Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.174
Filtrar
1.
Food Chem ; 399: 133843, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35998488

RESUMO

A facile approach was proposed for the preparation of boric acid-functionalized core-shell structured magnetic covalent organic framework (COF) nanocomposites through employing the Fe3O4 nanoparticles as magnetic core, boric acid-functionalized COFs as the shell via sequential post-synthetic modification (denoted as Fe3O4@COF@BA). The synthesized nanocomposites showed large specific surface area, high magnetic responsiveness, and desirable chemical and thermal stability. Combined with HPLC-MS/MS, the as-prepared Fe3O4@COF@BA composite was applied as a sorbent for magnetic solid-phase extraction (MSPE) of endocrine disrupting compounds (EDCs) from meat samples. Under optimal conditions, the method displays low limits of detection (LODs, 0.08-0.72 µg kg-1) and good precision with relative standard deviations (RSD) lower than 5.4 %. The approach was successfully employed for the extraction and detection of EDCs in blank and spiked beef, chicken and pork samples with recovery ranging from 88.8 to 104.2 %.


Assuntos
Disruptores Endócrinos , Estruturas Metalorgânicas , Adsorção , Animais , Ácidos Bóricos , Bovinos , Cromatografia Líquida de Alta Pressão , Limite de Detecção , Fenômenos Magnéticos , Carne/análise , Estruturas Metalorgânicas/química , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem
2.
Front Microbiol ; 13: 840562, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369425

RESUMO

Antibiotic resistance is one of the most important environmental challenges. Microalgae has been considered as a promising green media for environmental purification. In this work, sulfadimethoxine (SDM) biodegradation potential of Chlorella sp. L38 and Phaeodactylum tricornutum MASCC-0025 is investigated. Experimental results indicated that the tested freshwater and marine microalgae strains presented stress response to SDM addition. For Chlorella sp. L38, it has a good adaptability to SDM condition via antioxidant enzyme secretion (SOD, MDA, and CAT up to 23.27 U/mg, 21.99 µmol/g, and 0.31 nmol/min/mg) with removal rate around 88%. P. tricornutum MASCC-0025 exhibited 100% removal of 0.5 mg/L SDM. With increasing salinity (adding a certain amount of NaCl) of cultivation media, the removal rate of SDM by microalgae increased. Although its adaptive process was slower than Chlorella sp. L38, the salinity advantage would facilitate enzyme accumulation. It indicated that microalgae could be used to remove SDM from freshwater and marine environment via suitable microalgae strain screening.

3.
J Am Acad Dermatol ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36075285

RESUMO

BACKGROUND: Evidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited. OBJECTIVE: To determine the prognostic impact of Breslow thickness in AM. METHODS: This multicenter study enrolled patients diagnosed with localized AM between 1 January 2000 and 31 December 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by Kaplan-Meier method. Comparisons were performed by log-rank test and multivariable Cox regression. RESULTS: A total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The median follow-up time was 60.1 months. The median MSS in patients with T1-T4 disease was not reached, 111.0, 92.8, and 67.1 months, respectively. MSS differed significantly among cN0 patients with T1-T3 AM (log-rank P=0.004, 0.012, <0.001 for T1 vs. T2, T2 vs. T3, and T1 vs. T3, respectively); however, there was no significant difference between T3 and T4 AM (hazard ratio=0.82, 95% confidence interval, 0.62-1.09). Six-subgroup analyses confirmed that survival outcomes were similar between different subgroups with tumor thickness >2 mm. LIMITATIONS: Retrospective design and some missing variables. CONCLUSIONS: There was no association between tumor thickness and survival in AM patients with a Breslow thickness >2 mm.

