 5.47, 95% CI 2.22-13.49). In addition, the pooled disease-free survival (DFS) rates in patients undergoing HR after successful downstaging were 78% (95% CI 0.62-0.93) at 1 year, 47% (95% CI 0.25-0.68) at 3 years, and 46% (95% CI 0.32-0.59) at 5 years. The pooled OS rates were 88% (95% CI 0.82-0.95) at 1 year, 64% (95% CI 0.59-0.69) at 3 years, and 42% (95% CI 0.29-0.54) at 5 years. Conclusions: Downstaging may serve as a screening tool to identify patients who might benefit from surgery. Resection after successful downstaging can improve prognosis.

5.
Bioengineered ; 12(2): 10147-10159, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34872451

RESUMO

Polygonatum sibiricum polysaccharides (PSP) can decrease the levels of fasting blood glucose, total cholesterol, and triglyceride (TG) in hyperlipidemic and diabetic animals. It can also reduce inflammatory cytokines and promote glucose uptake in adipocytes. However, the underlying molecular mechanisms of PSP in improving insulin resistance (IR) in skeletal muscle remain unclear. In this study, palmitic acid (PA) induced an IR model in L6 myotubes. After treatment, cell proliferation was measured using the CCK8. miR-340-3p, glucose transporter 4 (GLUT-4), and interleukin-1 receptor-associated kinase 3 (IRAK3) expression was measured by qRT-PCR. IRAK3 protein levels were measured by Western blotting. Glucose in the cell supernatant, TG concentration in L6 myotubes, and the levels of IL-1ß, IL-6, and TNF-α were measured by an ELISA. We found that cell survival, glucose uptake, and GLUT-4 expression in L6 myotubes were significantly suppressed, while lipid accumulation and inflammatory factor levels were enhanced by PA stimulation. Furthermore, PSP treatment markedly alleviated these effects. Interestingly, PSP also significantly reduced the upregulated expression of miR-340-3p in the L6 myotube model of IR. Furthermore, overexpression of miR-340-3p reversed the beneficial effects of PSP in the same IR model. miR-340-3p can bind to the 3'-untranslated regions of IRAK3. Additionally, PA treatment inhibited IRAK3 expression, whereas PSP treatment enhanced IRAK3 expression in L6 myotubes. Additionally, miR-340-3p also inhibited IRAK3 expression in L6 myotubes. Taken together, PSP improved inflammation and glucose uptake in PA-treated L6 myotubes by regulating miR-340-3p/IRAK3, suggesting that PSP may be suitable as a novel therapeutic agent for IR.

6.
Biochem Biophys Res Commun ; 586: 163-170, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34852960

RESUMO

SOX2, a well-established pluripotency factor supporting the self-renewal of pluripotent stem cells (PSCs), is also a crucial factor for maintaining the properties and functionalities of neural progenitor cells (NPCs). It regulates the transcription of target genes by forming complexes with its partner factors, but systematic comparison of SOX2 binding partners in human PSCs versus NPCs is lacking. Here, by deciphering and comparing the SOX2-protein interactomes in human embryonic stem cells (hESCs) versus the NPCs derived from them, we identified 23 proteins with high reproducibility that are most differentially associated with SOX2, of which 9 are DNA repair proteins (PARP1, PARP2, PRKDC, XRCC1, XRCC5, XRCC6, RPA1, LIG3, DDB1). Genetic knocking-down or pharmacological inhibiting two of the DNA repair proteins (PARP1 and PRKDC) significantly up-regulated certain NPC or ectodermal biomarkers that are transcriptionally-suppressed by the SOX2/DNA repair protein complexes. These findings point to a crucial role of DNA repair proteins in pluripotent state transition and neural induction.

7.
Aging (Albany NY) ; 13(undefined)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862329

RESUMO

Circadian dysregulation involves malignant tumor initiation and progression, but the understanding of circadian rhythm's roles in bladder cancer (BCa) remains insufficient. The circadian rhythm-related genes were collected and clustered based on the Cancer Genome Atlas (TCGA), and the clustering was significantly associated with the prognosis and risk clinicopathological features. Through genomic difference analysis and gene pairing, a circadian rhythm-related signature was successfully established. Kaplan-Meier survival analysis and time-dependent receiver operating curves displayed that the prognosis model was a reliable prognosis biomarker both in the training cohort (n = 396, P = 2.687e-10) and external validation cohort (n = 224, P = 1.45e-02). The patients with high risk have high immune infiltration and high expression of immune checkpoint genes, which partly account for the poor prognosis. TIDE algorithm and the validation in IMvigor210 cohort indicated that the risk signature was a promising marker for the immunotherapeutic response. The risk model could also predict the therapeutic response of cisplatin, which was validated in the Genomics of Drug Sensitivity in Cancer database (P = 0.0049), TCGA (P = 0.038), and T24 BCa cells treated with cisplatin. The functional enrichment showed the risk model was significantly correlated with some malignant phenotypes, such as angiogenesis, epithelial-mesenchymal transition, and KRAS signaling pathway. Totally, we proposed a novel circadian rhythm-related signature for prognosis evaluation, which also helped to predict the immune infiltration and cisplatin sensitivity in BCa.

