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1.
Cell ; 186(10): 2092-2110.e23, 2023 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-37172563

RESUMEN

The third and fourth weeks of gestation in primates are marked by several developmental milestones, including gastrulation and the formation of organ primordia. However, our understanding of this period is limited due to restricted access to in vivo embryos. To address this gap, we developed an embedded 3D culture system that allows for the extended ex utero culture of cynomolgus monkey embryos for up to 25 days post-fertilization. Morphological, histological, and single-cell RNA-sequencing analyses demonstrate that ex utero cultured monkey embryos largely recapitulated key events of in vivo development. With this platform, we were able to delineate lineage trajectories and genetic programs involved in neural induction, lateral plate mesoderm differentiation, yolk sac hematopoiesis, primitive gut, and primordial germ-cell-like cell development in monkeys. Our embedded 3D culture system provides a robust and reproducible platform for growing monkey embryos from blastocysts to early organogenesis and studying primate embryogenesis ex utero.


Asunto(s)
Embrión de Mamíferos , Desarrollo Embrionario , Animales , Macaca fascicularis , Blastocisto , Organogénesis , Primates
2.
Cell ; 167(3): 774-788.e17, 2016 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-27768896

RESUMEN

Expansion of a hexanucleotide repeat GGGGCC (G4C2) in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Transcripts carrying (G4C2) expansions undergo unconventional, non-ATG-dependent translation, generating toxic dipeptide repeat (DPR) proteins thought to contribute to disease. Here, we identify the interactome of all DPRs and find that arginine-containing DPRs, polyGly-Arg (GR) and polyPro-Arg (PR), interact with RNA-binding proteins and proteins with low complexity sequence domains (LCDs) that often mediate the assembly of membrane-less organelles. Indeed, most GR/PR interactors are components of membrane-less organelles such as nucleoli, the nuclear pore complex and stress granules. Genetic analysis in Drosophila demonstrated the functional relevance of these interactions to DPR toxicity. Furthermore, we show that GR and PR altered phase separation of LCD-containing proteins, insinuating into their liquid assemblies and changing their material properties, resulting in perturbed dynamics and/or functions of multiple membrane-less organelles.


Asunto(s)
Esclerosis Amiotrófica Lateral/metabolismo , Dipéptidos/metabolismo , Demencia Frontotemporal/metabolismo , Proteínas/metabolismo , Proteínas de Unión al ARN/metabolismo , Esclerosis Amiotrófica Lateral/genética , Animales , Proteína C9orf72 , Nucléolo Celular/metabolismo , Gránulos Citoplasmáticos/metabolismo , Expansión de las Repeticiones de ADN , Dipéptidos/genética , Drosophila melanogaster/genética , Demencia Frontotemporal/genética , Humanos , Membranas Intracelulares/metabolismo , Poro Nuclear/metabolismo , Péptidos/genética , Péptidos/metabolismo , Proteínas/genética
3.
Proc Natl Acad Sci U S A ; 120(45): e2205463120, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37917793

RESUMEN

Zero-knowledge proof (ZKP) is a fundamental cryptographic primitive that allows a prover to convince a verifier of the validity of a statement without leaking any further information. As an efficient variant of ZKP, noninteractive zero-knowledge proof (NIZKP) adopting the Fiat-Shamir heuristic is essential to a wide spectrum of applications, such as federated learning, blockchain, and social networks. However, the heuristic is typically built upon the random oracle model that makes ideal assumptions about hash functions, which does not hold in reality and thus undermines the security of the protocol. Here, we present a quantum solution to the problem. Instead of resorting to a random oracle model, we implement a quantum randomness service. This service generates random numbers certified by the loophole-free Bell test and delivers them with postquantum cryptography (PQC) authentication. By employing this service, we conceive and implement NIZKP of the three-coloring problem. By bridging together three prominent research themes, quantum nonlocality, PQC, and ZKP, we anticipate this work to inspire more innovative applications that combine quantum information science and the cryptography field.

