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Significance During pathogenic invasion, neutralizing antibodies (nAbs) are involved in regulating immune clearance and evoking the host-protective response. We previously reported a highly potent nAb 8C11 against HEV, an RNA virus with an icosahedral capsid and associated with abundant acute hepatitis. Structural analysis demonstrates that the binding of 8C11 to HEV VLPs would result in tremendous spatial clashing with the capsid. Cryo-EM analysis showed that 8C11 binding leads to complete disorder of the outer rim of the VLP at earlier stages (∼15 min) and causes the dissociation of HEV VLPs into homodimer species within 2 h. Similar 8C11-mediated dissociation was observed for the native HEV virion. Our results categorize a viral neutralization mechanism and suggest a strategy to generate 8C11-like antibodies., In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.

The influence of dispersed-phase viscosity on droplet breakup in a pump-mixer was determined using a direct measurement approach, which was performed using a high-speed online camera. The experimen...

Fluoropolymers with low surface energies are widely used in friction reduction, anti-corrosion, and anti-ice coatings. The fabrication of hierarchical micro- and nanostructures with fluoropolymers is beneficial for industrial application. In this study, a superhydrophobic composite coating was prepared by an improved air plasma spraying technique using feedstocks of Cr and polyfluoroalkoxy (PFA). A fluffy structure was found on the surface of the coating. A similar structure could not be found on the surface when the Fe and PFA powders were used as the feedstocks under the same condition. The characterization results suggest that the fluffy layer was derived from PFA. The formation of such a fluffy structure was attributed to the evaporation of Cr during spraying and their interaction with PFA droplets. This spraying method provides a new route for preparing hierarchical polymers, which have potential applicability in functional coatings.

Aim: Traditional antigenicity assay requires antigen recovery from the particulate adjuvants prior to analysis. An in situ method was developed for interrogating vaccine antigens with monoclonal antibodies while being adsorbed on adjuvants. Materials & methods: The fluorescence imaging-based high content analysis was used to visualize the antigen distribution on adjuvant agglomerates and to analyze the antigenicity for adsorbed antigens. Results: Simultaneous visualization and quantitation were achieved for dual antigens in a bivalent human papillomavirus vaccine with uniquely labeled antibodies. Good agreement was observed between the in situ multiplexed assays with well-established sandwich enzyme-linked immunosorbent assays. Conclusion: The streamlined procedures and the amenability for multiplexing make the in situ antigenicity analysis a favorable choice for in vitro functional assessment of bionanoparticles as vaccine antigens.

Entangling gates with error rates reaching the threshold for quantum error correction have been reported for CZ gates using adiabatic longitudinal control based on the interaction between the |11〉 and |20〉 states. Here, we design and implement nonadiabatic CZ gates, which outperform adiabatic gates in terms of speed and fidelity, with gate times reaching $$1.25/(2\sqrt 2 g_{01,10})$$ 1.25 ∕ ( 2 2 g 01 , 10 ) , and fidelities reaching 99.54 ± 0.08%. Nonadiabatic gates are found to have proportionally less incoherent error than adiabatic gates thanks to their fast gate times, which leave more room for further improvements in the design of the control pules to eliminate coherent errors. We also show that state leakage can be reduced to below 0.2% with optimisation. Furthermore, the gate optimisation process is highly feasible: experimental optimisation can be expected to take less than four hours. Finally, the gate design process can be extended to CCZ gates, and our preliminary results suggest that this process would be feasible as well, if we can measure the CCZ fidelity separate from the initialisation and readout errors in experimental optimisation.

Octadecylamine-coated CuS nanoparticles were designed and confirmed to play an important role in their electric response and boundary lubrication in the ester lubricant. For the case of CuS nanoparticles coated with crystalline surfactant, the surface potential is 18.47 ± 0.99 mV higher than with amorphous surfactant, owing to the random chain conformations of the octadecylamine molecules. When used as a lubricant additive, CuS nanoparticles (in the form of nanoplates or nanoarrays) with a crystalline surfactant were positively charged due to the presence of the amino headgroup in octadecylamine. The observed friction coefficient decreased from 0.18 to 0.09 and 0.05, respectively, when negative potential (for the copper lower pair) was applied across untreated CuS nanoparticles. However, thermally treated CuS nanoparticles showed good lubricating effect, but almost no effect of potential control since the amino groups were obscured by the disordered carbon chains, hindering electron transfer and weakening the response to externally applied electric field.

