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1.
Proc Natl Acad Sci U S A ; 120(1): e2120582120, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574652

RESUMO

Unraveling cell-cell interaction is fundamental to understanding many biological processes. To date, genetic tools for labeling neighboring cells in mammals are not available. Here, we developed a labeling strategy based on the Cre-induced intercellular labeling protein (CILP). Cre-expressing donor cells release a lipid-soluble and membrane-permeable fluorescent protein that is then taken up by recipient cells, enabling fluorescent labeling of neighboring cells. Using CILP, we specifically labeled endothelial cells surrounding a special population of hepatocytes in adult mice and revealed their distinct gene signatures. Our results highlight the potential of CILP as a platform to reveal cell-cell interactions and communications in vivo.


Assuntos
Células Endoteliais , Proteínas de Membrana , Animais , Camundongos , Hepatócitos/metabolismo , Proteínas de Membrana/metabolismo
2.
Plant Physiol ; 195(2): 1277-1292, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38431526

RESUMO

Low temperatures occurring at the booting stage in rice (Oryza sativa L.) often result in yield loss by impeding male reproductive development. However, the underlying mechanisms by which rice responds to cold at this stage remain largely unknown. Here, we identified MITOCHONDRIAL ACYL CARRIER PROTEIN 2 (OsMTACP2), the encoded protein of which mediates lipid metabolism involved in the cold response at the booting stage. Loss of OsMTACP2 function compromised cold tolerance, hindering anther cuticle and pollen wall development, resulting in abnormal anther morphology, lower pollen fertility, and seed setting. OsMTACP2 was highly expressed in tapetal cells and microspores during anther development, with the encoded protein localizing to both mitochondria and the cytoplasm. Comparative transcriptomic analysis revealed differential expression of genes related to lipid metabolism between the wild type and the Osmtacp2-1 mutant in response to cold. Through a lipidomic analysis, we demonstrated that wax esters, which are the primary lipid components of the anther cuticle and pollen walls, function as cold-responsive lipids. Their levels increased dramatically in the wild type but not in Osmtacp2-1 when exposed to cold. Additionally, mutants of two cold-induced genes of wax ester biosynthesis, ECERIFERUM1 and WAX CRYSTAL-SPARSE LEAF2, showed decreased cold tolerance. These results suggest that OsMTACP2-mediated wax ester biosynthesis is essential for cold tolerance in rice at the booting stage.


Assuntos
Proteína de Transporte de Acila , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Pólen , Oryza/genética , Oryza/fisiologia , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pólen/genética , Pólen/metabolismo , Pólen/crescimento & desenvolvimento , Pólen/fisiologia , Proteína de Transporte de Acila/metabolismo , Proteína de Transporte de Acila/genética , Flores/genética , Flores/fisiologia , Flores/crescimento & desenvolvimento , Metabolismo dos Lipídeos/genética , Mutação/genética , Ceras/metabolismo
3.
Nature ; 573(7772): 83-86, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31485059

RESUMO

Quasars, which are exceptionally bright objects at the centres (or nuclei) of galaxies, are thought to be produced through the accretion of gas into disks surrounding supermassive black holes1-3. There is observational evidence at galactic and circumnuclear scales4 that gas flows inwards towards accretion disks around black holes, and such an inflow has been measured at the scale of the dusty torus that surrounds the central accretion disk5. At even smaller scales, inflows close to an accretion disk have been suggested to explain the results of recent modelling of the response of gaseous broad emission lines to continuum variations6,7. However, unambiguous observations of inflows that actually reach accretion disks have been elusive. Here we report the detection of redshifted broad absorption lines of hydrogen and helium atoms in a sample of quasars. The lines show broad ranges of Doppler velocities that extend continuously from zero to redshifts as high as about 5,000 kilometres per second. We interpret this as the inward motion of gases at velocities comparable to freefall speeds close to the black hole, constraining the fastest infalling gas to within 10,000 gravitational radii of the black hole (the gravitational radius being the gravitational constant multiplied by the object mass, divided by the speed of light squared). Extensive photoionization modelling yields a characteristic radial distance of the inflow of approximately 1,000 gravitational radii, possibly overlapping with the outer accretion disk.

