Pemivibart, a class 1/4 monoclonal antibody (mAb), is currently the only FDA-authorized SARS-CoV-2 mAb under an Emergency Use Authorization (EUA) in clinical use. The emergence of subvariants, including KP.3.1.1 and XFG, raises concerns about antibody efficacy. SA55, a fully human class 1/4 mAb, is currently under clinical trial, including a nasal spray formulation. Using the well-validated organoid-based neutralization assays, we compared the potency and breadth of Pemivibart and SA55. Our results demonstrated a significant decrease in Pemivibart's activity against KP.3.1.1 and XFG, with an approximately 80-fold increase in IC50 relative to the ancestral strain. Given KP.3.1.1's strong reliance on the TMPRSS2 pathway for cell entry, we further demonstrated that combinational treatment with Pemivibart and the broad-spectrum S2 antibody results in potent neutralization. Notably, SA55 maintained potent neutralization (IC50 ≤ 40 ng/mL) across all tested variants. Topical administration, which models nasal spray, dramatically suppressed viral replication of BA.5.2 and XFG in organoid models. Our findings evidence the high potency of SA55, supporting its potential for clinical application against emerging SARS-CoV-2 variants.

The degradation mechanisms of high-entropy alloy (HEA) coatings under corrosion-wear synergistic environments remain imperative to elucidate. This work systematically investigates the influence of Mo content gradient on the microstructure and comprehensive corrosion-wear resistance of laser-clad FeCoCrNiMox HEA coatings. Results indicate that low Mo content (x <= 0.6) yields a single FCC solid solution, while high Mo content (x =1.0) promotes the formation of a multiphase FCC + sigma + mu structure. Mo induces substantial grain refinement via lattice distortion and Cr/Mo grain boundary segregation, accompanied by localized eutectic microstructures. Coating hardness significantly increases with Mo content, attributed to the synergistic effects of solid solution, grain refinement, and second-phase strengthening, while the fine-grained structure imparts moderate toughness. The Mo1.0 coating exhibits the highest corrosion potential and charge transfer resistance in 3.5 wt% NaCl solution. Its superior pitting resistance stems from a dense composite passive film formed by Cr/Mo synergy, effectively inhibiting Cl- penetration. Regarding tribocorrosion resistance, the Mo1.0 coating demonstrates the lowest tribocorrosion wear rate. A gradient nano/micro-crystalline structure, dislocation entanglement, and nano-twins formed near the worn surface under high frictional extrusion/shear stress. In-situ generated Fe-rich/ Cr-rich bilayer tribocorrosion films act as corrosion barriers at the friction interface. The wear mechanism shifts from corrosion-induced abrasive wear in low-Mo coatings to passive film-dominated synergistic wear in high-Mo coatings.

We established robust protocols to generate physiological and functional alveolar organoids (nsoAlvO) from readily accessible and expandable nasal cell-derived organoids, and alveolar macrophages (monoAM) from peripheral blood monocytes. Through co-culture of nsoAlvO and monoAM, we generated organoid-macrophage assembloids, in which both components exhibited enhanced maturation. Comprehensive analyses, including immunostaining, functional assays, and single-cell RNA sequencing, demonstrated that the nsoAlvO and monoAM phenotypically and functionally resemble their native counterparts and engage in dynamic and extensive epithelial-macrophage communications. SSEA-1+ club cells were identified as the primary alveolar progenitor cells for nsoAlvO. Influenza virus infection in nsoAlvO revealed differential replicative fitness of H5N1 and H1N1 viruses, which recapitulate their authentic tropism in vivo. Notably, the addition of monoAM reduced H5N1 and H1N1 infection in nsoAlvO, suggesting a protective effect of alveolar macrophages against virus dissemination. These human alveolar organoids and organoid-macrophage assembloids provide universally accessible and physiologically relevant in vitro lung models for biomedical research and translational medicine.