4.
Pharm Res ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076007

RESUMO

Physiologically based biopharmaceutics modeling (PBBM) emphasizes the integration of physicochemical properties of drug substance and formulation characteristics with system physiological parameters to predict the absorption and pharmacokinetics (PK) of a drug product. PBBM has been successfully utilized in drug development from discovery to postapproval stages and covers a variety of applications. The use of PBBM facilitates drug development and can reduce the number of preclinical and clinical studies. In this review, we summarized the major applications of PBBM, which are classified into six categories: formulation selection and development, biopredictive dissolution method development, biopharmaceutics risk assessment, clinically relevant specification settings, food effect evaluation and pH-dependent drug-drug-interaction risk assessment. The current state of PBBM applications is illustrated with examples from published studies for each category of application. Despite the variety of PBBM applications, there are still many hurdles limiting the use of PBBM in drug development, that are associated with the complexity of gastrointestinal and human physiology, the knowledge gap between the in vitro and the in vivo behavior of drug products, the limitations of model interfaces, and the lack of agreed model validation criteria, among other issues. The challenges and essential considerations related to the use of PBBM are discussed in a question-based format along with the scientific thinking on future research directions. We hope this review can foster open discussions between the pharmaceutical industry and regulatory agencies and encourage collaborative research to fill the gaps, with the ultimate goal to maximize the applications of PBBM in oral drug product development.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36083797

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is defined by increased left ventricular (LV) stiffness, impaired vascular compliance and fibrosis. Although systemic inflammation, driven by comorbidities, has been proposed to play a key role, the precise pathogenesis remains elusive. To test the hypothesis that inflammation drives endothelial dysfunction in HFpEF, we used cardiosphere-derived cells (CDCs), which reduce inflammation and fibrosis, improving function, structure and survival in HFpEF rats. Dahl salt-sensitive rats fed a high-salt diet developed HFpEF, as manifested by diastolic dysfunction, systemic inflammation and accelerated mortality. Rats were randomly allocated to receive intracoronary infusion of CDCs or vehicle. Two weeks later, inflammation, oxidative stress and endothelial function were analyzed. Single-cell RNA-sequencing of heart tissue was used to assay transcriptomic changes. CDCs improved endothelial-dependent vasodilation while reducing oxidative stress and restoring eNOS expression. RNA-sequencing revealed CDC-induced attenuation of pathways underlying endothelial cell leukocyte binding and innate immunity. Exposure of endothelial cells to CDC-secreted extracellular vesicles in vitro reduced VCAM-1 protein expression and attenuated monocyte adhesion and transmigration. Cell therapy with CDCs corrects diastolic dysfunction, reduces oxidative stress, and restores vascular reactivity. These findings lend credence to the hypothesis that inflammatory changes of the vascular endothelium are important, if not central, to HFpEF pathogenesis.

6.
Anal Chim Acta ; 1226: 340164, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36068049

RESUMO

Cytosine and protonated cytosine base pairs (C·CH+)-supported i-motif conformation has been widely employed in some interdisciplinary fields such as biology, medicine and chemistry. In this work, we report a new electrochemical biosensing method for the detection of glucose oxidase (GOx) and urease based on pH-induced DNA conformational-change. The constructed platform mainly includes TdT-mediated catalytic synthesis, GOx- or urease-catalyzed biological reaction and pH-induced DNA conformational-change. In the beginning, a kind of C-rich DNA is produced by TdT catalysis, and multiple C·CH+-supported i-motif structures appear under acidic condition. Then, the oxidation of glucose catalyzed by GOx or the hydrolyzation of urea aroused by urease can result in a generation of acidic or alkaline environment owing to the generated gluconic acid or ammonia. Herein, protonation and deprotonation interaction in TdT-yielded C-rich DNA can lead to different electrochemical impedance spectroscopy (EIS) toward Fe(CN)63-/4-. Based on it, the EIS response changes proportionally toward GOx concentrations from 0.01 to 20 U/L or urease concentrations from 0.01 to 50 U/L, and the detection limit of GOx or urease is 0.0061 U/L or 0.0028 U/L (S/N = 3), respectively. Beyond this, we also construct a series of molecular logic gates (YES, AND, NOT, and NAND) with good performance by altering inputs under long C-rich DNA substrate. These excellent properties indicate that the unique sensing platform is potential to monitor GOx or urease in practical biosystems and clinical medical examinations.