4.
Hepatology ; 80(3): 578-594, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38271673

RESUMEN

BACKGROUND AND AIMS: Transforming growth factor-beta 1 (TGFß1) induces HSC activation into metastasis-promoting cancer-associated fibroblasts (CAFs), but how the process is fueled remains incompletely understood. We studied metabolic reprogramming induced by TGFß1 in HSCs. APPROACHES AND RESULTS: Activation of cultured primary human HSCs was assessed by the expression of myofibroblast markers. Glucose transporter 1 (Glut1) of murine HSC was disrupted by Cre recombinase/LoxP sequence derived from bacteriophage P1 recombination (Cre/LoxP). Plasma membrane (PM) Glut1 and glycolysis were studied by biotinylation assay and the Angilent Seahorse XFe96 Analyzer. S.c. HSC/tumor co-implantation and portal vein injection of MC38 colorectal cancer cells into HSC-specific Glut1 knockout mice were performed to determine in vivo relevance. Transcriptome was obtained by RNA sequencing of HSCs and spatialomics with MC38 liver metastases. TGFß1-induced CAF activation of HSCs was accompanied by elevation of PM Glut1, glucose uptake, and glycolysis. Targeting Glut1 or Src by short hairpin RNA, pharmacologic inhibition, or a Src SH3 domain deletion mutant abrogated TGFß1-stimulated PM accumulation of Glut1, glycolysis, and CAF activation. Mechanistically, binding of the Src SH3 domain to SH3 domain-binding protein 5 led to a Src/SH3 domain-binding protein 5/Rab11/Glut1 complex that activated Rab11-dependent Glut1 PM transport under TGFß1 stimulation. Deleting the Src SH3 domain or targeting Glut1 of HSCs by short hairpin RNA or Cre recombinase/LoxP sequence derived from bacteriophage P1 recombination suppressed CAF activation in mice and MC38 colorectal liver metastasis. Multi-omics revealed that Glut1 deficiency in HSCs/CAFs suppressed HSC expression of tumor-promoting factors and altered MC38 transcriptome, contributing to reduced MC38 liver metastases. CONCLUSION: The Src SH3 domain-facilitated metabolic reprogramming induced by TGFß1 represents a target to inhibit CAF activation and the pro-metastatic liver microenvironment.


Asunto(s)
Neoplasias Colorrectales , Glucólisis , Neoplasias Hepáticas , Miofibroblastos , Transcriptoma , Dominios Homologos src , Animales , Ratones , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Humanos , Miofibroblastos/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Ratones Noqueados
5.
Chem Rev ; 123(7): 3625-3692, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-36946890

RESUMEN

Heavy-metal (Cd, Hg, and Pb)-containing semiconductor nanocrystals (NCs) have been explored widely due to their unique optical and electrical properties. However, the toxicity risks of heavy metals can be a drawback of heavy-metal-containing NCs in some applications. Anisotropic heavy-metal-free semiconductor NCs are desirable replacements and can be realized following the establishment of anisotropic growth mechanisms. These anisotropic heavy-metal-free semiconductor NCs can possess lower toxicity risks, while still exhibiting unique optical and electrical properties originating from both the morphological and compositional anisotropy. As a result, they are promising light-emitting materials in use various applications. In this review, we provide an overview on the syntheses, properties, and applications of anisotropic heavy-metal-free semiconductor NCs. In the first section, we discuss hazards of heavy metals and introduce the typical heavy-metal-containing and heavy-metal-free NCs. In the next section, we discuss anisotropic growth mechanisms, including solution-liquid-solid (SLS), oriented attachment, ripening, templated-assisted growth, and others. We discuss mechanisms leading both to morphological anisotropy and to compositional anisotropy. Examples of morphological anisotropy include growth of nanorods (NRs)/nanowires (NWs), nanotubes, nanoplatelets (NPLs)/nanosheets, nanocubes, and branched structures. Examples of compositional anisotropy, including heterostructures and core/shell structures, are summarized. Third, we provide insights into the properties of anisotropic heavy-metal-free NCs including optical polarization, fast electron transfer, localized surface plasmon resonances (LSPR), and so on, which originate from the NCs' anisotropic morphologies and compositions. Finally, we summarize some applications of anisotropic heavy-metal-free NCs including catalysis, solar cells, photodetectors, lighting-emitting diodes (LEDs), and biological applications. Despite the huge progress on the syntheses and applications of anisotropic heavy-metal-free NCs, some issues still exist in the novel anisotropic heavy-metal-free NCs and the corresponding energy conversion applications. Therefore, we also discuss the challenges of this field and provide possible solutions to tackle these challenges in the future.

