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1.
Science ; 384(6702): 1344-1349, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38900891

RESUMO

Directional liquid transport has been widely observed in various species including cacti, spiders, lizards, the pitcher plant Nepenthes alata, and Araucaria leaves. However, in all these examples the liquid transport for a specific liquid is completely restricted in a fixed direction. We demonstrate that Crassula muscosa shoot surfaces have the ability to transport a specific liquid unidirectionally in either direction. This is accomplished through the presence of asymmetric reentrant leaves with varying reentrant angles, which yields the variation in liquid meniscus heterogeneity. These findings enable engineered biomimetic structures capable of selective directional liquid transport, with functions such as intelligent flow direction switching, liquid distribution, and mixing.

2.
Cell Oncol (Dordr) ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753155

RESUMO

T lymphocytes are indispensable for the host systems of defense against pathogens, tumors, and environmental threats. The therapeutic potential of harnessing the cytotoxic properties of T lymphocytes for antigen-specific cell elimination is both evident and efficacious. Genetically engineered T-cells, such as those employed in CAR-T and TCR-T cell therapies, have demonstrated significant clinical benefits in treating cancer and autoimmune disorders. However, the current landscape of T-cell genetic engineering is dominated by strategies that necessitate in vitro T-cell isolation and modification, which introduce complexity and prolong the development timeline of T-cell based immunotherapies. This review explores the complexities of gene delivery systems designed for T cells, covering both viral and nonviral vectors. Viral vectors are known for their high transduction efficiency, yet they face significant limitations, such as potential immunogenicity and the complexities involved in large-scale production. Nonviral vectors, conversely, offer a safer profile and the potential for scalable manufacturing, yet they often struggle with lower transduction efficiency. The pursuit of gene delivery systems that can achieve targeted gene transfer to T cell without the need for isolation represents a significant advancement in the field. This review assesses the design principles and current research progress of such systems, highlighting the potential for in vivo gene modification therapies that could revolutionize T-cell based treatments. By providing a comprehensive analysis of these systems, we aim to contribute valuable insights into the future development of T-cell immunotherapy.

3.
Proc Natl Acad Sci U S A ; 121(22): e2318412121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38781205

RESUMO

Lysosomes are central players in cellular catabolism, signaling, and metabolic regulation. Cellular and environmental stresses that damage lysosomal membranes can compromise their function and release toxic content into the cytoplasm. Here, we examine how cells respond to osmotic stress within lysosomes. Using sensitive assays of lysosomal leakage and rupture, we examine acute effects of the osmotic disruptant glycyl-L-phenylalanine 2-naphthylamide (GPN). Our findings reveal that low concentrations of GPN rupture a small fraction of lysosomes, but surprisingly trigger Ca2+ release from nearly all. Chelating cytoplasmic Ca2+ makes lysosomes more sensitive to GPN-induced rupture, suggesting a role for Ca2+ in lysosomal membrane resilience. GPN-elicited Ca2+ release causes the Ca2+-sensor Apoptosis Linked Gene-2 (ALG-2), along with Endosomal Sorting Complex Required for Transport (ESCRT) proteins it interacts with, to redistribute onto lysosomes. Functionally, ALG-2, but not its ESCRT binding-disabled ΔGF122 splice variant, increases lysosomal resilience to osmotic stress. Importantly, elevating juxta-lysosomal Ca2+ without membrane damage by activating TRPML1 also recruits ALG-2 and ESCRTs, protecting lysosomes from subsequent osmotic rupture. These findings reveal that Ca2+, through ALG-2, helps bring ESCRTs to lysosomes to enhance their resilience and maintain organelle integrity in the face of osmotic stress.


Assuntos
Cálcio , Complexos Endossomais de Distribuição Requeridos para Transporte , Lisossomos , Pressão Osmótica , Lisossomos/metabolismo , Humanos , Cálcio/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Membranas Intracelulares/metabolismo , Células HeLa , Canais de Potencial de Receptor Transitório/metabolismo , Canais de Potencial de Receptor Transitório/genética , Proteínas de Ligação ao Cálcio , Proteínas Reguladoras de Apoptose
4.
IEEE Trans Biomed Eng ; PP2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739521