8.
Am J Transl Res ; 13(11): 12509-12522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956469

RESUMO

Tunneling nanotubes (TNTs) are thin channel-like structures connecting distant cells, providing a route for intercellular communication. In this study, we investigated the physical properties, including the cytoskeletal components, length and diameter, of the TNTs formed by HEK293T, U87 MG, and U251 cell lines. We found that organelles such as lysosomes, mitochondria, and Golgi bodies can be transported through TNTs, indicating that TNTs can mediate material transport. Moreover, we investigated the transport of the Tau protein and ß-amyloid (Aß), which are both closely related to Alzheimer's disease (AD) pathology, through TNTs. The results showed that TNTs formed by various neuronal cell lines can mediate the transport of different forms of the Tau protein and fluorescently labeled Aß and that this transport is bidirectional, with different velocities in various cell lines. Our results confirmed the transport of the Tau protein and Aß between cells and provided a possible explanation for the cascade of cell death in specific brain regions during the progression of AD. Our findings suggest new possibilities for the treatment of AD.

9.
Chemosphere ; 292: 133458, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34971622

RESUMO

Acrylamide (AA), a class 2A probable carcinogen to humans classified by the International Agency for Research on Cancer, has attracted extensive attention worldwide since it was widely used in industrial and domestic water treatment and detected in thermal processing foods. The metabolic adducts of AA and its primary metabolite glycidamide (GA) have been served as biomonitoring markers of AA intake, but the physiologically based toxicokinetics (PBTK) models to estimate internal dosimetry still remain unclear. An updated PBTK model for AA, GA and their metabolic biomarkers in rats and humans was developed and extended with time-course datasets from both literatures and our experiments. With adjustments to the model parameters, linear regression correlation coefficient (R2) between the fitting values and the validation datasets of rats and humans was greater than 0.76. The current model fits well with the experimental datasets of urinary N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and (N-(R,S)-acetyl-S-(carbamoyl-2-hydroxyethyl)-l-cysteine) (GAMA) of rats exposed to AA from 0.1 to 50 mg/kg b.w. and humans exposed to AA from 0.0005 to 0.020 mg/kg b.w., indicating the robustness of the current models. Parameters for adduct of AA with N-terminal valine of hemoglobin (AAVal) were extended to humans and validated. Kinetic parameters for rats were assessed and validated based upon fit to the experimental datasets for liver N3-(2-carbamoyl-2-hydroxyethyl)-adenine (N3-GA-Ade) and N7-(2-carbamoyl-2-hydroxyethyl)-guanine (N7-GA-Gua) adducts. Compared with the previous model, the developed model included the correlation between AA intake and its mercapturic acid adducts, AAMA and GAMA, in a larger dose range with new experimental data, and parameters for AAVal, N3-GA-Ade and N7-GA-Gua were improved and verified. The current multi-component PBTK models provide a superior foundation for the estimation of short-term to medium and long-term intake levels of human exposure to AA.

10.
PLoS One ; 16(11): e0258204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34735466

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO-1) is an immunosuppressive enzyme expressed in the placenta, neoplastic cells, and macrophages to reject T cells by converting tryptophan into kynurenine. However, the role of IDO-1 in brain immunity, especially in the meninges, is unclear. We aim to elucidate the distribution pattern of IDO-1+ macrophages/microglia in the human brain tissues, human glioblastoma, APP/PS1 mouse brains, and quinolinic acid model brains and explore the physiological and immunological roles of IDO-1+ macrophages/microglia. Here, we find that both human and mouse macrophages/microglia of the perivascular and subarachnoid space and in glioblastoma (GBM) expressed IDO-1 but not macrophages/microglia of parenchyma. Using IDO-1 inhibitors including 1-MT and INCB24360, we observed that inhibiting IDO-1 reduced the cellular size and filopodia growth, fluid uptake, and the macropinocytic and phagocytic abilities of human blood monocytes and RAW264.7/BV-2 cells. Inhibiting IDO-1 with 1-MT or INCB24360 increased IL-1ß secretion and suppressed NLRP3 expression in RAW264.7/BV-2 cells. Our data collectively show that IDO-1 expression in perivascular and meninges macrophages/microglia increases cellular phagocytic capacity and might suppress overactivation of inflammatory reaction.

