RESUMO
Visualization and characterization of the intestinal membrane transporter-mediated drug absorption and interaction are challenging due to the complex physical and chemical environment. In this work, an integrated strategy was developed for in situ visualization and assessment of the drug absorption and interaction in rat intestines using quadruple single-pass intestinal perfusion (Q-SPIP) technique coupled with matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). Compared with the traditional SPIP only available for perfusion of one single intestinal segment, the Q-SPIP model can simultaneously perfuse four individual segments of each rat intestine (duodenum, jejunum, ileum, and colon), enabling to obtain rich data from one rat. Subsequently, the drug distribution and absorption in rat intestinal tissue were accurately visualized by using an optimized MALDI MSI approach. The utility and versatility of this strategy were demonstrated via the examination of P-glycoprotein (P-gp)-mediated intestinal absorption of berberine (BBR) and its combination with natural products possessing inhibitory potency against P-gp. The change in the spatial distribution of BBR was resolved, and MALDI results showed that the signal intensity of BBR in defined regions was enhanced following coperfusion with P-gp inhibitors. However, enhanced absorption of BBR after coperfusion with the P-gp inhibitor was not observed in the ulcerative colitis rat model, which may be due to the damage to the intestinal barrier. This study exemplifies the availability and utility of Q-SPIP coupled with MALDI MSI in the examination of transporter-mediated intestinal drug absorption and interaction for fundamental inquiries into the preclinical prediction of oral absorption and drug interaction potential.
Assuntos
Duodeno , Intestinos , Ratos , Animais , Absorção Intestinal , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Perfusão/métodos , Proteínas de Membrana Transportadoras/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , PermeabilidadeRESUMO
Computer-aided diagnosis has been extensively investigated for more rapid and accurate screening during the outbreak of COVID-19 epidemic. However, the challenge remains to distinguish COVID-19 in the complex scenario of multi-type pneumonia classification and improve the overall diagnostic performance. In this paper, we propose a novel periphery-aware COVID-19 diagnosis approach with contrastive representation enhancement to identify COVID-19 from influenza-A (H1N1) viral pneumonia, community acquired pneumonia (CAP), and healthy subjects using chest CT images. Our key contributions include: 1) an unsupervised Periphery-aware Spatial Prediction (PSP) task which is designed to introduce important spatial patterns into deep networks; 2) an adaptive Contrastive Representation Enhancement (CRE) mechanism which can effectively capture the intra-class similarity and inter-class difference of various types of pneumonia. We integrate PSP and CRE to obtain the representations which are highly discriminative in COVID-19 screening. We evaluate our approach comprehensively on our constructed large-scale dataset and two public datasets. Extensive experiments on both volume-level and slice-level CT images demonstrate the effectiveness of our proposed approach with PSP and CRE for COVID-19 diagnosis.
RESUMO
The subcellular localization of polyQ-expanded huntingtin exon1 (Httex1) modulates polyQ toxicity in models of Huntington's disease. Using genome-wide screens in a yeast model system, we report that the ribosome quality control (RQC) machinery, recently implicated in neurodegeneration, is a key determinant for the nucleocytoplasmic distribution of Httex1-103Q. Deletion of the RQC genes, LTN1 or RQC1, caused the accumulation of Httex1-103Q in the nucleus through a process that required the CAT-tail tagging activity of Rqc2 and transport via the nuclear pore complex. We provide evidence that nuclear accumulation of Httex1-103Q enhances its cytotoxicity, suggesting that the RQC machinery plays an important role in protecting cells against the adverse effects of polyQ expansion proteins.