6.
J Am Chem Soc ; 146(17): 11679-11693, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38482849

RESUMEN

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.


Asunto(s)
Vacunas contra el Cáncer , Lípidos , Liposomas , Nanopartículas , ARN Mensajero , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Nanopartículas/química , Animales , Ratones , ARN Mensajero/genética , ARN Mensajero/inmunología , Lípidos/química , Humanos , Ácido Tióctico/química , Ácido Tióctico/farmacología , Polímeros/química , Guanidinas/química , Guanidinas/farmacología , Línea Celular Tumoral
7.
Cancer Immunol Immunother ; 73(11): 220, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235609

RESUMEN

BACKGROUND: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking. METHODS: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing. RESULTS: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival. CONCLUSION: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.


Asunto(s)
Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Humanos , Masculino , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/genética , Adulto , Pronóstico
8.
Opt Express ; 32(7): 12092-12103, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571042

RESUMEN

To achieve an autonomously controlled reconfigurable microwave waveform generator, this study proposes and demonstrates a self-adjusting synthesis method based on a photonic delay reservoir computer with ring resonator. The proposed design exploits the ring resonator to configure the reservoir, facilitating a nonlinear transformation and providing delay space. A theoretical analysis is conducted to explain how this configuration addresses the challenges of microwave waveform generation. Considering the generalization performance of waveform generation, the simulations demonstrate the system's capability to produce six distinct representative waveforms, all exhibiting a highly impressive root mean square error (RMSE) of less than 1%. To further optimize the system's flexibility and accuracy, we explore the application of various artificial intelligence algorithms at the reservoir computer's output layer. Furthermore, our investigation delves deeply into the complexities of system performance, specifically exploring the influence of reservoir neurons and micro-ring resonator parameters on calculation performance. We also delve into the scalability of reservoirs, considering both parallel and cascaded arrangements.

9.
Phys Chem Chem Phys ; 26(30): 20470-20482, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39027937

RESUMEN

Direct conversion of syngas into ethanol is an attractive process because of its short route and high-added value, but remains an enormous challenge due to the low selectivity caused by unclear active sites. Here, the Cu(111) supported N-modified graphene fragments C13-mNm/Cu(111) (m = 0-2) are demonstrated to be an efficient catalyst for fabricating ethanol from syngas and methanol. Our results suggest that the Cu-carbon interaction not only facilitates CO activation, but also significantly affects the adsorption stability of C2 intermediates and finally changes the fundamental reaction mechanism. The impeded hydrogenation performance of C13/Cu(111) due to the introduced Cu-carbon interaction is dramatically improved by N-doping. Multiple analyses reveal that the promoted electron transfer and the enhanced electron endowing ability of C13-mNm/Cu(111) (m = 1-2) to the co-adsorbed CH3CHxOH (x = 0-1) and H are deemed to be mainly responsible for the remarkable enhancement in hydrogenation ability. From the standpoint of the frontier molecular orbital, the decreased HOMO-LUMO gap and the increased overlap extent of HOMO and LUMO with the doping of N atoms also further verify the more facile hydrogenation reactions. Clearly, the Cu-carbon interaction through N-modification is of critical importance in ethanol formation. The final hydrogenation reaction during ethanol formation is deemed to be the rate-controlling step. The insights gained here could shed new light on the nature of Cu-carbon interaction in carbon material modified Cu-based catalysts for ethanol synthesis, which could be extended to design and modify other metal-carbon catalysts.

