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"Hong, Ye"
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Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9
Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concerns about pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. We previously demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. We now confirm that PERVs infect human cells, and we observe the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all of the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlights the value of PERV inactivation to prevent cross-species viral transmission and demonstrates the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.
Journal Article
Electrochemically mediated carbon dioxide separation with quinone chemistry in salt-concentrated aqueous media
Carbon capture is essential for mitigating carbon dioxide emissions. Compared to conventional chemical scrubbing, electrochemically mediated carbon capture utilizing redox-active sorbents such as quinones is emerging as a more versatile and economical alternative. However, the practicality of such systems is hindered by the requirement of toxic, flammable organic electrolytes or often costly ionic liquids. Herein, we demonstrate that rationally designed aqueous electrolytes with high salt concentration can effectively resolve the incompatibility between aqueous environments and quinone electrochemistry for carbon capture, eliminating the safety, toxicity, and at least partially the cost concerns in previous studies. Salt-concentrated aqueous media also offer distinct advantages including extended electrochemical window, high carbon dioxide activity, significantly reduced evaporative loss and material dissolution, and importantly, greatly suppressed competing reactions including under simulated flue gas. Correspondingly, we achieve continuous carbon capture-release operations with outstanding capacity, stability, efficiency and electrokinetics, advancing electrochemical carbon separation further towards practical applications.
Redox-active organic compounds that reversibly bind and release CO
2
are promising candidates for carbon capture but are limited by the use of flammable, toxic aprotic electrolytes. Here the authors use salt-concentrated aqueous electrolytes in continuous CO
2
separation with good performance metrics.
Journal Article
Light scattering in stacked mesophyll cells results in similarity characteristic of solar spectral reflectance and transmittance of natural leaves
Solar spectral reflectance and transmittance of natural leaves exhibit dramatic similarity. To elucidate the formation mechanism and physiological significance, a radiative transfer model was constructed, and the effects of stacked mesophyll cells, chlorophyll content and leaf thickness on the visible light absorptance of the natural leaves were analyzed. Results indicated that light scattering caused by the stacked mesophyll cells is responsible for the similarity. The optical path of visible light in the natural leaves is increased with the scattering process, resulting in that the visible light transmittance is significantly reduced meanwhile the visible light reflectance is at a low level, thus the visible light absorptance tends to a maximum and the absorption of photosynthetically active radiation (PAR) by the natural leaves is significantly enhanced. Interestingly, as two key leaf functional traits affecting the absorption process of PAR, chlorophyll content and leaf thickness of the natural leaves in a certain environment show a convergent behavior, resulting in the high visible light absorptance of the natural leaves, which demonstrates the PAR utilizing strategies of the natural leaves. This work provides a new perspective for revealing the evolutionary processes and ecological strategies of natural leaves, and can be adopted to guide the improvement directions of crop photosynthesis.
Journal Article
Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury
Background
Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear.
Methods
An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen–glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated.
Results
LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model.
Lcn2
knockout (
Lcn2
−/−
) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in
Lcn2
−/−
mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950.
Conclusion
LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury.
Journal Article
Marine Algal Toxins and Public Health: Insights from Shellfish and Fish, the Main Biological Vectors
Exposure to toxigenic harmful algal blooms (HABs) can result in widely recognized acute poisoning in humans. The five most commonly recognized HAB-related illnesses are diarrhetic shellfish poisoning (DSP), paralytic shellfish poisoning (PSP), amnesic shellfish poisoning (ASP), neurotoxic shellfish poisoning (NSP), and ciguatera poisoning (CP). Despite being caused by exposure to various toxins or toxin analogs, these clinical syndromes share numerous similarities. Humans are exposed to these toxins mainly through the consumption of fish and shellfish, which serve as the main biological vectors. However, the risk of human diseases linked to toxigenic HABs is on the rise, corresponding to a dramatic increase in the occurrence, frequency, and intensity of toxigenic HABs in coastal regions worldwide. Although a growing body of studies have focused on the toxicological assessment of HAB-related species and their toxins on aquatic organisms, the organization of this information is lacking. Consequently, a comprehensive review of the adverse effects of HAB-associated species and their toxins on those organisms could deepen our understanding of the mechanisms behind their toxic effects, which is crucial to minimizing the risks of toxigenic HABs to human and public health. To this end, this paper summarizes the effects of the five most common HAB toxins on fish, shellfish, and humans and discusses the possible mechanisms.
Journal Article
Robust gold nanorods stabilized by bidentate N-heterocyclic-carbene–thiolate ligands
Although N-heterocyclic carbenes (NHCs) have demonstrated outstanding potential for use as surface anchors, synthetic challenges have limited their application to either large planar substrates or very small spherical nanoparticles. The development of a strategy to graft NHCs onto non-spherical nanomaterials, such as gold nanorods, would greatly expand their utility as surface ligands. Here, we use a bidentate thiolate–NHC–gold(
i
) complex that is easily grafted onto commercial cetyl trimethylammonium bromide-stabilized gold nanorods through ligand exchange. On mild reduction of the resulting surface-tethered NHC–gold(
i
) complexes, the gold atom attached to the NHC complex is added to the surface as an adatom, thereby precluding the need for reorganization of the underlying surface lattice upon NHC binding. The resulting thiolate–NHC-stabilized gold nanorods are stable towards excess glutathione for up to six days, and under conditions with large variations in pH, high and low temperatures, high salt concentrations, or in biological media and cell culture. We also demonstrate the utility of these nanorods for in vitro photothermal therapy.