Assuntos
Núcleo Celular/metabolismo , Éxons/genética , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , Ribossomos/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Humanos , Proteínas de Transporte Nucleocitoplasmático/genética , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Ligação ProteicaRESUMO
CONTEXT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects millions of elderly people worldwide. However, no efficient therapeutic method for AD has yet been developed. Recently, Salvia miltiorrhiza Bunge (Lamiaceae), a well-known traditional Chinese medicine which is widely used for treating cardio-cerebrovascular, exerts multiple neuroprotective effects and is attracting increased attention for the treatment of AD. OBJECTIVE: The objective of this study is to discuss the neuroprotective effects and neurogenesis-inducing activities of S. miltiorrhiza components. METHODS: A detailed search using major electronic search engines (such as Pubmed, ScienceDirect, and Google Scholar) was undertaken with the search terms: Salvia miltiorrhiza, the components of S. miltiorrhiza such as salvianolic acid B, salvianolic acid A, danshensu, tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone, and neuroprotection. RESULTS: Salvia miltiorrhiza components exert multiple neuroprotective potentials relevant to AD, such as anti-amyloid-ß, antioxidant, anti-apoptosis, acetylcholinesterase inhibition, and anti-inflammation. Moreover, S. miltiorrhiza promotes neurogenesis of neural progenitor cells/stem cells in vitro and in vivo. CONCLUSIONS: The properties of S. miltiorrhiza indicate their therapeutic potential in AD via multiple mechanisms. In addition, S. miltiorrhiza provides lead compounds for developing new drugs against AD.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Salvia miltiorrhiza/química , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Placa Amiloide , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: The N-terminal domain of angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity. Its C-terminal fibrinogen-like (FBN) domain is a ligand of macrophage integrin αvß3. OBJECTIVES: ANGPTL3 might home to plaque where it directly regulates macrophage function via integrin αvß3 for atherosclerosis progression. METHODS: Ldlr-/- mice on a high-fat diet and ApoE-/- mice on a chow diet were received adeno-associated virus (AAV)-mediated Angptl3 gene transfer and followed up for 12 weeks. ApoE-/- mice were injected AAV containing FLAG-tagged Angptl3 cDNA for tracing. Atherosclerotic features were compared between Angptl3-/-ApoE-/- mice and ApoE-/- littermates. THP-1 cells were exposed to 0 or 50 µg/ml ANGPTL3 FBN domain for 24 h to evaluate Toll-like receptor (TLR)4 expression using western blot analysis and circulating cytokine and chemokine profiles by the MILLIPLEX MAP assay. Phospho-proteomic profile was established in ANGPTL3-treated macrophages. Integrin ß3 deficient THP-1 cells were obtained by sgRNAs targeting RGD sequence using Lentivirus-Cas9 system. RESULTS: Angptl3 overexpression increased atherosclerotic progression and CD68+ macrophages in plaque (p < 0.05 for all). By immunostaining, FLAG+ cells were identified in plaque of gene transferred ApoE-/- mice. Fluorescent immunostaining detected co-localisation of Angptl3 and CD68 in plaque macrophages. Phospho-proteomic analysis revealed that Angptl3 induced phosphorylation of proteins that were involved in the IL-17 signalling pathway in THP-1 cells. In vitro, ANGPTL3 treatment increased the production of interleukin (IL)-1ß and tumour necrosis factor-α in THP-1 cells (p < 0.05 for both). Exposure of ANGPTL3 to THP-1 cells induced Akt phosphorylation which was weakened in integrin ß3 deficient ones. ANGPTL3 elevated TLR4 expression via Akt phosphorylation. In response to lipopolysaccharide, nuclear factor-κB activity was 2.2-fold higher in THP-1 cells pre-treated with ANGPTL3 than in untreated cells (p < 0.05). CONCLUSIONS: Targeting ANGPTL3 could yield a dual benefit of lowering lipid levels in the blood and suppressing macrophage activation in plaque.