Assuntos
Técnicas Biossensoriais , Glucose Oxidase , Técnicas Biossensoriais/métodos , Citosina , Técnicas Eletroquímicas/métodos , Glucose/análise , Glucose Oxidase/química , Urease
7.
Mol Plant ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071671

RESUMO

Evolution is driven by various mechanisms. Directional increase in embryo to endosperm ratio is an evolutionary trend within angiosperms. Endosperm constitutes a major seed volume of Poales and some dicots. In other dicots such as Arabidopsis and soybean, endosperm proliferates early followed by embryo growth to replace the endosperm. Arabidopsis Leucine-rich repeat receptor protein kinase AtHAIKU2 (AtIKU2) is a key regulator of early endosperm proliferation. IKU2s from Brachypodium, rice and soybean complement Atiku2 phenotype. AtIKU2 also rescues endosperm proliferation in Brachypodium BdIKU2 knockout. AtIKU2 and soybean GmIKU2 are actively expressed in a few days after fertilization. Thereafter, AtIKU2 is suppressed by FIS-PRC2 and GmIKU2 locus is enriched with H3K27me3 marks. Histone methyltransferase AtMEA is unique to Brassicaceae, but one GmSWN is an early version of AtMEA. In contrast, the BdIKU2 and rice OsIKU2 loci sustain a continuous expression and are devoid of H3K27me3 marks. IKU2 retains an ancestral function. Its expression duration contributes to silenced or persistent endosperm proliferation. We reveal an epigenetic mechanism that drives the development of vastly different seed ontogeny.

8.
Mol Cell Endocrinol ; : 111755, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36049597

RESUMO

We recently demonstrated that combined therapy of GABA and sitagliptin promoted beta-cell proliferation, and decreased beta-cell apoptosis in a multiple low-dose streptozotocin (STZ)-induced beta-cell injury mouse model. In this study, we examined whether this combined therapy is effective in ameliorating the impairment of beta-cell function caused by high-fat diet (HFD) feeding in mice. Male C57BL/6J mice were fed normal chow diet, HFD, or HFD combined with GABA, sitagliptin, or both drugs. Oral drug daily administration was initiated one week before HFD and maintained for two weeks. After two weeks of intervention, we found that GABA or sitagliptin administration ameliorated the impairment of glucose tolerance induced by HFD. This was associated with improved insulin secretion in vivo. Notably, combined administration of GABA and sitagliptin significantly enhanced these effects as compared to each of the monotherapies. Combined GABA and sitagliptin was superior at increasing beta-cell mass, and associated Ki67+ and PDX-1+ beta-cell counts. In addition, we found that HFD-induced compensatory beta-cell proliferation was associated with increased activation of unfolded protein response (UPR), as indicated by BiP expression. This could be an important mechanism of compensatory beta-cell proliferation, and beta cells treated with GABA and sitagliptin showed greater UPR activation. Our results suggest that the combined use of these agents produces superior therapeutic outcomes.

9.
Pharm Res ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050545

RESUMO

To date, mechanistic modeling of oral drug absorption has been achieved via the use of physiologically based pharmacokinetic (PBPK) modeling, and more specifically, physiologically based biopharmaceutics model (PBBM). The concept of finite absorption time (FAT) has been developed recently and the application of the relevant physiologically based finite time pharmacokinetic (PBFTPK) models to experimental data provides explicit evidence that drug absorption terminates at a specific time point. In this manuscript, we explored how PBBM and PBFTPK models compare when applied to the same dataset. A set of six compounds with clinical data from immediate-release formulation were selected. Both models resulted in absorption time estimates within the small intestinal transit time, with PBFTPK models generally providing shorter time estimates. A clear relationship between the absorption rate and the product of permeability and luminal concentration was observed, in concurrence with the fundamental assumptions of PBFTPK models. We propose that future research on the synergy between the two modeling approaches can lead to both improvements in the initial parameterization of PBPK/PBBM models but to also expand mechanistic oral absorption concepts to more traditional pharmacometrics applications.