N-heterocyclic carbenes (NHCs) are valuable surface anchors, but their use has remained limited to either spherical or planar nanomaterials. Now, they have been grafted onto gold nanorods through a bidentate ligand featuring a thiolate and a NHC–gold complex. The resulting nanorods are robust towards a wide range of harsh conditions and show promise for photothermal therapy.
Journal Article
Demonstration of robust and efficient quantum property learning with shallow shadows
Extracting information efficiently from quantum systems is crucial for quantum information processing. Classical shadows enable predicting many properties of arbitrary quantum states using few measurements. While random single-qubit measurements are experimentally friendly and suitable for learning low-weight Pauli observables, they perform poorly for nonlocal observables. Introducing a shallow random quantum circuit before measurements improves sample efficiency for high-weight Pauli observables and low-rank properties. However, in practice, these circuits can be noisy and bias the measurement results. Here, we propose the robust shallow shadows, which employs Bayesian inference to learn and mitigate noise in postprocessing. We analyze noise effects on sample complexity and the optimal circuit depth. We provide theoretical guarantees for the success of error mitigation under a wide class of noise processes. Experimental validation on a superconducting quantum processor confirms the advantage of our method, even in the presence of realistic noise, over single-qubit measurements for predicting diverse state properties, such as fidelity and entanglement entropy. Our protocol thus offers a scalable, robust, and sample-efficient method for quantum state characterization on near-term quantum devices.
Fast and reliable characterisation of quantum systems is a key part of quantum technologies development. Here, the authors propose and demonstrate a way to embed noise characterisation in classical shadow estimation of nonlocal properties, enabling an efficient way to extract information from noisy quantum systems.
Journal Article
Conformal Microfluidic‐Blow‐Spun 3D Photothermal Catalytic Spherical Evaporator for Omnidirectional Enhanced Solar Steam Generation and CO2 Reduction
Solar‐driven water evaporation and valuable fuel generation is an environmentally friendly and sustainable way for clean water and energy production. However, a few bottlenecks for practical applications are high‐cost, low productivity, and severe sunlight angle dependence. Herein, solar evaporation with enhanced photocatalytic capacity that is light direction insensitive and of efficiency breakthrough by virtue of a three‐dimensional (3D) photothermal catalytic spherical isotopic evaporator is demonstrated. A homogeneous layer of microfluidic blow spun polyamide nanofibers loaded with efficient light absorber of polypyrrole nanoparticles conformally wraps onto a lightweight, thermal insulating plastic sphere, featuring favorable interfacial solar heating and efficient water transportation. The 3D spherical geometry not only guarantees the omnidirectional solar absorbance by the light‐facing hemisphere, but also keeps the other hemisphere under shadow to harvest energy from the warmer environment. As a result, the light‐to‐vapor efficiency exceeds the theoretical limit, reaching 217% and 156% under 1 and 2 sun, respectively. Simultaneously, CO2 photoreduction with generated steam reveals a favorable clean fuels production rate using photocatalytic spherical evaporator by secondary growth of Cu2O nanoparticles. Finally, an outdoor demonstration manifests a high evaporation rate and easy‐to‐perform construction on‐site, providing a promising opportunity for efficient and decentralized water and clean fuel production. A three‐dimensional (3D) photothermal catalytic spherical evaporator with double‐layer structure that enables the theoretical light‐to‐vapor efficiency limits breakthrough and efficient clean fuels production. The isotropy of spherical structure exhibits the omnidirectional light absorption, reducing the influence of natural light incident angle on solar evaporation rate and circumventing the trade‐off between water condensation and photocatalytic reaction, which is significant for practical applications.
Journal Article
Low-density lipoprotein receptor (LDLR) regulates NLRP3-mediated neuronal pyroptosis following cerebral ischemia/reperfusion injury
Background
Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemic stroke. NLRP3 inflammasome, involved in the regulation of inflammatory cascade, can simultaneously lead to GSDMD-executed pyroptosis in cerebral ischemia. Low-density lipoprotein receptor (LDLR), responsible for cholesterol uptake, was noted to exert potential anti-inflammatory bioactivities. Nevertheless, the role of LDLR in neuroinflammation mobilized by cerebral ischemia/reperfusion (I/R) has not been investigated.
Methods
Ischemic stroke mice model was accomplished by middle cerebral artery occlusion. Oxygen-glucose deprivation was employed after primary cortical neuron was extracted and cultured. A pharmacological inhibitor of NLRP3 (CY-09) was administered to suppress NLPR3 activation. Histological and biochemical analysis were performed to assess the neuronal death both in vitro and in vivo. In addition, neurological deficits and behavioral deterioration were evaluated in mice.
Results
The expression of LDLR was downregulated following cerebral I/R injury. Genetic knockout of
Ldlr
enhanced caspase-1-dependent cleavage of GSDMD and resulted in severe neuronal pyroptosis. LDLR deficiency contributed to excessive NLRP3-mediated maturation and release of IL-1β and IL-18 under in vitro and in vivo ischemic conditions. These influences ultimately led to aggravated neurological deficits and long-term cognitive dysfunction. Blockade of NLRP3 substantially retarded neuronal pyroptosis in
Ldlr
−/−
mice and cultured
Ldlr
−/−
neuron after experimental stroke.
Conclusions
These results demonstrated that LDLR modulates NLRP3-mediated neuronal pyroptosis and neuroinflammation following ischemic stroke. Our findings characterize a novel role for LDLR as a potential therapeutic target in neuroinflammatory responses to acute cerebral ischemic injury.
Journal Article