RESUMO
Background: This study aims to develop and validate a pretreatment MRI-based radiomics model to predict lymph node metastasis (LNM) following neoadjuvant chemotherapy (NACT) in patients with locally advanced cervical cancer (LACC). Methods: Patients with LACC who underwent NACT from two centers between 2013 and 2022 were enrolled retrospectively. Based on the lymph node (LN) status determined in the pathology reports after radical hysterectomy, patients were categorized as LN positive or negative. The patients from center 1 were assigned as the training set while those from center 2 formed the validation set. Radiomics features were extracted from pretreatment sagittal T2-weighted imaging (Sag-T2WI), axial diffusion-weighted imaging (Ax-DWI), and the delayed phase of dynamic contrast-enhanced sagittal T1-weighted imaging (Sag-T1C) for each patient. The K-best and least absolute shrinkage and selection operator (LASSO) methods were employed to reduce dimensionality, and the radiomics features strongly associated with LNM were selected and used to construct three single-sequence models. Furthermore, clinical variables were incorporated through multivariate regression analysis and fused with the selected radiomics features to construct the clinical-radiomics combined model. The diagnostic performance of the models was assessed using receiver operating characteristic (ROC) curve analysis. The clinical utility of the models was evaluated by the area under the ROC curve (AUC) and decision curve analysis (DCA). Results: A total of 282 patients were included, comprising 171 patients in the training set, and 111 patients in the validation set. Compared to the Sag-T2WI model (AUC, 95%CI, training set, 0.797, 0.722-0.782; validation set, 0.648, 0.521-0.776) and the Sag-T1C model (AUC, 95%CI, training set, 0.802, 0.723-0.882; validation set, 0.630, 0.505-0.756), the Ax-DWI model exhibited the highest diagnostic performance with AUCs of 0.855 (95%CI, 0.791-0.919) in training set, and 0.753 (95%CI, 0.638-0.867) in validation set, respectively. The combined model, integrating selected features from three sequences and FIGO stage, surpassed predictive ability compared to the single-sequence models, with AUC of 0.889 (95%CI, 0.833-0.945) and 0.859 (95%CI, 0.781-0.936) in the training and validation sets, respectively. Conclusions: The pretreatment MRI-based radiomics model, integrating radiomics features from three sequences and clinical variables, exhibited superior performance in predicting LNM following NACT in patients with LACC.
RESUMO
Visual impairments and blindness are major public health concerns globally. Effective eye disease screening aided by artificial intelligence (AI) is a promising countermeasure, although it is challenged by practical constraints such as poor image quality in community screening. The recently developed ophthalmic foundation model RETFound has shown higher accuracy in retinal image recognition tasks. This study developed an RETFound-enhanced deep learning (DL) model for multiple-eye disease screening using real-world images from community screenings. Our results revealed that our DL model improved the sensitivity and specificity by over 15% compared with commercial models. Our model also shows better generalisation ability than AI models developed using traditional processes. Additionally, decision curve analysis underscores the higher net benefit of employing our model in both urban and rural settings in China. These findings indicate that the RETFound-enhanced DL model can achieve a higher net benefit in community-based screening, advocating its adoption in low- and middle-income countries to address global eye health challenges.
RESUMO
Artificial intelligence (AI) decision support systems in pediatric healthcare have a complex application background. As an AI decision support system (AI-DSS) can be costly, once applied, it is crucial to focus on its performance, interpret its success, and then monitor and update it to ensure ongoing success consistently. Therefore, a set of evaluation indicators was explicitly developed for AI-DSS in pediatric healthcare, enabling continuous and systematic performance monitoring. The study unfolded in two stages. The first stage encompassed establishing the evaluation indicator set through a literature review, a focus group interview, and expert consultation using the Delphi method. In the second stage, weight analysis was conducted. Subjective weights were calculated based on expert opinions through analytic hierarchy process, while objective weights were determined using the entropy weight method. Subsequently, subject and object weights were synthesized to form the combined weight. In the two rounds of expert consultation, the authority coefficients were 0.834 and 0.846, Kendall's coordination coefficient was 0.135 in Round 1 and 0.312 in Round 2. The final evaluation indicator set has three first-class indicators, fifteen second-class indicators, and forty-seven third-class indicators. Indicator I-1(Organizational performance) carries the highest weight, followed by Indicator I-2(Societal performance) and Indicator I-3(User experience performance) in the objective and combined weights. Conversely, 'Societal performance' holds the most weight among the subjective weights, followed by 'Organizational performance' and 'User experience performance'. In this study, a comprehensive and specialized set of evaluation indicators for the AI-DSS in the pediatric outpatient clinic was established, and then implemented. Continuous evaluation still requires long-term data collection to optimize the weight proportions of the established indicators.
Assuntos
Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Humanos , Pediatria/métodos , Instituições de Assistência Ambulatorial , CriançaRESUMO
Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables-ferroelectric polarization and magnetization-we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.
