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1.
J Environ Sci (China) ; 149: 149-163, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181630

RESUMO

Developing heterojunction photocatalyst with well-matched interfaces and multiple charge transfer paths is vital to boost carrier separation efficiency for photocatalytic antibiotics removal, but still remains a great challenge. In present work, a new strategy of chloride anion intercalation in Bi2O3 via one-pot hydrothermal process is proposed. The as-prepared Ta-BiOCl/Bi24O31Cl10 (TBB) heterojunctions are featured with Ta-Bi24O31Cl10 and Ta-BiOCl lined shoulder-by-shouleder via semi-coherent interfaces. In this TBB heterojunctions, the well-matched semi-coherent interfaces and shoulder-by-shoulder structures provide fast electron transfer and multiple transfer paths, respectively, leading to enhanced visible light response and improved photogenerated charge separation. Meanwhile, a type-II heterojunction for photocharge separation has been obtained, in which photogenerated electrons are drove from the CB (conduction band) of Ta-Bi24O31Cl10 to the both of bilateral empty CB of Ta-BiOCl and gathered on the CB of Ta-BiOCl, while the photogenerated holes are left on the VB (valence band) of Ta-Bi24O31Cl10, effectively hindering the recombination of photogenerated electron-hole pairs. Furthermore, the separated electrons can effectively activate dissolved oxygen for the generation of reactive oxygen species (·O2-). Such TBB heterojunctions exhibit remarkably superior photocatalytic degradation activity for tetracycline hydrochloride (TCH) solution to Bi2O3, Ta-BiOCl and Ta-Bi24O31Cl10. This work not only proposes a Ta-BiOCl/Bi24O31Cl10 shoulder-by-shoulder micro-ribbon architectures with semi-coherent interfaces and successive type-II heterojunction for highly efficient photocatalytic activity, but offers a new insight into the design of highly efficient heterojunction through phase-structure synergistic transformation strategy.


Assuntos
Antibacterianos , Bismuto , Poluentes Químicos da Água , Bismuto/química , Antibacterianos/química , Poluentes Químicos da Água/química , Catálise , Processos Fotoquímicos
2.
Sensors (Basel) ; 24(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39275543

RESUMO

The intelligent detection of chili peppers is crucial for achieving automated operations. In complex field environments, challenges such as overlapping plants, branch occlusions, and uneven lighting make detection difficult. This study conducted comparative experiments to select the optimal detection model based on YOLOv8 and further enhanced it. The model was optimized by incorporating BiFPN, LSKNet, and FasterNet modules, followed by the addition of attention and lightweight modules such as EMBC, EMSCP, DAttention, MSBlock, and Faster. Adjustments to CIoU, Inner CIoU, Inner GIoU, and inner_mpdiou loss functions and scaling factors further improved overall performance. After optimization, the YOLOv8 model achieved precision, recall, and mAP scores of 79.0%, 75.3%, and 83.2%, respectively, representing increases of 1.1, 4.3, and 1.6 percentage points over the base model. Additionally, GFLOPs were reduced by 13.6%, the model size decreased to 66.7% of the base model, and the FPS reached 301.4. This resulted in accurate and rapid detection of chili peppers in complex field environments, providing data support and experimental references for the development of intelligent picking equipment.


Assuntos
Capsicum , Algoritmos
3.
Artigo em Inglês | MEDLINE | ID: mdl-39265074

RESUMO

Subunit vaccines have emerged as a promising strategy in immunotherapy for combating viral infections and cancer. Nevertheless, the clinical application of subunit vaccines is hindered by limitations in antigen delivery efficiency, characterized by rapid clearance and inadequate cellular uptake. Here, a novel subunit vaccine delivery system utilizing ovalbumin@magnetic nanoparticles (OVA@MNPs) encapsulated within biodegradable gelatin methacryloyl (GelMA) microspheres was proposed to enhance the efficacy of antigen delivery. OVA@MNPs-loaded GelMA microspheres, denoted as OMGMs, can be navigated through magnetic fields to deliver subunit vaccines into the lymphatic system efficiently. Moreover, the biodegradable OMGMs enabled the sustained release of subunit vaccines, concentrating OVA around lymph nodes and enhancing the efficacy of induced immune response. OMGMs were produced through a microfluidic droplet generation technique, enabling mass production. In murine models, OMGMs successfully accumulated antigens in lymph nodes abundant in antigen-presenting cells, leading to enhanced cellular and humoral immunity and pronounced antitumor effects with a single booster immunization. In conclusion, these findings highlight the promise of OMGMs as a practical subunit vaccination approach, thus addressing the limitations associated with antigen delivery efficiency and paving the way for advanced immunotherapeutic strategies.

