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1.
J Control Release ; 372: 95-112, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38851536

RESUMO

Glioma is an aggressive malignant brain tumor with a very poor prognosis for survival. The poor tumor targeting efficiency and tumor microenvironment penetration barrier also as troubles inhibited the effective glioma chemotherapy. Here, we design a core-shell structure cascade amplified hybrid catalytic nanopotentiators CFpAD with DM1 encapsulated to overcome the glioma therapeutic obstacles. NIR laser-based BBB penetrating enhances the tumor accumulation of CFpAD. When CFpAD, as the cascade amplified drug, is treated on the cancer cells, the bomb-like CFpAD releases gold nanoparticles as glucose oxidase (GOx) and ferric oxide nanoparticles (FNPs) as peroxides (POx) after blasting, producing ROS via a cascade amplification for tumor cell apoptosis. Gold nanoparticles can rest CAFs and reduce ECM secretion, achieving deep penetration of CFpAD. Moreover, CFpAD also cuts off the nutritional supply of the tumor, reduces the pH value, and releases free radicals to destroy the cancer. The glioma cell viability was significantly decreased through DNA damage and ROS aggregation due to the DM1-based chemotherapy synergistically combined with interventional photothermal therapy (IPTT) and radiotherapy (RT). This domino cascade amplified loop, combined with starvation therapy with IPTT and RT, has good tumor penetration and outstanding antitumor efficacy, and is a promising glioma treatment system.

2.
J Extracell Vesicles ; 13(6): e12466, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38887165

RESUMO

Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.


Assuntos
Vesículas Extracelulares , Fígado , Humanos , Vesículas Extracelulares/metabolismo , Fígado/metabolismo , Microbioma Gastrointestinal , Animais , Trato Gastrointestinal/metabolismo , Alimentos
3.
ACS Nano ; 18(23): 15249-15260, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38818704

RESUMO

Bimetallic iron-noble metal alloy nanoparticles have emerged as promising contrast agents for magnetic resonance imaging (MRI) due to their biocompatibility and facile control over the element distribution. However, the inherent surface energy discrepancy between iron and noble metal often leads to Fe atom segregation within the nanoparticle, resulting in limited iron-water molecule interactions and, consequently, diminished relaxometric performance. In this study, we present the development of a class of ligand-induced atomically segregation-tunable alloy nanoprobes (STAN) composed of bimetallic iron-gold nanoparticles. By manipulating the oxidation state of Fe on the particle surface through varying molar ratios of oleic acid and oleylamine ligands, we successfully achieve surface Fe enrichment. Under the application of a 9 T MRI system, the optimized STAN formulation, characterized by a surface Fe content of 60.1 at %, exhibits an impressive r1 value of 2.28 mM-1·s-1, along with a low r2/r1 ratio of 6.2. This exceptional performance allows for the clear visualization of hepatic tumors as small as 0.7 mm in diameter in vivo, highlighting the immense potential of STAN as a next-generation contrast agent for highly sensitive MR imaging.


Assuntos
Ligas , Meios de Contraste , Ouro , Imageamento por Ressonância Magnética , Nanopartículas Metálicas , Ligas/química , Ligantes , Ouro/química , Animais , Meios de Contraste/química , Nanopartículas Metálicas/química , Humanos , Camundongos , Ferro/química , Propriedades de Superfície , Tamanho da Partícula , Neoplasias Hepáticas/diagnóstico por imagem , Ácido Oleico/química
4.
Nano Lett ; 24(22): 6696-6705, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38796774

RESUMO

Ultra-high-field (UHF) magnetic resonance imaging (MRI) stands as a pivotal cornerstone in biomedical imaging, yet the challenge of false imaging persists, constraining its full potential. Despite the development of dual-mode contrast agents improving conventional MRI, their effectiveness in UHF remains suboptimal due to the high magnetic moment, resulting in diminished T1 relaxivity and excessively enhanced T2 relaxivity. Herein, we report a DNA-mediated magnetic-dimer assembly (DMA) of iron oxide nanoparticles that harnesses UHF-tailored nanomagnetism for fault-free UHF-MRI. DMA exhibits a dually enhanced longitudinal relaxivity of 4.42 mM-1·s-1 and transverse relaxivity of 26.23 mM-1·s-1 at 9 T, demonstrating a typical T1-T2 dual-mode UHF-MRI contrast agent. Importantly, DMA leverages T1-T2 dual-modality image fusion to achieve artifact-free breast cancer visualization, effectively filtering interference from hundred-micrometer-level false-positive signals with unprecedented precision. The UHF-tailored T1-T2 dual-mode DMA contrast agents hold promise for elevating the accuracy of MR imaging in disease diagnosis.