The yield, composition, structure and biofunction of microorganism exopolysaccharide (EPS) depended on their genetics and metabolic pathways. An EPS-producing endophytic fungus was isolated from Angelica sinensis planted in Dingxi, Gansu, China, and identified as Alternaria tenuissima F1. The production optimization, purification and characterization of the purified EPS from A. tenuissima F1 and the in-vitro antioxidant potentials was investigated. Results showed the optimal medium composition were 8% mannose, 2% yeast extract, 0.04% MgSO4·7H2O, 0.005% Vc, and the optimal cultivation conditions were set at initial pH 7.0, culture temperature 30 °C, inoculum size of 3%, 180 r/min for 5 d. The EPS purified by ion exchange column chromatography and gel chromatography was a non-reducing sugar and glycoprotein with pyranoid ring by Fourier transform infrared spectroscopy (FT-IR) analysis, displayed a porous network structure by scanning electron microscope (SEM) observation and exhibited a high thermal stability with the degradation temperature of 303.9 °C by thermogravimetric analysis (TG/DSC). Molecular weight of the purified EPS was 3.246 × 104 g/mol, and EPS was composed of d -galacturonic acid, rhamnose, d -mannose, glucose, and d -galactose in ratio of 0.45:3.02:3.25:1.0:0.95. The EPS exhibited strong scavenging activity and may be a new source of natural antioxidant.

The pulsed disc and doughnut column (PDDC) is a widely used type of liquid–liquid extraction equipment. Both the research and design of this type of equipment require in-depth knowledge of the dispersed phase droplet size distribution (DSD). The coupling of computational fluid dynamics (CFD) and population balance model (PBM) has exhibited a significant potential for predicting the DSD by considering droplet breakage and coalescence. In the present work, the CFD–PBM simulation is adopted to predict the DSD, and to investigate local liquid–liquid flow behaviors in a square-sectioned PDDC. The empirical correlations of the breakup kernels, which are based on our previous work [Hao Zhou et al., Direct measurement of droplet breakage in a pulsed disc and doughnut column. AIChE Journal, 2017, 63(9), 4188–4200], are implemented in the CFD code. For comparison, the kernel functions obtained by Coulaloglou and Tavlarides [Coulaloglou and Tavlarides. Description of interaction processes in agitated liquid–liquid dispersions. Chemical Engineering Science, 1977, 32, 1289–1297] are also tested. The class method with the fixed pivot technique is utilized to solve the population balance equations. The droplet size distribution predicted by the CFD–PBM simulation combined with the kernel functions that we have previously determined experimentally are observed to be more precise than those of Coulaloglou and Tavlarides. Accordingly, the CFD–PBM simulation results with the kernel functions of our proposed correlations are used to investigate the liquid–liquid flow behaviors in the PDDC. The influences of droplet size range and initial droplet size distribution at the dispersed phase inlet in the predicted DSD are discussed. The hydraulic performance of simulation results agrees well with experimental data. Local flow behaviors are illustrated to depict the typical flow characteristics of PDDC. The simulation results suggest that CFD–PBM method with the proposed PBM kernel functions is a promising approach for the simulation of liquid–liquid flow in the PDDC.

Quantum walks are the quantum analogs of classical random walks, which allow for the simulation of large-scale quantum many-body systems and the realization of universal quantum computation without time-dependent control. We experimentally demonstrate quantum walks of one and two strongly correlated microwave photons in a one-dimensional array of 12 superconducting qubits with short-range interactions. First, in one-photon quantum walks, we observed the propagation of the density and correlation of the quasiparticle excitation of the superconducting qubit and quantum entanglement between qubit pairs. Second, when implementing two-photon quantum walks by exciting two superconducting qubits, we observed the fermionization of strongly interacting photons from the measured time-dependent long-range anticorrelations, representing the antibunching of photons with attractive interactions. The demonstration of quantum walks on a quantum processor, using superconducting qubits as artificial atoms and tomographic readout, paves the way to quantum simulation of many-body phenomena and universal quantum computation.

Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.

In noise source identification based on the inverse boundary element method (IBEM), the boundary vibration velocity is predicted based on the field pressure through a transfer matrix of the vibration velocity and field pressure established on the Helmholtz integral equation. Because the matrix is often ill-posed, it needs to be regularized before reconstructing the vibration velocity. Two regularization methods and two methods of selecting the regularization parameter are investigated through the simulation analysis of a pulsating sphere. The result of transfer matrix regularization is further verified through the reconstruction of the vibration of an aluminum plate. Additionally, to reduce the large errors at some frequencies in the reconstruction result, increasing the number of measuring points is more effective than reducing the distance between the measurement plane and the sound source.

