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1.
Cell ; 182(2): 447-462.e14, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32758418

RESUMO

The precise mechanism by which oral infection contributes to the pathogenesis of extra-oral diseases remains unclear. Here, we report that periodontal inflammation exacerbates gut inflammation in vivo. Periodontitis leads to expansion of oral pathobionts, including Klebsiella and Enterobacter species, in the oral cavity. Amassed oral pathobionts are ingested and translocate to the gut, where they activate the inflammasome in colonic mononuclear phagocytes, triggering inflammation. In parallel, periodontitis results in generation of oral pathobiont-reactive Th17 cells in the oral cavity. Oral pathobiont-reactive Th17 cells are imprinted with gut tropism and migrate to the inflamed gut. When in the gut, Th17 cells of oral origin can be activated by translocated oral pathobionts and cause development of colitis, but they are not activated by gut-resident microbes. Thus, oral inflammation, such as periodontitis, exacerbates gut inflammation by supplying the gut with both colitogenic pathobionts and pathogenic T cells.


Assuntos
Colite/patologia , Enterobacter/fisiologia , Microbioma Gastrointestinal , Klebsiella/fisiologia , Boca/microbiologia , Animais , Colite/microbiologia , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Enterobacter/isolamento & purificação , Feminino , Inflamassomos/metabolismo , Interleucina-10/deficiência , Interleucina-10/genética , Interleucina-1beta/metabolismo , Klebsiella/isolamento & purificação , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Periodontite/microbiologia , Periodontite/patologia , Células Th17/citologia , Células Th17/imunologia , Células Th17/metabolismo
2.
Nat Immunol ; 23(11): 1588-1599, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36266363

RESUMO

Dysfunctional CD8+ T cells, which have defective production of antitumor effectors, represent a major mediator of immunosuppression in the tumor microenvironment. Here, we show that SUSD2 is a negative regulator of CD8+ T cell antitumor function. Susd2-/- effector CD8+ T cells showed enhanced production of antitumor molecules, which consequently blunted tumor growth in multiple syngeneic mouse tumor models. Through a quantitative mass spectrometry assay, we found that SUSD2 interacted with interleukin (IL)-2 receptor α through sushi domain-dependent protein interactions and that this interaction suppressed the binding of IL-2, an essential cytokine for the effector functions of CD8+ T cells, to IL-2 receptor α. SUSD2 was not expressed on regulatory CD4+ T cells and did not affect the inhibitory function of these cells. Adoptive transfer of Susd2-/- chimeric antigen receptor T cells induced a robust antitumor response in mice, highlighting the potential of SUSD2 as an immunotherapy target for cancer.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Animais , Camundongos , Linhagem Celular Tumoral , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo , Receptores de Interleucina-2/metabolismo , Transdução de Sinais , Microambiente Tumoral
3.
Immunity ; 50(3): 576-590.e6, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30770249

RESUMO

Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis. However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood. Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked ß-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP). Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation. Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation. Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling. Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.


Assuntos
Apoptose/fisiologia , Inflamação/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Necrose/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Animais , Linhagem Celular , Glucose/metabolismo , Humanos , Imunidade Inata/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Serina/metabolismo , Transdução de Sinais/fisiologia , Treonina/metabolismo
4.
Nature ; 591(7849): 275-280, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33442058

RESUMO

The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA. DNA sensing by STING leads to the induction of type-I interferons (IFN-I) and other cytokines, which promote immune-cell-mediated eradication of pathogens and neoplastic cells1,2. STING is also a robust driver of antitumour immunity, which has led to the development of STING activators and small-molecule agonists as adjuvants for cancer immunotherapy3. Pain, transmitted by peripheral nociceptive sensory neurons (nociceptors), also aids in host defence by alerting organisms to the presence of potentially damaging stimuli, including pathogens and cancer cells4,5. Here we demonstrate that STING is a critical regulator of nociception through IFN-I signalling in peripheral nociceptors. We show that mice lacking STING or IFN-I signalling exhibit hypersensitivity to nociceptive stimuli and heightened nociceptor excitability. Conversely, intrathecal activation of STING produces robust antinociception in mice and non-human primates. STING-mediated antinociception is governed by IFN-Is, which rapidly suppress excitability of mouse, monkey and human nociceptors. Our findings establish the STING-IFN-I signalling axis as a critical regulator of physiological nociception and a promising new target for treating chronic pain.