4.
J Cell Biochem ; 125(4): e30541, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38372186

RESUMO

Epithelial cells (ECs) have been proposed to contribute to myofibroblasts or fibroblasts through epithelial-mesenchymal transition (EMT) during renal fibrosis. However, since EMT may occur dynamically, transiently, and reversibly during kidney fibrosis, conventional lineage tracing based on Cre-loxP recombination in renal ECs could hardly capture the transient EMT activity, yielding inconsistent results. Moreover, previous EMT research has primarily focused on renal proximal tubule ECs, with few reports of distal tubules and collecting ducts. Here, we generated dual recombinases-mediated genetic lineage tracing systems for continuous monitoring of transient mesenchymal gene expression in E-cadherin+ and EpCAM+ ECs of distal tubules and collecting ducts during renal fibrosis. Activation of key EMT-inducing transcription factor (EMT-TF) Zeb1 and mesenchymal markers αSMA, vimentin, and N-cadherin, were investigated following unilateral ureteral obstruction (UUO). Our data revealed that E-cadherin+ and EpCAM+ ECs did not transdifferentiate into myofibroblasts, nor transiently expressed these mesenchymal genes during renal fibrosis. In contrast, in vitro a large amount of cultured renal ECs upregulated mesenchymal genes in response to TGF-ß, a major inducer of EMT.


Assuntos
Transição Epitelial-Mesenquimal , Nefropatias , Humanos , Molécula de Adesão da Célula Epitelial/genética , Molécula de Adesão da Célula Epitelial/metabolismo , Fibrose , Nefropatias/metabolismo , Células Epiteliais/metabolismo , Caderinas/genética , Caderinas/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
5.
Small ; 20(7): e2306219, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37803926

RESUMO

Nanocontainers that can sense and respond to environmental stimuli like cells are desirable for next-generation delivery systems. However, it is still a grand challenge for synthetic nanocontainers to mimic or even surpass the shape adaption of cells, which may produce novel compartments for cargo loading. Here, this work reports the engineering of compartment network with a single polymer vesicle by unraveling osmotic stress-dependent deformation. Specifically, by manipulating the way in exerting the stress, sudden increase or gradual increase, polymer vesicles can either undergo deflation into the stomatocyte, a bowl-shaped vesicle enclosing a new compartment, or tubulation into the tubule of varied length. Such stress-dependent deformation inspired us to program the shape transformation of polymer vesicles, including tubulation, deflation, or first tubulation and then deflation. The coupled deformation successfully transforms the polymer vesicle into the stomatocyte with tubular arms and a network of two or three small stomatocytes connected by tubules. To the author's knowledge, these morphologies are still not accessed by synthetic nanocontainers. This work envisions that the network of stomatocytes may enable the loading of different catalysts to construct novel motile systems, and the well-defined morphology of vesicles helps to define the effect of morphology on cellar uptake.

6.
Ann Surg Oncol ; 31(6): 3887-3893, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38472675

RESUMO

BACKGROUND: The rise of artificial intelligence (AI) in medicine has revealed the potential of ChatGPT as a pivotal tool in medical diagnosis and treatment. This study assesses the efficacy of ChatGPT versions 3.5 and 4.0 in addressing renal cell carcinoma (RCC) clinical inquiries. Notably, fine-tuning and iterative optimization of the model corrected ChatGPT's limitations in this area. METHODS: In our study, 80 RCC-related clinical questions from urology experts were posed three times to both ChatGPT 3.5 and ChatGPT 4.0, seeking binary (yes/no) responses. We then statistically analyzed the answers. Finally, we fine-tuned the GPT-3.5 Turbo model using these questions, and assessed its training outcomes. RESULTS: We found that the average accuracy rates of answers provided by ChatGPT versions 3.5 and 4.0 were 67.08% and 77.50%, respectively. ChatGPT 4.0 outperformed ChatGPT 3.5, with a higher accuracy rate in responses (p < 0.05). By counting the number of correct responses to the 80 questions, we then found that although ChatGPT 4.0 performed better (p < 0.05), both versions were subject to instability in answering. Finally, by fine-tuning the GPT-3.5 Turbo model, we found that the correct rate of responses to these questions could be stabilized at 93.75%. Iterative optimization of the model can result in 100% response accuracy. CONCLUSION: We compared ChatGPT versions 3.5 and 4.0 in addressing clinical RCC questions, identifying their limitations. By applying the GPT-3.5 Turbo fine-tuned model iterative training method, we enhanced AI strategies in renal oncology. This approach is set to enhance ChatGPT's database and clinical guidance capabilities, optimizing AI in this field.