RESUMO

OBJECTIVE: Magnetic Particle Imaging (MPI) is a radiation-free tracer-based imaging technology that visualizes the spatial distribution of superparamagnetic iron oxide nanoparticles. Conventional spatial encoding methods in MPI rely on a gradient magnetic field with a constant gradient strength to generate a field-free point or line for spatial scanning. However, increasing the gradient strength can enhance theoretical spatial resolution but also lead to a decrease in the Signal-to-Noise Ratio (SNR) and sensitivity of the imaging system. This poses a technical challenge in balancing spatial resolution and sensitivity, necessitating intricate hardware design. METHODS: To address this, we present a Space-Specific Mixing Excitation (SSME) technique for achieving high-SNR spatial encoding in MPI. By utilizing a dual-frequency excitation magnetic field with a non-homogeneous field strength, magnetic particles at each position generate unique intermodulation responses. By performing multi-channel acquisitions across the entire field of view, high SNR MPI signals can be acquired. When combined with reconstruction techniques based on system matrix, multi-dimensional SSME-MPI can be achieved. RESULTS: The effectiveness of the proposed method was validated through phantom and in vivo imaging experiments. The results demonstrate significant improvements in sensitivity (3.6-fold improvement) and spatial resolution (better than 1 mm) without any hardware modifications. CONCLUSION: These findings demonstrate the capability of SSME to enhance both the spatial resolution and sensitivity of MPI. SIGNIFICANCE: This method provides a solution to the ongoing challenge of balancing spatial resolution and sensitivity in MPI, potentially facilitating the implementation of MPI in a wider range of medical applications.

5.
J Stroke Cerebrovasc Dis ; 33(6): 107727, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641218

RESUMO

BACKGROUND: F-actin is involved in the progression of ischemic stroke and is associated with the disruption of the blood-brain barrier. In this article, we evaluated serum F-actin as a biomarker in stroke severity and early neurological deterioration (END) in acute ischemic stroke. METHODS: In this study, serum F-actin was measured in consecutively collected 140 AIS patients and 144 healthy controls matched in gender and age by ELISA. Early neurological deterioration (END) was defined as the deterioration of neurological dysfunction within 72 hours of admission, with an increase of ≥ 4 points in the NIHSS score. Severe stroke was defined as a NIHSS score>8 at admission. RESULTS: The serum F-actin level in AIS was significantly higher than healthy controls (p = 0.041). In large-artery atherosclerosis stroke and cardioembolic stroke, serum F-actin were significantly higher than that in small artery occlusion stroke (padjust = 0.019, padjust < 0.001, respectively).F-actin level above the critical value (>1.37 µg/L) was significantly associated with severe stroke (OR, 3.015; 95 %CI, 1.014-8.963; p = 0.047) . In addition, elevated level of F-actin was significantly associated with END (OR, 1.323; 95 % CI, 1.001-1.747, p = 0.049). When the level of F-actin was above the critical value (>2.17 µg/L), its association with END remained significant (OR, 6.303; 95 %CI, 2.160-18.394; p < 0.001) . CONCLUSION: F-actin is an important blood biomarker in the early stage of AIS, and high levels of F-actin are valuable in determining the severity of stroke and predicting early neurological deterioration.


Assuntos
Actinas , Biomarcadores , AVC Isquêmico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Actinas/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Avaliação da Deficiência , Progressão da Doença , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Regulação para Cima
6.
Sensors (Basel) ; 24(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38475041

RESUMO

The choice of torque curve in lower-limb enhanced exoskeleton robots is a key problem in the control of lower-limb exoskeleton robots. As a human-machine coupled system, mapping from sensor data to joint torque is complex and non-linear, making it difficult to accurately model using mathematical tools. In this research study, the knee torque data of an exoskeleton robot climbing up stairs were obtained using an optical motion-capture system and three-dimensional force-measuring tables, and the inertial measurement unit (IMU) data of the lower limbs of the exoskeleton robot were simultaneously collected. Nonlinear approximations can be learned using machine learning methods. In this research study, a multivariate network model combining CNN and LSTM was used for nonlinear regression forecasting, and a knee joint torque-control model was obtained. Due to delays in mechanical transmission, communication, and the bottom controller, the actual torque curve will lag behind the theoretical curve. In order to compensate for these delays, different time shifts of the torque curve were carried out in the model-training stage to produce different control models. The above model was applied to a lightweight knee exoskeleton robot. The performance of the exoskeleton robot was evaluated using surface electromyography (sEMG) experiments, and the effects of different time-shifting parameters on the performance were compared. During testing, the sEMG activity of the rectus femoris (RF) decreased by 20.87%, while the sEMG activity of the vastus medialis (VM) increased by 17.45%. The experimental results verify the effectiveness of this control model in assisting knee joints in climbing up stairs.