RESUMO
Primitive proteins are proposed to have utilized organic cofactors more frequently than transition metals in redox reactions. Thus, an experimental validation on whether a protein constituted solely by early amino acids and an organic cofactor can perform electron transfer activity is an urgent challenge. In this paper, by substituting "late amino acids (C, F, M, T, W, and Y)" with "early amino acids (A, L, and V)" in a flavodoxin, we constructed a flavodoxin mutant and evaluated its characteristic properties. The major results showed that: (1) The flavodoxin mutant has structural characteristics similar to wild-type protein; (2) Although the semiquinone and hydroquinone flavodoxin mutants possess lower stability than the corresponding form of wild-type flavodoxin, the redox potential of double electron reduction Em,7 (fld) reached -360 mV, indicating that the flavodoxin mutant constituted solely by early amino acids can exert effective electron transfer activity.
Assuntos
Aminoácidos/metabolismo , Megasphaera/enzimologia , Mutagênese/genética , NADH NADPH Oxirredutases/metabolismo , Dicroísmo Circular , Fluorescência , Cinética , Proteínas Mutantes/isolamento & purificação , Proteínas Mutantes/metabolismo , Mutação/genética , NADH NADPH Oxirredutases/isolamento & purificação , Oxirredução , Proteínas Recombinantes/isolamento & purificaçãoRESUMO
Beyond glycemic control, applications of glucagon-like peptide-1 receptor (GLP-1r) agonists (GLP-1 RAs) inhibit inflammation and plaque development in murine atherosclerotic models. However, whether they modulate hematopoietic stem/progenitor cells (HSPCs) to prohibit skewed myelopoiesis in hypercholesteremia remains unknown. In this study, GLP-1r expression in fluorescence-activated cell sorting (FACS)-sorted wild-type HSPCs was determined by capillary western blotting. Bone marrow cells (BMCs) of wild-type or GLP-1r-/- mice were transplanted into lethally irradiated low-density lipoprotein receptor deficient (LDLr-/-) recipients followed by high-fat diet (HFD) for chimerism analysis by FACS. In parallel, LDLr-/- mice were placed on HFD for 6 weeks and then treated with saline or Exendin-4 (Ex-4) for another 6 weeks. HSPC frequency and cell cycle were analyzed by FACS, and intracellular metabolite levels were assessed by targeted metabolomics. The results demonstrated that HSPCs expressed GLP-1r and transplantation of GLP-1r-/- BMCs resulted in skewed myelopoiesis in hypercholesterolemic LDLr-/- recipients. In vitro, Ex-4 treatment of FACS-purified HSPCs suppressed cell expansion and granulocyte production induced by LDL. In vivo, Ex-4 treatment inhibited plaque progression, suppressed HSPC proliferation, and modified glycolytic and lipid metabolism in HSPCs of hypercholesteremic LDLr-/- mice. In conclusion, Ex-4 could directly inhibit HSPC proliferation induced by hypercholesteremia.
Assuntos
Aterosclerose , Transplante de Células-Tronco Hematopoéticas , Hipercolesterolemia , Camundongos , Animais , Exenatida/farmacologia , Exenatida/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Proliferação de Células , Camundongos Endogâmicos C57BLRESUMO
We present room-temperature measurements of magnon spin diffusion in epitaxial ferrimagnetic insulator MgAl0.5Fe1.5O4 (MAFO) thin films near zero applied magnetic field where the sample forms a multi-domain state. Due to a weak uniaxial magnetic anisotropy, the domains are separated primarily by 180° domain walls. We find, surprisingly, that the presence of the domain walls has very little effect on the spin diffusion - nonlocal spin transport signals in the multi-domain state retain at least 95% of the maximum signal strength measured for the spatially-uniform magnetic state, over distances at least five times the typical domain size. This result is in conflict with simple models of interactions between magnons and static domain walls, which predict that the spin polarization carried by the magnons reverses upon passage through a 180° domain wall.
