21,198 results match your criteria activation intrinsic


3'-Terminal Repair-Powered Dendritic Nanoassembly of Polyadenine Molecular Beacons for One-Step Quantification of Alkaline Phosphatase in Human Serum.

Anal Chem 2021 Jul 22. Epub 2021 Jul 22.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, China.

Alkaline phosphatase (ALP) is an important hydrolase with crucial roles in biological processes, and the dysregulation of ALP may cause various human diseases. The conventional ALP assays usually involve cumbersome procedures with poor sensitivity. Herein, taking advantage of intrinsic superiorities of molecular beacons (MBs) and unique features of terminal deoxynucleotidyl transferase (TdT), we demonstrate for the first time the 3'-terminal repair-powered dendritic nanoassembly of polyadenine (A) MBs for one-step quantification of ALP in human serum. Read More

View Article and Full-Text PDF

A resident stromal cell population actively restrains innate immune response in the propagation phase of colitis pathogenesis in mice.

Sci Transl Med 2021 Jul;13(603)

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200240, China.

Inflammatory bowel disease (IBD) affects 0.3% of the global population, yet the etiology remains poorly understood. Anti-inflammation therapy has shown great success, but only 60% of patients with IBD benefit from it, indicating that new targets are needed. Read More

View Article and Full-Text PDF

New insights into M1/M2 macrophages: key modulators in cancer progression.

Cancer Cell Int 2021 Jul 21;21(1):389. Epub 2021 Jul 21.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Infiltration of macrophages in and around tumor nest represents one of the most crucial hallmarks during tumor progression. The mutual interactions with tumor cells and stromal microenvironment contribute to phenotypically polarization of tumor associated macrophages. Macrophages consist of at least two subgroups, M1 and M2. Read More

View Article and Full-Text PDF

Mechanistic Connections between CO and CO Hydrogenation on Dispersed Ruthenium Nanoparticles.

J Am Chem Soc 2021 Jul 21. Epub 2021 Jul 21.

Department of Chemical Engineering, University of California at Berkeley, Berkeley, California 94720, United States.

Catalytic routes for upgrading CO to CO and hydrocarbons have been studied for decades, and yet the mechanistic details and structure-function relationships that control catalytic performance have remained unresolved. This study elucidates the elementary steps that mediate these reactions and examines them within the context of the established mechanism for CO hydrogenation to resolve the persistent discrepancies and to demonstrate inextricable links between CO and CO hydrogenation on dispersed Ru nanoparticles (6-12 nm mean diameter, 573 K). The formation of CH from both CO-H and CO-H reactants requires the cleavage of strong C≡O bonds in chemisorbed CO, formed as an intermediate in both reactions, via hydrogen-assisted activation pathways. Read More

View Article and Full-Text PDF

Garlic (Allium sativum)-derived SEVs inhibit cancer cell proliferation and induce caspase mediated apoptosis.

Sci Rep 2021 Jul 20;11(1):14773. Epub 2021 Jul 20.

Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, 26 Ağustos Campus, Kayisdagi Cad., Kayisdagi, 34755, Istanbul, Turkey.

As a key component of the cell-to-cell communication, small extracellular vesicles (SEVs) released from various sources are known to be affecting the physiological conditions of the target cells. Although it has been suggested that edible plant-derived nanoparticles contributes to the cross kingdom communication with the mammalian cells, the effect of these particles on cancer cell progression still needs a further exploration. Here, we isolated and then characterized garlic derived SEVs by nanoparticle tracking analysis, electron microscopy and SEV surface antibodies. Read More

View Article and Full-Text PDF

Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy.

BMC Med 2021 Jul 21;19(1):154. Epub 2021 Jul 21.

Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Background: Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Read More

View Article and Full-Text PDF

Multiscale neural modeling of resting-state fMRI reveals executive-limbic malfunction as a core mechanism in major depressive disorder.

Neuroimage Clin 2021 Jul 6;31:102758. Epub 2021 Jul 6.

Department of Radiology and BRIC, University of North Carolina at Chapel Hill, Chapel Hill, NC USA. Electronic address:

Major depressive disorder (MDD) represents a grand challenge to human health and society, but the underlying pathophysiological mechanisms remain elusive. Previous neuroimaging studies have suggested that MDD is associated with abnormal interactions and dynamics in two major neural systems including the default mode - salience (DMN-SAL) network and the executive - limbic (EXE-LIM) network, but it is not clear which network plays a central role and which network plays a subordinate role in MDD pathophysiology. To address this question, we refined a newly developed Multiscale Neural Model Inversion (MNMI) framework and applied it to test whether MDD is more affected by impaired circuit interactions in the DMN-SAL network or the EXE-LIM network. Read More

View Article and Full-Text PDF

Rheological and NMR Studies of Cellulose Dissolution in the Ionic Liquid BmimAc.