10.
Clin Exp Rheumatol ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36062744

RESUMO

OBJECTIVES: Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of antiphospholipid syndrome (APS) with high mortality. We try to develop a predictive model to achieve early recognition of CAPS. METHODS: Data of APS patients referred into Peking Union Medical College Hospital from May 2013 to October 2021 was collected. A binary logistic regression method was used to identify predictors of CAPS, coefficient B was assigned with score value in the development of prediction model, and risk-stratification was based on the calculated scores using the model. RESULTS: Twenty-seven CAPS (11.9%) occurred in 226 APS patients. CAPS was more likely to occur in male secondary APS patients with a history of hypertension, hyperlipidaemia, and arterial thrombosis, presented with haematological, nephrological and immunological abnormalities simultaneously. Hypertension history (OR 5.091, 95% CI 1.119-23.147), anaemia (OR 116.231, 95% CI 10.512-1285.142), elevated LDH (OR 59.743, 95% CI 7.439-479.815) and proteinuria (OR 11.265, 95% CI 2.118-59.930) were independent predictors for CAPS, and the scores were 1, 3, 3 and 2 points, respectively. The risk scores were divided into high-risk (6-9) and low risk (0-5), the risk for CAPS were 54.1% and 0.6%, with sensitivity of 0.963 and specificity of 0.886. The Nagelkerke's R2 (0.739) and the Omnibus test (χ2 =109.231, df=4, p=0.000) indicated the model has a good fit. The AUC of 0.971 indicated good discrimination. The calibration curve in internal validation showed good calibration of this predictive model. CONCLUSIONS: A predictive model of CAPS was developed with hypertension, anaemia, elevated LDH and proteinuria. This model could help identify CAPS in high-risk patients, achieve early recognition and intervention to improve prognosis.

11.
Adv Mater ; : e2204801, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047911

RESUMO

Flexible scintillator screens with environmental stability, high sensitivity and low cost have emerged as candidates for X-ray imaging applications. Here, we demonstrated a large-scale and cost-efficient solution synthesis of vacancy-ordered double perovskite Cs2 ZrCl6 , which is characterized by thermal activation delay fluorescence (TADF) dominated by triplet emission under X-ray irradiation. The large Stokes shift and efficient luminescence collection of TADF effectively ensure the light out-coupling efficiency. Further, flexible X-ray scintillator screens with an area of 400 cm2 were prepared using polydimethylsiloxane (PDMS) as the carrier, which exhibit excellent scintillation properties with light yields as high as 49 400 photons/MeV, spatial resolutions up to 18 lp/mm and detection limits as low as 65 nGy/s. Finally, we demonstrated the high-quality imaging results of non-planar and dynamic objects by such screens. We believe that the explored Cs2 ZrCl6 @PDMS flexible scintillator screens would offer a big step towards expanding the application range of scintillators in different environments. This article is protected by copyright. All rights reserved.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36083962

RESUMO

Performing highly accurate representation learning on a high-dimensional and sparse (HiDS) matrix is of great significance in a big data-related application such as a recommender system. A latent factor (LF) model is one of the most efficient approaches to the HiDS matrix representation. However, an LF model's representation learning ability relies heavily on an HiDS matrix's known data density, which is extremely low due to numerous missing data entities. To address this issue, this work proposes a prediction-sampling-based multilayer-structured LF (PMLF) model with twofold ideas: 1) constructing a loosely connected multilayered LF architecture to increase the known data density of an input HiDS matrix by generating synthetic data layer by layer and 2) constraining this synthetic data generating process through a random prediction-sampling strategy and nonlinear activations to avoid overfitting. In the experiments, PMLF is compared with six state-of-the-art LF-and deep neural network (DNN)-based models on four HiDS matrices from industrial applications. The results demonstrate that PMLF outperforms its peers in well-balancing prediction accuracy and computational efficiency.