10.
Nature ; 562(7728): 548-551, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30287887

RESUMEN

Randomness is important for many information processing applications, including numerical modelling and cryptography1,2. Device-independent quantum random-number generation (DIQRNG)3,4 based on the loophole-free violation of a Bell inequality produces genuine, unpredictable randomness without requiring any assumptions about the inner workings of the devices, and is therefore an ultimate goal in the field of quantum information science5-7. Previously reported experimental demonstrations of DIQRNG8,9 were not provably secure against the most general adversaries or did not close the 'locality' loophole of the Bell test. Here we present DIQRNG that is secure against quantum and classical adversaries10-12. We use state-of-the-art quantum optical technology to create, modulate and detect entangled photon pairs, achieving an efficiency of more than 78 per cent from creation to detection at a distance of about 200 metres that greatly exceeds the threshold for closing the 'detection' loophole of the Bell test. By independently and randomly choosing the base settings for measuring the entangled photon pairs and by ensuring space-like separation between the measurement events, we also satisfy the no-signalling condition and close the 'locality' loophole of the Bell test, thus enabling the realization of the loophole-free violation of a Bell inequality. This, along with a high-voltage, high-repetition-rate Pockels cell modulation set-up, allows us to accumulate sufficient data in the experimental time to extract genuine quantum randomness that is secure against the most general adversaries. By applying a large (137.90 gigabits × 62.469 megabits) Toeplitz-matrix hashing technique, we obtain 6.2469 × 107 quantum-certified random bits in 96 hours with a total failure probability (of producing a random number that is not guaranteed to be perfectly secure) of less than 10-5. Our demonstration is a crucial step towards transforming DIQRNG from a concept to a key aspect of practical applications that require high levels of security and thus genuine randomness7. Our work may also help to improve our understanding of the origin of randomness from a fundamental perspective.

11.
J Nanobiotechnology ; 22(1): 261, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760744

RESUMEN

Delayed repair of fractures seriously impacts patients' health and significantly increases financial burdens. Consequently, there is a growing clinical demand for effective fracture treatment. While current materials used for fracture repair have partially addressed bone integrity issues, they still possess limitations. These challenges include issues associated with autologous material donor sites, intricate preparation procedures for artificial biomaterials, suboptimal biocompatibility, and extended degradation cycles, all of which are detrimental to bone regeneration. Hence, there is an urgent need to design a novel material with a straightforward preparation method that can substantially enhance bone regeneration. In this context, we developed a novel nanoparticle, mPPTMP195, to enhance the bioavailability of TMP195 for fracture treatment. Our results demonstrate that mPPTMP195 effectively promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts while inhibiting the differentiation of bone marrow mononuclear macrophages into osteoclasts. Moreover, in a mouse femur fracture model, mPPTMP195 nanoparticles exhibited superior therapeutic effects compared to free TMP195. Ultimately, our study highlights that mPPTMP195 accelerates fracture repair by preventing HDAC4 translocation from the cytoplasm to the nucleus, thereby activating the NRF2/HO-1 signaling pathway. In conclusion, our study not only proposes a new strategy for fracture treatment but also provides an efficient nano-delivery system for the widespread application of TMP195 in various other diseases.


Asunto(s)
Diferenciación Celular , Histona Desacetilasas , Células Madre Mesenquimatosas , Nanopartículas , Animales , Ratones , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Nanopartículas/química , Diferenciación Celular/efectos de los fármacos , Histona Desacetilasas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratones Endogámicos C57BL , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoblastos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Masculino , Regeneración Ósea/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Núcleo Celular/metabolismo , Curación de Fractura/efectos de los fármacos , Humanos , Proteínas de la Membrana
12.
Chem Soc Rev ; 52(4): 1519, 2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36756836

RESUMEN

Correction for 'Atomically flat semiconductor nanoplatelets for light-emitting applications' by Bing Bai et al., Chem. Soc. Rev., 2023, 52, 318-360, https://doi.org/10.1039/D2CS00130F.