J Phys Chem B 2021 Jul 19. Epub 2021 Jul 19.

School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, U.K.

Solutions of two types of cellulose in the ionic liquid 1-butyl-3-methyl-imidazolium acetate (BmimAc) have been analyzed using rheology and fast-field cycling nuclear magnetic resonance (NMR) spectroscopy, in order to analyze the macroscopic (bulk) and microscopic environments, respectively. The degree of polymerization (DP) was observed to have a significant effect on both the overlap (*) and entanglement () concentrations and the intrinsic viscosity ([η]). For microcrystalline cellulose (MCC)/BmimAc solutions, [η] = 116 mL g, which is comparable to that of MCC/1-ethyl-3-methyl-imidazolium acetate (EmimAc) solutions, while [η] = 350 mL g for the commercial cellulose (higher DP). Read More

View Article and Full-Text PDF

Atomically Dispersed Copper Sites in a Metal-Organic Framework for Reduction of Nitrogen Dioxide.

J Am Chem Soc 2021 Jul 19. Epub 2021 Jul 19.

Department of Chemistry, University of Manchester, Manchester M13 9PL, United Kingdom.

Metal-organic framework (MOF) materials provide an excellent platform to fabricate single-atom catalysts due to their structural diversity, intrinsic porosity, and designable functionality. However, the unambiguous identification of atomically dispersed metal sites and the elucidation of their role in catalysis are challenging due to limited methods of characterization and lack of direct structural information. Here, we report a comprehensive investigation of the structure and the role of atomically dispersed copper sites in UiO-66 for the catalytic reduction of NO at ambient temperature. Read More

View Article and Full-Text PDF

Defects, diffusion and dopants in LiSnO.

Heliyon 2021 Jul 2;7(7):e07460. Epub 2021 Jul 2.

Department of Materials, Imperial College London, London, SW7 2AZ, United Kingdom.

Octalithium tin (IV) oxide (LiSnO) is an important electrode material considered for lithium ion batteries (LIBs) because of its high lithium content. We employed atomistic simulations to examine the intrinsic defects, diffusion of Li-ions together with their migration energies and solution of potential dopants in LiSnO. The most thermodynamically favourable intrinsic defect is the Li Frenkel which increases the concentration of Li vacancies needed for the vacancy mediated diffusion of Li-ions in LiSnO. Read More

View Article and Full-Text PDF

Type 1 conventional dendritic cells and interferons are required for spontaneous CD4 and CD8 T-cell protective responses to breast cancer.

Clin Transl Immunology 2021 14;10(7):e1305. Epub 2021 Jul 14.

Centre d'Immunologie de Marseille-Luminy Turing Center for Living Systems CNRS INSERM Aix Marseille Univ Marseille France.

Objectives: To better understand how immune responses may be harnessed against breast cancer, we investigated which immune cell types and signalling pathways are required for spontaneous control of a mouse model of mammary adenocarcinoma.

Methods: The NOP23 mammary adenocarcinoma cell line expressing epitopes derived from the ovalbumin model antigen is spontaneously controlled when orthotopically engrafted in syngeneic C57BL/6 mice. We combined this breast cancer model with antibody-mediated depletion of lymphocytes and with mutant mice affected in interferon (IFN) or type 1 conventional dendritic cell (cDC1) responses. Read More

View Article and Full-Text PDF

AID and APOBECs as Multifaceted Intrinsic Virus-Restricting Factors: Emerging Concepts in the Light of COVID-19.

Front Immunol 2021 1;12:690416. Epub 2021 Jul 1.

Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

The AID (activation-induced cytidine deaminase)/APOBEC (apolipoprotein B mRNA editing enzyme catalytic subunit) family with its multifaceted mode of action emerges as potent intrinsic host antiviral system that acts against a variety of DNA and RNA viruses including coronaviruses. All family members are cytosine-to-uracil deaminases that either have a profound role in driving a strong and specific humoral immune response (AID) or restricting the virus itself by a plethora of mechanisms (APOBECs). In this article, we highlight some of the key aspects apparently linking the AID/APOBECs and SARS-CoV-2. Read More

View Article and Full-Text PDF

Insight into the Improvement Effect of Nitrogen Dopant in Ag/CoO Nanocubes for Soot Oxidation: Experimental and Theoretical Studies.

