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1.
Mycology ; 15(1): 17-29, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558845

RESUMO

Colorectal cancer (CRC) is a prevalent tumour with high morbidity rates worldwide, and its incidence among younger populations is rising. Early diagnosis of CRC can help control the associated mortality. Fungi are common microorganisms in nature. Recent studies have shown that fungi may have a similar association with tumours as bacteria do. As an increasing number of tumour-associated fungi are discovered, this provides new ideas for the diagnosis and prognosis of tumours. The relationship between fungi and colorectal tumours has also been recently identified by scientists. Therefore, this paper describes the limitations and prospects of the application of fungi in diagnosing CRC and predicting CRC prognosis.

2.
Clin Exp Metastasis ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568295

RESUMO

Central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) is common. In our study, we built a nomogram to predict CLNM. We retrospectively analyzed 1,392 PTC patients. This group of patients was divided into a training cohort (including 1,009 patients) and a validation cohort (including 383 patients). Analyses of the correlation between inflammatory indicators, ultrasonic characteristics, pathological characteristics and CLNM were conducted. In the training cohort and validation cohort, the metastatic rates of CLNM were 60.16% and 64.23%, respectively. Univariate and multivariate logistic regression analyses demonstrated that Hashimoto's thyroiditis (HT), calcification, multifocality, capsule invasion, PLR (platelet-lymphocyte ratio) ≤ 130.34, large tumors and middle and lower positions were independent risk factors for CLNM. Then, we constructed a nomogram. The nomogram had good discrimination regardless of whether there was CLNM, with a C-index of 0.809. The calibration curve indicated that the nomogram had good visual and quantitative consistency (p = 0.213). Decision curve analysis showed that the nomogram improved the net clinical benefit with a threshold probability of 0-82% in the training cohort and 0-71% in the validation cohort. We constructed a nomogram to predict CLNM in PTC and assist surgeons in making personalized clinical decisions for PTC.

3.
Opt Lett ; 49(7): 1749-1752, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38560853

RESUMO

Non-contact optical temperature measurement can effectively avoid the disadvantages of traditional contact thermometry and thus, become a hot research topic. Herein, a fluorescence intensity ratio (FIR) thermometry using a time-resolved technique based on La2CaZrO6:Cr3+ (LCZO) is proposed, with a maximum relative sensitivity (Sr - FIR) of 2.56% K-1 at 473 K and a minimum temperature resolution of 0.099 K. Moreover, the relative sensitivity and temperature resolution can be effectively controlled by adjusting the width of the time gate based on the time-resolved technique. Our work provides, to our knowledge, new viewpoints into the development of novel optical thermometers with adjustable relative sensitivity and temperature resolution on an as-needed basis.

4.
Am J Med Genet C Semin Med Genet ; : e32085, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563234

RESUMO

LINS1 is the human homolog of the Drosophila segment polarity gene that encodes an essential regulator of the wingless/Wnt signaling. By 2011, only seven pedigrees (16 patients) with eight causative variants in LINS1 gene have been reported. These cases mainly presented with infancy-/child-onset neurodevelopmental disorders, facial dysmorphia, and other clinical features, and a wide spectrum of clinically distinct phenotypes were also manifested. In our study, two brothers in a family were admitted and diagnosed with child-onset movement disorders, slight intellectual disability, psychological symptoms, eye problems, urinary and bowel dysfunction, mitral value prolapse, and Q-T prolongation. By exome sequencing, we identified a nonsense homozygous pathogenic variant (LINS1: c.274C > T (p.Q92X)), which had been reported in a case diagnosed with intellectual disability and psychiatric disorders (such as schizophrenia and anxiety). Compared with this case, the clinical features of our cases were distinct. In particular, our cases displayed unusual features of heart and blood system. Furthermore, the genotype-phenotype relationship analysis suggested that distinct phenotypes presented in cases carrying variants in different domains of the LINS1 gene. In conclusions, our findings suggest the high clinical variations in the LINS1 variants-related disorders. Moreover, the Q92X might be a recurrent variant in Hans of Southern China.