11.
Nat Commun ; 12(1): 6953, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845233

RESUMO

The Japanese government has announced a commitment to net-zero greenhouse gas emissions by 2050. It envisages an important role for hydrogen in the nation's future energy economy. This paper explores the possibility that a significant source for this hydrogen could be produced by electrolysis fueled by power generated from offshore wind in China. Hydrogen could be delivered to Japan either as liquid, or bound to a chemical carrier such as toluene, or as a component of ammonia. The paper presents an analysis of factors determining the ultimate cost for this hydrogen, including expenses for production, storage, conversion, transport, and treatment at the destination. It concludes that the Chinese source could be delivered at a volume and cost consistent with Japan's idealized future projections.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34846851

RESUMO

The lamellar structure of (Bi,Sb)2(Te,Se)3 alloys makes it difficult to achieve isotropic thermoelectric properties in the directions along and perpendicular to the c-axis, especially for n-type samples. In this work, by introducing Cu in polycrystalline n-type CuxBi2Te2.7Se0.3 and applying the traditional synthesis process of high-energy ball milling and hot pressing, substantial enhancement of the thermoelectric figure of merit zT is obtained in both in-plane and out-of-plane directions. The intercalated Cu not only provides electron transport media for mobility improvement but also reduces the lattice thermal conductivity owing to the strain fluctuation. Typically, the van der Waals gap in the out-of-plane direction leads to relatively slower mobility and lower lattice thermal conductivity. Taking into account the same average density-of-state effective mass (mavg* ∼ 1.5me) predicted based on a single parabolic model, the obtained quality factor ß is comparable in both directions. As a result, a peak zT ∼ 1.05 at 420 K and the average zT approaching to 1.0 in the temperature range 300-500 K are obtained in both directions for the Cu0. 02Bi2Te2.7Se0.3 sample. The simple synthesis process and isotropic thermoelectric properties in this work make n-type Bi2Te3 more convenient for potential production and application.

13.
Front Psychiatry ; 12: 753909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733192

RESUMO

Objectives: Dementia of the Alzheimer's type (DAT) is the most common chronic neurodegenerative disease. At present, the pathogenesis of DAT is not completely clear, and there are no drugs that can cure the disease. Once an individual is diagnosed with DAT, the survival time is only 3 to 9 years. Therefore, there is an urgent need to determine the etiology of DAT and the associated influencing factors to find a breakthrough in the treatment of DAT. Methods: We studied the relationship between polymorphisms in several genes (including BIN1 and APOE) and DAT susceptibility and the effects of sex differences on DAT. Our study included 137 patients with DAT and 509 healthy controls (HCs). Results: The APOE rs429358 polymorphism CC and CT genotypes were associated with an increased risk of DAT in women. We found a significant association between APOE ε4 and DAT. The frequency of the ε4 allele in the DAT group (15.5%) was higher than that in the HC group (8.7%). The BIN1 rs7561528 polymorphism was associated with a decreased risk of DAT in men. Conclusions: APOE gene rs429358 and BIN1 gene 7561528 genes may affect the susceptibility to DAT in a Chinese Han population.

14.
Chin J Integr Med ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839455

RESUMO

OBJECTIVE: To investigate whether the antihypertensive mechanism of electroacupuncture (EA) is associated with attenuating phenotype transformation of vascular smooth muscle cells (VSMCs) via phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. METHODS: Eight Wistar-ktoyo (WKY) rats were set as normal blood pressure group (normal group). A total of 32 spontaneous hypertensive rats (SHRs) were randomly divided into 4 groups using random number tables: a model group, an EA group, an EA+PI3K antagonist group (EA+P group), and an EA+p38 MAPK agonist+extracellular signal-regulated kinase (ERK) agonist group (EA+M group) (n=8/group). SHRs in EA group, EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks, while rats in the normal and model groups were bundled in same condition. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of each rat was measured at 0 week and the 4th week. After 4-week intervention, thoracic aorta was collected for hematoxylin-eosin (HE) staining, immunohistochemistry [the contractile markers α-smooth muscle actin (α-SMA) and calponin and the synthetic marker osteopontin (OPN)] and Western blot [α-SMA, calponin, OPN, PI3K, phosphorylated-Akt (p-Akt), Akt, p-p42/44 ERK, total p42/44 ERK, p-p38 MAPK and total p38 MAPK]. RESULTS: EA significantly reduced SBP, DBP and MAP (P<0.01). HE staining showed that the wall thickness of thoracic aorta in EA group was significantly decreased (P<0.01). From results of immunohistochemistry and Western blot, EA increased the expression of α-SMA and calponin, and decreased the expression of OPN (P<0.01). In addition, the expression of PI3K and p-Akt increased (P<0.01), while the expression of p-p42/44 ERK and p-p38 MAPK decreased in EA group (P<0.01). However, these effects were reversed by PI3K antagonist, p38 MAPK agonist and ERK agonist. CONCLUSIONS: EA was an effective treatment for BP management. The antihypertensive effect of EA may be related with inhibition of phenotypic transformation of VSMCs, in which the activation of PI3K/Akt and the repression of MAPK pathway were involved.