J Hazard Mater 2021 Jul 8;420:126604. Epub 2021 Jul 8.

School of Environment and Energy, South China University of Technology, Guangzhou 510640, China; Guangdong Provincial Key Laboratory of Atmospheric Environment and Pollution Control (SCUT), Guangzhou 510640, China; National Engineering Laboratory for VOCs Pollution Control Technology and Equipment (SCUT), Guangzhou 510640, China. Electronic address:

Different doping amounts of N-doped Ag/CoO nanocubes were synthesized for the first time for catalytic soot oxidation. The N-doped sample exhibited remarkably improved catalytic activity, of which the maximum decrease in temperature for 90% soot conversion was almost 40 ℃. Characterization results analyzed by TEM, XPS, EPR, H-TPR, O-TPD, etc. Read More

View Article and Full-Text PDF

Meet the authors: Mirjana Lilic and Elizabeth Campbell.

Authors:

Mol Cell 2021 Jul;81(14):2869-2870

We talk to Mirjana (Mira) Lilic and Elizabeth (Liz) Campbell about their paper, "Structural basis of transcriptional activation by the Mycobacterium tuberculosis intrinsic antibiotic-resistance transcription factor WhiB7," the collaborations that made it happen, and the people who mentored and motivated them along the way. Read More

View Article and Full-Text PDF

The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy.

Front Oncol 2021 29;11:641428. Epub 2021 Jun 29.

Department of Life & Consumer Sciences, University of South Africa, Johannesburg, South Africa.

Through genetic and epigenetic alterations, cancer cells present the immune system with a diversity of antigens or neoantigens, which the organism must distinguish from self. The immune system responds to neoantigens by activating naïve T cells, which mount an anticancer cytotoxic response. T cell activation begins when the T cell receptor (TCR) interacts with the antigen, which is displayed by the major histocompatibility complex (MHC) on antigen-presenting cells (APCs). Read More

View Article and Full-Text PDF

Mechanisms modulating spinal excitability after nerve stimulation inducing extra torque.

J Appl Physiol (1985) 2021 07 15. Epub 2021 Jul 15.

INSERM U1093, Faculté des Sciences du Sport, Université Bourgogne Franche-Comté, France.

The study included 3 experiments aiming to examine the mechanisms responsible for spinal excitability modulation, as assessed by the H-reflex, following stimulation trains delivered at two different frequencies (20 and 100Hz) inducing extra torque (ET). A first experiment (n=15) was conducted to evaluate changes in presynaptic inhibition acting on Ia afferents induced by these electrical stimulation trains, assessed by conditioning the soleus H-reflex (tibial nerve stimulation) with stimulation of the common peroneal nerve (D1 inhibition) and of the femoral nerve (heteronymous Ia facilitation, HF). A second experiment (n=12) permitted to investigate homosynaptic post-activation depression (HPAD) changes after the stimulation trains. Read More

View Article and Full-Text PDF

The 2021 Carl Ludwig Lecture. Unsympathetic autonomic regulation in heart failure: patient-inspired insights.

Authors:
John S Floras

Am J Physiol Regul Integr Comp Physiol 2021 Jul 14. Epub 2021 Jul 14.

University Health Network and Sinai Health Division of Cardiology, Toronto General Hospital Research Institute and Department of Medicine, grid.17063.33University of Toronto, Ontario, Canada.

Defined as a structural or functional cardiac abnormality accompanied by symptoms, signs or biomarkers of altered ventricular pressures or volumes, heart failure also is a state of autonomic disequilibrium. A large body of evidence affirms that autonomic disturbances are intrinsic to heart failure; that basal or stimulated sympathetic nerve firing or neural norepinephrine (NE) release more often than not exceed homeostatic need, such that an initially adaptive adrenergic or vagal reflex response, becomes maladaptive; and, that the magnitude of such maladaptation predicts prognosis. This Ludwig lecture develops two theses: that the elucidation and judiciously targeted amelioration of maladaptive autonomic disturbances offers opportunities to complement contemporary guideline-based heart failure therapy; and, that serendipitous single-participant insights, acquired in the course of experimental protocols with entirely different intent, can generate novel insight, inform mechanisms, and launch entirely new research directions. Read More

View Article and Full-Text PDF

The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPAR.

Adv Sci (Weinh) 2021 07 3;8(13):2100209. Epub 2021 May 3.

Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China.

Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Currently, little is known about how the intrinsic regulators modulate proinflammatory (M1) versus prohealing (M2) macrophages activation. Here, it is observed that insulin-like growth factor 2 messenger RNA (mRNA)-binding protein 2 (IGF2BP2)-deleted macrophages exhibit enhanced M1 phenotype and promote dextran sulfate sodium induced colitis development. Read More

View Article and Full-Text PDF

circFAT1 Promotes Cancer Stemness and Immune Evasion by Promoting STAT3 Activation.

Adv Sci (Weinh) 2021 07 2;8(13):2003376. Epub 2021 May 2.

Jonsson Comprehensive Cancer Center UCLA Los Angeles CA 90095 USA.

Cancer stemness and immune evasion are closely associated, and play critical roles in tumor development and resistance to immunotherapy. However, little is known about the underlying molecular mechanisms that coordinate this association. Here, it is reported that elevated circular RNA FAT1 (circFAT1) in squamous cell carcinoma (SCC) unifies and regulates the positive association between cancer stemness and immune evasion by promoting STAT3 activation. Read More

View Article and Full-Text PDF

Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival.

J Exp Clin Cancer Res 2021 Jul 13;40(1):230. Epub 2021 Jul 13.

Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.

Background: The intrinsic immuno-ge7nomic characteristics of colorectal cancer cells that affect tumor biology and shape the tumor immune microenvironment (TIM) are unclear.

Methods: We developed a patient-derived colorectal cancer organoid (CCO) model and performed pairwise analysis of 87 CCOs and their matched primary tumors. The TIM type of the primary tumor was classified as immuno-active, immuno-exhausted, or immuno-desert. Read More

View Article and Full-Text PDF

Neural basis of implicit cognitive reappraisal in panic disorder: an event-related fMRI study.

J Transl Med 2021 Jul 13;19(1):304. Epub 2021 Jul 13.

Department of Neurology and Psychiatry, The First Affiliated Hospital of Dalian Medical University, No.222, Zhongshan Road, Dalian, 116011, Liaoning Province, China.

Background: Panic disorder (PD) is thought to be related with deficits in emotion regulation, especially in cognitive reappraisal. According to the cognitive model, PD patients' intrinsic and unconscious misappraisal strategies are the cause of panic attacks. However, no studies have yet been performed to explore the underlying neuromechanism of cognitive reappraisal that occur on an unconscious level in PD patients. Read More

View Article and Full-Text PDF

Dynamic functional brain networks underlying the temporal inertia of negative emotions.

Neuroimage 2021 Jul 10;240:118377. Epub 2021 Jul 10.

Laboratory for Behavioral Neurology and Imaging of Cognition, Department of Fundamental Neurosciences, University of Geneva, Geneva, Switzerland; Swiss Center for Affective Sciences, University of Geneva, Geneva, Switzerland.

Affective inertia represents the lasting impact of transient emotions at one time point on affective state at a subsequent time point. Here we describe the neural underpinnings of inertia following negative emotions elicited by sad events in movies. Using a co-activation pattern analysis of dynamic functional connectivity, we examined the temporal expression and reciprocal interactions among brain-wide networks during movies and subsequent resting periods in twenty healthy subjects. Read More

View Article and Full-Text PDF

Advance investigation on synthetic small-molecule inhibitors targeting PD-1/PD-L1 signaling pathway.

Life Sci 2021 Jul 10:119813. Epub 2021 Jul 10.

Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

Immune checkpoint blockade has displayed substantial anti-tumor resistance in a variety of forms of cancer, but the fundamental regulation role remains unclear, and several questions continue to be addressed. PD-1/PD-L1 has been recognized as an anti-cancer drug target for several years, and through targeting the PD-1/PD-L1 signaling pathway, many monoclonal antibodies have thus far produced promising results in cancer therapy. The discovery of small-molecule inhibitors focused on the PD-1/PD-L1 signaling pathway is steadily reviving over decades, owing to the intrinsic shortcomings of the antibodies. Read More

View Article and Full-Text PDF

Visible light enables catalytic formation of weak chemical bonds with molecular hydrogen.

Nat Chem 2021 Jul 12. Epub 2021 Jul 12.

Department of Chemistry, Frick Laboratory, Princeton University, Princeton, NJ, USA.