5.
Clin Chem ; 70(4): 683-684, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38565211
6.
Environ Toxicol ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598732

RESUMO

Mono-(2-ethylhexyl) phthalate (MEHP) can accumulate in the liver and then lead to hepatic steatosis, while the underlying mechanism remains unclear. Inflammation plays an important role in the disorder of hepatic lipid metabolism. This study aims to clarify the role of the inflammatory response mediated by formyl peptide receptor 2 (FPR2) in steatosis of L02 cells exposed to MEHP. L02 cells were exposed to MEHP of different concentrations and different time. A steatosis model of L02 cells was induced with oleic acid and the cells were exposed to MEHP simultaneously. In addition, L02 cells were incubated with FPR2 antagonist and then exposed to MEHP. Lipid accumulation was determined by oil red O staining and extraction assay. The indicators related to lipid metabolism and inflammatory response were measured with appropriate kits. The relative expression levels of FPR2 and its ligand were determined by Western blot, and the interaction of them was detected by co-immunoprecipitation. As a result, MEHP exposure could promote the occurrence and progression of steatosis and the secretion of chemokines and inflammatory factors in L02 cells. MEHP could also affect the expression and activation of FPR2 and the secretion of FPR2 ligands. In addition, the promotion effect of MEHP on the secretion of total cholesterol and interleukin 1ß in L02 cells could be significantly inhibited by the FPR2 antagonist. We concluded that FPR2 might affect the promotion effect of MEHP on steatosis of L02 cells by mediating inflammatory response.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38593387

RESUMO

Upcycling plastic waste into valuable commodity chemicals with clean energy is an appealing strategy for mitigating environmental issues. Polylactic acid (PLA), a biodegradable plastic that is produced annually in millions of tons, can be chemically recycled to valuable products instead of being degraded to carbon dioxide. Here, we demonstrate an electrochemical reforming of PLA hydrolysate to acetate and acetonate using nickel phosphide nanosheets on nickel foam (Ni2P/NF) as the catalyst. The Ni2P/NF catalyst was synthesized by electrochemical deposition and phosphide treatment and showed excellent catalytic activity and ∼100% Faraday efficiency for electroreforming PLA to acetate and acetonate in an H-cell. Moreover, a stable performance of more than 90% Faraday efficiency for value-added organics was achieved for a duration of 100 h in a flow cell at a current density of 100 mA cm-2 and a potential below 1.5 V vs. RHE. In situ characterization revealed that the catalyst underwent electrochemical reforming during the reaction to produce γ-phase NiOOH with high electrochemical activity. This work introduces a new and green solution for the treatment of waste PLA, presenting a low-cost and highly efficient strategy for electrically reforming plastics.

8.
Front Bioeng Biotechnol ; 12: 1352098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585708

RESUMO

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%-22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

9.
Langmuir ; 40(15): 8115-8125, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38563662

RESUMO

Core-shell composite abrasive particles are a topic of great interest in surface finishing. It is important to explore the preparation technology and performance parameters associated with them. In this paper, a core-shell composite abrasive particle made of polystyrene and cerium oxide (PS&CeO2, CSPC), which is rigid on the outside and flexible on the inside, is proposed. The microstructure, physical phase characteristics, and mechanical properties of the inner core and composite abrasive particles are investigated. PS microspheres and CSPC composite abrasive particles with different structural features were prepared through a series of experiments, morphological observations, and physical and chemical characterization experiments. Their microstructures and physical phase properties were investigated. The indentation load curves of the PS microspheres and CSPC composite abrasive samples were measured by using an atomic force microscope. The analysis focused on the effects of various dimensional and structural parameters on the modulus of elasticity of both PS microspheres and CSPC composite abrasive particles. The analysis shows that the experimentally prepared PS microspheres have good dispersion, a smooth surface, and a uniform particle size distribution. The prepared CSPC composite abrasive particles are regular spheres with rough, rice-like surfaces, low modulus of elasticity, and overall nonrigid and soft elastic properties. The results of this paper can provide a guide for the preparation technology, performance regulation, and application of polymer microspheres and core-shell composite abrasive particles in CMP.