Assuntos
Exoesqueleto Energizado , Robótica , Humanos , Torque , Extremidade Inferior , Articulação do Joelho
7.
Acta Ophthalmol ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38516719

RESUMO

PURPOSE: To develop and validate an effective nomogram for predicting poor response to orthokeratology. METHODS: Myopic children (aged 8-15 years) treated with orthokeratology between February 2018 and January 2022 were screened in four hospitals of different tiers (i.e. municipal and provincial) in China. Potential predictors included 32 baseline clinical variables. Nomogram for the outcome (1-year axial elongation ≥0.20 mm: poor response; <0.20 mm: good response) was computed from a logistic regression model with the least absolute shrinkage and selection operator. The data from the First Affiliated Hospital of Chengdu Medical College were randomly assigned (7:3) to the training and validation cohorts. An external cohort from three independent multicentre was used for the model test. Model performance was assessed by discrimination (the area under curve, AUC), calibration (calibration plots) and utility (decision curve analysis). RESULTS: Between January 2022 and March 2023, 1183 eligible subjects were screened from the First Affiliated Hospital of Chengdu Medical College, then randomly divided into training (n = 831) and validation (n = 352) cohorts. A total of 405 eligible subjects were screened in the external cohort. Predictors included in the nomogram were baseline age, spherical equivalent, axial length, pupil diameter, surface asymmetry index and parental myopia (p < 0.05). This nomogram demonstrated excellent calibration, clinical net benefit and discrimination, with the AUC of 0.871 (95% CI 0.847-0.894), 0.863 (0.826-0.901) and 0.817 (0.777-0.857) in the training, validation and external cohorts, respectively. An online calculator was generated for free access (http://39.96.75.172:8182/#/nomogram). CONCLUSION: The nomogram provides accurate individual prediction of poor response to overnight orthokeratology in Chinese myopic children.

8.
bioRxiv ; 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38352356

RESUMO

Lysosomes are central players in cellular catabolism, signaling, and metabolic regulation. Cellular and environmental stresses that damage lysosomal membranes can compromise their function and release toxic content into the cytoplasm. Here, we examine how cells respond to osmotic stress within lysosomes. Using sensitive assays of lysosomal leakage and rupture, we examine acute effects of the cathepsin C-metabolized osmotic disruptant glycyl-L-phenylalanine 2-naphthylamide (GPN). Our findings reveal that widely used concentrations of GPN rupture only a small fraction of lysosomes, but surprisingly trigger Ca 2+ release from nearly all. Chelating cytoplasmic Ca 2+ using BAPTA makes lysosomes more likely to rupture under GPN-induced stress, suggesting that Ca 2+ plays a role in protecting or rapidly repairing lysosomal membranes. Mechanistically, we establish that GPN causes the Ca 2+ -sensitive protein Apoptosis Linked Gene-2 (ALG-2) and interacting ESCRT proteins to redistribute onto lysosomes, improving their resistance to membrane stress created by GPN as well as the lysosomotropic drug chlorpromazine. Furthermore, we show that activating the cation channel TRPML1, with or without blocking the endoplasmic reticulum Ca 2+ pump, creates local Ca 2+ signals that protect lysosomes from rupture by recruiting ALG-2 and ESCRTs without any membrane damage. These findings reveal that Ca 2+ , through ALG-2, helps bring ESCRTs to lysosomes to enhance their resilience and maintain organelle integrity in the face of osmotic stress. SIGNIFICANCE: As the degradative hub of the cell, lysosomes are full of toxic content that can spill into the cytoplasm. There has been much recent interest in how cells sense and repair lysosomal membrane damage using ESCRTs and cholesterol to rapidly fix "nanoscale damage". Here, we extend understanding of how ESCRTs contribute by uncovering a preventative role of the ESCRT machinery. We show that ESCRTs, when recruited by the Ca 2+ -sensor ALG-2, play a critical role in stabilizing the lysosomal membrane against osmotically-induced rupture. This finding suggests that cells have mechanisms not just for repairing but also for actively protecting lysosomes from stress-induced membrane damage.