4.
J Colloid Interface Sci ; 678(Pt C): 143-149, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39288575

RESUMO

Direct and consistent monitoring of respiratory patterns is crucial for disease prognostication. Although the wired clinical respiratory monitoring apparatus can operate accurately, the existing defects are evident, such as the indispensability of an external power supply, low mobility, poor comfort, and limited monitoring timeframes. Here, we present a self-powered in-nostril hydrogel sensor for long-term non-irritant anti-interference respiratory monitoring, which is developed from a dual-network binary-solvent thermogalvanic polyvinyl alcohol hydrogel fiber (d = 500 µm, L=30 mm) with Fe2+/Fe3+ ions serving as a redox couple, which can generate a thermoelectrical signal in the nasal cavity based on the temperature difference between the exhaled gas and skin as well as avoid interference from the external environment. Due to strong hydrogen bonding between solvent molecules, the sensor retains over 90 % of its moisture after 14 days, exhibiting great potential in wearable respiratory surveillance. With the assistance of deep learning, the hydrogel fiber-based respiration monitoring strategy can actively recognize seven typical breathing patterns with an accuracy of 97.1 % by extracting the time sequence and dynamic parameters of the thermoelectric signals generated by respiration, providing an alert for high-risk respiratory symptoms. This work demonstrates the significant potential of thermogalvanic gels for next-generation wearable bioelectronics for early screening of respiratory diseases.

5.
Small ; : e2407676, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39279556

RESUMO

Intracellular delivery of proteins has largely been relying on cationic nanoparticles to induce efficient endosome escape, which, however, poses serious concerns on the inflammatory and cytotoxic effects. Herein, a versatile noncationic nano biohybrid platform is introduced for efficient cytosolic protein delivery by utilizing a nano-confined biocatalytic reaction. This platform is constructed by co-immobilizing glucose oxidase (GOx) and the target protein into nanoscale hydrogen-bonded organic frameworks (HOFs). The biocatalytic reaction of nano-confined GOx is leveraged to induce controlled perturbation of intracellular redox homeostasis by sustained hydrogen peroxide (H2O2) production and diminishing the flux of the pentose phosphate pathway (PPP). This in turn induces the endosome escape of nanobiohybrids. Concomitantly, GOx-mediated hypoxia leads to overexpression of azo reductase that initiated the materials' self-destruction for releasing target proteins. These biological effects collectively induce highly efficient cytosolic protein delivery. The versatility of this delivery platform is further demonstrated for various types of proteins, different protein loading approaches (in situ immobilization or post-adsorption), and in multiple cell lines. Finally, the protein delivery efficiency and biosafety are demonstrated in a tumor-bearing mouse model. This nanohybrid system opens up new avenues for intracellular protein delivery and is expected to be extensively applicable for a broad range of biomolecuels.

6.
Talanta ; 281: 126819, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245005

RESUMO

Multimodal biosensors with independent signaling pathways can self-calibrate and improve the reliability of disease biomarker detection. Herein, a colorimetric-fluorescent dual-mode paper-based biosensor with PAN/Fe(III)-CNOs (FPCs) as core components has been developed, which information is recognized by smartphone and naked eye. Using 1-(2-pyridylazo)-2-naphthol (PAN) as a mediator, Fe(III) is enriched on the surface of carbon nano-onions (CNOs), endowing FPCs with excellent mimetic enzyme activity and photothermal conversion ability, which allows it to output amplified colorimetric signals under laser irradiation. In addition, the complexation of PAN with Fe(III) broadens its absorption spectrum, which makes FPCs more suitable to be energy acceptors to quench fluorescence of polymer dots (Pdots), resulting in the changes of output fluorescent signal. Based on the above design, a portable colorimetric-fluorescent dual-mode biosensor is proposed for trypsin detection with Pdots as fluorescence sources and FPCs as fluorescence quenchers and nanoenzymes. This work provides a convenient way for constructing portable visual multimodal biosensors, which is expected to applied in various disease diagnosis.