15.
Nat Sci Sleep ; 13: 1807-1822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675728

RESUMO

Study Objectives: To evaluate the efficacy and safety of acupuncture at HT 7 (Shenmen) and KI 7 (Fuliu) on sleep and comorbid symptoms for chronic insomnia. Methods and Design: A randomized, single-blind, parallel and sham-controlled trial consisted of an acupuncture group (n = 41) and a sham acupuncture group (n = 41). Setting: a tertiary hospital of integrated Chinese and Western medicine. Participants: 82 subjects with chronic insomnia based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Interventions: a 10-session acupuncture treatment at bilateral HT 7 and KI 7 or sham acupoints with shallow needling was performed over 3 weeks. Measurements: the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI) were evaluated at baseline, posttreatment, and at two follow-ups as the primary outcome measures. Polysomnography (PSG) on two consecutive nights, the Beck anxiety inventory (BAI), the Beck depression inventory (BDI) fatigue severity scale (FSS) and the Epworth sleepiness scale (ESS) were evaluated at baseline and posttreatment as the secondary outcome measures. Results: After the treatments, PSQI scores decreased by 5.04 in the acupuncture group and 2.92 in the sham acupuncture group. ISI scores decreased by 7.65 in the acupuncture group and 5.05 in the sham acupuncture group. The between-group differences in the primary outcome measures posttreatment were statistically significant. However, no differences were found between the two groups during the two follow-ups. Regarding the PSG data, there were significantly lower levels of sleep onset latency (SOL), a lower percentage of sleep stage N1 and a higher percentage of sleep stage N3 in the acupuncture group than in the sham acupuncture group. After treatment, there were lower levels of comorbid symptoms (BAI, BDI, FSS and ESS) in both groups. However, no significant differences were observed between the groups. Conclusion: Acupuncture at HT 7 and KI 7 is an effective and safe nonpharmacologic intervention option for chronic insomnia. Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR1900023787, China.

16.
Brief Bioinform ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34718395

RESUMO

Since the first report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, over 100 million people have been infected by COVID-19, millions of whom have died. In the latest year, a large number of omics data have sprung up and helped researchers broadly study the sequence, chemical structure and function of SARS-CoV-2, as well as molecular abnormal mechanisms of COVID-19 patients. Though some successes have been achieved in these areas, it is necessary to analyze and mine omics data for comprehensively understanding SARS-CoV-2 and COVID-19. Hence, we reviewed the current advantages and limitations of the integration of omics data herein. Firstly, we sorted out the sequence resources and database resources of SARS-CoV-2, including protein chemical structure, potential drug information and research literature resources. Next, we collected omics data of the COVID-19 hosts, including genomics, transcriptomics, microbiology and potential drug information data. And subsequently, based on the integration of omics data, we summarized the existing data analysis methods and the related research results of COVID-19 multi-omics data in recent years. Finally, we put forward SARS-CoV-2 (COVID-19) multi-omics data integration research direction and gave a case study to mine deeper for the disease mechanisms of COVID-19.

17.
Nat Commun ; 12(1): 5953, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642325

RESUMO

Triggered by the pioneering research on graphene, the family of two-dimensional layered materials (2DLMs) has been investigated for more than a decade, and appealing functionalities have been demonstrated. However, there are still challenges inhibiting high-quality growth and circuit-level integration, and results from previous studies are still far from complying with industrial standards. Here, we overcome these challenges by utilizing machine-learning (ML) algorithms to evaluate key process parameters that impact the electrical characteristics of MoS2 top-gated field-effect transistors (FETs). The wafer-scale fabrication processes are then guided by ML combined with grid searching to co-optimize device performance, including mobility, threshold voltage and subthreshold swing. A 62-level SPICE modeling was implemented for MoS2 FETs and further used to construct functional digital, analog, and photodetection circuits. Finally, we present wafer-scale test FET arrays and a 4-bit full adder employing industry-standard design flows and processes. Taken together, these results experimentally validate the application potential of ML-assisted fabrication optimization for beyond-silicon electronic materials.