9.
Nanoscale ; 16(5): 2565-2573, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38224263

RESUMO

Nanoparticle-functionalized carbon nanotubes are promising in many research fields, especially in sensing, due to their intriguing performance in catalysis. However, these nanomaterials are mainly produced through batch processes under harsh conditions, thus encountering inherent limitations of low throughput and uncontrollable morphology of functional nanoparticles (NPs). In this work, we propose a method for high-yield and continuous production of bimetallic (Pt-Pd) NPs on multi-walled carbon nanotubes (MWCNTs) at room temperature through a custom 3D-printed microfluidic platform. A homogenous particle nucleation and growth environment could be created on the microfluidic platform that was equipped with two 3D-printed micromixers. Pt-Pd NPs loaded on MWCNTs were prepared in the microfluidic platform with high throughput and controlled size, dispersity and composition. The synthetic parameters for these nanocomposites were investigated to optimize their electrocatalytic performance. The optimized nanocomposites exhibited excellent electrocatalytic activity with exceptional sensitivity and wide detection range, superior to their counterparts prepared via conventional approaches. This method proposed here could be further adapted for manufacturing other catalyst support materials, opening more avenues for future large-scale production and catalytic investigation of functional nanomaterials.

10.
Nat Genet ; 56(2): 294-305, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38267607

RESUMO

The human placenta has a vital role in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here we conducted integrated single-nucleus RNA sequencing and single-nucleus ATAC sequencing analyses of human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their correspondence with human trophoblast stem cell (hTSC)-derived STB. Furthermore, we identified transcription factors associated with diverse STB nuclear lineages through their gene regulatory networks and experimentally confirmed their function in hTSC and trophoblast organoid-derived STBs. Together, our data provide insights into the heterogeneity of human STB and represent a valuable resource for interpreting associated pregnancy complications.


Assuntos
Multiômica , Placenta , Gravidez , Humanos , Feminino , Trofoblastos , Núcleo Celular/genética , Fatores de Transcrição , Diferenciação Celular
11.
Biomacromolecules ; 25(2): 1330-1339, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38254252

RESUMO

The design of imaging agents with a high fluorine content is necessary for overcoming the challenges of low sensitivity in 19F magnetic resonance imaging (MRI)-based molecular imaging. Chemically self-assembled nanorings (CSANs) provide a strategy to increase the fluorine content through multivalent display. We previously reported an 19F NMR-based imaging tracer, in which case a CSAN-compatible epidermal growth factor receptor (EGFR)-targeting protein E1-dimeric dihydrofolate (E1-DD) was bioconjugated to a highly fluorinated peptide. Despite good 19F NMR performance in aqueous solutions, a limited signal was observed in cell-based 19F NMR using this monomeric construct, motivating further design. Here, we design several new E1-DD proteins bioconjugated to peptides of different fluorine contents. Flow cytometry analysis was used to assess the effect of variable fluorinated peptide sequences on the cellular binding characteristics. Structure-optimized protein, RTC-3, displayed an optimal spectral performance with high affinity and specificity for EGFR-overexpressing cells. To further improve the fluorine content, we next engineered monomeric RTC-3 into CSAN, η-RTC-3. With an approximate eightfold increase in the fluorine content, multivalent η-RTC-3 maintained high cellular specificity and optimal 19F NMR spectral behavior. Importantly, the first cell-based 19F NMR spectra of η-RTC-3 were obtained bound to EGFR-expressing A431 cells, showing a significant amplification in the signal. This new design illustrated the potential of multivalent fluorinated CSANs for future 19F MRI molecular imaging applications.


Assuntos
Flúor , Imageamento por Ressonância Magnética , Flúor/química , Espectroscopia de Ressonância Magnética , Proteínas , Peptídeos , Receptores ErbB/metabolismo
12.
IEEE Trans Biomed Eng ; 71(4): 1209-1218, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37938949

RESUMO

OBJECTIVE: Open-sided field-free line magnetic particle imaging (OS FFL MPI) is a novel medical imaging system configuration that has received significant attention in recent years. However, the measurement-based system matrix (SM) image reconstruction for OS FFL MPI typically requires multiple angle calibration (MAC), which is time-consuming in practice. METHODS: To address this issue, we propose a fast 2D SM generation method that requires only a single angle calibration (SAC). The SAC method exploits the rotational invariance of the system function. Based on the measured single angle system function, the system function is rotated to generate system functions at other angles, and then the SM for image reconstruction is constructed. Then, we conducted various simulation experiments and built an OS FFL MPI scanner to evaluate the proposed SAC method. RESULTS: The experiments demonstrating the effectiveness of SAC in reducing calibration workload, requiring fewer scanning numbers while maintaining a similar image reconstruction quality compared to MAC method. Furthermore, the SM generated by SAC produces consistent imaging results with the SM generated by MAC, regardless of the interpolation algorithms, the number of rotation angles, or the signal-to-noise ratios employed in phantom imaging experiments. CONCLUSION: SAC has been experimentally verified to reduce acquisition time while maintaining accurate and robust reconstruction performance. SIGNIFICANCE: The significance of SAC lies in its contribution to improving calibration efficiency in OS FFL MPI, potentially facilitating the implementation of MPI in a wider range of applications.