10.
Sci Rep ; 14(1): 7652, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561456

RESUMO

Considering the effect of SIRT1 on improving myocardial fibrosis and GAS5 inhibiting occurrence and development of myocardial fibrosis at the cellular level, the aim of the present study was to investigate whether LncRNA GAS5 could attenuate cardiac fibrosis through regulating mir-217/SIRT1, and whether the NLRP3 inflammasome activation was involved in this process. Isoprenaline (ISO) was given subcutaneously to the male C57BL/6 mice to induce myocardial fibrosis and the AAV9 vectors were randomly injected into the left ventricle of each mouse to overexpress GAS5. Primary myocardial fibroblasts (MCFs) derived from neonatal C57BL/6 mice and TGF-ß1 were used to induce fibrosis. And the GAS5 overexpressed MCFs were treated with mir-217 mimics and mir-217 inhibitor respectively. Then the assays of expression levels of NLRP3, Caspase-1, IL-1ß and SIRT1 were conducted. The findings indicated that the overexpression of GAS5 reduced the expression levels of collagen, NLRP3, Capase-1, IL-1ß and SIRT1 in ISO treated mice and TGF-ß1 treated MCFs. However, this effect was significantly weakened after mir-217 overexpression, but was further enhanced after knockdown of mir-217. mir-217 down-regulates the expression of SIRT1, leading to increased activation of the NLRP3 inflammasome and subsequent pyroptosis. LncRNA GAS5 alleviates cardiac fibrosis induced via regulating mir-217/SIRT1 pathway.


Assuntos
MicroRNAs , RNA Longo não Codificante , Camundongos , Masculino , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Isoproterenol/toxicidade , MicroRNAs/genética , MicroRNAs/metabolismo , Inflamassomos , Sirtuína 1/genética , Camundongos Endogâmicos C57BL , Fibrose
11.
Opt Express ; 32(7): 12394-12404, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571062

RESUMO

Since carbon dots (CDs) with good water solubility are preferred by researchers and biological applications, a hydrothermal method was used to synthesize green fluorescent CDs with an excitation-independent peak at 526 nm using deionized water as the solvent and neutral red as the carbon source. To achieve spectral modulation, the pH of the solvent was adjusted with KOH to obtain orange CDs (O-CDs) in an alkaline environment, with the emission peak red-shifted to 630 nm. The water-soluble CDs were prepared for multidimension sensing as Fe3+ sensing (on/off). Carbon dots dispersed into a silica gel matrix can be used for fingerprint detection of various materials.

12.
Sci Total Environ ; 927: 172272, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38583626

RESUMO

To combat with climate change, most countries have set carbon neutrality target. However, our understanding on carbon removal, release and sequestration by mariculture remains unclear. Here, carbon removal, release and sequestration by maricultured seaweeds, shellfish and fish in Shandong Province during 2003-2022 were assessed using a comprehensive method that considers the processes of biological metabolism, seawater chemistry and carbon footprint. Saccharina japonica productivity has been largely enhanced since 2014, resulting in increased production and CO2 removal and sequestration. Seaweeds removed 172 Gg C and sequestered 62 Gg C in 2022. CO2 removal and release by shellfish demonstrated a slow increase trend, ranging from 231 to 374 Gg C yr-1 and 897 to 1438 Gg C yr-1 during 2003-2022, respectively. Contrary to seaweed and shellfish, maricultured fish added CO2 to seawater due to the use of feeds. The added CO2 by fish culture achieved the peak of 60 Gg C in 2011 and decreased to 25 Gg C in 2022. Most of this added CO2 was released to atmosphere by microbial mineralization and it was in the range of 21-52 Gg C yr-1 during 2003-2022. After summing up the contribution of seaweeds, shellfish and fish, both total CO2 removal (from 110 to 259 Gg C yr-1) and total CO2 release (from 929 to 1429 Gg C yr-1) increased remarkably during the past 20 years. To neutralize CO2 release by shellfish and fish, Pyropia yezoensis needs the largest culture area (1.65 ± 0.15 × 106 ha) while Gracilariopsis lemaneiformis requires the smallest area (0.11 ± 0.03 × 106 ha). In addition, there are enough available areas for culturing G. lemaneiformis, Ulva prolifera and Sargassum fusifarme to neutralize total CO2 emission in Shandong Province. This study elucidates carbon removal, release and sequestration capacities of mariculture and indicates that seaweed culture has a tremendous potential to achieve carbon neutrality target in Shandong.


Assuntos
Aquicultura , Sequestro de Carbono , China , Alga Marinha/metabolismo , Dióxido de Carbono/análise , Mudança Climática , Água do Mar/química , Animais , Carbono/metabolismo , Carbono/análise , Frutos do Mar , Peixes/metabolismo , Monitoramento Ambiental
13.
Exp Cell Res ; : 114049, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642790