Assuntos
Meios de Contraste , DNA , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Meios de Contraste/química , Humanos , DNA/química , Camundongos , Nanopartículas Magnéticas de Óxido de Ferro/química , Feminino , Animais , Neoplasias da Mama/diagnóstico por imagem , Nanopartículas de Magnetita/química , Linhagem Celular Tumoral
5.
Adv Mater ; : e2401538, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738793

RESUMO

The identification of metastasis "seeds," isolated tumor cells (ITCs), is of paramount importance for the prognosis and tailored treatment of metastatic diseases. The conventional approach to clinical ITCs diagnosis through invasive biopsies is encumbered by the inherent risks of overdiagnosis and overtreatment. This underscores the pressing need for noninvasive ITCs detection methods that provide histopathological-level insights. Recent advancements in ultra-high-field (UHF) magnetic resonance imaging (MRI) have ignited hope for the revelation of minute lesions, including the elusive ITCs. Nevertheless, currently available MRI contrast agents are susceptible to magnetization-induced strong T2-decaying effects under UHF conditions, which compromises T1 MRI capability and further impedes the precise imaging of small lesions. Herein, this study reports a structural defect-enabled magnetic neutrality nanoprobe (MNN) distinguished by its paramagnetic properties featuring an exceptionally low magnetic susceptibility through atomic modulation, rendering it almost nonmagnetic. This unique characteristic effectively mitigates T2-decaying effect while concurrently enhancing UHF T1 contrast. Under 9 T MRI, the MNN demonstrates an unprecedentedly low r2/r1 value (≈1.06), enabling noninvasive visualization of ITCs with an exceptional detection threshold of ≈0.16 mm. These high-performance MNNs unveil the domain of hitherto undetectable minute lesions, representing a significant advancement in UHF-MRI for diagnostic purposes and fostering comprehensive metastasis research.

6.
Adv Sci (Weinh) ; 11(24): e2306671, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38639383

RESUMO

Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy-saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide-induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.


Assuntos
Carcinoma Hepatocelular , Dipeptídeos , Neoplasias Hepáticas , Transportador 1 de Peptídeos , Transdução de Sinais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Dipeptídeos/metabolismo , Dipeptídeos/farmacologia , Camundongos , Transdução de Sinais/genética , Transportador 1 de Peptídeos/metabolismo , Transportador 1 de Peptídeos/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Metástase Neoplásica , Masculino , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Movimento Celular/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Camundongos Nus
8.
J Orthop Surg Res ; 19(1): 155, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429720

RESUMO

BACKGROUND: Sports-related ACL (anterior cruciate ligament) injuries are frequent. Successful management requires early diagnosis and treatment. One of the clinical tests used to identify ACL damage is the lever sign test. This meta-analysis aimed to assess the lever sign test's diagnostic efficacy for ACL injuries. METHODS: An extensive investigation of the Cochrane Library, Embase, and PubMed databases was conducted until April 2023. Studies assessing the lever sign test's diagnostic efficacy for ACL injuries were also included. A bivariate random-effects model was employed to acquire the pooled estimates of diagnostic odds ratios, specificity, positive and negative likelihood ratios, sensitivity, and curves of the summary receiver operating characteristic (SROC). RESULTS: The meta-analysis comprised twelve investigations with a total of 1365 individuals. The lever sign test's combined sensitivity and specificity for the purpose of diagnosing injuries to the ACL were 0.810 (95% confidence interval [CI] 0.686-0.893) and 0.784 (95% CI 0.583-0.904), respectively. The positive and negative likelihood ratios were 3.148 (95% CI 1.784-5.553) and 0.210 (95% CI 0.084-0.528), respectively. The study revealed a diagnostic odds ratio of 17.656, with a 95% CI ranging from 4.800 to 64.951. The SROC curve's area was determined to be 0.912 (95% CI 0.857-0.967). CONCLUSION: With high specificity and sensitivity, the lever sign test is a reliable diagnostic modality for ACL injuries. However, the test should be used in combination with other diagnostic tests to increase the accuracy of the diagnosis. Further investigations are warranted to assess the clinical practicability of the lever sign test in various populations and settings.