Reported herein is tantalum (Ta)-based film, including TaN, TaOx, composite TaOxNγ, multilayered TaN/TaOx-(5:5) and TaN/TaOx-(10:10), prepared by atomic layer deposition (ALD) technology via adjusting the sub-cycle of TaN and TaOx films. The influence of different growth parameters on microstructure, crystal form, chemical bonding state and corrosion resistance of Ta-based films was systematically investigated. Representative results include the following: (1) The surface of the Ta-based films prepared by ALD is continuous, dense and smooth, and the root mean square roughness (Rq) of those are TaN: 0.74 nm, TaOx: 0.69 nm, TaOxNγ: 0.55 nm, TaN/TaOx-5:5: 0.56 nm and TaN/TaOx-10:10: 0.77 nm. (2) The TaN film presents a polycrystalline structure with good crystallinity, while the incorporation of oxygen significantly inhibits the crystallinity of the film. (3) Electrochemical tests in 3.5 wt.% NaCl solution and neutral salt spray experiments show that ALD deposition of Ta-based films can significantly improve the corrosion resistance of carbon steel substrates. The order of corrosion resistance of different films is TaOxNγ film > TaN/TaOx multilayer film > TaN film. Among them, the TaOxNγ film exhibited the most excellent corrosion resistance, with a charge transfer resistance (Rct) as high as 24.75 Ω·cm2 and a corrosion current density (Icorr) as low as 1.20 × 10−6 A/cm2, and no obvious rusting phenomenon was observed on the surface of that film after the 2 h neutral salt spray test.

Carbon-based supercapacitor electrodes face critical challenges, including disordered pore architecture, surface inertness, and insufficient graphitization, leading to compromised electron transport and interfacial reactivity. This study systematically investigates the effects of physical or chemical activation strategies on the structural and electrochemical properties of carbon electrode materials. Comparative analysis reveals that physical activation (N2/CO2 annealing) primarily induces partial graphitization and moderate particle refinement, while chemical activation involving melamine-assisted heteroatom doping followed by NaOH etching enables comprehensive structural reorganization. The optimized process converts the particle structure into three-dimensional interconnected porous frameworks with enhanced surface functionality. The chemically activated N doped hierarchical porous carbon frameworks (N-CNFs) exhibit (1) hierarchical porosity with optimized meso/micropore coexistence, (2) effective nitrogen incorporation generating redox-active sites, (3) improved charge transfer kinetics through structural graphitization, (4) electrochemical evaluation demonstrates exceptional performance metrics with high specific capacitance of 443 F g-1 at 1 A g-1, outstanding cycling stability with 100% capacitance retention after 10,000 cycles at 10 A g-1 and maximum energy/power density of 21.25 Wh kg-1 and 15.0 kW kg-1. This work establishes a paradigm for developing advanced carbon electrodes through coordinated microstructure engineering and surface chemistry modulation, providing critical insights into structure-property relationships for energy storage applications.

The efficacy of VIR-7831, a class 3 anti-SARS-CoV-2 monoclonal antibody (mAb), was demonstrated repeatedly in clinical trials; yet, reduced neutralization against Omicron variants in cell-line-based neutralization assays led to its withdrawal from clinical use. We developed organoid-based neutralization assays to measure mAb potency. We found that most class 3 mAbs, especially those not blocking receptor-binding domain-ACE2 binding, including VIR-7831, were substantially underestimated in cell-line-based assays. Nasal organoids adequately recapitulated the real-world effectiveness of VIR-7831 because of biologically relevant low ACE2 expression, and exclusively reproduced the in vivo protection of S2 mAbs due to the high TMPRSS2 expression, reminiscent of native human respiratory epithelial cells. Collectively, the robust organoid culture system and biologically relevant expression profiles of ACE2 and TMPRSS2 make nasal organoids present a correlate of in vivo protection of neutralizing mAbs exclusively. The organoid-based neutralization assays, superior to conventional cell-line-based assays, can recapitulate and predict the real-world efficacy of mAbs.

Atomic layer deposition (ALD) of Y2O3 thin films was performed on Si substrate by pulsing an unconventional heteroleptic yttrium precursor Y(MeCp)2(Me2Pz) and H2O alternatively. The thin film grew 0.26 - 0.28Å per cycle at relatively low temperature of 195 - 225°C in a self-limiting manner with negligible nucleation delay, and is close to stoichiometric (O/Y = 1.48, C, 2.56at.%; N, 1.81at.%) in as-deposited form. Integration of the post-annealed ALD Y2O3 film in a metal oxide semiconductor (MOS) capacitor structure exhibits representative electrical properties including a high dielectric constant k of 11.4, high electrical breakdown field of 6.1MVcm-1 and low leakage current density of 9.1×10-8Acm-2 at -2 MV cm-1.

AbstractThe lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention. Nasal organoids are more susceptible to HRV-C than airway organoids. Intriguingly, upon HRV-C infection, we observe an innate immune response that is stronger in airway organoids than in nasal organoids, which is reproduced in a Poly(I:C) stimulation assay. Treatment with α-CDHR3 and antivirals significantly reduces HRV-C viral growth in airway and nasal organoids. Additionally, an organoid-based immunofluorescence assay is established to titrate HRV-C infectious particles. Collectively, we develop an organoid-based system to reproducibly propagate the poorly cultivable HRV-C, followed by a comprehensive characterization of HRV-C infection and innate immunity in physiologically active respiratory organoids. The organoid-based HRV-C infection model can be extended for developing antiviral strategies. More importantly, our study has opened an avenue for propagating and studying other uncultivable human and animal viruses.