Assuntos
Inteligência Artificial , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Neoplasias Renais/patologia , Carcinoma de Células Renais/patologia , Prognóstico
7.
Opt Express ; 32(11): 19196-19209, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859059

RESUMO

We believe this to be a new superposition twisted Hermite-Gaussian Schell-model (STHGSM) beam hat is proposed. Analytic formulas for the intensity distribution and propagation factor of the STHGSM beam in non-Kolmogorov turbulence are derived by utilizing the generalized Huygens-Fresnel principle (HFP) and the Wigner function. The evolution characteristics of STHGSM beams propagating are numerically calculated and analyzed. Our findings indicate that the light intensity of the STHGSM beam gradually undergoes splitting and rotation around the axis during propagation through non-Kolmogorov turbulence, eventually evolving into a diagonal lobe shape at a certain distance of transmission. The anti-turbulence capability of the beam strengthens with higher beam order or twist factor values.

8.
Curr Microbiol ; 81(4): 107, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427056

RESUMO

Rhizospheric microbial community of emergent macrophytes plays an important role in nitrogen removal, especially in the eutrophic wetlands. The objective of this study was to identify the differences in anammox bacterial community composition among different emergent macrophytes and investigate revealed the the main factors affecting on the composition, diversity, and abundance of anammox bacterial community. Results showed that the composition, diversity, and abundance of the anammox community were significantly different between the vegetated sediments of three emergent macrophytes and unvegetated sediment. The composition of the anammox bacterial community was different in the vegetated sediments of different emergent macrophytes. Also, the abundance of nitrogen cycle-related functional genes in the vegetated sediments was found to be higher than that in the unvegetated sediment. Canonical correspondence analysis (CCA) and structural equation models analysis (SEM) showed that salinity and pH were the main environmental factors influencing the composition and diversity of the anammox bacterial community and NO2--N indirectly affected anammox bacterial community diversity by affecting TOC. nirK-type denitrifying bacteria abundance had significant effects on the bacterial community composition, diversity, and abundance of anammox bacteria. The community composition of anammox bacteria varies with emergent macrophyte species. The rhizosphere of emergent macrophytes provides a favorable environment and promotes the growth of nitrogen cycling-related microorganisms that likely accelerate nitrogen removal in eutrophic wetlands.


Assuntos
Rizosfera , Áreas Alagadas , Oxidação Anaeróbia da Amônia , Lagos/microbiologia , Bactérias/genética , Ciclo do Nitrogênio , Nitrogênio , Oxirredução , Sedimentos Geológicos/microbiologia
9.
Bull Entomol Res ; 114(1): 57-66, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38180086

RESUMO

The coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae), is a major destructive insect pest of coffee, which impacts the coffee crops negatively. As a draft genome has been completed for this insect, most molecular studies on gene transcriptional levels under different experimental conditions will be conducted using real-time reverse-transcription quantitative polymerase chain reactions (RT-qPCR). However, the lack of suitable internal reference genes will affect the accuracy of RT-qPCR results. In this study, the expression stability of nine candidate reference genes was evaluated under different developmental stages, temperature stress, and Beauveria bassiana infection. Data analyses were completed by four commonly used programs, BestKeeper, NormFinder, geNorm, and RefFinder. The result showed that RPL3 and EF1α combination were recommended as the most stable reference genes for developmental stages. EF1α and RPS3a combination were the top two stable reference genes for B. bassiana infection. RPS3a and RPL3 combination performed as the optimal reference genes both in temperature stress and all samples. Our results should provide a good foundation for the expression profile analyses of target genes in the future, especially for molecular studies on insect genetic development, temperature adaptability, and immune mechanism to entomogenous fungi in H. hampei.