We have developed a direct measurement method for the breakage of droplet swarm in our previous work. However, experimental data for droplet breakage is still extremely indispensable for the development and employment of population balance model (PBM). In this paper, the direct measurement of droplet breakage for a series of liquid-liquid systems has been carried out in a pulsed disc and doughnut column (PDDC) to meet the requirement. The data together with that in our previous work cover the main factors affecting the droplet breakage in the PDDC and are sufficient to support the establishment of useful empirical correlations for breakup frequency and daughter droplet size distribution. The experimental results and correlations all indicate that the breakup frequency function increases as the dispersed-phase viscosity or the interfacial tension decreases. The daughter droplet size distribution broadens considerably with decreasing interfacial tension.

The impacts of climate change and human activities on forage nutritional quality will affect nutrient capacity, livestock development and wildlife conservation in alpine regions. However, the response of forage nutritional quality to climate change and human activities remains indistinguishable across the whole Tibet. Here, six forage variables (i.e., crude protein, CP; ether extract, EE; crude ash, Ash; acid detergent fiber, ADF; neutral detergent fiber, NDF; water-soluble carbohydrates, WSC) together represented forage nutritional quality. We estimated potential forage CP, EE, Ash, ADF, NDF and WSC contents using growing mean air temperature, total precipitation and total radiation based on random forest models. We also estimated actual forage CP, EE, Ash, ADF, NDF and WSC contents using growing mean air temperature, total precipitation and total radiation, and maximum normalized difference vegetation index based on random forest models. Climate change had nonlinear effects on potential forage CP, EE, Ash, ADF, NDF and WSC contents. Radiation change predominated the variations of potential forage nutritional quality. Human activities altered the sensitivities of forage nutritional quality to climate change. The effects of human activities on forage nutritional quality increased with increasing longitude and precipitation, and decreasing elevation and radiation. Consequently, we should pay attention to the radiation change besides climate warming and precipitation change, at least for forage nutritional quality in alpine grasslands. The effects of human activities on forage nutritional quality can vary with longitude, elevation, precipitation and radiation in alpine grasslands.

Continuous monoculture can increase plant morbidity and reduce crop yields. However, the Ganoderma lucidum mushroom possesses unique nutrient acquisition methods and displays an altered response to the generation of reactive oxygen species (ROS). The effects of continuous cropping on G. lucidum remain unclear. Here, we investigated the effects of consecutive monoculture soil on the yield, bioactive components, antioxidant properties, nutrient metabolism, and enzyme activity of G. lucidum. The results showed no significant differences in terms of yield between the control check and treatment groups after 2 years. However, the content of polysaccharides and triterpenoids after 2 years of treatment and the content of total phenols and flavonoids after 3 years of treatment significantly increased. Moreover, the antioxidant activity (AOA) of the polysaccharides under consecutive monoculture soil treatments also significantly increased. These differences were caused by changes in nutrient metabolism and the activities of antioxidant and ligninolytic enzymes. Under continuous monoculture soil treatment, the content of reducing sugars, water-soluble sugars, free amino acids, and water-soluble proteins significantly increased. The activities of superoxide dismutase, manganese peroxidase, and lignin peroxidase increased with the time of continuous monoculture, while the activities of peroxidase, catalase, and laccase decreased. The increase in ligninolytic enzymes was postulated to mediate the ROS scavenging ability of G. lucidum. In conclusion, continuous cropping soil could increase the levels of bioactive components and AOAs of G. lucidum.