13.
Front Pharmacol ; 13: 930614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120348

RESUMO

Endometriosis (EMs) is defined as the presence of tissue somewhat resembling endometrial glands and stroma outside the uterus; the retrograded endometrium grows in the peritoneal cavity and elicits fibrosis. Ferroptosis is a recently discovered form of programmed cell death, which is iron-dependent. The induction of ferroptosis has been found to participate in fibrosis. However, the relationship between EMs fibrosis and ferroptosis remains unknown. In this study, we confirmed that the iron content in ectopic stromal tissue in ovarian EMs is significantly increased. We explored the role of iron-induced ferroptosis in the pathogenesis of ovarian EMs fibrosis for the first time. We found that ferroptosis in ectopic tissues was significantly enhanced than that in eutopic tissues. Furthermore, we performed in vivo drug screening and found that ferroptosis induced by ferric ammonium citrate (FAC) could aggravate fibrosis. To clarify the mechanism of this process, the stromal composition of human uterine endometrium and endometrial tissue was characterized. Fibroblast-specific protein-1 was used for fibroblasts, smooth muscle actin alpha for myofibroblasts, and platelet-derived growth factor receptor beta (CD140b) for mesenchymal stromal cells (MSCs). The results demonstrated that the percentage of myofibroblasts was higher and the portion of MSCs was lower in ectopic endometrial stroma than those in eutopic endometrium. Moreover, the proportion of MSCs decreased significantly and the percentage of myofibroblasts increased considerably after FAC treatment in vitro. However, disruption of intracellular iron levels or ferroptosis via chelation of intracellular iron deferoxamine mesylate or ferroptosis inhibitor ferrostatin-1 could reverse this process, indicating that iron-induced ferroptosis plays a vital role in ovarian EMs fibrosis. Considering that iron accumulation can feed the Fenton reaction to generate unquenchable amounts of free radicals, causing ferroptosis and tissue damage and thereby contributing to fibrosis, we validated the underlying mechanism that excess iron can facilitate fibrotic responses. Collectively, these data provide evidence that supernumerary iron is a key regulator in promoting MSCs ferroptosis and inducing ovarian EMs fibrosis.

14.
Small Methods ; : e2200794, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114150

RESUMO

Infectious pathogens cause severe human illnesses and great deaths per year worldwide. Rapid, sensitive, and accurate detection of pathogens is of great importance for preventing infectious diseases caused by pathogens and optimizing medical healthcare systems. Inspired by a microbial defense system (i.e., CRISPR/ CRISPR-associated proteins (Cas) system, an adaptive immune system for protecting microorganisms from being attacked by invading species), a great many new biosensors have been successfully developed and widely applied in the detection of infectious viruses and pathogenic bacteria. Moreover, advanced nanotechnologies have also been integrated into these biosensors to improve their detection stability, sensitivity, and accuracy. In this review, the recent advance in CRISPR/Cas systems-based nano/biosensors and their applications in the detection of infectious viruses and pathogenic bacteria are comprehensively reviewed. First of all, the categories and working principles of CRISPR/Cas systems for establishing the nano/biosensors are simply introduced. Then, the design and construction of CRISPR/Cas systems-based nano/biosensors are comprehensively discussed. In the end, attentions are focused on the applications of CRISPR/Cas systems-based nano/biosensors in the detection of infectious viruses and pathogenic bacteria. Impressively, the remaining opportunities and challenges for the further design and development of CRISPR/Cas system-based nano/biosensors and their promising applications are proposed.

15.
J Clin Lab Anal ; : e24706, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36114782

RESUMO

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical disease with an increasing incidence. The absorption route of CSDH is not clear. Whether inflammatory factors enter the peripheral blood and cause systemic reactions is unknown. METHODS: We screened 105 CSDH patients and 105 control individuals. Their clinical characteristics and blood routine results were collected and compared. The blood routine changes of CSDH patients before and after treatment were compared. Age-stratified analysis was performed due to age may affect the inflammatory markers. RESULTS: The white blood cell count, absolute neutrophil count, neutrophil percentage, neutrophil-lymphocyte count ratio (NLR), and platelet to lymphocyte count ratio (PLR) of CSDH patients before treatment were within the normal range, while were significantly higher than the control individuals (p < 0.001). The absolute lymphocyte count and lymphocyte percentage of control individuals were higher than those of patients (p < 0.001). The inflammatory cells in patients of different age groups were similar. After the patient was cured, the white blood cell count, the absolute value and percentage of neutrophils decreased (p < 0.05), while the number of monocytes increased. CONCLUSIONS: CSDH caused slight systemic inflammatory responses in the peripheral blood, implying that there is a non-hematologic route for the absorption of hematoma.