Assuntos
Beauveria , Coffea , Besouros , Gorgulhos , Animais , Coffea/genética , Temperatura
10.
Int J Neurosci ; : 1-13, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38315119

RESUMO

BACKGROUND: As a traditional medical therapy, electroacupuncture (EA) has been demonstrated to have beneficial effects on ischemic stroke-induced cognitive impairment. However, the underlying mechanism is largely unclear. METHODS: Adult rats received occlusion of the middle cerebral artery and reperfusion (MCAO/R) to establish the ischemic stroke model. Morris water maze test was performed following EA stimulation at the GV20, PC6, and KI1 acupoints in rats to test the learning and memory ability. Western blot, immunofluorescent staining, and enzyme-linked immunosorbent assay were conducted to assess the cellular and molecular mechanisms. RESULTS: EA stimulation attenuated neurological deficits. In the Morris water maze test, EA treatment ameliorated the MCAO/R-induced learning and memory impairment. Moreover, we observed that MCAO/R induced microglial activation and polarization in the ischemic hippocampus, whereas, EA treatment dampened microglial activation and inhibited M1 microglial polarization but enhanced M2 microglial polarization. EA treatment inhibited the increased expression of proinflammatory cytokines and enhanced the increased expression of anti-inflammatory cytokines. Finally, we found that EA treatment dampened microglial p38 mitogen-activated protein kinase (MAPK) phosphorylation. CONCLUSION: Collectively, our data suggested that EA treatment ameliorated cognitive impairment induced by MCAO/R and the underlying mechanism may be p38-mediated microglia polarization and neuroinflammation.

11.
Genomics ; 115(5): 110690, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37488054

RESUMO

Infection of Taenia pisiformis cysticercus is very frequently found in lagomorphs and causes serious economic losses to rabbit breeding industry. T. pisiformis cysticercus has evolved numerous strategies to manipulate their hosts. The release of exosomes is of importance in the interaction between host and parasite. However, the mechanism by which T. pisiformis cysticercus evades the host immune system for long-term survival within the host remains unclear. Using small RNA sequencing and TMT labelling proteomic, we profiled the expression patterns of miRNAs and proteins in rabbit peritoneal macrophages treated with T. pisiformis cysticercus exosomes. Seven differentially expressed (DE)-miRNAs and six DE-proteins were randomly selected to validate the accuracy of the sequencing data by qRT-PCR or western blot. Functions of DE-miRNAs and proteins were analyzed using public data bases. And DE-miRNAs-DE-proteins correlation network were established. CCK-8 assay was used to evaluate the effect of exosomes on macrophages proliferation. Cell cycle of macrophages, isolated from T. pisiformis-infected rabbits, was determined using flow cytometry. A total of 21 miRNAs were significantly differentially expressed, including three worm-derived miRNAs. The expressions of miRNAs and proteins were consistent with the sequencing results. DE-miRNAs targets were related to cell proliferation and apoptosis. Exosomes treatment resulted in a decrease of macrophages proliferation. In vivo, T. pisiformis cysticercus significantly induced S phase cell arrest. Moreover, DE-proteins were related to production of interferon-gamma and interleukin-12, and immunoregulation. Correlation network analysis revealed a negative correlation relationship between DE-miRNAs and DE-proteins. Among them, novel334 and tpi-let-7-5p have potential regulatory effects on IL1ß and NFκB2 respectively, which imply that novel334-IL1ß/tpi-let-7-5p-NFκB2 axis may be an important way that T. pisiformis cysticercus modulates host immune response through exosomes. Further understanding of these potential regulatory mechanisms will contribute to clarify the mechanism of escape mediated by T. pisiformis exosomes.