RESUMO

BACKGROUND: Acellular nerve allografts (ANAs) have been successfully applied to bridge facial nerve defects, and transplantation of stem cells may enhance the regenerative results. Up to now, application of hair follicle epidermal neural crest stem cell-derived Schwann cell-like cells (EPI-NCSC-SCLCs) combined with ANAs for bridging facial nerve defects has not been reported. METHODS: The effect of ANAs laden with green fluorescent protein (GFP)-labeled EPI-NCSC-SCLCs (ANA + cells) on bridging rat facial nerve trunk defects (5-mm-long) was detected by functional and morphological examination, as compared with autografts and ANAs, respectively. RESULTS: (1) EPI-NCSC-SCLCs had good compatibility with ANAs in vitro. (2) In ANA + cells group, the GFP signals were observed by in vivo imaging system for small animals within 8 weeks, and GFP-labeled EPI-NCSC-SCLCs were detected in the tissue slices at 16 weeks postoperatively. (3) The facial symmetry at rest after surgery in the ANA + cells group was better than that in the ANA group (p < 0.05), and similar to that in the autograft group (p > 0.05). The initial recovery time of vibrissal and eyelid movement in the ANA group was 2 weeks later than that in the other two groups. (4) The myelinated fibers, myelin sheath thickness and diameter of the axons of the buccal branches in the ANA group were significantly worse than those in the other two groups (P < 0.05), and the results in the ANA + cells group were similar to those in the autograft group (p > 0.05). CONCLUSIONS: EPI-NCSC-SCLCs could promote functional and morphological recovery of rat facial nerve defects, and GFP labeling could track the transplanted EPI-NCSC-SCLCs in vivo for a certain period of time. These may provide a novel choice for clinical treatment of peripheral nerve defects.

14.
Opt Lett ; 49(8): 1896-1899, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621033

RESUMO

Next-generation display and lighting based on quantum dot light-emitting diodes (QLEDs) require a balanced electron injection of electron transport layers (ETLs). However, classical ZnO nanoparticles (NPs) as ETLs face inherent defects such as excessive electron injection and positive aging effects, urgently requiring the development of new types of ETL materials. Here, we show that high stability SnO2 NPs as ETL can significantly improve the QLED performance to 100567 cd·m-2 luminance, 14.3% maximum external quantum efficiency, and 13.1 cd·A-1 maximum current efficiency using traditional device structures after optimizing the film thickness and annealing the temperature. Furthermore, experimental tests reveal that by doping Zr4+ ions, the size of SnO2 NPs will reduce, dispersion will improve, and energy level will shift up. As expected, when using Zr-SnO2 NPs as the ETL, the maximum external quantum efficiency can reach 16.6%, which is close to the state-of-the-art QLEDs based on ZnO ETL. This work opens the door for developing novel, to the best of our knowledge, type ETLs for QLEDs.

15.
Front Cell Infect Microbiol ; 14: 1378379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606295

RESUMO

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Pneumonia , Síndrome do Desconforto Respiratório , Humanos , Estudos Prospectivos , Estudos de Coortes , Influenza Humana/complicações , Qualidade de Vida , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Sobreviventes
16.
Anal Chim Acta ; 1303: 342517, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38609276

RESUMO

BACKGROUND: As an emerging and attractive low-dimensional functional materials, Ti3C2 MXene quantum dots (QDs) enlarge the toolbox of fluorescence sensing. However, monochromatic fluorescence, which only provide one single signal, is often beset by challenges such as false-positive readouts and limitations in selectivity. Consequently, to improve the sensing accuracy by means of cross-verified dual-signal authentication, the endeavor to engineer dual-mode nanoprobes based on Ti3C2 QDs, incorporating both the capability of fluorescence and an alternative sensing mechanism, emerges as a compelling avenue. RESULTS: Here, based on the alterations in colorimetric and fluorescent signals of Ti3C2 QDs with the addition of Ag+, we propose a dual-mode sensor obviating the necessity for nanoprobe labeling. Owing to the decent reducibility of Ti3C2 QDs, Ag+ is adsorbed and reduced, resulting in the generation of plasmonic Ag nanoparticles (NPs), which simultaneously trigger colorimetric responses of the solution and enhance the fluorescent emission of Ti3C2 QDs. The confluence of colorimetry and fluorometry within this strategy optimally harnesses the modulating role of the acquired Ag NPs on the reducing capability and fluorescence characteristics of Ti3C2 QDs. The equilibrium imparts versatility and promising prospects to this analyte-triggered label-free method, which enables a remarkable specificity and an excellent detecting limit (0.45 µM) for Ag+. SIGNIFICANCE: The balance between reducibility and fluorescence of Ti3C2 QDs for dual-mode detection is inventively demonstrated. With the exemplification of a direct influence of both features of the nanoprobe via the introduction of analytes, this study opens the feasibility of the analyte-perturbed felicitous equilibrium, which endows label-free methods with versatility and promising prospects. This design may evoke more biosensing strategies with the function of double-signal mutual verification.