Assuntos
Interferon Tipo I/metabolismo , Proteínas de Membrana/metabolismo , Nociceptividade/fisiologia , Dor/metabolismo , Células Receptoras Sensoriais/metabolismo , Analgesia , Animais , Feminino , Humanos , Interferon Tipo I/deficiência , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Macaca mulatta , Masculino , Proteínas de Membrana/agonistas , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Nociceptividade/efeitos dos fármacos , Transdução de Sinais
5.
Nat Mater ; 23(4): 460-469, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38561520

RESUMO

Non-layered transition metal carbides (TMCs) and layered transition metal dichalcogenides (TMDs) are two well-studied material families that have individually received considerable attention over the past century. In recent years, with the shift towards two-dimensional materials and heterostructures, a field has emerged that is focused on the structure and properties of TMC/TMD heterostructures, which through chemical conversion exhibit diverse types of heterostructure configuration that host coupled 2D-3D interfaces, giving rise to exotic properties. In this Review, we highlight experimental and computational efforts to understand the routes to fabricate TMC/TMD heterostructures. Furthermore, we showcase how controlling these heterostructures can lead to emergent electronic transport, optical properties and improved catalytic properties.

6.
Nat Mater ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977883

RESUMO

Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells in the small intestine, suppressed pathogenic type 2 immune responses, increased interferon-γ+ and interleukin-10+ regulatory T cell populations, and restored ileal abundances of Eggerthellaceae and Enterorhabdus in allergic mice. Overall, our findings underscore the therapeutic potential of the engineered allergen gel as a suitable microbiome-modulating platform for food allergy and other allergic diseases.

7.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38342687

RESUMO

The alteration of neural interactions across different cerebral perfusion states remains unclear. This study aimed to fulfill this gap by examining the longitudinal brain dynamic information interactions before and after cerebral reperfusion. Electroencephalogram in eyes-closed state at baseline and postoperative 7-d and 3-month follow-ups (moyamoya disease: 20, health controls: 23) were recorded. Dynamic network analyses were focused on the features and networks of electroencephalogram microstates across different microstates and perfusion states. Considering the microstate features, the parameters were disturbed of microstate B, C, and D but preserved of microstate A. The transition probabilities of microstates A-B and B-D were increased to play a complementary role across different perfusion states. Moreover, the microstate variability was decreased, but was significantly improved after cerebral reperfusion. Regarding microstate networks, the functional connectivity strengths were declined, mainly within frontal, parietal, and occipital lobes and between parietal and occipital lobes in different perfusion states, but were ameliorated after cerebral reperfusion. This study elucidates how dynamic interaction patterns of brain neurons change after cerebral reperfusion, which allows for the observation of brain network transitions across various perfusion states in a live clinical setting through direct intervention.


Assuntos
Encéfalo , Eletroencefalografia , Encéfalo/fisiologia , Mapeamento Encefálico , Perfusão , Circulação Cerebrovascular
8.
Nucleic Acids Res ; 51(16): 8623-8642, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37449409

RESUMO

Corynebacterium glutamicum is an important industrial workhorse for production of amino acids and chemicals. Although recently developed genome editing technologies have advanced the rational genetic engineering of C. glutamicum, continuous genome evolution based on genetic mutators is still unavailable. To address this issue, the DNA replication and repair machinery of C. glutamicum was targeted in this study. DnaQ, the homolog of ϵ subunit of DNA polymerase III responsible for proofreading in Escherichia coli, was proven irrelevant to DNA replication fidelity in C. glutamicum. However, the histidinol phosphatase (PHP) domain of DnaE1, the α subunit of DNA polymerase III, was characterized as the key proofreading element and certain variants with PHP mutations allowed elevated spontaneous mutagenesis. Repression of the NucS-mediated post-replicative mismatch repair pathway or overexpression of newly screened NucS variants also impaired the DNA replication fidelity. Simultaneous interference with the DNA replication and repair machinery generated a binary genetic mutator capable of increasing the mutation rate by up to 2352-fold. The mutators facilitated rapid evolutionary engineering of C. glutamicum to acquire stress tolerance and protein overproduction phenotypes. This study provides efficient tools for evolutionary engineering of C. glutamicum and could inspire the development of mutagenesis strategy for other microbial hosts.


