RESUMO
Quantum many-body systems away from equilibrium host a rich variety of exotic phenomena that are forbidden by equilibrium thermodynamics. A prominent example is that of discrete time crystals1-8, in which time-translational symmetry is spontaneously broken in periodically driven systems. Pioneering experiments have observed signatures of time crystalline phases with trapped ions9,10, solid-state spin systems11-15, ultracold atoms16,17 and superconducting qubits18-20. Here we report the observation of a distinct type of non-equilibrium state of matter, Floquet symmetry-protected topological phases, which are implemented through digital quantum simulation with an array of programmable superconducting qubits. We observe robust long-lived temporal correlations and subharmonic temporal response for the edge spins over up to 40 driving cycles using a circuit of depth exceeding 240 and acting on 26 qubits. We demonstrate that the subharmonic response is independent of the initial state, and experimentally map out a phase boundary between the Floquet symmetry-protected topological and thermal phases. Our results establish a versatile digital simulation approach to exploring exotic non-equilibrium phases of matter with current noisy intermediate-scale quantum processors21.
RESUMO
Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.
Assuntos
Macaca fascicularis , Transcriptoma , Animais , Comunicação Celular , Macaca fascicularis/genética , Receptores Virais/genética , Transcriptoma/genética , Via de Sinalização WntRESUMO
We herein present a study on the Ag(I)-mediated semipinacol rearrangement of iododifluorohomoallyl alcohols, the resulting allylic difluoromethyl ketones underwent oxidative allylic C-H esterification under palladium catalysis in the absence of external ligand. This process yielded a range of difluoromethyl ketones derived from allyl esters in a single operation. The reaction features broad scope of o-nitrobenzoic acids and homoallylic iododifluoroalcohols affording the targeted molecules in synthetically useful yields. Control experiments illustrated that the silver salt acted as not only a Lewis acid to promote the cleavage of a C-I bond and furnish the semipinacol rearrangement but also a co-oxidant in the catalytic cycle for the allylic C-H esterification.
RESUMO
The first regio- and stereoselective difluoroalkylthiocyanation of alkynes with BrCF2R and KSCN has been disclosed under visible light-induced copper catalysis. The copper complex photosensitizer formed in situ not only promotes the generation of CF2-alkyl radicals but also facilitates the construction of C-SCN bonds, allowing the reaction to proceed smoothly without any additional photocatalysts or radical initiators. Moreover, the challenging internal alkynes can also be transformed to deliver CF2-derived tetrasubstituted olefins with potential applications in agricultural and medicinal chemistry.
RESUMO
Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids generated human glutamatergic neurons that acquired electrophysiological maturity in the mouse brain. Importantly, the grafted human cerebral organoids functionally integrated into pre-existing neural circuits by forming bidirectional synaptic connections with the mouse host neurons. Furthermore, compared to control mice, the mice transplanted with cerebral organoids showed an increase in freezing time in response to auditory conditioned stimuli, suggesting the potentiation of the startle fear response. Our study showed that subcortical projections can be established by microtransplantation and may provide crucial insights into the therapeutic potential of human cerebral organoids for neurological diseases.
Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Animais , Encéfalo , Diferenciação Celular , Fenômenos Eletrofisiológicos , Humanos , Camundongos , Neurônios , OrganoidesRESUMO
Stereochemically defined organofluorine compounds are vital to drug discovery and many applicable catalytic strategies have been introduced for accessing these entities stereoselectively. One approach entails incorporation of a fluorine atom (C-F bond formation) or an organofluorine moiety (e.g., CF3 or CF2 H), and another exploits commercially available compounds with one or more fluorine atoms. Here, we present the state-of-the-art regarding the use of alkenyl and allylic fluorides in preparation of stereochemically defined fluoro-organic molecules. Allylic and alkenyl fluorides may be purchased or generated from a commercially available acid, carboxylate salt, ester, aldehyde hydrate, or ketone bearing several fluorine atoms next to a carbonyl group. We underscore the untapped potential of purchasable organofluorine compounds, many allylic and alkenyl fluorides, as launching points for development of stereoselective processes that are of value to therapeutic science.
Assuntos
Fluoretos , Flúor , Fluoretos/química , Estereoisomerismo , Catálise , Cetonas/químicaRESUMO
Quantum emulators, owing to their large degree of tunability and control, allow the observation of fine aspects of closed quantum many-body systems, as either the regime where thermalization takes place or when it is halted by the presence of disorder. The latter, dubbed many-body localization (MBL) phenomenon, describes the nonergodic behavior that is dynamically identified by the preservation of local information and slow entanglement growth. Here, we provide a precise observation of this same phenomenology in the case where the quenched on-site energy landscape is not disordered, but rather linearly varied, emulating the Stark MBL. To this end, we construct a quantum device composed of 29 functional superconducting qubits, faithfully reproducing the relaxation dynamics of a nonintegrable spin model. At large Stark potentials, local observables display periodic Bloch oscillations, a manifesting characteristic of the fragmentation of the Hilbert space in sectors that conserve dipole moments. The flexible programmability of our quantum emulator highlights its potential in helping the understanding of nontrivial quantum many-body problems, in direct complement to simulations in classical computers.