17.
Nano Lett ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630899

RESUMO

CuInS2 (CIS) quantum dots (QDs) represent an important class of colloidal materials with broad application potential, owing to their low toxicity and unique optical properties. Although coating with a ZnS shell has been identified as a crucial method to enhance optical performance, the occurrence of cation exchange has historically resulted in the unintended formation of Cu-In-Zn-S alloyed QDs, causing detrimental blueshifts in both absorption and photoluminescence (PL) spectral profiles. In this study, we present a facile one-pot synthetic strategy aimed at impeding the cation exchange process and promoting ZnS shell growth on CIS core QDs. The suppression of both electron-phonon interaction and Auger recombination by the rigid ZnS shell results in CIS/ZnS core/shell QDs that exhibit a wide near-infrared (NIR) emission coverage and a remarkable PL quantum yield of 92.1%. This effect boosts the fabrication of high-performance, QD-based NIR light-emitting diodes with the best stability of such materials so far.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38655619

RESUMO

DPP3, a dipeptidyl peptidase, participates in a variety of pathophysiological processes. DPP3 is upregulated in cancer and might serve as a key factor in the tumorigenesis and progression of various malignancies. However, its specific role and molecular mechanism are still unknown. In this study, the expression of DPP3 in breast cancer tissues is analyzed using TCGA database. Kaplan-Meier survival analysis is performed to estimate the effect of DPP3 on the survival outcomes. To explore the biological function and mechanisms of DPP3 in breast cancer, biochemical and cell biology assays are conducted in vitro. DPP3 expresses at a higher level in breast cancer tissues than that in adjacent tissues in both TCGA database and clinical samples. Patients with high expression of DPP3 have poor survival outcomes. The proliferation and migration abilities of tumor cells with stable DPP3 knockout in breast cancer cell lines are significantly inhibited, and apoptosis is increased in vitro. GSEA analysis shows that DPP3 can affect lipid metabolism and fatty acid synthesis in tumors. Subsequent experiments show that DPP3 could stabilize FASN expression and thus promote fatty acid synthesis in tumor cells. The results of the metabolomic analysis also confirm that DPP3 can affect the content of free fatty acids. This study demonstrates that DPP3 plays a role in the reprogramming of fatty acid metabolism in tumors and is associated with poor prognosis in breast cancer patients. These findings will provide a new therapeutic target for the treatment of breast cancer.

19.
Nature ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657677

RESUMO

Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology1-3. The γδ T cell receptor (TCR), generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex2. The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy4. Here, we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes5,6, unveiling two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ/TCRδ extracellular domain (ECD) and connecting peptides (CPs). The length of CPs regulates the ligand association and T cell activation. Additionally, a cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signaling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, where two protomers nestle back-to-back via their Vγ5 domains of TCR ECDs. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the γδ TCR unique properties and facilitating immunotherapeutic interventions.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38651323

RESUMO

Flexible bioelectronic devices that can perform real-time and accurate intraocular pressure (IOP) monitoring in both clinical and home settings hold significant implications for the diagnosis and treatment of glaucoma, yet they face challenges due to the open physiological environment of the ocular. Herein, we develop an intelligent wireless measuring contact lens (WMCL) incorporating a dual inductor-capacitor-resistor (LCR) resonant system to achieve temperature self-compensation for quantitative IOP monitoring in different application environments. The WMCL utilizes a compact circuitry design, which enables the integration of low-frequency and high-frequency resonators within a single layer of a sensing circuit without causing visual impairment. Mechanically guided microscale 3D encapsulation strategy combined with flexible circuit printing techniques achieves the surface-adaptive fabrication of the WMCL. The specific design of frequency separation imparts distinct temperature response characteristics to the dual resonators, and the linear combination of the dual resonators can eliminate the impact of temperature variations on measurement accuracy. The WMCL demonstrates outstanding sensitivity and linearity in monitoring the IOP of porcine eyes in vitro while maintaining satisfactory measurement accuracy even with internal temperature variations exceeding 10 °C. Overcoming the impact of temperature variations on IOP monitoring from the system level, the WMCL showcases immense potential as the next generation of all-weather IOP monitoring devices.

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