13.
Chem Soc Rev ; 52(1): 318-360, 2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36533300

RESUMEN

The last decade has witnessed extensive breakthroughs and significant progress in atomically flat two-dimensional (2D) semiconductor nanoplatelets (NPLs) in terms of synthesis, growth mechanisms, optical and electronic properties and practical applications. Such NPLs have electronic structures similar to those of quantum wells in which excitons are predominantly confined along the vertical direction, while electrons are free to move in the lateral directions, resulting in unique optical properties, such as extremely narrow emission line width, short photoluminescence (PL) lifetime, high gain coefficient, and giant oscillator strength transition (GOST). These unique optical properties make NPLs favorable for high color purity light-emitting applications, in particular in light-emitting diodes (LEDs), backlights for liquid crystal displays (LCDs) and lasers. This review article first introduces the intrinsic characteristics of 2D semiconductor NPLs with atomic flatness. Subsequently, the approaches and mechanisms for the controlled synthesis of atomically flat NPLs are summarized followed by an insight on recent progress in the mediation of core/shell, core/crown and core/crown@shell structures by selective epitaxial growth of passivation layers on different planes of NPLs. Moreover, an overview of the unique optical properties and the associated light-emitting applications is elaborated. Despite great progress in this research field, there are some issues relating to heavy metal elements such as Cd2+ in NPLs, and the ambiguous gain mechanisms of NPLs and others are the main obstacles that prevent NPLs from widespread applications. Therefore, a perspective is included at the end of this review article, in which the current challenges in this stimulating research field are discussed and possible solutions to tackle these challenges are proposed.

14.
Molecules ; 29(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38998960

RESUMEN

The United Nations proposed the Sustainable Development Goals with the aim to make human settlements in cities resilient and sustainable. The excessive discharge of urban waste including sludge and garden waste can pollute groundwater and lead to the emission of greenhouse gases (e.g., CH4). The proper recycling of urban waste is essential for responsible consumption and production, reducing environmental pollution and addressing climate change issues. This study aimed to prepare biochar with high adsorption amounts of iodine using urban sludge and peach wood from garden waste. The study was conducted to examine the variations in the mass ratio between urban sludge and peach wood (2/1, 1/1, and 1/2) as well as pyrolysis temperatures (300 °C, 500 °C, and 700 °C) on the carbon yield and adsorption capacities of biochar. Scanning electron microscopy, Brunauer-Emmett-Teller analysis, Fourier transform infrared spectrometry, powder X-ray diffraction, and elemental analysis were used to characterize the biochar produced at different pyrolysis temperatures and mass ratios. The results indicate that the carbon yield of biochar was found to be the highest (>60%) at a pyrolysis temperature of 300 °C across different pyrolysis temperatures. The absorbed amounts of iodine in the aqueous solution ranged from 86 to 223 mg g-1 at a mass ratio of 1:1 between urban sludge and peach wood, which were comparably higher than those observed in other mass ratios. This study advances water treatment by offering a cost-effective method by using biochar derived from the processing of urban sludge and garden waste.


Asunto(s)
Carbón Orgánico , Yodo , Pirólisis , Aguas del Alcantarillado , Carbón Orgánico/química , Yodo/química , Aguas del Alcantarillado/química , Adsorción , Temperatura , Jardines , Espectroscopía Infrarroja por Transformada de Fourier , Ciudades
15.
Angew Chem Int Ed Engl ; 63(3): e202316903, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-37997556

RESUMEN

Proton exchange membrane water electrolysis is a highly promising hydrogen production technique for sustainable energy supply, however, achieving a highly active and durable catalyst for acidic water oxidation still remains a formidable challenge. Herein, we propose a local microenvironment regulation strategy for precisely tuning In-RuO2 /graphene (In-RuO2 /G) catalyst with intrinsic electrochemical activity and stability to boost acidic water oxidation. The In-RuO2 /G displays robust acid oxygen evolution reaction performance with a mass activity of 671 A gcat -1 at 1.5 V, an overpotential of 187 mV at 10 mA cm-2 , and long-lasting stability of 350 h at 100 mA cm-2 , which arises from the asymmetric Ru-O-In local structure interactions. Further, it is unraveled theoretically that the asymmetric Ru-O-In structure breaks the thermodynamic activity limit of the traditional adsorption evolution mechanism which significantly weakens the formation energy barrier of OOH*, thus inducing a new rate-determining step of OH* absorption. Therefore, this strategy showcases the immense potential for constructing high-performance acidic catalysts for water electrolyzers.

16.
Angew Chem Int Ed Engl ; 63(13): e202318515, 2024 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-38320193

RESUMEN

Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.