RESUMO
BACKGROUND: Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant. RESULTS: The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats. CONCLUSIONS: The obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics.
Assuntos
Fósforo , Polifenóis/farmacologia , Pontos Quânticos/química , Espécies Reativas de Oxigênio/metabolismo , Chá/química , Animais , Queimaduras/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fósforo/química , Fósforo/farmacologia , Processos Fotoquímicos , Ratos , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacosRESUMO
This paper proposes a star-bus topology optic fiber sensor network with an efficient mechanism for network communication to accomplish monitoring and protection operations. The master node scans each channel for its healthy conditions with an N * M optical switch, just as in time-division multiplexing, accomplishing a comprehensive monitoring of the whole sensor network. In addition, we analyze the impact of structural parameters on network robustness, then obtain a basic design principle of network topology. We also demonstrate the proposed network's feasibility by multiplexing different fiber sensor systems simultaneously; in addition, an optimized structure is proposed to accomplish the measurement in extreme environments and proved to be effective.
RESUMO
A widely applicable, practical, and scalable strategy for efficient and enantioselective synthesis of ß,γ-unsaturated ketones that contain an α-stereogenic center is disclosed. Accordingly, aryl, heteroaryl, alkynyl, alkenyl, allyl, or alkyl ketones that contain an α-stereogenic carbon with an alkyl, an aryl, a benzyloxy, or a siloxy moiety can be generated from readily available starting materials and by the use of commercially available chiral ligands in 52-96% yield and 93:7 to >99:1 enantiomeric ratio. To develop the new method, conditions were identified so that high enantioselectivity would be attained and the resulting α-substituted NH-ketimines, wherein there is strong CâN â B(pin) coordination, would not epimerize before conversion to the derived ketone by hydrolysis. It is demonstrated that the ketone products can be converted to an assortment of homoallylic tertiary alcohols in 70-96% yield and 92:8 to >98:2 dr-in either diastereomeric form-by reactions with alkyl-, aryl-, heteroaryl-, allyl-, vinyl-, alkynyl-, or propargyl-metal reagents. The utility of the approach is highlighted through transformations that furnish other desirable derivatives and a concise synthesis route affording more than a gram of a major fragment of anti-HIV agents rubriflordilactones A and B and a specific stereoisomeric analogue.
Assuntos
Cetonas/síntese química , Compostos Organometálicos/química , Propanóis/síntese química , Catálise , Cristalografia por Raios X , Cetonas/química , Ligantes , Modelos Moleculares , Estrutura Molecular , Propanóis/química , EstereoisomerismoRESUMO
A NiCl2 (PEt3 )2 -catalyzed regioselective C-H coupling of 8-aminoquinoline-derived benzamides with oxetanes has been developed. The reaction proceeds with concomitant removal of the 8-aminoquinoline auxiliary to directly form the corresponding seven-membered benzolactones, which frequently occur in natural products and bioactive molecules. Additionally, no stereochemical erosion is observed during the course of the reaction, and the use of enantioenriched and substituted oxetane thus provides a new avenue to the optically active benzolactone.
RESUMO
Two kinds of photonic crystal fiber (PCF) sensors based on surface plasmon resonance (SPR) with silver nano-continuous gratings (i) and (ii) are designed. The coupling characteristics and sensing properties are analyzed numerically by the finite element method (FEM). The results show that the proposed sensor based on silver nano-continuous grating (i) can achieve better performance than that of the sensors based on silver nano-continuous grating (ii) and plane silver film structures. When the segmented number is 50 and segmented angle is 0.5°, a wavelength sensitivity of the proposed sensor with silver nano-continuous grating (i) is obtained as high as 13,600 nm/RIU in the refractive index (RI) range from 1.330 to 1.365, corresponding to a maximum RI resolution of 7.35×10-6 RIU, which can have promising applications in medical and environmental monitoring and biochemical detection.
RESUMO
A Ni(OAc)2 -catalyzed C-H coupling of 8-aminoquinoline-derived benzamides with epoxides has been developed. The reaction proceeds with concomitant removal of the 8-aminoquinoline auxiliary to form the corresponding 3,4-dihydroisocoumarins directly. Additionally, the nickel catalysis is stereospecific, and the cis- and trans-epoxides are converted into the corresponding cis- and trans-dihydroisocoumarins with retention of configuration, which is complementary to previously reported palladium catalysis. Moreover, while still preliminary, the Csp3 -H functionalization is also achieved in the presence of modified NiCl2 catalysts.