Assuntos
Lesões do Ligamento Cruzado Anterior , Humanos , Lesões do Ligamento Cruzado Anterior/diagnóstico , Ligamento Cruzado Anterior , Sensibilidade e Especificidade , Curva ROC , Bases de Dados Factuais
9.
Adv Sci (Weinh) ; 11(18): e2309748, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460157

RESUMO

Pulmonary delivery of therapeutic agents has been considered the desirable administration route for local lung disease treatment. As the latest generation of therapeutic agents, nucleic acid has been gradually developed as gene therapy for local diseases such as asthma, chronic obstructive pulmonary diseases, and lung fibrosis. The features of nucleic acid, specific physiological structure, and pathophysiological barriers of the respiratory tract have strongly affected the delivery efficiency and pulmonary bioavailability of nucleic acid, directly related to the treatment outcomes. The development of pharmaceutics and material science provides the potential for highly effective pulmonary medicine delivery. In this review, the key factors and barriers are first introduced that affect the pulmonary delivery and bioavailability of nucleic acids. The advanced inhaled materials for nucleic acid delivery are further summarized. The recent progress of platform designs for improving the pulmonary delivery efficiency of nucleic acids and their therapeutic outcomes have been systematically analyzed, with the application and the perspectives of advanced vectors for pulmonary gene delivery.


Assuntos
Terapia Genética , Ácidos Nucleicos , Humanos , Ácidos Nucleicos/administração & dosagem , Terapia Genética/métodos , Transfecção/métodos , Administração por Inalação , Pneumopatias/terapia , Pneumopatias/genética , Técnicas de Transferência de Genes , Pulmão/metabolismo , Animais
10.
Nano Lett ; 24(13): 3851-3857, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38502010

RESUMO

A two-dimensional (2D) quantum electron system is characterized by quantized energy levels, or subbands, in the out-of-plane direction. Populating higher subbands and controlling the intersubband transitions have wide technological applications such as optical modulators and quantum cascade lasers. In conventional materials, however, the tunability of intersubband spacing is limited. Here we demonstrate electrostatic population and characterization of the second subband in few-layer InSe quantum wells, with giant tunability of its energy, population, and spin-orbit coupling strength, via the control of not only layer thickness but also the out-of-plane displacement field. A modulation of as much as 350% or over 250 meV is achievable, underscoring the promise of InSe for tunable infrared and THz sources, detectors, and modulators.

11.
Acta Pharm Sin B ; 14(3): 1132-1149, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38486992

RESUMO

Cancer, a complex and heterogeneous disease, arises from genomic instability. Currently, DNA damage-based cancer treatments, including radiotherapy and chemotherapy, are employed in clinical practice. However, the efficacy and safety of these therapies are constrained by various factors, limiting their ability to meet current clinical demands. Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy. Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms. In this review, we delve into the design principles and optimization strategies of metal nanoparticles. We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles. These encompass targeted drug delivery, inhibition of DNA repair mechanisms, induction of cell death, and the cascading immune response. Moreover, we explore the pivotal role of physicochemical factors such as nanoparticle size, stimuli-responsiveness, and surface modification in shaping metal nanoparticle platforms. Finally, we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy, paving the way for novel treatment paradigms.

12.
Electrophoresis ; 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308502

RESUMO

Active electric-driven droplet manipulation in digital microfluidics constitutes a promising domain owing to the unique and programmable wettability inherent in sessile ionic droplets. The coupling between the electric field and flow field enables precise control over wetting characteristics and droplet morphology. This study delves into the deformation phenomena of ionic sessile ferrofluid droplets in ambient air induced by uniform electric fields. Under the assumption of a pinned mode throughout the process, the deformation is characterized by variations in droplet height and contact angle in response to the applied electric field intensity. A numerical model is formulated to simulate the deformation dynamics of ferrofluid droplets, employing the phase field method for tracking droplet deformation. The fidelity of the numerical outcomes is assessed through the validation process, involving a comparison of droplet geometric deformations with corresponding experimental results. The impact of the electric field on the deformation of dielectric droplets is modulated by parameters such as electric field strength and droplet size. Through meticulously designed experiments, the substantial influence of both field strength and droplet size is empirically verified, elucidating the behavior of ionic sessile droplets. Considering the interplay of electric force, viscous force, and interfacial tension, the heightened field intensity is observed to effectively reduce the contact angle, augment droplet height, and intensify internal droplet flow. Under varying electric field conditions, droplets assume diverse shapes, presenting a versatile approach for microfluidic operations. The outcomes of this research hold significant guiding implications for microfluidic manipulation, droplet handling, and sensing applications.