Assuntos
Exossomos , MicroRNAs , Taenia , Animais , Coelhos , Cysticercus/genética , Taenia/genética , MicroRNAs/genética , Macrófagos Peritoneais , Exossomos/genética , Proteômica
12.
J Biol Chem ; 298(6): 101965, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35461809

RESUMO

Genetic technology using site-specific recombinases, such as the Cre-loxP system, has been widely employed for labeling specific cell populations and for studying their functions in vivo. To enhance the precision of cell lineage tracing and functional study, a similar site-specific recombinase system termed Dre-rox has been recently used in combination with Cre-loxP. To enable more specific cell lineage tracing and ablation through dual recombinase activity, we generated two mouse lines that render Dre- or Dre+Cre-mediated recombination to excise a stop codon sequence that prevents the expression of diphtheria toxin receptor (DTR) knocked into the ubiquitously expressed and safe Rosa26 locus. Using different Dre- and Cre-expressing mouse lines, we showed that the surrogate gene reporters tdTomato and DTR were simultaneously expressed in target cells and in their descendants, and we observed efficient ablation of tdTomato+ cells after diphtheria toxin administration. These mouse lines were used to simultaneously trace and deplete the target cells of interest through the inducible expression of a reporter and DTR using dual Cre and Dre recombinases, allowing a more precise and efficient study of the role of specific cell subsets within a heterogeneous population in pathophysiological conditions in vivo.


Assuntos
Linhagem da Célula , Integrases , Recombinases , Animais , Integrases/genética , Integrases/metabolismo , Camundongos , Camundongos Transgênicos , Recombinases/genética , Recombinases/metabolismo , Recombinação Genética
13.
J Am Chem Soc ; 145(28): 15496-15506, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37427769

RESUMO

The field of supramolecular chemistry has witnessed tremendous progress in bringing the system away from equilibrium for traditionally inaccessible structures and functions. Vesicular assemblies with complex energy landscapes and pathways, which are reminiscent of diverse cellular vesicles like exosomes, remain exceedingly rare. Here, relying on the activation of oligo(ethylene glycol) (OEG) interdigitation and the encoded conformational freedom in monodisperse Janus dendrimers, we reveal a rich landscape and a pathway selection of distinct vesicles. The interdigitation can be selectively switched on and off using temperature ramps, and the critical temperatures can be further determined by molecular design. Our findings suggest that synthetic vesicles, with different energy states and unexpected transition pathways, emulate dynamic cellular vesicles in nature. We anticipate that vesicles with an activated OEG corona conformation will open new routes for nanomedicine and advanced materials.

14.
J Am Chem Soc ; 145(19): 10458-10462, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37074689

RESUMO

An adaptive surface that can sense and respond to environmental stimuli is integral to smart functional materials. Here, we report pH-responsive anchoring systems onto the poly(ethylene glycol) (PEG) corona of polymer vesicles. The hydrophobic anchor, pyrene, is reversibly inserted into the PEG corona through the reversible protonation of its covalently linked pH-sensing group. Depending on the pKa of the sensor, the pH-responsive region is engineered from acidic to neutral and basic conditions. The switchable electrostatic repulsion between the sensors contributes to the responsive anchoring behavior. Our findings provide a new responsive binding chemistry for the creation of smart nanomedicine and a nanoreactor.

15.
Oncologist ; 28(10): e859-e866, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37218076

RESUMO

BACKGROUND: Antibody-drug conjugates (ADCs) have been the preferred regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after trastuzumab. Unfortunately, there is little data showing which ADCs should be chosen for those patients whose treatment with tyrosine kinase inhibitors (TKIs) failed. This study aims to analyze the efficacy and safety between novel anti-HER2 ADCs and trastuzumab emtansine (T-DM1) for those with TKIs failure. MATERIALS AND METHODS: HER2-positive MBC using ADCs from January 2013 to June 2022 were included, and all of them were treated with TKIs. The primary study endpoint was progression-free survival (PFS), and the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety. RESULTS: A total of 144 patients with 73 patients in the novel anti-HER2 ADCs group and 71 patients in the T-DM1 group. In these novel ADCs, 30 patients received trastuzumab deruxtecan (T-Dxd), 43 patients receive other novel ADCs. The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1. The most common grades 3-4 adverse events in the novel anti-HER-2 ADCs group were neutropenia (20.5%) and thrombocytopenia (28.1%) in the T-DM1 group. CONCLUSIONS: In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.