7.
Sci Adv ; 10(38): eadn3002, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39292792

RESUMO

In situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle-based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond-bridged organosilica nanoparticles, followed by coating with a Mn2+-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn2+ and SN38 comediated signaling and simultaneously scavenge preexisting H2O2 in the TME and Mn2+-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.


Assuntos
Vacinas Anticâncer , Células Dendríticas , Proteínas de Membrana , Nanopartículas , Espécies Reativas de Oxigênio , Microambiente Tumoral , Espécies Reativas de Oxigênio/metabolismo , Animais , Nanopartículas/química , Camundongos , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/imunologia , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Linhagem Celular Tumoral , Imunoterapia/métodos , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
9.
Heliyon ; 10(15): e34796, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39144973

RESUMO

Energy-intensive load benefits from low electricity tariff and carbon emission, since they occupy certain amounts in the total cost of the product. This paper considers energy-intensive load participation in the electricity as well as carbon trading to reduce the cost. Firstly, an electricity-carbon model is established based on the correlation value method to calculate the carbon emissions of energy-intensive load based on their electricity consumption to realize the carbon amount. Afterwards, the baseline method is used to allocate free carbon emission quotas to energy-intensive load and a reward-penalty carbon trading price mechanism considering offset is proposed. Next, the objective function to achieve maximum benefits, and to reduce output fluctuation, and to improve new energy accommodation is proposed. The case studies show that, by comparing multi-objective function optimization, the optimization target proposed in this paper can effectively reduce wind power output fluctuations and improve wind power accommodation. Through the total participation in carbon trading and electricity market income, multi-objective optimization can increase the system income while ensuring that energy-intensive load meets production requirements under the premise of reducing carbon emissions, verifying the effectiveness of the low-carbon optimal operation model proposed in this paper.

11.
Respir Res ; 25(1): 311, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39154188

RESUMO

BACKGROUND: Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma. METHODS: After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting. RESULTS: Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs. CONCLUSIONS: Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.


Assuntos
Asma , Plaquetas , Nanopartículas , Polifenóis , Chá , Animais , Camundongos , Polifenóis/administração & dosagem , Polifenóis/farmacologia , Asma/tratamento farmacológico , Asma/metabolismo , Nanopartículas/administração & dosagem , Chá/química , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Administração por Inalação , Humanos , Camundongos Endogâmicos BALB C , Feminino , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia
12.
Inorg Chem ; 63(34): 16103-16113, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39149799

RESUMO

The construction of doped molecular clusters is an intriguing way to perform bimetallic doping for electrocatalysts. However, efficiently harnessing the benefits of a doping strategy and alloy engineering to create a nanostructure for electrocatalytic application at the molecular level has consistently posed a challenge. Here we propose an in situ reconstruction strategy aimed at producing an alloy nanostructure through a pyrolysis process, originating from bowknot-like heterometallic clusters. The Schiff base, denoted as ligand L1 (o-vanillin ethylenediamine), was introduced as a precursor to coordinate Fe and Co metals, thereby yielding a heteronuclear metal cluster [(FeCo)(L1)2O]CH3CN. Subsequently, a comprehensive investigation of the in situ reconstruction process [(FeCo)(L1)2O](CH3CN) → [(FeCo)(L1)2O] → [M-O-M/M-O] [CH3+/CH3O+/H2C═N/C2H5+/C4H4+] → [FeCo/Fe3O4/Fe2O3/Co3O4][carbon layer] led to the formation of MOx/CoFe@NC-700 during the pyrolysis. This process reveals that the metals Fe and Co in the clusters undergo partly in situ evolution into FeCo alloys, resulting in the successful preparation of MOx/CoFe@NC (M = Fe, Co) nanomaterials that leverage the advantages of both doping strategies and alloy engineering. The synergistic interaction between alloy particles and metal oxides establishes active sites that contribute to the excellent oxygen evolution (OER) and hydrogen evolution (HER) catalytic behaviors. Notably, these materials exhibit outstanding OER and HER properties under alkaline conditions, with overpotentials of 191 and 88 mV for OER and HER, respectively, at 10 mA cm-2. Investigation of the in situ conversion of Schiff base bimetal clusters into alloy materials through pyrolysis offers a novel strategy for advancing electrocatalytic applications.