13.
Nat Commun ; 15(1): 460, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212655

RESUMO

Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Furina , Fototerapia , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Nanopartículas/química , Catálise , Cobre/química
14.
Angew Chem Int Ed Engl ; 63(10): e202318948, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38212253

RESUMO

Ultra-high field (UHF) magnetic resonance imaging (MRI) has emerged as a focal point of interest in the field of cancer diagnosis. Despite the ability of current paramagnetic or superparamagnetic smart MRI contrast agents to selectively enhance tumor signals in low-field MRI, their effectiveness at UHF remains inadequate due to inherent magnetism. Here, we report a ligand-mediated magnetism-conversion nanoprobe (MCNP) composed of 3-mercaptopropionic acid ligand-coated silver-gadolinium bimetallic nanoparticles. The MCNP exhibits a pH-dependent magnetism conversion from ferromagnetism to diamagnetism, facilitating tunable nanomagnetism for pH-activatable UHF MRI. Under neutral pH, the thiolate (-S- ) ligands lead to short τ'm and increased magnetization of the MCNPs. Conversely, in the acidic tumor microenvironment, the thiolate ligands are protonated and transform into thiol (-SH) ligands, resulting in prolonged τ'm and decreased magnetization of the MCNP, thereby enhancing longitudinal relaxivity (r1) values at UHF MRI. Notably, under a 9 T MRI field, the pH-sensitive changes in Ag-S binding affinity of the MCNP lead to a remarkable (>10-fold) r1 increase in an acidic medium (pH 5.0). In vivo studies demonstrate the capability of MCNPs to amplify MRI signal of hepatic tumors, suggesting their potential as a next-generation UHF-tailored smart MRI contrast agent.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias , Humanos , Ligantes , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Concentração de Íons de Hidrogênio , Microambiente Tumoral
15.
Clin Transl Med ; 14(1): e1521, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38279895

RESUMO

BACKGROUND: One-carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune-related adverse events in patients. METHODS: We collected numerous literatures to explain the roles of one-carbon metabolism in cancer immunotherapy. RESULTS: In this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future. CONCLUSION: Targeting one-carbon metabolism is useful for cancer immunotherapy.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Redes e Vias Metabólicas , Carbono/metabolismo , Carbono/uso terapêutico
16.
Environ Int ; 183: 108389, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38118213

RESUMO

Herein, the trapping effectiveness of N95, filter KN95, medical surgical masks (MSMs), and disposable medical masks (DMMs) against 19 airborne traditional and novel organophosphate esters (OPEs) was evaluated. Laboratory simulations (n = 24 for each type of mask) showed that time-dependent accumulation of ∑19OPEs on the four types of masks ranged between 30.1 and 86.6 ng in 24 h, with the highest and lowest median amounts trapped by the N95 masks (53.3 ng) and DMMs (43.2 ng), respectively. The trapping efficiency of the four types of masks for ∑19OPEs decreased over time from 84 % to 39 % in 24 h, with N95 masks showing the highest median efficiency (70 %). Further, field investigations were conducted in five types of microenvironments (train, hospital, bus, supermarket, and canteen), and an analysis of 200 samples showed that ∑19OPEs were accumulated in the masks with a variable amount from 3.7 to 117 ng/mask. Consistent with the laboratory simulations, the N95 masks (29.0 ng/mask) exhibited the highest hourly median amount of trapped OPEs, followed by the KN95 masks (24.5 ng/mask), MSMSs (17.4 ng/mask), and DMMs (15.8 ng/mask). Triethyl phosphate (TEP), tris(1-chloro-2-propyl) phosphate (TCIPP), tri-n-butyl phosphate (TNBP), and cresyl diphenyl phosphate (CDP) as well as 4-isopropylphenyl diphenyl phosphate (4IPPDPP) and 2,4-diisopropylphenyl diphenyl phosphate (24DIPPDPP) were the most commonly detected traditional and novel OPEs. Based on the amount of OPEs trapped on the masks, we estimated the concentration of ∑19OPEs in the train microenvironment to be the highest (222 ng/m3), which is approximately 2-5 times higher than that in the other microenvironments. The results of this study prove that masks can effectively protect humans from exposure to OPEs and act as low-cost indicators of indoor contamination.