BackgroundThe various advantages associated with the growth properties of Escherichia coli have justified their use in the production of genetically engineered vaccines. However, endotoxin contamination, plasmid vector instability, and the requirement for antibiotic supplementation are frequent bottlenecks in the successful production of recombinant proteins that are safe for industrial-scaled applications. To overcome these drawbacks, we focused on interrupting the expression of several key genes involved in the synthesis of lipopolysaccharide (LPS), an endotoxin frequently responsible for toxicity in recombinant proteins, to eliminate endotoxin contamination and produce better recombinant proteins with E. coli.ResultsOf 8 potential target genes associated with LPS synthesis, we successfully constructed 7 LPS biosynthesis-defective recombinant strains to reduce the production of LPS. The endotoxin residue in the protein products from these modified E. coli strains were about two orders of magnitude lower than that produced by the wild-type strain. Further, we found that 6 loci—lpxM, lpxP, lpxL, eptA, gutQ and kdsD­—were suitable for chromosomal integrated expression of HPV L1 protein. We found that a single copy of the expression cassette conferred stable expression during long-term antibiotic-free cultivation as compared with the more variable protein production from plasmid-based expression. In large-scale fermentation, we found that recombinant strains bearing 3 to 5 copies of the expression cassette had 1.5- to 2-fold higher overall expression along with lower endotoxin levels as compared with the parental ER2566 strain. Finally, we engineered and constructed 9 recombinant E. coli strains for the later production of an HPV 9-valent capsid protein with desirable purity, VLP morphology, and antigenicity. ConclusionReengineering the LPS synthesis loci in the E. coli ER2566 strain through chromosomal integration of expression cassettes has potential uses for the production of a 9-valent HPV vaccine candidate, with markedly reduced residual endotoxin levels. Our results offer a new strategy for recombinant E. coli strain construction, engineering, and the development of suitable recombinant protein drugs.

BackgroundUrethrocutaneous fistula is one of the most common complications arising from hypospadias surgery. The purpose of our study was to investigate the effectiveness and safety of allogeneic human acellular dermal matrix (HADM) application as a means of preventing the occurrence of urethrocutaneous fistula following hypospadias surgery.MethodsThis is a non-randomized study of 219 cases (out of 270 patients with hypospadias) which satisfied inclusion and exclusion criteria. These patients were divided into two groups: 101 HADM patients, and 118 control patients (who did not receive HADM). In the control group, 77 boys were treated by single-stage urethroplasty (TIP) and 41 underwent staged urethroplasty (Thiersch-Duplay). In the HADM group, 59 boys underwent the TIP and 42 underwent the Thiersch-Duplay. In the postoperative period, we recorded the incidence of infection, urethrocutaneous fistula, and urethral stricture complications in these two groups of patients. The effectiveness and safety of HADM in preventing urethrocutaneous fistula following hypospadias surgery were evaluated according to these indicators.ResultsIn the control group, following the operation there were 16 cases of infection, 38 cases of urethrocutaneous fistula after extubating, and 5 cases of urethral stricture. In the HADM group, there were 19 cases of postoperative infection, 12 cases of urethrocutaneous fistula after extubating, and 5 children with urethral stricture. In comparing the two groups, it was found that the postoperative infection rate (13.6 vs. 18.8%) and the incidence of urethral stricture (4.2 vs. 5.0%) were not statistically significant (P > 0.05), while the postoperative urethrocutaneous fistula rate (32.2 vs. 11.9%) was statistically significant (P < 0.001).ConclusionIt is found that HADM application can significantly reduce the incidence of urethrocutaneous fistula complications, without increasing the risk of infection and urethral stricture.

To report the clinical manifestation and genetic characteristics of a child with Thiamine metabolism dysfunction syndrome 5.Clinical data and genetic results were collected and analyzed. Peripheral blood samples of the child and their parents were collected for whole exome sequencing, and the functional effect of the variants on the TPK1 enzyme activity was verified by an in vitro assay.A four-year-old boy presented with preschool onset of ataxia were characterized. High-throughput sequencing identified a novel homozygous variant of TPK1 gene c.382GA (p.Leu128Phe). His father and mother were both found carrying the variant. The variant protein showed a 30.9% reduction in TPK1 enzyme activity compared with the wildtype.A novel pathogenic variant has been identified in a boy with thiamine metabolic dysfunction syndrome type 5.

Quantum machine learning is expected to be one of the first practical applications of near-term quantum devices. Pioneer theoretical works suggest that quantum generative adversarial networks (GANs) may exhibit a potential exponential advantage over classical GANs, thus attracting widespread attention. However, it remains elusive whether quantum GANs implemented on near-term quantum devices can actually solve real-world learning tasks. Here, we devise a flexible quantum GAN scheme to narrow this knowledge gap, which could accomplish image generation with arbitrarily high-dimensional features, and could also take advantage of quantum superposition to train multiple examples in parallel. For the first time, we experimentally achieve the learning and generation of real-world hand-written digit images on a superconducting quantum processor. Moreover, we utilize a gray-scale bar dataset to exhibit the competitive performance between quantum GANs and the classical GANs based on multilayer perceptron and convolutional neural network architectures, respectively, benchmarked by the Fr\'echet Distance score. Our work provides guidance for developing advanced quantum generative models on near-term quantum devices and opens up an avenue for exploring quantum advantages in various GAN-related learning tasks., Comment: This work was completed in 2019, and the first version of manuscript was submitted to the journal in January 2020

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both TH1- and TH2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.