The demand for lithium resources is growing rapidly due to the continuous development of the lithium-ion battery, which plays an important part in the renewable energy industry. Global sources of lithium are ores and brine, of which 59% are distributed in saline brine. However, the significant lithium resources in saline brine have not been fully utilized. The electrochemical deintercalation method (EDM) for lithium extraction from saline brine is a promising technique because of its environmental friendliness, high selectivity, and cost-effectiveness. Nevertheless, the application of EDM is greatly limited by the easy dissolution of electrode materials like LiMn2O4 and the cost of mass production. Also, there are a few existing review articles on the EDM for lithium extraction. To address this gap, this review provides a comprehensive overview of the current methods for lithium extraction from saline brine, systematically summarizes the technical status of the EDM, and pays special attention to the preparation method and modification of electrode materials. This review gives new insight into the mechanism of EDM and provides a new design strategy for the evaluation methods of EDM. This review presents the global lithium supply, demand, and distribution, and explains the importance of saline lithium extraction. It compares several common methods for salt lake lithium extraction. image

The electrochemical deintercalation method has been considered as an effective way to address the demand for lithium resources due to its environmental friendliness, high selectivity, and high efficiency. However, the performance of electrochemical lithium extraction is closely dependent on the electrode material and needs to be compatible under plateau environments with high-altitude and low-temperature. Herein, an in situ self-oxidation method is conducted to construct a hybrid conductive network on the surface of LiFePO4 (LFP-HN). The introduction of a hybrid conductive network enhanced the interfacial electron/lithium-ion transfer. In addition, structural stability is strengthened through suppressing the intercalation of impurity cations. Consequently, the LFP-HN delivered extremely high lithium extraction capacity (27.42 mg g-1), low energy consumption (4.91 Wh mol-1), and superior purity (91.05%) in Baqiancuo real brine (4788 m, -10 °C). What's more, LFP-HN-based large-scale prototypes are constructed and operated at Baqiancuo, which is calculated to extract 25 kg Lithium Carbonate Equivalent per cycle (4.55 h, 100 pairs of plates). Based on the excellent performance, the modification strategy developed in this work can be a promising solution for industrial lithium extraction under high-altitude environment.

The respiratory epithelium, particularly the airway epithelium, is the primary infection site for respiratory pathogens. The apical surface of epithelial cells is constantly exposed to external stimuli including invading pathogens. Efforts have been made to establish organoid cultures to recapitulate the human respiratory tract. However, a robust and simple model with an easily accessible apical surface would benefit respiratory research. Here, we report the generation and characterization of apical-out airway organoids from the long-term expandable lung organoids that we previously established. The apical-out airway organoids morphologically and functionally recapitulated the human airway epithelium at a comparable level to the apical-in airway organoids. Moreover, apical-out airway organoids sustained productive and multicycle replication of SARS-CoV-2, and accurately recapitulated the higher infectivity and replicative fitness of the Omicron variants BA.5 and B.1.1.529 and an ancestral virus. In conclusion, we established a physiologically relevant and convenient apical-out airway organoid model for studying respiratory biology and diseases.

A novel nanoporous Ni(OH) 2 @ZnO core–shell architecture is successfully synthesized via a hydrothermal reaction and atomic layer deposition (ALD). This hybrid material exhibited a well‐defined core–shell nanostructure with high purity and good crystallinity. The conductivity of the electrodes is obviously enhanced by the ALD ZnO thin film. Compared to the conventional Ni(OH) 2 , the Ni(OH) 2 coated with 10 nm of ZnO exhibited significantly enhanced performance, with a maximum specific capacitance value of ≈1,400 F g −1 at a current density of 1 A g −1 , which is attributed to the improved charge‐transfer resistance. The asymmetric Ni(OH) 2 @ZnO//graphene supercapacitor exhibited a good capacitance retention rate and an energy density of 32 Wh kg −1 at a power density of 480 W kg −1 , which are higher than those of pure nanostructured Ni(OH) 2 and ZnO‐based asymmetric supercapacitors. The remarkable electrochemical performance is contributed to the synergetic presence of the core–shell nanostructure with a high surface area and the highly conductive ZnO films with optimized thickness, which achieve appropriate mass ratio control of the active material. The design of the core–shell architectures demonstrated in this work is expected to be a new and promising approach to ALD for the development of hybrid electrode materials for high‐performance supercapacitor applications.