16.
Dis Markers ; 2022: 3144742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046377

RESUMO

The incidence of hepatocellular carcinoma (HCC), which is one of the most frequent types of cancer seen all over the world, is steadily growing from year to year. EGR genes are members of the early growth response (EGR) gene family. It has been shown that EGR genes play an increasingly essential role in the development of tumors and the progression of numerous malignancies. However, the possible diagnostic and prognostic roles of EGR genes in HCC have only been examined in a limited number of studies. Expression and methylation data on EGR family members were obtained from TCGA datasets. The prognostic values of EGR members were studied. Additionally, the correlations of EGR members with immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA). In this study, we found that the expression of EGR1, EGR2, EGR3, and EGR4 was distinctly decreased in HCC specimens compared with nontumor specimens. ROC assays confirmed that they have a strong ability in screening HCC specimens from nontumor specimens. According to the findings of Pearson's correlation, EGR1, EGR2, EGR3, and EGR4 were found to have a negative association with the methylation level. Survival study revealed that EGR1, EGR2, and EGR3 were associated with the clinical outcome of HCC patients. Immune cell enrichment analysis demonstrated that the expressions of all EGR members were positively related to the levels of most types of immune cells, such as macrophages, NK cells, B cells, T cells, eosinophils, and CD8 T cells. Overall, the current work demonstrated the expression mode and prognostic value of EGR members in HCC in a comprehensive manner, offering insights for further research of the EGR family as possible clinical biomarkers in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Proteína 1 de Resposta de Crescimento Precoce , Proteína 2 de Resposta de Crescimento Precoce , Proteína 3 de Resposta de Crescimento Precoce , Fatores de Transcrição de Resposta de Crescimento Precoce , Família , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética
17.
Int Immunopharmacol ; 112: 109201, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36067652

RESUMO

Tubulointerstitial fibrosis (TIF) is a prominent pathological manifestation for the progression of almost all chronic kidney diseases (CKDs) to end-stage renal failure. However, there exist few efficient therapies to cure TIF. Our recent results showed that (8R, 12S)-isoandrographolide (ISA), a diterpenoid lactone ingredient of traditional Chinese herbal Andrographis paniculata (Burm.f.) Nees, exhibited anti-pulmonary fibrosis in silica-induced mice. Herein, we investigated the therapeutic effect of ISA on TIF, using mice subjected to unilateral ureteral obstruction (UUO) and human kidney proximal tubular epithelial (HK-2) cells treated with transforming growth factor-ß1 (TGF-ß1) or tumor necrosis factor-α (TNF-α). The pathological changes and collagen deposition results displayed that ISA administration significantly attenuated inflammatory response, ameliorated TIF, and protected the kidney injury. Interestingly, ISA revealed much lower cytotoxicity on HK-2 cells, but exhibited stronger inhibitory effect on tubular epithelial mesenchymal transformation (EMT) and inflammation, as compared to andrographolide (AD), the major ingredient of A. paniculata extract that has been reported to ameliorate TIF in diabetic nephropathy mice. It was further clarified that the amelioration of TIF by ISA was associated with suppressing the aberrant activation of AKT/GSK-3ß/ß-catenin pathway through network pharmacology analysis and experimental validation. Taken together, these findings indicate that ISA is a promising lead compound for development of anti-TIF, and even broad-spectrum anti-fibrotic drugs.

18.
Nature ; 609(7927): 496-501, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36104554

RESUMO

Lithium niobate (LiNbO3) is viewed as a promising material for optical communications and quantum photonic chips1,2. Recent breakthroughs in LiNbO3 nanophotonics have considerably boosted the development of high-speed electro-optic modulators3-5, frequency combs6,7 and broadband spectrometers8. However, the traditional method of electrical poling for ferroelectric domain engineering in optic9-13, acoustic14-17 and electronic applications18,19 is limited to two-dimensional space and micrometre-scale resolution. Here we demonstrate a non-reciprocal near-infrared laser-writing technique for reconfigurable three-dimensional ferroelectric domain engineering in LiNbO3 with nanoscale resolution. The proposed method is based on a laser-induced electric field that can either write or erase domain structures in the crystal, depending on the laser-writing direction. This approach offers a pathway for controllable nanoscale domain engineering in LiNbO3 and other transparent ferroelectric crystals, which has potential applications in high-efficiency frequency mixing20,21, high-frequency acoustic resonators14-17 and high-capacity non-volatile ferroelectric memory19,22.