Assuntos
Corynebacterium glutamicum , DNA Polimerase III , DNA Polimerase III/genética , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/metabolismo , Replicação do DNA/genética , Mutação , Taxa de Mutação , Engenharia Metabólica
9.
J Am Chem Soc ; 146(8): 5333-5342, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38369932

RESUMO

Electrochemical CO2 reduction reaction (CO2RR) in acid can solve alkalinity issues while highly corrosive and reductive acidic electrolytes usually cause catalyst degradation. Inhibiting catalyst degradation is crucial for the stability of acidic CO2RR. Here, we reveal the microenvironment changes of dynamic Bi-based catalysts and develop a pulse chronoamperometry (CA) strategy to improve the stability of acidic CO2RR. In situ fluorescence mappings show that the local pH changes from neutral to acid, and the in situ Raman spectra reveal the dynamic evolution of interfacial water structures in the microenvironment. We propose that the surface charge properties of dynamic catalysts affect the competitive adsorption of K+ and protons, thereby causing the differences in local pH and CO2RR intermediate adsorption. We also develop a pulse CA strategy to reactivate catalysts, and the stability of acidic CO2RR is improved by 2 orders of magnitude for 100 h operation, which is higher than most reports on the stability of acidic CO2RR. This work gives insights on how microenvironment changes affecting the stability of acidic CO2RR, and provides guidance for designing stable catalysts in acidic electrolytes.

10.
J Am Chem Soc ; 146(8): 5414-5422, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38353405

RESUMO

Molecular-based multiferroic materials that possess ferroelectric and ferroelastic orders simultaneously have attracted tremendous attention for their potential applications in multiple-state memory devices, molecular switches, and information storage systems. However, it is still a great challenge to effectively construct novel molecular-based multiferroic materials with multifunctionalities. Generally, the structure of these materials possess high symmetry at high temperatures, while processing an obvious order-disorder or displacement-type ferroelastic or ferroelectric phase transition triggered by symmetry breaking during the cooling processes. Therefore, these materials can only function below the Curie temperature (Tc), the low of which is a severe impediment to their practical application. Despite great efforts to elevate Tc, designing single-phase crystalline materials that exhibit multiferroic orders above room temperature remains a challenge. Here, an inverse temperature symmetry-breaking phenomenon was achieved in [FPM][Fe3(µ3-O)(µ-O2CH)8] (FPM stands for 3-(3-formylamino-propyl)-3,4,5,6-tetrahydropyrimidin-1-ium, which acts as the counterions and the rotor component in the network), enabling a ferroelastoelectric phase at a temperature higher than Tc (365 K). Upon heating from room temperature, two-step distinct symmetry breaking with the mm2Fm species leads to the coexistence of ferroelasticity and ferroelectricity in the temperature interval of 365-426 K. In the first step, the FPM cations undergo a conformational flip-induced inverse temperature symmetry breaking; in the second step, a typical ordered-disordered motion-induced symmetry breaking phase transition can be observed, and the abnormal inverse temperature symmetry breaking is unprecedented. Except for the multistep ferroelectric and ferroelastic switching, this complex also exhibits fascinating nonlinear optical switching properties. These discoveries not only signify an important step in designing novel molecular-based multiferroic materials with high working temperatures, but also inspire their multifunctional applications such as multistep switches.

11.
Anal Chem ; 96(19): 7367-7372, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38696818

RESUMO

Immunogold, that is, gold nanoparticles (AuNPs) conjugated with biomolecules such as antibodies and peptides, have been widely used to construct sandwiched immunosensors for biodetection. Two main challenges in these immunoassays are difficulties in finding and validating a suitable antibody, and the nonspecific interaction between the substrate and immunogold, which lowers the detection sensitivity and even causes false results. To avoid these issues, we took advantage of the nonspecific interaction between AuNPs and capture antibodies and proposed a new sensing mechanism. That is, after the capture of analyte targets by the capture antibodies on the substrate, AuNPs of certain chemical functionality would preferably bind to the free capture antibodies. Consequently, the amount of deposited AuNPs will inversely depend on the concentration of the analytes. As a proof-of-concept, we designed a mass-based sensor where anti-IgG antibodies were coated on a quartz crystal microbalance substrate. After IgG was introduced, tannic acid-capped AuNPs were applied to bind with the free anti-IgG antibody molecules. A frequency change (Δf) of the quartz substrate was induced by the increased mass loading. To further amplify the loading mass, an Ag enhancer solution was added, and Ag growth was catalyzed by the bound AuNPs. The Δf response showed a concentration-dependent decrease when increasing IgG concentration with a detection limit of 2.6 ng/mL. This method relies on the nonspecific interaction between AuNPs and anti-IgG antibodies to realize sensitive detection of IgG and eliminates the use of detection antibodies. The concept is an alternative to many existing immunoassay technologies.