Assuntos
Antineoplásicos , Neoplasias da Mama , Imunoconjugados , Feminino , Humanos , Ado-Trastuzumab Emtansina/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Imunoconjugados/uso terapêutico , Receptor ErbB-2/metabolismo , Trastuzumab/efeitos adversos , Trastuzumab/uso terapêutico , /uso terapêutico
16.
Anal Chem ; 95(6): 3468-3475, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36725367

RESUMO

Circulating tumor cells (CTCs) have emerged as promising circulating biomarkers for non-invasive cancer diagnosis and management. Isolation and detection of CTCs in clinical samples are challenging due to the extreme rarity and high heterogeneity of CTCs. Here, we describe a poly(ethylene oxide) (PEO) concentration gradient-based microfluidic method for rapid, label-free, highly efficient isolation of CTCs directly from whole blood samples. Stable concentration gradients of PEO were formed within the microchannel by co-injecting the side fluid (blood sample spiked with 0.025% PEO) and center fluid (0.075% PEO solution). The competition between the elastic lift force and the inertial lift force enabled size-based separation of large CTCs and small blood cells based on their distinct migration patterns. The microfluidic device could process 1 mL of blood sample in 30 min, with a separation efficiency of >90% and an enrichment ratio of >700 for tumor cells. The isolated CTCs from blood samples were enumerated by immunofluorescence staining, allowing for discrimination of breast cancer patients from healthy donors with an accuracy of 84.2%. The concentration gradient-based microfluidic separation provides a powerful tool for label-free isolation of CTCs for a wide range of clinical applications.


Assuntos
Neoplasias da Mama , Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes , Humanos , Feminino , Microfluídica , Óxido de Etileno , Separação Celular/métodos , Células Neoplásicas Circulantes/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral
17.
Biochem Biophys Res Commun ; 659: 10-19, 2023 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-37030020

RESUMO

The activating receptor natural killer group 2D (NKG2D) expressed by Natural killer (NK) cells functions as a "master-switch" in governing the awakening status of NK cells. The NKG2D-mediated cytotoxicity has been declared to be related with the expression levels of NKG2D ligands (NKG2DLs) expressed on tumor cells. Therefore, selective induction of NKG2DLs could be a reliable approach to enhance the efficacy of NK cell-mediated immunotherapy. Our existing study demonstrated that Ciclopirox Olamine (CPX), an off-patent antifungal agent, effectively elevated the expression of NKG2DLs on leukemia cells and sensitized leukemia cells to NK-cell mediated cytolysis. Induction of ROS production and AKT phosphorylation by CPX is essential for the up-regulation of NKG2DLs expressions. Inhibition of AKT by using AKT inhibitor MK2206 decreased both NKG2DLs expressions and NK cell cytotoxicity. These data indicated that increased sensitivity of CPX-treated leukemia cells to NK cell cytolysis was attributed to higher NKG2DLs expressions, resulting from activated AKT signaling pathway. Our findings support the ongoing development of CPX as an anti-tumor agent and suggest its promising immunotherapeutic value in the medication of leukemia.


Assuntos
Leucemia , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ciclopirox/farmacologia , Ciclopirox/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Células Matadoras Naturais/metabolismo , Transdução de Sinais , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Linhagem Celular Tumoral
18.
Langmuir ; 39(47): 16750-16759, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37963300

RESUMO

Low-molecular-weight peptide hydrogels can be formed by self-assembly through weak interactions, but the application of the hydrogel is influenced by its weak mechanical properties. Therefore, it is important to construct low-molecular-weight peptide hydrogels with excellent mechanical properties. In this work, we designed the pentapeptide molecule Fmoc-FFCKK-OH (abbreviated as FFCKK) with a sulfhydryl group, and another low-molecular-weight cross-linker N,N'-methylenebis(acrylamide) (MBA) was introduced to construct a hydrogel with excellent mechanical properties. The secondary structure change process of FFCKK and the assembly mechanism of hydrogel were analyzed using theoretical calculations and experimental characterizations. The occurrence of thiol-ene click chemistry provides covalent interaction in the hydrogel, and the synergistic effect ofcovalent interaction and hydrogen bonding improves the mechanical properties of the hydrogel by nearly 10-fold. The hydrogel was observed to be able to withstand a stress of 368 Pa and to break in a layer-by-layer manner by compression testing. The micromechanics of the hydrogels were characterized, and the excellent mechanical properties of the hydrogels were confirmed. The synergistic approach provides a new idea for the preparation of low-molecular-weight peptide hydrogels and facilitates the expansion of their potential applications in biomedical fields.