The synthesis of weak chemical bonds at or near thermodynamic potential is a fundamental challenge in chemistry, with applications ranging from catalysis to biology to energy science. Proton-coupled electron transfer using molecular hydrogen is an attractive strategy for synthesizing weak element-hydrogen bonds, but the intrinsic thermodynamics presents a challenge for reactivity. Here we describe the direct photocatalytic synthesis of extremely weak element-hydrogen bonds of metal amido and metal imido complexes, as well as organic compounds with bond dissociation free energies as low as 31 kcal mol. Read More

View Article and Full-Text PDF

Hepatitis B virus evades immune recognition via RNA adenosine deaminase ADAR1-mediated viral RNA editing in hepatocytes.

Cell Mol Immunol 2021 Jul 12. Epub 2021 Jul 12.

Key Laboratory for Experimental Teratology, Ministry of Education, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong, China.

HBV is considered as a "stealth" virus that does not invoke interferon (IFN) responses; however, the mechanisms by which HBV bypasses innate immune recognition are poorly understood. In this study, we identified adenosine deaminases acting on RNA 1 (ADAR1), which is a key factor in HBV evasion from IFN responses in hepatocytes. Mechanically, ADAR1 interacted with HBV RNAs and deaminated adenosine (A) to generate inosine (I), which disrupted host immune recognition and thus promoted HBV replication. Read More

View Article and Full-Text PDF

Overcoming intrinsic resistance of cancer cells to CAR T-cell killing.

Clin Cancer Res 2021 Jul 12. Epub 2021 Jul 12.

Department of Hematology, CHU Rennes

In the past few years, chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for cancers that failed standard treatments. Such therapies have already been approved in several blood cancers such as B-cell leukemia and lymphoma. Despite this progress, a significant proportion of patients experience primary or secondary resistance to CAR-T cell therapy. Read More

View Article and Full-Text PDF

Influence of hybrid assistive limb gait training on spatial muscle activation patterns in spinal muscular atrophy type III.

F1000Res 2021 16;10:214. Epub 2021 Mar 16.

Department of Physical Therapy, Marquette University, Milwaukee, Wisconsin, 53233, USA.

Despite the potential benefits, the effects of Hybrid Assistive Limb (HAL) gait training on changes in neuromuscular activation that accompany functional gains in individuals with spinal muscular atrophy (SMA) type III is not well known. In this article, we quantify the effects of HAL gait training on spatial muscle activity patterns in a patient with SMA type III using multi-channel surface electromyography (SEMG). A 21-years old male (168 cm, 47. Read More

View Article and Full-Text PDF

Loss of RND-type multidrug efflux pumps triggers iron starvation and lipid A modifications in .

Antimicrob Agents Chemother 2021 Jul 12:AAC0059221. Epub 2021 Jul 12.

University of Oklahoma, Department of Chemistry and Biochemistry, Norman, OK 73019, USA.

Transporters belonging to the Resistance-Nodulation-Division (RND) superfamily of proteins are invariably present in the genomes of Gram-negative bacteria and are largely responsible for the intrinsic antibiotic resistance of these organisms. The number of genes encoding RND transporters per genome vary from one to sixteen and correlates with environmental versatilities of bacterial species. PAO1 strain, a ubiquitous nosocomial pathogen, possesses twelve RND pumps, which are implicated in development of clinical multidrug resistance and known to contribute to virulence, quorum sensing and many other physiological functions. Read More

View Article and Full-Text PDF

Theoretical Assessment of Dinitrogen Fixation on Carbon Atom.

Chem Asian J 2021 Jul 11. Epub 2021 Jul 11.

Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.

Dinitrogen activation in non-metallic systems has received considerable attention in recent years. Herein, we report the theoretical feasibility of N fixation using aminocarbenes (L) or their anionic derivatives. The molecular descriptors of L and anionic L , which affect the interaction of L and anionic L with N , were identified through multiple linear regression analysis. Read More

View Article and Full-Text PDF

Inhibitory Effect of Gallotannin on Lung Metastasis of Metastatic Colorectal Cancer Cells by Inducing Apoptosis, Cell Cycle Arrest and Autophagy.

Am J Chin Med 2021 Jul 10:1-21. Epub 2021 Jul 10.

Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea.

Colorectal cancer (CRC) is the second most common cause of cancer death in the world, and metastatic CRC is a major cause of cancer death. Gallotannin (GT), a polyphenolic compound, has shown various biological effects such as anti-oxidant, anti-inflammatory, antimicrobial, and antitumor effects. However, the effects of GT on metastatic CRC cells are not completely understood. Read More

View Article and Full-Text PDF