Asunto(s)
Vacunas contra el Cáncer , Liposomas , Nanopartículas , Neoplasias , Humanos , Presentación de Antígeno , Vacunas de ARNm , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Dendríticas/metabolismo , Neoplasias/terapia , Neoplasias/metabolismo
17.
Proteomics ; 23(18): e2200330, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37271885

RESUMEN

Cardiovascular diseases (CVDs) are among the most morbid and deadly types of diseases worldwide, while the existing therapeutic approaches all have their limitations. Mouse heart undergoes a very complex postnatal developmental process, including the 1-week window in which cardiomyocytes (CMs) maintain relatively high cell activity. The underlying mechanism provides an attractive direction for CVDs treatment. Herein, we collected ventricular tissues from mice of different ages from E18.5D to P8W and performed iTRAQ-based quantitative proteomics to characterize the atlas of cardiac development. A total of 3422 proteins were quantified at all selected time points, revealing critical proteomic changes related to cardiac developmental events such as the metabolic transition from glycolysis to beta-oxidation. A cluster of significantly dysregulated proteins containing proteins that have already been reported to be associated with cardiac regeneration (Erbb2, Agrin, and Hmgb) was identified. Meanwhile, the peroxisome proliferator-activated receptor (PPAR) signaling pathway (Cpt1α, Hmgcs2, Plin2, and Fabp4) was also found specifically enriched. We further revealed that bezafibrate, a pan-activator of PPAR signaling pathway markedly enhanced H9C2 cardiomyocyte activity via enhancing Cpt1α expression. This work provides new hint that activation of PPAR signaling pathway could potentially be a therapeutic strategy for the treatment of CVDs.


Asunto(s)
Enfermedades Cardiovasculares , Miocitos Cardíacos , Ratones , Animales , Miocitos Cardíacos/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Animales Recién Nacidos , Proteómica , Transducción de Señal , Enfermedades Cardiovasculares/metabolismo
18.
Small ; 19(30): e2300217, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37021733

RESUMEN

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.


Asunto(s)
Puntos Cuánticos , Daño por Reperfusión , Selenio , Humanos , Antioxidantes/farmacología , Especies Reactivas de Oxígeno , Carbono , Lecitinas , Hígado , Daño por Reperfusión/tratamiento farmacológico
19.
Opt Express ; 31(18): 29627-29638, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37710759

RESUMEN

Light manipulation for all-fiber devices has played a vital role in controllable photonic devices. A graphene-based metasurface is proposed to realize light manipulation. A row of VCSEL-based optical engines with low crosstalk is used as the control light to modulate the signal transmitted in the microstructured fiber. In this configuration, the proposed device can work independently of the wavelength division multiplexing (WDM) system. With an insertion loss of only 0.28 dB, evanescent wave coupling to graphene layers is polarisation-insensitive. The device could be effectively manipulated for a few days (not less than 72 hours), which possesses the capacity to dynamically modulate the signal light with both low-temperature sensitivity and low-wavelength sensitivity. The 35 nm wavelength interval results in a change of only about 0.1 dB in the output light intensity of the microstructured fiber when the wavelength changes from 1530 nm to 1565 nm. Moreover, the modulation depth is approximately 2 dB when the modulating voltage is 2.2 V, which may open avenues for channel detection techniques and have deep implications in top tuning applications.

20.
Opt Express ; 31(21): 34843-34854, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37859231

RESUMEN

Integrated photonic reservoir computing has been demonstrated to be able to tackle different problems because of its neural network nature. A key advantage of photonic reservoir computing over other neuromorphic paradigms is its straightforward readout system, which facilitates both rapid training and robust, fabrication variation-insensitive photonic integrated hardware implementation for real-time processing. We present our recent development of a fully-optical, coherent photonic reservoir chip integrated with an optical readout system, capitalizing on these benefits. Alongside the integrated system, we also demonstrate a weight update strategy that is suitable for the integrated optical readout hardware. Using this online training scheme, we successfully solved 3-bit header recognition and delayed XOR tasks at 20 Gbps in real-time, all within the optical domain without excess delays.

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