RESUMO
BACKGROUND: Medical artificial intelligence (AI) has significantly contributed to decision support for disease screening, diagnosis, and management. With the growing number of medical AI developments and applications, incorporating ethics is considered essential to avoiding harm and ensuring broad benefits in the lifecycle of medical AI. One of the premises for effectively implementing ethics in Medical AI research necessitates researchers' comprehensive knowledge, enthusiastic attitude, and practical experience. However, there is currently a lack of an available instrument to measure these aspects. OBJECTIVE: The aim of this study was to develop a comprehensive scale for measuring the knowledge, attitude, and practice of ethics implementation among medical AI researchers, and to evaluate its measurement properties. METHODS: The construct of the Knowledge-Attitude-Practice in Ethics Implementation (KAP-EI) scale was based on the Knowledge-Attitude-Practice (KAP) model, and the evaluation of its measurement properties was in compliance with the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) reporting guidelines for studies on measurement instruments. The study was conducted in 2 phases. The first phase involved scale development through a systematic literature review, qualitative interviews, and item analysis based on a cross-sectional survey. The second phase involved evaluation of structural validity and reliability through another cross-sectional study. RESULTS: The KAP-EI scale had 3 dimensions including knowledge (10 items), attitude (6 items), and practice (7 items). The Cronbach α for the whole scale reached .934. Confirmatory factor analysis showed that the goodness-of-fit indices of the scale were satisfactory (χ2/df ratio:=2.338, comparative fit index=0.949, Tucker Lewis index=0.941, root-mean-square error of approximation=0.064, and standardized root-mean-square residual=0.052). CONCLUSIONS: The results show that the scale has good reliability and structural validity; hence, it could be considered an effective instrument. This is the first instrument developed for this purpose.
RESUMO
OBJECTIVES: Implementing ethics is crucial to prevent harm and promote widespread benefits in social experiments based on medical artificial intelligence (MAI). However, insufficient information is available concerning this within the paediatric healthcare sector. We aimed to conduct a comparative survey among paediatricians, nurses and health information technicians regarding ethics implementation knowledge of and attitude towards MAI social experiments at children's hospitals in Shanghai. DESIGN AND SETTING: A cross-sectional electronic questionnaire was administered from 1 July 2022 to 31 July 2022, at tertiary children's hospitals in Shanghai. PARTICIPANTS: All the eligible individuals were recruited. The inclusion criteria were as follows: (1) should be a paediatrician, nurse and health information technician, (2) should have been engaged in or currently participating in social experiments based on MAI, and (3) voluntary participation in the survey. PRIMARY OUTCOME: Ethics implementation knowledge of and attitude to MAI social experiments among paediatricians, nurses and health information technicians. RESULTS: There were 137 paediatricians, 135 nurses and 60 health information technicians who responded to the questionnaire at tertiary children's hospitals. 2.4-9.6% of participants were familiar with ethics implementation knowledge of MAI social experiments. 31.9-86.1% of participants held an 'agree' ethics implementation attitude. Health information technicians accounted for the highest proportion of the participants who were familiar with the knowledge of implementing ethics, and paediatricians or nurses accounted for the highest proportion among those who held 'agree' attitudes. CONCLUSIONS: There is a significant knowledge gap and variations in attitudes among paediatricians, nurses and health information technicians, which underscore the urgent need for individualised education and training programmes to enhance MAI ethics implementation in paediatric healthcare.
Assuntos
Inteligência Artificial , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Criança , Estudos Transversais , China , Pediatras , Inquéritos e Questionários , Atitude do Pessoal de Saúde , HospitaisRESUMO
Non-alcoholic fatty liver disease (NAFLD) occurs in 25% of the global population and manifests as lipid deposition, hepatocyte injury, activation of Kupffer and stellate cells, and steatohepatitis. Predominantly expressed in hepatocytes, the augmenter of liver regeneration (ALR) is a key factor in liver regulation that can alleviate fatty liver disease and protect the liver from abnormal liver lipid metabolism. ALR has three isoforms (15-, 21-, and 23-kDa), amongst which 23-kDa ALR is the most extensively studied. The 23-kDa ALR isoform is a sulfhydryl oxidase that resides primarily in the mitochondrial intermembrane space (IMS), whereby it protects the liver against various types of injury. In this review, we describe the role of ALR in regulating hepatocytes in the context of NAFLD. We also discuss questions about ALR that remain to be explored in the future. In conclusion, ALR appears to be a promising therapeutic target for treating NAFLD.