RESUMO
The AlCl3-promoted cyclization of readily available allenoates with methyleneindolinone is disclosed. The present strategy provides a rapid access to spirocyclic oxindole-cyclohexenones in an efficient manner. Remarkably, the allenoate is implemented as a four-carbon (4C) component to form the ring, which shows high synthetic efficiency. Flexibility of this method allows quick synthesis of spirocyclic oxindole-dihydropyrans by varying one of the components. It is also noteworthy that AlCl3 serves as the chlorine source as well as an effective catalyst to facilitate this interesting transformation.
Assuntos
Compostos de Alumínio/química , Carbono/química , Cloretos/química , Indóis/síntese química , Compostos de Espiro/síntese química , Cloreto de Alumínio , Catálise , Ciclização , Indóis/química , Estrutura Molecular , Oxindóis , Compostos de Espiro/químicaRESUMO
An organophotoredox-catalyzed oxidative C-H functionalization of benzophospholes has been developed. The C-H alkoxycarbonylation with methyl carbazate occurs in the presence of Rose bengal, whereas Eosin Y enables the dehydrogenative coupling with secondary phosphine oxides and ethers, delivering the C-H phosphinylated and alkylated products. The scope of coupling partners is complementary to that of conventional metal-promoted C-H activation, thus successfully expanding the chemical space of substituted phospholes accessed by C-H functionalization protocols.
RESUMO
A palladium-catalysed C2-H alkynylation of benzophospholes with alkynyl bromides has been developed to afford the corresponding phosphole-alkyne conjugations in good to high yields. The C-C triple bond as well as terminal alkyne C-H bond in the obtained products is a good synthetic handle for further manipulations, thus giving the versatile π-conjugated benzophosphole derivatives. The optoelectronic properties of the newly synthesized conjugated benzophospholes are also described.
RESUMO
Human stem cells and derivatives transplantation are widely used to treat nervous system diseases, while the fate determination of transplanted cells is not well elucidated. To explore cell fate changes of human brain organoids before and after transplantation, human brain organoids are transplanted into prefrontal cortex (PFC) and hippocampus (HIP), respectively. Single-cell sequencing is then performed. According to time-series sample comparison, transplanted cells mainly undergo neural development at 2 months post-transplantation (MPT) and then glial development at 4MPT, respectively. A different brain region sample comparison shows that organoids grafted to PFC have obtained cell fate close to those of host cells in PFC, other than HIP, which may be regulated by the abundant expression of dopamine (DA) and acetylcholine (Ach) in PFC. Meanwhile, morphological complexity of human astrocyte grafts is greater in PFC than in HIP. DA and Ach both activate the calcium activity and increase morphological complexity of astrocytes in vitro. This study demonstrates that human brain organoids receive host niche factor regulation after transplantation, resulting in the alignment of grafted cell fate with implanted brain regions, which may contribute to a better understanding of cell transplantation and regenerative medicine.
Assuntos
Organoides , Transcriptoma , Humanos , Organoides/metabolismo , Organoides/citologia , Organoides/transplante , Transcriptoma/genética , Encéfalo/metabolismo , Análise de Célula Única/métodos , Diferenciação Celular/genética , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/citologia , Hipocampo/metabolismoRESUMO
The ability to realize high-fidelity quantum communication is one of the many facets required to build generic quantum computing devices. In addition to quantum processing, sensing, and storage, transferring the resulting quantum states demands a careful design that finds no parallel in classical communication. Existing experimental demonstrations of quantum information transfer in solid-state quantum systems are largely confined to small chains with few qubits, often relying upon non-generic schemes. Here, by using a superconducting quantum circuit featuring thirty-six tunable qubits, accompanied by general optimization procedures deeply rooted in overcoming quantum chaotic behavior, we demonstrate a scalable protocol for transferring few-particle quantum states in a two-dimensional quantum network. These include single-qubit excitation, two-qubit entangled states, and two excitations for which many-body effects are present. Our approach, combined with the quantum circuit's versatility, paves the way to short-distance quantum communication for connecting distributed quantum processors or registers, even if hampered by inherent imperfections in actual quantum devices.
RESUMO
A metal-free, phosphenium-dication-mediated sequential C-P and C-C bond forming reaction has been developed. This protocol can provide concise access to the (di)benzophosphole derivatives in one synthetic operation from the readily available and simple arylalkynes and phosphinic acids. Application to the multiple cyclization reaction and the fully intermolecular three-component-coupling-type reaction are also described.