Assuntos
Técnicas Biossensoriais , Ouro , Nanopartículas Metálicas , Ouro/química , Nanopartículas Metálicas/química , Imunoensaio/métodos , Técnicas Biossensoriais/métodos , Imunoglobulina G/imunologia , Imunoglobulina G/análise , Técnicas de Microbalança de Cristal de Quartzo
12.
Small ; : e2307410, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778499

RESUMO

The detection of monoamine neurotransmitters is of paramount importance as the neurotransmitters are the chemical messengers regulating the gut-brain axis (GBA). It requires real-time, ultrasensitive, and selective sensing of the neurotransmitters in the gastric/intestinal fluid. However, multi-components present in the gastric/intestinal fluid make sensing challenging to achieve in terms of ultra-high sensitivity and selectivity. Herein, an approach is introduced to utilize vanadium single atom catalytic (SAC) centers in van der Waals MoS2 (V-MoS2) to selectively detect real-time serotonin (5-HT) in artificial gastric/intestinal fluid. The synergetic effect of V-SACs and the surface S-bonds on the MoS2 surface, enables an extremely wide range of 5-HT detection (from 1 pM to 100 µM), with optimum selectivity and interference resistance. By combining density functional theory calculations and scanning transmission electron microscopy, it is concluded that the V-SACs embedded in the MoS2 network create active sites that greatly facilitate the charge exchange between the material and the 5-HT molecules. This result allows the 5-HT detection in GBA studies to be more reliable, and the material tunability provides a general platform to achieve real-time and multi-component detection of other monoamine neurotransmitters in GBA such as dopamine and norepinephrine.

13.
BMC Microbiol ; 24(1): 98, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528458

RESUMO

OBJECTIVE: The association between heart failure (HF) and intestinal inflammation caused by a disturbed intestinal microbiota in infants with congenital heart disease (CHD) was investigated. METHODS: Twenty infants with HF and CHD who were admitted to our hospital between October 2021 and March 2022 were included in this study. Twenty age- and sex-matched infants without HF at our hospital were selected as the control group. Faecal samples were obtained from each participant and analysed by enzyme-linked immunoassay and 16 S rDNA sequencing to assess intestinal inflammatory factors and the microbiota. RESULTS: The levels of intestinal inflammatory factors, including IL-1ß, IL-4, IL-6, IL-17 A and TNF-α, were greatly increased, while the levels of IL-10 were significantly decreased in the HF group compared to the control group (p < 0.05). The intestinal microbial diversity of patients in the HF group was markedly lower than that in the control group (p < 0.05). The abundance of Enterococcus was significantly increased in the HF group compared to the control group (p < 0.05), but the abundance of Bifidobacterium was significantly decreased in the HF group compared to the control group (p < 0.05). The diversity of the intestinal microbiota was negatively correlated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the intestinal tract but was positively correlated with that of IL-10. The abundance of Enterococcus was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the intestinal tract but was negatively correlated with that of IL-10. NT-proBNP was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the HF group but was negatively correlated with that of IL-10. The heart function score was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the HF group but was negatively correlated with that of IL-10. CONCLUSIONS: Infants with CHD-related HF had a disordered intestinal microbiota, decreased diversity of intestinal microbes, increased levels of pathogenic bacteria and decreased levels of beneficial bacteria. The increased abundance of Enterococcus and the significant decrease in the diversity of the intestinal microbiota may exacerbate the intestinal inflammatory response, which may be associated with the progression of HF.


Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , Lactente , Humanos , Interleucina-10 , Fator de Necrose Tumoral alfa , Interleucina-6 , Interleucina-4 , Insuficiência Cardíaca/complicações , Cardiopatias Congênitas/complicações , Enterococcus/genética , Inflamação
14.
Opt Express ; 32(7): 11873-11885, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571025

RESUMO

In recent years, the rotational Doppler effect (RDE) has been widely used in rotational motion measurement. However, the performance of existing detection systems based on the RDE are generally limited by the drastic reduction of signal-to-noise ratio (SNR) due to the influence of atmospheric turbulence, partial obscuration of the vortex beam (VB) during propagation, and misalignment between the optical axis of VB and the rotational axis of the object, which poses a challenge for practical applications. In this paper, we proposed a coherent detection method of the RDE measurement based on triple Fourier transform. First, the weak RDE signal in backscattered light is amplified by using the balanced homodyne detection method, and the amplified signal still retains the same characteristic of severe broadening in the frequency domain as the original signal. Furthermore, we proposed the triple Fourier transform to extract the broadened RDE frequency shift signal after the coherent amplification. The proposed method significantly improves the SNR of RDE measurement and facilitates the accurate extraction of rotational speed, which helps to further improve the RDE detection range and promote its practical application.

15.
Virol J ; 21(1): 142, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910238

RESUMO

We describe the case of a 57-year-old male with jaundice, abdominal distension and fatigue. He was diagnosed as chronic active Epstein-Barr virus infection (CAEBV) due to intermittent elevated liver enzymes, hepatosplenomegaly and pancytopenia, with persistent positive of EBV biomarkers in blood and also positive in liver tissue. The patient was reinfected by SARS-CoV-2 within 2 months companied with CAEBV. The patient's second infection with SARS-CoV-2 led to the aggravated liver dysfunction with pneumonia and re-admission. After receiving symptomatic treatment, the patient showed significantly improvement of symptoms with partially restoration of liver function. After discharge, the patient's health status continued to deteriorate and eventually died. The instances of SARS-CoV-2 co-infection with the original chronic virus are not uncommon, but the exact mechanism of EBV and SARS-CoV-2 coinfection and the relationship between them are still unclear. Since co-infection of SARS-CoV-2 with original chronic virus might affect each other and lead disease aggravated and complicated, it is necessary to differentiate in the diagnosis of disease and it is important to be aware of the re-infection signs of SARS-CoV-2 in people with chronic virus infection diseases, as well as the risk of co-infection of SARS-CoV-2 with other viruses.


Assuntos
COVID-19 , Coinfecção , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Reinfecção , SARS-CoV-2 , Humanos , Masculino , COVID-19/diagnóstico , COVID-19/complicações , COVID-19/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Pessoa de Meia-Idade , Reinfecção/virologia , Reinfecção/diagnóstico , Coinfecção/virologia , Coinfecção/diagnóstico , Herpesvirus Humano 4/genética , Doença Crônica , Evolução Fatal
16.
Cell Commun Signal ; 22(1): 246, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671436

RESUMO

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a critical tumor suppressor protein that regulates various biological processes such as cell proliferation, apoptosis, and inflammatory responses by controlling the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PI3K/AKT) signaling pathway. PTEN plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). Loss of PTEN may contribute to survival, proliferation, and pro-inflammatory cytokine release of fibroblast-like synoviocytes (FLS). Also, persistent PI3K signaling increases myeloid cells' osteoclastic potential, enhancing localized bone destruction. Recent studies have shown that the expression of PTEN protein in the synovial lining of RA patients with aggressive FLS is minimal. Experimental upregulation of PTEN protein expression could reduce the damage caused by RA. Nonetheless, a complete comprehension of aberrant PTEN drives RA progression and its interactions with other crucial molecules remains elusive. This review is dedicated to promoting a thorough understanding of the signaling mechanisms of aberrant PTEN in RA and aims to furnish pertinent theoretical support for forthcoming endeavors in both basic and clinical research within this domain.


Assuntos
Artrite Reumatoide , PTEN Fosfo-Hidrolase , Humanos , Artrite Reumatoide/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/genética , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Animais , Transdução de Sinais
17.
Langmuir ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39047167