15.
Am J Med Sci ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39154961

RESUMO

BACKGROUND: Sepsis is a critical condition with a significant risk of mortality. Advanced age is one factor in increasing mortality in intensive care. OBJECTIVES: The aim of this study is to investigate the association between mean heart rate (MHR) and 30-day mortality among older patients with sepsis in the intensive care unit (ICU). METHODS: All older patients (age 65 or older) with sepsis for first time in ICU admission in Medical Information Mart for Intensive Care-IV (MIMIC-IV) were included in this retrospective study. The effect of MHR within 24 h of ICU admission on 30-day mortality was assessed according to multivariable Cox regression models, restricted cubic splines and two-piecewise Cox regression models. RESULTS: The total number of participants was 6598 (mean heart rate, 83.8 ± 14.3 bpm). A total of 1295 (19.6%) patients died within 30 days after ICU admission. MHR within 24 h of admission was associated with 30-day mortality (J-shaped association) in older patients with sepsis in the ICU, with an inflection point at about 74 bpm and a minimal risk observed at 73 to 82 bpm of MHR. CONCLUSIONS: In this retrospective cohort study, there was a J-shaped association between MHR and 30-day mortality in older patients with sepsis admitted to the ICU and a minimal risk observed at 73 to 82 bpm of MHR. If further confirmed, this association may provide a theoretical basis for formulating the target strategy of heart rate therapy for these patients.

16.
BMC Cancer ; 24(1): 797, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961378

RESUMO

PURPOSE: Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. METHODS: Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined "EBV response" as 3 consecutive timepoints of load below 50% of baseline, and "EBV progression" as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. RESULTS: We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171-0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS. CONCLUSION: In summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.


Assuntos
DNA Viral , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Nivolumabe , Carga Viral , Humanos , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Masculino , Feminino , Pessoa de Meia-Idade , DNA Viral/sangue , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/sangue , Estudos Retrospectivos , Adulto , Recidiva Local de Neoplasia/virologia , Nivolumabe/uso terapêutico , Genoma Viral , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Resultado do Tratamento
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124794, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39024785

RESUMO

Herein, hydrothermal method was used to prepare a series of multi-color polythiophene modified carbon quantum dots. Under UV excitation, fluorescence their maximum emission wavelengths appear at 612 nm, 570 nm, and 540 nm respectively. The prepared CD-BTH and CD-BN can have specific detection of Au3+ and Hg2+ through fluorescence quenching effect. The detection limits for Au3+ are 3 nM and 5.4 nM respectively, and for Hg2+ are 23 nM and 90 nM respectively. CD-KN detects Au3+ specifically through fluorescence resonance, with a detection limit of 33 nM. Under the interference of other metal ions, three types of polythiophene modified quantum carbon dots exhibit excellent selectivity for the responsive ions. Meanwhile, this article also elucidates the law that as the electron withdrawing ability of the side chains of polythiophene derivatives increasing, the fluorescence emission peaks of the prepared polythiophene modified carbon dots shifts red and the fluorescence quantum yield is higher.

18.
Ultrason Sonochem ; 109: 106989, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39059252

RESUMO

The aim of this study is to optimize the extraction process of oat saponins (Os) and to evaluate their antioxidant potential. Single factor experiment, response surface optimization design, and orthogonal test were employed to optimize the process of ultrasonic-assisted extraction of Os, and the optimal extraction conditions were as followed: ethanol volume fraction of 80 %, material-solvent ratio of 1:14, ultrasonic power of 400 W, ultrasonic time of 25 min, extraction temperature of 60℃, extraction time of 180 min, and the extraction rate of Os was 0.317 %±0.105 %. Using the method, the crude extract of Os was prepared and its abilities of scavenging radicals in vitro and inhibiting protein oxidation in pork were determined, with ascorbic acid (Vc) as the control. Results revealed that the scavenging ability of Os against DPPH radical, hydroxyl radical (·OH) and superoxide anion (O2-) increased with the concentration of Os. Interestingly, the scavenging abilities of Os against DPPH and O2- were far lower than that of Vc, but its scavenging ability against ·OH was very close to that of Vc, reaching 84.59 % and 96.33 %, respectively. Furthermore, the experiments of pork storage and Fenton oxidation system showed that Os with 0.09-0.72 mg/mL could reduce the production of carbonyl (8.49 %-50.05 %) and the oxidation of total sulfhydryl (1.29 %-25.86 %), and effectively inhibit the oxidation of protein in pork by 7.82 %-22.53 %. The results of this study will provide a theoretical basis for the application of oat saponins as a natural anti-protein oxidant in meat processing and storage.