Assuntos
Química Click , Hidrogéis , Hidrogéis/química , Compostos de Sulfidrila/química , Peptídeos/química
19.
BMC Neurol ; 23(1): 136, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37003976

RESUMO

BACKGROUND: Seeking positive and comprehensive rehabilitation methods after stroke is an urgent problem to be solved, which is very important to improve the dysfunction of stroke. The aim of this study was to investigate the effects of motor imagery-based brain-computer interface training (MI-BCI) on upper limb function and attention in stroke patients with hemiplegia. METHODS: Sixty stroke patients with impairment of upper extremity function and decreased attention were randomly assigned to the control group (CR group) or the experimental group (BCI group) in a 1:1 ratio. Patients in the CR group received conventional rehabilitation. Patients in the BCI group received 20 min of MI-BCI training five times a week for 3 weeks (15 sessions) in addition to conventional rehabilitation. The primary outcome measures were the changes in Fugl-Meyer Motor Function Assessment of Upper Extremities (FMA-UE) and Attention Network Test (ANT) from baseline to 3 weeks. RESULTS: About 93% of the patients completed the allocated training. Compared with the CR group, among those in the BCI group, FMA-UE was increased by 8.0 points (95%CI, 5.0 to 10.0; P < 0.001). Alert network response time (32.4ms; 95%CI, 58.4 to 85.6; P < 0.001), orienting network response (5.6ms; 95%CI, 29.8 to 55.8; P = 0.010), and corrects number (8.0; 95%CI, 17.0 to 28.0; P < 0.001) also increased in the BCI group compared with the CR group. Additionally, the executive control network response time (- 105.9ms; 95%CI, - 68.3 to - 23.6; P = 0.002), the total average response time (- 244.8ms; 95%CI, - 155.8 to - 66.2; P = 0.002), and total time (- 122.0ms; 95%CI, - 80.0 to - 35.0; P = 0.001) were reduced in the BCI group compared with the CR group. CONCLUSION: MI-BCI combined with conventional rehabilitation training could better enhance upper limb motor function and attention in stroke patients. This training method may be feasible and suitable for individuals with stroke. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry with Portal Number ChiCTR2100050430(27/08/2021).


Assuntos
Interfaces Cérebro-Computador , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Hemiplegia/etiologia , Recuperação de Função Fisiológica/fisiologia , Eletroencefalografia/métodos , Acidente Vascular Cerebral/complicações , Extremidade Superior
20.
Nanotechnology ; 34(31)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37137299

RESUMO

Graphene composites possess great application potential in various fields including flexible electrodes, wearable sensors and biomedical devices owing to their excellent mechanical and electrical properties. However, it remains challenging to fabricate graphene composites-based devices with high consistency due to the gradual aggression effect of graphene during fabrication process. Herein, we propose a method for one-step fabricating graphene/polymer composite-based devices from graphite/polymer solution by using electrohydrodynamic (EHD) printing with the Weissenberg effect (EPWE). Taylor-Couette flows with high shearing speed were generated to exfoliate high-quality graphene with a rotating steel microneedle coaxially set in a spinneret tube. The effects of the rotating speed of the needle, spinneret size and precursor ingredients on the graphene concentration were discussed. As a proof of concept, EPWE was used to successfully fabricate graphene/polycaprolactone (PCL) bio-scaffolds with good biocompatibility and graphene/thermoplastic polyurethane strain sensor for detecting human motions with a maximum gauge factor more than 2400 from 40% to 50% strain. As such, this method sheds a new light on one-stepin situfabrication of graphene/polymer composite-based devices from graphite solution with low cost.

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