Assuntos
Algoritmos , Diagnóstico por Imagem , Calibragem , Imagens de Fantasmas , Razão Sinal-Ruído , Fenômenos Magnéticos , Processamento de Imagem Assistida por Computador/métodos
13.
Biotechnol Bioeng ; 121(3): 835-852, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151887

RESUMO

Animal models are routinely employed to assess the treatments for human cancer. However, due to significant differences in genetic backgrounds, traditional animal models are unable to meet bioresearch needs. To overcome this restriction, researchers have generated and optimized immunodeficient mice, and then engrafted human genes, cells, tissues, or organs in mice so that the responses in the model mice could provide a more reliable reference for treatments. As a bridge connecting clinical application and basic research, humanized mice are increasingly used in the preclinical evaluation of cancer treatments, particularly after gene interleukin 2 receptor gamma mutant mice were generated. Human cancer models established in humanized mice support exploration of the mechanism of cancer occurrence and provide an efficient platform for drug screening. However, it is undeniable that the further application of humanized mice still faces multiple challenges. This review summarizes the construction approaches for humanized mice and their existing limitations. We also report the latest applications of humanized mice in preclinical evaluation for the treatment of cancer and point out directions for future optimization of these models.


Assuntos
Neoplasias , Camundongos , Humanos , Animais , Modelos Animais de Doenças , Neoplasias/terapia
14.
Anal Chem ; 95(51): 18850-18858, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38091507

RESUMO

The development of chiral alignment media for measuring anisotropic NMR parameters provides an opportunity to determine the absolute configuration of chiral molecules without the need for derivatization. However, chiral alignment media with a high and robust enantiodiscriminating property for a wide range of chiral molecules are still scarce. In this study, we synthesized cholesterol-end-functionalized helical polyisocyanides from a chiral monomer using a cholesterol-based alkyne-Pd(II) initiator. These stereoregular polyisocyanides form stable and weak anisotropic lyotropic liquid crystals (LLCs) in dichloromethane systems, exhibiting highly optical activities in both single left- and right-handed helices. The preparation process of the media was straightforward, and the aligning property of the LLCs could be controlled by adjusting the concentration and temperature. Using the chiral polyisocyanides, we extracted the residual dipolar coupling for an enantiomeric pair of isopinocampheol (IPC), as well as a number of pharmaceutical molecules, demonstrating excellent enantiodiscriminating properties for a broad range of chiral compounds.

15.
Int J Ophthalmol ; 16(12): 2011-2017, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38111928

RESUMO

AIM: To describe the outcome of using low-dose laser cycloplasty (LCP) in chronic angle-closure glaucoma (CACG). METHODS: A retrospective case series. Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed. The main outcomes included intraocular pressure (IOP), the number of glaucoma medication, anterior segment parameters and surgery-related complications. RESULTS: A total of 7 eyes of 7 CACG patients (age 38.9±11.0y) underwent LCP with a mean follow-up of 27.1±13.7mo (range 16-48mo). Following LCP, mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg (P=0.027) with 0.4±1.1 glaucoma medications (P=0.001) at final follow-up. The anterior chamber depth (ACD), angle opening distance500 and trabecular-iris angle increased from 1.65±0.33 mm, 0.05 mm (range 0-0.30 mm) and 5.1° (range, 0-31.97°) at baseline to 1.98±0.43 mm (P=0.073), 0.53 mm (range 0.42-0.91 mm, P=0.015), 45.9° (range, 40.2°-59.4°, (P=0.015) in the long-term follow-up, respectively. The deepening of ACD and reopening of anterior chamber angle (ACA) was observed in 6 eyes (85.7%). CONCLUSION: LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications. In addition, LCP can bring a significant deepening in ACD and reopening of ACA.