Assuntos
Compostos de Bifenilo , Retardadores de Chama , Máscaras , Humanos , Retardadores de Chama/análise , Ésteres/análise , Organofosfatos/análise , Fosfatos/análise , Monitoramento Ambiental , China
17.
Adv Mater ; 36(13): e2310404, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38149464

RESUMO

The alpha-synuclein (α-syn) oligomers hold a central role in the pathology of Parkinson's disease (PD). Achieving accurate detection of α-syn oligomers in vivo presents a promising avenue for early and accurate diagnosis of PD. Magnetic resonance imaging (MRI), with non-invasion and exceptional tissue penetration, offers a potent tool for visualizing α-syn oligomers in vivo. Nonetheless, ensuring diagnostic specificity remains a formidable challenge. Herein, a novel MRI probe (ASOSN) is introduced, which encompasses highly sensitive antiferromagnetic nanoparticles functionalized with single-chain fragment variable antibodies, endowing it with the capacity for discerning recognition and binding to α-syn oligomers and triggering a switchable T1-T2 MRI signal. Significantly, ASOSN possesses the unique capability to accurately discriminate α-syn oligomers from neuroinflammation in vivo. Moreover, ASOSN facilitates the non-invasive and precise visualizing of endogenous α-syn oligomers in living systems. This innovative design heralds the development of a non-invasive visualization strategy for α-syn oligomers, marking a pivotal advancement for early and accurate diagnosis of PD.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , alfa-Sinucleína/metabolismo
18.
Pharmacol Ther ; 250: 108527, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37703952

RESUMO

Medulloblastoma (MB) is a major pediatric malignant brain tumor that arises in the cerebellum. MB tumors exhibit highly heterogeneous driven by diverse genetic alterations and could be divided into four major subgroups based on their different biological drivers and molecular features (Wnt, Sonic hedgehog (Shh), group 3, and group 4 MB). Even though the therapeutic strategies for each MB subtype integrate their pathogenesis and were developed to focus on their specific target sites, the unexpected drug non-selective cytotoxicity, low drug accumulation in the brain, and complexed MB tumor microenvironment still be huge obstacles to achieving satisfied MB therapeutic efficiency. This review discussed the current advances in modern MB therapeutic strategy development. Through the recent advances in knowledge of the origin, molecular pathogenesis of MB subtypes and their current therapeutic barriers, we particularly reviewed the current development in advanced MB therapeutic strategy committed to overcome MB treatment obstacles, focusing on novel signaling pathway targeted therapeutic agents and their combination discovery, advanced drug delivery systems design, and MB immunotherapy strategy development.

19.
Plant Physiol ; 193(4): 2430-2441, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37590954

RESUMO

Endosperm cell number is critical in determining grain size in maize (Zea mays). Here, zma-miR159 overexpression led to enlarged grains in independent transgenic lines, suggesting that zma-miR159 contributes positively to maize grain size. Targeting of ZmMYB74 and ZmMYB138 transcription factor genes by zma-miR159 was validated using 5' RACE and dual-luciferase assay. Lines in which ZmMYB74 was knocked out using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) presented a similar enlarged grain phenotype as those with zma-miR159 overexpression. Downstream genes regulating cell division were identified through DNA affinity purification sequencing using ZmMYB74 and ZmMYB138. Our results suggest that zma-miR159-ZmMYB modules act as an endosperm development hub, participating in the division and proliferation of endosperm cells.


Assuntos
Fatores de Transcrição , Zea mays , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zea mays/genética , Zea mays/metabolismo , Endosperma/genética , Endosperma/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Sequência de Bases
20.
Adv Sci (Weinh) ; 10(29): e2303058, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37596721

RESUMO

Structural biomimicry is an intelligent approach for developing lightweight, strong, and tough materials (LSTMs). Current fabrication technologies, such as 3D printing and two-photon lithography often face challenges in constructing complex interlaced structures, such as the sinusoidal crossed herringbone structure that contributes to the ultrahigh strength and fracture toughness of the dactyl club of peacock mantis shrimps. Herein, bioinspired LSTMs with laminated or herringbone structures is reported, by combining textile processing and silk fiber "welding" techniques. The resulting biomimetic silk LSTMs (BS-LSTMs) exhibit a remarkable combination of lightweight with a density of 0.6-0.9 g cm-3 , while also being 1.5 times stronger and 16 times more durable than animal horns. These findings demonstrate that BS-LSTMs are among the toughest natural materials made from silk proteins. Finite element simulations further reveal that the fortification and hardening of BS-LSTMs arise primarily from the hierarchical organization of silk fibers and mechanically transferable meso-interfaces. This study highlights the rational, cost-effective, controllable mesostructure, and transferable strategy of integrating textile processing and fiber "welding" techniques for the fabrication of BS-LSTMs with advantageous structural and mechanical properties. These findings have significant implications for a wide range of applications in biomedicine, mechanical engineering, intelligent textiles, aerospace industries, and beyond.


Assuntos
Biomimética , Seda , Animais , Seda/química , Biomimética/métodos , Têxteis
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