RESUMO
Neutrophils are primary effector cells of the innate immune system. Emerging evidence has consistently shown that activated neutrophils produce and release neutrophil extracellular traps (NETs) that play roles in immunity and non-infectious diseases. NETs are composed of DNA and proteins and serve as a structural platform for pathogen sequestration and degradation. In contrast to their protective role during pathogenic infection, NETs are pathologically involved in cardiovascular disease (CVD). In this review, we introduce the formation, release, and clearance of NETs and the regulatory mechanisms of NETs formation, followed by an overview of the clinical evidence for the involvement of NETs in CVD. Because atherosclerosis is a fundamental part of the pathogenesis of CVD, we chose to focus on the mechanisms by which NETs promote endothelial cell damage and collaborate with macrophages and platelets to accelerate plaque progression and thrombosis. Finally, we present options for clinical intervention to inhibit NETs production and release in the treatment of CVD. In conclusion, this review integrates the latest findings and provides new insights into NETs, which represent a novel biomarker and therapeutic target in clinical practice.
RESUMO
Hyperglycemia-induced myelopoiesis and atherosclerotic progression occur in mice with type I diabetes. However, less is known about the effects of metabolites on myelopoesis in type 2 diabetes. Here, we use fluorescence-activated cell sorting to analyze the proliferation of granulocyte/monocyte progenitors (GMP) in db/db mice. Using targeted metabolomics, we identify an increase in inosine monophosphate (IMP) in GMP cells of 24-week-old mice. We show that IMP treatment stimulates cKit expression, ribosomal S6 activation, GMP proliferation, and Gr-1+ granulocyte production in vitro. IMP activates pAkt in non-GMP cells. In vivo, using an established murine acute pancreatitis (AP) model, administration of IMP-treated bone marrow cells enhances the severity of AP. This effect is abolished in the presence of a pAkt inhibitor. Targeted metabolomics show that plasma levels of guanosine monophosphate are significantly higher in diabetic patients with AP. These findings provid a potential therapeutic target for the control of vascular complications in diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Pancreatite , Doença Aguda , Animais , Guanosina Monofosfato , Inosina Monofosfato , Camundongos , Mielopoese , Purinas/metabolismo , Purinas/farmacologiaRESUMO
The spin-momentum locking of surface states in topological materials can produce a resistance that scales linearly with magnetic and electric fields. Such a bilinear magnetoelectric resistance (BMER) effect offers a new approach for information reading and field sensing applications, but the effects demonstrated so far are too weak or for low temperatures. This article reports the first observation of BMER effects in topological Dirac semimetals; the BMER responses were measured at room temperature and were substantially stronger than those reported previously. The experiments used topological Dirac semimetal α-Sn thin films grown on silicon substrates. The films showed BMER responses that are 106 times larger than previously measured at room temperature and are also larger than those previously obtained at low temperatures. These results represent a major advance toward realistic BMER applications. Significantly, the data also yield the first characterization of three-dimensional Fermi-level spin texture of topological surface states in α-Sn.
RESUMO
Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 µg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients (1 × 107cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively (p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection (p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups (p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately (p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC (p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis.
Assuntos
Células da Medula Óssea/imunologia , Complicações do Diabetes/imunologia , Pancreatite/imunologia , Animais , Células da Medula Óssea/metabolismo , Transplante de Medula Óssea , Ceruletídeo/administração & dosagem , Ceruletídeo/toxicidade , Citocinas/metabolismo , Complicações do Diabetes/patologia , Modelos Animais de Doenças , Progressão da Doença , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Necrose , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite/induzido quimicamente , Pancreatite/patologiaRESUMO
Recent experiments show that topological surface states (TSS) in topological insulators (TI) can be exploited to manipulate magnetic ordering in ferromagnets. In principle, TSS should also exist for other topological materials, but it remains unexplored as to whether such states can also be utilized to manipulate ferromagnets. Herein, current-induced magnetization switching enabled by TSS in a non-TI topological material, namely, a topological Dirac semimetal α-Sn, is reported. The experiments use an α-Sn/Ag/CoFeB trilayer structure. The magnetization in the CoFeB layer can be switched by a charge current at room temperature, without an external magnetic field. The data show that the switching is driven by the TSS of the α-Sn layer, rather than spin-orbit coupling in the bulk of the α-Sn layer or current-produced heating. The switching efficiency is as high as in TI systems. This shows that the topological Dirac semimetal α-Sn is as promising as TI materials in terms of spintronic applications.