Assuntos
Antioxidantes , Avena , Saponinas , Ondas Ultrassônicas , Saponinas/química , Saponinas/isolamento & purificação , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Avena/química , Fracionamento Químico/métodos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Oxirredução , Animais , Suínos
19.
Int Immunopharmacol ; 139: 112663, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39079196

RESUMO

Psoriasis and atopic dermatitis (AD) are both chronic inflammatory skin diseases, which are common and difficult to cure. Currently, the emerging biologics have demonstrated outstanding efficacy, but not all patients are able to benefit from them, and traditional systemic treatments come with many severe side effects. The emergence of immune checkpoints brings new hope to solve this problem. Immune checkpoints regulate T cell activation. Upon damage to the co-inhibitory molecules, the inhibition on T cells is removed, leading to the excessive activation of T cells. In this review, we delineate and highlight the expression and function of immune checkpoint molecules (CTLA-4, PD-1, TIM-3, TIGIT, VISTA, LAG-3, OX40, GITR) in psoriasis and AD. We provide preclinical and clinical studies supporting a potential therapeutic approach of targeting these checkpoints for inflammatory skin diseases. Moreover, the complexity of immune checkpoints and safety of clinical application are discussed.


Assuntos
Dermatite Atópica , Psoríase , Humanos , Dermatite Atópica/imunologia , Dermatite Atópica/tratamento farmacológico , Psoríase/imunologia , Psoríase/tratamento farmacológico , Animais , Proteínas de Checkpoint Imunológico/metabolismo , Proteínas de Checkpoint Imunológico/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos T/imunologia
20.
J Am Chem Soc ; 146(31): 21700-21709, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39052014

RESUMO

Interactions between glycan-binding proteins (GBPs) and glycosphingolipids (GSLs) present in cell membranes are implicated in a wide range of biological processes. However, studying GSL binding is hindered by the paucity of purified GSLs and the weak affinities typical of monovalent GBP-GSL interactions. Native mass spectrometry (nMS) performed using soluble model membranes is a promising approach for the discovery of GBP ligands, but the detection of weak interactions remains challenging. The present work introduces MEmbrane ANchor-assisted nMS (MEAN-nMS) for the detection of low-affinity GBP-GSL complexes. The assay utilizes a membrane anchor, produced by covalent cross-linking of the GBP and a lipid in the membrane, to localize the GBP on the surface and promote GSL binding. Ligands are identified by nMS detection of intact GBP-GSL complexes (MEAN-nMS) or using a catch-and-release (CaR) strategy, wherein GSLs are released from GBP-GSL complexes upon collisional activation and detected (MEAN-CaR-nMS). To establish reliability, a library of purified gangliosides incorporated into nanodiscs was screened against human immune lectins, and the results compared with affinities of the corresponding ganglioside oligosaccharides. Without a membrane anchor, nMS analysis yielded predominantly false negatives. In contrast, all ligands were identified by MEAN-(CaR)-nMS, with no false positives. To highlight the potential of MEAN-CaR-nMS for ligand discovery, a natural library of GSLs was incorporated into nanodiscs and screened against human and viral proteins to uncover elusive ligands. Finally, nMS-based detection of GSL ligands directly from cells is demonstrated. This breakthrough paves the way for shotgun glycomics screening using intact cells.


Assuntos
Glicoesfingolipídeos , Espectrometria de Massas , Glicoesfingolipídeos/química , Glicoesfingolipídeos/metabolismo , Espectrometria de Massas/métodos , Humanos , Membrana Celular/metabolismo , Membrana Celular/química , Ligantes , Ligação Proteica
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