Artificial intelligence and machine learning are growing computing paradigms, but current algorithms incur undesirable energy costs on conventional hardware platforms, thus motivating the exploration of more efficient neuromorphic architectures. Toward this end, we introduce here a memtransistor with gate-tunable dynamic learning behavior. By fabricating memtransistors from monolayer MoS

Periodically driven systems, or Floquet systems, exhibit many novel dynamics and interesting out-of-equilibrium phases of matter. Those phases arising with the quantum systems' symmetries, such as global $U(1)$ symmetry, can even show dynamical stability with symmetry-protection. Here we experimentally demonstrate a $U(1)$ symmetry-protected prethermal phase, via performing a digital-analog quantum simulation on a superconducting quantum processor. The dynamical stability of this phase is revealed by its robustness against external perturbations. We also find that the spin glass order parameter in this phase is stabilized by the interaction between the spins. Our work reveals a promising prospect in discovering emergent quantum dynamical phases with digital-analog quantum simulators., 14 pages, 4 figures, and supplementary materials

We experimentally study the ergodic dynamics of a 1D array of 12 superconducting qubits with a transverse field, and identify the regimes of strong and weak thermalization with different initial states. We observe convergence of the local observable to its thermal expectation value in the strong-thermalizaion regime. For weak thermalization, the dynamics of local observable exhibits an oscillation around the thermal value, which can only be attained by the time average. We also demonstrate that the entanglement entropy and concurrence can characterize the regimes of strong and weak thermalization. Our work provides an essential step towards a generic understanding of thermalization in quantum systems., Comment: 6+6 pages, 4+8 figures

Background: Previously, data mining methodology was used to identify 71 patented prescriptions in Chinese patent databases, indicating that Yin-nourishing therapy (YNT) may be an adjunct medication to hydroxychloroquine in the treatment of primary Sjögren’s syndrome (pSS). The purpose of this study was to investigate effects of the addition of YNT, which includes tonifying liver and kidney therapy (TLKT) and replenishing Qi and nourishing Yin therapy (RQNYT), in the treatment of pSS. Methods: Fourteen databases (including Chinese, English, Japanese, Korean and Latin databases) were searched to identify randomised controlled trials (RCTs) of YNT plus hydroxychloroquine (YNTPH) versus hydroxychloroquine alone in patients with pSS. Relevant publications up to June 2021 were selected. A meta-analysis and trial sequential analysis (TSA) were performed using Review Manager 5.3, Stata 14.0 and TSA 0.9 software. The quality of identified studies was assessed based on the Cochrane risk of bias tool and GRADE (grading of recommendations, assessment, development and evaluation) criteria. Results: We included five RCTs with a total of 345 participants. Pooled results indicated significant differences in short-term outcomes, which were assessed via European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), tear production, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulin G (IgG) results when YNTPH was compared with hydroxychloroquine use alone ( p < 0.05). No significant difference in salivary flow rate was reported. The most common side effect reported for both groups was gastrointestinal reaction. Sensitivity analyses suggested that heterogeneity might be ascribed to clinical methodology. Subgroup analyses revealed heterogeneities regarding salivary flow rate were eliminated. TLKT appeared to be better than RQNYT for improving salivary flow rate. TSA only supported changes in ESSPRI, ESSDAI and ESR values. For all studies, the quality of evidence was low. Conclusion: YNTPH may be an effective complementary therapy. Current evidence, however, is insufficient for determining whether YNTPH is more effective than hydroxychloroquine alone. Well-designed RCTs are needed to determine the role of YNT in pSS treatment.

Scaling up to a large number of qubits with high-precision control is essential in the demonstrations of quantum computational advantage to exponentially outpace the classical hardware and algorithmic improvements. Here, we develop a two-dimensional programmable superconducting quantum processor, Zuchongzhi, which is composed of 66 functional qubits in a tunable coupling architecture. To characterize the performance of the whole system, we perform random quantum circuits sampling for benchmarking, up to a system size of 56 qubits and 20 cycles. The computational cost of the classical simulation of this task is estimated to be 2-3 orders of magnitude higher than the previous work on 53-qubit Sycamore processor [Nature 574, 505 (2019)NATUAS0028-083610.1038/s41586-019-1666-5. We estimate that the sampling task finished by Zuchongzhi in about 1.2 h will take the most powerful supercomputer at least 8 yr. Our work establishes an unambiguous quantum computational advantage that is infeasible for classical computation in a reasonable amount of time. The high-precision and programmable quantum computing platform opens a new door to explore novel many-body phenomena and implement complex quantum algorithms.