The high transmissibility of SARS- CoV-2 Omicron subvariants was generally ascribed to immune escape. It remained unclear whether the emerging variants have gradually acquired replicative fitness in human respiratory epithelial cells. We sought to evaluate the replicative fitness of BA.5 and earlier variants in physiologically active respiratory orga-noids. BA.5 exhibited a dramatically increased replicative capacity and infectivity than B.1.1.529 and an ancestral strain wildtype (WT) in human nasal and airway organoids. BA.5 spike pseudovirus showed a significantly higher entry efficiency than that carry-ing WT or B.1.1.529 spike. Notably, we observed prominent syncytium formation in BA.5-infected nasal and airway organoids, albeit elusive in WT-and B.1.1.529-infected organoids. BA.5 spike-triggered syncytium formation was verified by lentiviral overex-pression of spike in nasal organoids. Moreover, BA.5 replicated modestly in alveolar organoids, with a significantly lower titer than B.1.1.529 and WT. Collectively, the higher entry efficiency and fusogenic activity of BA.5 spike potentiated viral spread through syncytium formation in the human airway epithelium, leading to enhanced replicative fitness and immune evasion, whereas the attenuated replicative capacity of BA.5 in the alveolar organoids may account for its benign clinical manifestation.

A robust in vitro model of the human respiratory epithelium, including the alveolar and the airway epithelium, is essential for understanding the biology and pathology of the human respiratory system. We previously described a protocol to derive human lung organoids from primary lung tissues. We now describe a protocol to induce bidirectional differentiation to generate mature alveolar or airway organoids. The lung organoids are consecutively expanded for over one year with high stability, while the differentiated alveolar and airway organoids morphologically and functionally simulate the human alveolar and airway epithelium to a near-physiological level. Thus, we establish a robust organoid culture system of the entire human respiratory epithelium, the first two-phase bipotential organoid culture system that enables long-term expansion and bidirectional differentiation of respiratory epithelial cells. The long-term expandable lung organoids and differentiated organoids generate a stable and renewable source of respiratory epithelial cells, enabling scientists to reconstruct and expand the human respiratory epithelium in culture dishes. The respiratory organoid system provides a unique and physiologically active in vitro model of the human respiratory epithelium for various applications, including studying respiratory viral infection, disease modeling, drug screening, and pre-clinical testing. Graphical abstract.

With potentially high lithium (Li) exchange capacity and long cycle ability, Ti-based oxides of H2TiO3 and H4Ti5O12 are considered to be promising Li-ion sieve (LIS) materials applied for Li resource extraction in the liquid phase. However, the LISs usually demonstrate unsatisfactory Li exchange performance under the approximately neutral condition without the strong impetus derived from the rapid combination between OH- in the surrounding solution and H+ ionized from LIS. Herein, a hybrid of H2TiO3/H4Ti5O12 with rich phase boundaries is constructed via a facile one-step solid-state method. Owing to the different Fermi energy levels of the two phases, the electrons are transferred at the phase interface between H2TiO3 and H4Ti5O12, developing an internal electric field (IEF). The built IEF provides an extra driving force to boost the solid-phase Li+ transport, hence enhancing the Li extraction kinetics. Threrfore, the H2TiO3/H4Ti5O12 hybrid exhibits outstanding Li exchange performance of 42.43 and 20.50 mg g-1 under alkaline and neutral conditions, corresponding to the hightest Li extraction rate of 5.30 and 2.05 mg g-1 h-1 reported so far. Our work offers an innovative strategy to promote the Li exchange performance of LIS especially under neutral conditions.

Horseshoe bats host numerous SARS-related coronaviruses without overt disease signs. Bat intestinal organoids, a unique model of bat intestinal epithelium, allow direct comparison with human intestinal organoids. We sought to unravel the cellular mechanism(s) underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids. We optimized the culture medium, which enabled a consecutive passage of bat intestinal organoids for over one year. Basal expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human counterparts. Notably, bat organoids mounted a more rapid, robust and prolonged antiviral defense than human organoids upon Poly(I:C) stimulation. TLR3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal organoids. The susceptibility of bat organoids to a bat coronavirus CoV-HKU4, but resistance to EV-71, an enterovirus of exclusive human origin, indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain viruses. Importantly, TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 infection. Collectively, the higher basal expression of antiviral genes, especially more rapid and robust induction of innate immune response, empowered bat cells to curtail virus propagation in the early phase of infection.