16.
Hum Gene Ther ; 34(23-24): 1248-1256, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37917093

RESUMO

Distant metastasis and primary tumor relapse are the two main hurdles to the success of surgical treatment for cancer patients. Circulating tumor cells (CTCs) and incomplete surgical resection are the primary cause of distant metastasis and local recurrence of tumors, respectively. Chimeric antigen receptor (CAR)-modified T cells target residual carcinomas and CTCs hold the potential to inhibit primary recurrence and reduce tumor metastasis, but the experimental evidence is lacking. Here, we developed a surgery-induced tumor metastasis model in immunocompetent mice to investigate the efficacy of CAR-T cells therapy in preventing metastasis and local recurrence. We observed that subcutaneous tumor resection has induced a large number of CTCs intravasated into circulation. EpCAM-specific CAR-T was effective in clearing CTCs following surgical removal of the tumor. This resulted in less pulmonary metastasis and longer survival in mice when compared to mice treated with surgery followed by Mock-T cells infusion. In addition, the local relapse was obviously inhibited at the surgical site followed by EpCAM-CAR-T cell treatment. This study demonstrated that CAR-T cell therapy can be an adjuvant treatment following surgery to prevent tumor metastasis and inhibit primary tumor relapse for cancer patients.


Assuntos
Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Receptores de Antígenos Quiméricos/genética , Molécula de Adesão da Célula Epitelial/genética , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/patologia , Imunoterapia Adotiva/métodos , Recidiva , Terapia Baseada em Transplante de Células e Tecidos
18.
Nat Commun ; 14(1): 5654, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704629

RESUMO

Peptide-based therapeutics have gained attention as promising therapeutic modalities, however, their prevalent drawback is poor circulation half-life in vivo. In this paper, we report the selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine SNAr chemistry, with decafluoro-diphenylsulfone (DFS). Testing of the binding of the selected peptides to albumin identified SICRFFC as the lead sequence. We replaced DFS with isosteric pentafluorophenyl sulfide (PFS) and the PFS-SICRFFCGG exhibited KD = 4-6 µM towards human serum albumin. When injected in mice, the concentration of the PFS-SICRFFCGG in plasma was indistinguishable from the reference peptide, SA-21. More importantly, a conjugate of PFS-SICRFFCGG and peptide apelin-17 analogue (N3-PEG6-NMe17A2) showed retention in circulation similar to SA-21; in contrast, apelin-17 analogue was cleared from the circulation after 2 min. The PFS-SICRFFC is the smallest known peptide macrocycle with a significant affinity for human albumin and substantial in vivo circulation half-life. It is a productive starting point for future development of compact macrocycles with extended half-life in vivo.


Assuntos
Albuminas , Albumina Sérica Humana , Humanos , Animais , Camundongos , Apelina , Albumina Sérica Humana/genética , Angiotensina II , Cisteína , Sulfetos
19.
ACS Omega ; 8(33): 30747-30756, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37636964

RESUMO

Garbractin A (1), a structurally complicated polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented 4,11-dioxatricyclo[4.4.2.01,5] dodecane skeleton, was isolated from the fruits of Garcinia bracteata, along with five new biosynthetic analogues named garcibracteatones A-E (2-6). Their structures containing absolute configurations were revealed using spectroscopic data, the residual dipolar coupling-enhanced NMR approach, and quantum chemical calculations. The antihyperglycemic effect of these PPAPs (1-6) was evaluated using insulin-resistant HepG2 cells (IR-HepG2 cells) induced through palmitic acid (PA). Compounds 1, 3, and 4 were found to significantly promote glucose consumption in the IR-HepG2 cells and, therefore, may hold potential as candidates for treating hyperglycemia.

20.
RSC Adv ; 13(29): 20365-20372, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37425627

RESUMO

Gallium-based liquid metal (GLM) is a promising lubricant candidate due to its high load capacity and high thermal stability. However, the lubrication performance of GLM is restricted by its metallic characteristics. Herein, this work proposes a facile method to obtain a GLM@MoS2 composite by integrating GLM with MoS2 nanosheets. The incorporation of MoS2 imparts GLM with different rheological properties. Since GLM is able to be separated from the GLM@MoS2 composite and agglomerates into bulk liquid metal again in alkaline solution, the bonding between GLM and MoS2 nanosheets is reversible. Moreover, our frictional tests demonstrate that the GLM@MoS2 composite exhibits enhanced tribological performance including reduction of friction coefficient and wear rate by 46% and 89%, respectively, in contrast to the pure GLM.

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