19.
Front Nutr ; 9: 919769, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091236

RESUMO

Early dietary exposure via human milk nutrients offers a window of opportunity to support cognitive and temperament development. While several studies have focused on associations of few pre-selected human milk nutrients with cognition and temperament, it is highly plausible that human milk nutrients synergistically and jointly support cognitive and behavioral development in early life. We aimed to discern the combined associations of three major classes of human milk nutrients with cognition and temperament during the first 6 months of life when human milk is the primary source of an infant's nutrition and explore whether there were persistent effects up to 18 months old. The Mullen Scales of Early Learning and Infant Behavior Questionnaires-Revised were used to assess cognition and temperament, respectively, of 54 exclusively/predominantly breastfed infants in the first 6 months of life, whose follow-ups were conducted at 6-9, 9-12, and 12-18 months old. Human milk samples were obtained from the mothers of the participants at less than 6 months of age and analyzed for fatty acids [total monounsaturated fatty acids, polyunsaturated fatty acid, total saturated fatty acid (TSFA), arachidonic acid (ARA), docosahexaenoic acid (DHA), ARA/DHA, omega-6/omega-3 polyunsaturated fatty acids ratio (n-6/n-3)], phospholipids [phosphatidylcholine, phosphatidylethanolamine (PE), phosphatidylinositol (PI), sphingomyelin], and choline [free choline, phosphocholine (PCho), glycerophosphocholine]. Feature selection was performed to select nutrients associated with cognition and temperament. The combined effects of selected nutrients were analyzed using multiple regression. A positive association between the arachidonic acid (ARA) and surgency was observed (p = 0.024). A significant effect of DHA, n-6/n-3, PE, and TSFA concentrations on receptive language (R 2 = 0.39, p = 0.025) and the elevated ARA, PCho, and PI with increased surgency (R 2 = 0.43, p = 0.003) was identified, suggesting that DHA and ARA may have distinct roles for temperament and language functions. Furthermore, the exploratory association analyses suggest that the effects of human milk nutrients on R.L. and surgency may persist beyond the first 6 months of life, particularly surgency at 12-18 months (p = 0.002). Our study highlighted that various human milk nutrients work together to support the development of cognition and temperament traits during early infancy.

20.
ACS Nano ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36126321

RESUMO

In transport, the topological Hall effect (THE) presents itself as nonmonotonic features (or humps and dips) in the Hall signal and is widely interpreted as a sign of chiral spin textures, like magnetic skyrmions. However, when the anomalous Hall effect (AHE) is also present, the coexistence of two AHEs could give rise to similar artifacts, making it difficult to distinguish between genuine THE with AHE and two-component AHE. Here, we confirm genuine THE with AHE by means of transport and magneto-optical Kerr effect (MOKE) microscopy, in which magnetic skyrmions are directly observed, and find that genuine THE occurs in the transition region of the AHE. In sharp contrast, the artifact "THE" or two-component AHE occurs well beyond the saturation of the "AHE component" (under the false assumption of THE + AHE). Furthermore, we distinguish artifact "THE" from genuine THE by three methods: (1) minor loops, (2) temperature dependence, and (3) gate dependence. Minor loops of genuine THE with AHE are always within the full loop, while minor loops of the artifact "THE" may reveal a single loop that cannot fit into the "AHE component". In addition, the temperature or gate dependence of the artifact "THE" may also be accompanied by a polarity change of the "AHE component", as the nonmonotonic features vanish, while the temperature dependence of genuine THE with AHE reveals no such change. Our work may help future researchers to exercise caution and use these methods for careful examination in order to ascertain the genuine THE.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...