RESUMO

A modified Hummer's method was used to synthesize aqueous dispersions of graphene oxide (GO). The morphology, chemical structure, and exfoliation state of GO were analyzed by combining scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The structural and rheological properties of the GO dispersions were studied as a function of GO concentration and pH. Increasing the concentration of GO revealed shorter interparticle distances between GO sheets. This induced a transition from fluid to nematic gel-like structures, as observed by polarized optical microscopy (POM). The Herschel-Bulkley model was used to fit the shear thinning curves and to demonstrate the viscoelastic behavior. Both the yield stress and viscoelastic moduli in the linear viscoelastic regime increased. As pH increases, the color of the aqueous GO dispersions becomes darker, the negative values of the zeta potential increase, the distances between the GO sheets decrease as observed by a slight shift of the correlation peak toward higher values of the scattering vector modulus in small-angle X-ray scattering (SAXS), and the rheological properties (yield stress and viscoelastic moduli in the linear viscoelastic region) decrease. These results can be explained by a change in the morphology of GO related to their hydrophilicity. This work presents relationships between rheological and structural properties of GO sheet dispersions, with particular emphasis on the effects of concentration and pH.

18.
Eur Radiol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724768

RESUMO

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

19.
Clin Transplant ; 38(5): e15337, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38762786

RESUMO

OBJECTIVE: This study aimed to investigate the occurrence and risk factors of postoperative neurocognitive disorder (NCD) in patients who underwent heart transplantation. METHODS: Seventy-six heart transplant patients were analyzed for clinical data including gender, age, height, weight, education level, left ventricular ejection fraction (LVEF), stroke volume (SV), transplantation duration, and pretransplant medical history. Cognitive function was assessed using the mini-mental status examination (MMSE) and Montreal cognitive assessment (MoCA) scales. Patients were categorized into cognitively normal and impaired groups based on the presence or absence of cognitive dysfunction, and their cognitive function scores were compared. Multivariate logistic regression was used to identify independent risk factors for cognitive impairment in postoperative cardiac transplant patients. RESULTS: Cognitive dysfunction was observed in 48 out of 76 heart transplant patients, representing an incidence of 63.2%. Cognitive impairment in heart transplant recipients predominantly affected multiple cognitive domains. Logistic regression analysis identified age (OR = 1.057, 95% CI 1.002-1.115), gender (OR = .200, 95% CI .044-.919), education level (OR = .728, 95% CI .600-.883), LVEF (OR = .891, 95% CI .820-.969), and history of diabetes (OR = 7.674, 95% CI 1.317-44.733) as independent risk factors for postoperative NCD in heart transplant recipients (P < .05). CONCLUSION: The study found a high incidence of postoperative NCD in heart transplant patients, with gender, age, education level, LVEF, and diabetes history being significant risk factors. Early identification and intervention targeting these risk factors may help prevent NCD in postheart transplant patients and improve long-term outcomes.


Assuntos
Disfunção Cognitiva , Transplante de Coração , Humanos , Masculino , Feminino , Transplante de Coração/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/epidemiologia , Seguimentos , Prognóstico , Adulto , Complicações Pós-Operatórias/etiologia , Complicações Cognitivas Pós-Operatórias/etiologia , Complicações Cognitivas Pós-Operatórias/epidemiologia , Incidência , Estudos Retrospectivos , Testes Neuropsicológicos
20.
Inorg Chem ; 63(15): 6988-6997, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38569109

RESUMO

Rechargeable Zn-MnO2 batteries using mild water electrolytes have garnered significant interest owing to their impressive theoretical energy density and eco-friendly characteristics. However, MnO2 suffers from huge structural changes during the cycles, resulting in very poor stability at high charge-discharge depths. Briefly, the above problems are caused by slow kinetic processes and the dissolution of Mn atoms in the cycles. In this paper, a 2D homojunction electrode material (δ/ε-MnO2) based on δ-MnO2 and ε-MnO2 has been prepared by a two-step electrochemical deposition method. According to the DFT calculations, the charge transfer and bonding between interfaces result in the generation of electronic states near the Fermi surface, giving δ/ε-MnO2 a more continuous distribution of electron states and better conductivity, which is conducive to the rapid insertion/extraction of Zn2+ and H+. Moreover, the strongly coupled Mn-O-Mn interfacial bond can effectively impede dissolution of Mn atoms and thus maintain the structural integrity of δ/ε-MnO2 during the cycles. Accordingly, the δ/ε-MnO2 cathode exhibits high capacity (383 mAh g-1 at 0.1 A g-1), superior rate performance (150 mAh g-1 at 5 A g-1), and excellent cycling stability over 2000 cycles (91.3% at 3 A g-1). Profoundly, this unique homojunction provides a novel paradigm for reasonable selection of different components.

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