18.
J Pharm Biomed Anal ; 206: 114389, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34601206

RESUMO

HKUST-1, a kind of metal-organic framework (MOF) composed by Cu2+ and trimesic acid, loaded on reduced graphene oxide and multi-walled carbon nanotubes nanocomposite [HKUST-1 @ (RGO-MWCNT)] was successfully synthesized by a facile and simple route. Then, a highly sensitive non-enzymatic salvianic acid A (SAA) electrochemical sensor was fabricated by modifying HKUST-1 @ (RGO-MWCNT) on a glassy carbon electrode, taking full advantage of the synergistic effect between the redox catalytic capacity of Cu2+ and the electrical conductivity of carbon materials. The sensor showed a low limit of detection of 0.081 µM, limit of quantitation of 0.27 µM, high sensitivity of 509.6 µA/mM and a good relationship between reduction peak current and concentration of SAA from 2 to 4600 µM. Meanwhile, the sensor had the advantages of repeatability and stability. Finally, it was used to detect SAA in real samples with noteworthy electroanalytical performance. In short, the sensor has considerable potential for the electroanalysis of SAA. Moreover, the study provides a promising composite of MOF and carbon materials with potential application in the analysis of effective components of herbaceous medicinal plants.


Assuntos
Grafite , Estruturas Metalorgânicas , Nanotubos de Carbono , Preparações Farmacêuticas , Técnicas Eletroquímicas
19.
Nat Commun ; 12(1): 6138, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686668

RESUMO

To investigate the pathogenesis of a congenital form of hepatic fibrosis, human hepatic organoids were engineered to express the most common causative mutation for Autosomal Recessive Polycystic Kidney Disease (ARPKD). Here we show that these hepatic organoids develop the key features of ARPKD liver pathology (abnormal bile ducts and fibrosis) in only 21 days. The ARPKD mutation increases collagen abundance and thick collagen fiber production in hepatic organoids, which mirrors ARPKD liver tissue pathology. Transcriptomic and other analyses indicate that the ARPKD mutation generates cholangiocytes with increased TGFß pathway activation, which are actively involved stimulating myofibroblasts to form collagen fibers. There is also an expansion of collagen-producing myofibroblasts with markedly increased PDGFRB protein expression and an activated STAT3 signaling pathway. Moreover, the transcriptome of ARPKD organoid myofibroblasts resemble those present in commonly occurring forms of liver fibrosis. PDGFRB pathway involvement was confirmed by the anti-fibrotic effect observed when ARPKD organoids were treated with PDGFRB inhibitors. Besides providing insight into the pathogenesis of congenital (and possibly acquired) forms of liver fibrosis, ARPKD organoids could also be used to test the anti-fibrotic efficacy of potential anti-fibrotic therapies.


Assuntos
Cirrose Hepática/patologia , Modelos Biológicos , Organoides/patologia , Doenças dos Ductos Biliares/genética , Doenças dos Ductos Biliares/metabolismo , Doenças dos Ductos Biliares/patologia , Colágeno/metabolismo , Células Epiteliais/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Mutação , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Organoides/efeitos dos fármacos , Organoides/metabolismo , Rim Policístico Autossômico Recessivo/tratamento farmacológico , Rim Policístico Autossômico Recessivo/genética , Rim Policístico Autossômico Recessivo/metabolismo , Rim Policístico Autossômico Recessivo/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
20.
Natl Sci Rev ; 8(5): nwaa301, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34691643

RESUMO

Collective dynamics of confined colloids are crucial in diverse scenarios such as self-assembly and phase behavior in materials science, microrobot swarms for drug delivery and microfluidic control. Yet, fine-tuning the dynamics of colloids in microscale confined spaces is still a formidable task due to the complexity of the dynamics of colloidal suspension and to the lack of methodology to probe colloids in confinement. Here, we show that the collective dynamics of confined magnetic colloids can be finely tuned by external magnetic fields. In particular, the mechanical properties of the confined colloidal suspension can be probed in real time and this strategy can be also used to tune microscale fluid transport. Our experimental and theoretical investigations reveal that the collective configuration characterized by the colloidal entropy is controlled by the colloidal concentration, confining ratio and external field strength and direction. Indeed, our results show that mechanical properties of the colloidal suspension as well as the transport of the solvent in microfluidic devices can be controlled upon tuning the entropy of the colloidal suspension. Our approach opens new avenues for the design and application of drug delivery, microfluidic logic, dynamic fluid control, chemical reaction and beyond.

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