The lack of a robust in vitro model of the human respiratory epithelium hinders the understanding of the biology and pathology of the respiratory system. We describe a defined protocol to derive human lung organoids from adult stem cells in the lung tissue and induce proximal differentiation to generate mature airway organoids. The lung organoids are then consecutively expanded for over 1 year with high stability, while the differentiated airway organoids are used to morphologically and functionally simulate human airway epithelium to a near-physiological level. Thus, we establish a robust organoid model of the human airway epithelium. The long-term expansion of lung organoids and differentiated airway organoids generates a stable and renewable source, enabling scientists to reconstruct and expand the human airway epithelial cells in culture dishes. The human lung organoid system provides a unique and physiologically active in vitro model for various applications, including studying virus-host interaction, drug testing, and disease modeling.

Cobalt oxides (Co x O y ) have shown great potential for applications in catalysts, sensors, and energy storage fields, and their performance remarkably depends on their oxidation states. Herein, Co x O y films with precisely controlled composition are first introduced by atomic layer deposition (ALD) using bis( N , N 0‐di‐iso‐propylacetamidinato)cobalt(II) (Co(iPr 2 ‐Me‐AMD) 2 ) as Co precursor and H 2 O/O 3 as oxidants. The results show that the ALD processes using both oxidants exhibit typical self‐limiting characteristic, where cubic‐CoO films, with growth rate of 0.045 nm per cycle, are obtained at 150–200 °C using H 2 O oxidant, while cubic‐Co 3 O 4 films, with growth rate of 0.05 nm per cycle, can be deposited at 200–225 °C using O 3 oxidant. Both CoO and Co 3 O 4 films show dense, smooth microstructure, and good crystallinity with typical columnar crystal feature, where the Co 3 O 4 film shows smaller columnar size because the O 3 promotes rapid nucleation with relatively higher density of nucleation sites. The thermodynamic growth mechanism of ALD process is established via density functional theory calculations, which demonstrates that the exothermic reaction path of O 3 is more energetically than that of H 2 O. Both films possess relatively low resistivity of ≈10 −1 Ω cm −1 with p‐type semiconductor behavior, which shows promising application potentials of these films.

ALD-metallic films are typically deposited with assistant of plasma due to lack of suitable reducing co-reactants. In this work, we propose to use RCpCo(CO)2, a cobalt precursor with cyclopentadienyl (Cp) ligand (R = H) or its trimethylsilylderivative (R = TMS), and tert-Butyl amine (tBuNH2) as co-reactant to grow metallic Co films by thermal atomic layer deposition (T-ALD). The influence of Co precursor type, substrate type and thermal treatment on the film growth, composition, and phase structure of the Co films was investigated. The results show that the ALD-Co processes exhibit similar temperature window from 275 degrees C to 325 degrees C, and the growth rate of Co films deposited from CpCo(CO)2 on Si substrate is about 0.045 nm/cycle, which is higher than that of using TMSCpCo(CO)2 (0.03 nm/cycle). Thermal annealing and Pt substrate can promote the crystallization and growth of Co crystals. The ALD-Co films grown by CpCo(CO)2 showed relatively low resistivity of 10.6 mu omega.cm and considerable conformality, indicating a significant application potential.

The airways and alveoli of the human respiratory tract are lined by two distinct types of epithelium, which are the primary targets of respiratory viruses. We previously established long-term expanding human lung epithelial organoids from lung tissues and developed a 'proximal' differentiation protocol to generate mucociliary airway organoids. However, a respiratory organoid system with bipotential of the airway and alveolar differentiation remains elusive. Here we defined a 'distal' differentiation approach to generate alveolar organoids from the same source for the derivation of airway organoids. The alveolar organoids consisting of type I and type II alveolar epithelial cells (AT1 and AT2, respectively) functionally simulate the alveolar epithelium. AT2 cells maintained in lung organoids serve as progenitor cells from which alveolar organoids derive. Moreover, alveolar organoids sustain a productive SARS-CoV-2 infection, albeit a lower replicative fitness was observed compared to that in airway organoids. We further optimized 2-dimensional (2D) airway organoids. Upon differentiation under a slightly acidic pH, the 2D airway organoids exhibit enhanced viral replication, representing an optimal in vitro correlate of respiratory epithelium for modeling the high infectivity of SARS-CoV-2. Notably, the higher infectivity and replicative fitness of the Omicron variant than an ancestral strain were accurately recapitulated in these optimized airway organoids. In conclusion, we have established a bipotential organoid culture system able to reproducibly expand the entire human respiratory epithelium in vitro for modeling respiratory diseases, including COVID-19.