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the still ravaging COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Significantly, both antibodies confer good mutation resistance to the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics, and can also inform the design of pan-sarbecovirus vaccines.

The discovery of interaction-driven insulating and superconducting phases in moir\'e van der Waals heterostructures has sparked considerable interest in understanding the novel correlated physics of these systems. While a significant number of studies have focused on twisted bilayer graphene, correlated insulating states and a superconductivity-like transition up to 12 K have been reported in recent transport measurements of twisted double bilayer graphene. Here we present a scanning tunneling microscopy and spectroscopy study of gate-tunable twisted double bilayer graphene devices. We observe splitting of the van Hove singularity peak by ~20 meV at half-filling of the conduction flat band, with a corresponding reduction of the local density of states at the Fermi level. By mapping the tunneling differential conductance we show that this correlated system exhibits energetically split states that are spatially delocalized throughout the different regions in the moir\'e unit cell, inconsistent with order originating solely from onsite Coulomb repulsion within strongly-localized orbitals. We have performed self-consistent Hartree-Fock calculations that suggest exchange-driven spontaneous symmetry breaking in the degenerate conduction flat band is the origin of the observed correlated state. Our results provide new insight into the nature of electron-electron interactions in twisted double bilayer graphene and related moir\'e systems., Comment: 24 pages, 5 figures

The Wigner crystal state, first predicted by Eugene Wigner in 19341, has fascinated condensed matter physicists for nearly 90 years2-10. Studies of two-dimensional (2D) electron gases first revealed signatures of the Wigner crystal in electrical transport measurements at high magnetic fields2-4. More recently optical spectroscopy has provided evidence of generalized Wigner crystal states in transition metal dichalcogenide (TMDC) moiré superlattices6-9. Direct observation of the 2D Wigner crystal lattice in real space, however, has remained an outstanding challenge. Scanning tunneling microscopy (STM) in principle has sufficient spatial resolution to image the Wigner crystal, but conventional STM measurements can potentially alter fragile Wigner crystal states in the process of measurement. Here we demonstrate real-space imaging of 2D Wigner crystals in WSe2/WS2 moiré heterostructures using a novel non-invasive STM spectroscopy technique. We employ a graphene sensing layer in close proximity to the WSe2/WS2 moiré superlattice for Wigner crystal imaging, where local STM tunneling current into the graphene sensing layer is modulated by the underlying electron lattice of the Wigner crystal in the WSe2/WS2 heterostructure. Our measurement directly visualizes different lattice configurations associated with Wigner crystal states at fractional electron fillings of n = 1/3, 1/2, and 2/3, where n is the electron number per site. The n=1/3 and n=2/3 Wigner crystals are observed to exhibit a triangle and a honeycomb lattice, respectively, in order to minimize nearest-neighbor occupations. The n = 1/2 state, on the other hand, spontaneously breaks the original C3 symmetry and forms a stripe structure in real space. Our study lays a solid foundation toward the fundamental understanding of rich Wigner crystal states in WSe2/WS2 moiré heterostructures. Furthermore, this new STM technique is generally applicable to imaging novel correlated electron lattices in different van der Waals moiré heterostructures.

The Wigner crystal

To investigate structural changes in scleral collagen fibers at various tissue depths before and after photosensitized crosslinking (CXL) both isolated scleral patch versus whole globe using second-harmonic generation (SHG) imaging.Scleral tissues were harvested from Sprague-Dawley rats and separated into three groups: untreated sclera (control), full-thickness scleral patch for CXL (Free Scleral CXL group), and sclera in intact globe for CXL (Globe CXL group). The CXL groups were soaked in 0.1% riboflavin and irradiated with 365 nm ultraviolet-A light (power, 0.45 mW/cm2) for 30 minutes. SHG images were acquired every 5 µm between 10 and 60 µm from the outer scleral surface. Collagen fiber waviness was calculated as the ratio of the total length of a traced fiber and the length of a straight path between the fiber ends.In the Free Scleral CXL group, collagen waviness was significantly increased compared to the control group at 35 to 50 µm (P0.05). In the Globe CXL group, collagen waviness was decreased compared to control at all depths with statistical significance (P0.05) achieved from 10 to 45 µm.Depending upon its initial state (i.e., free scleral patch versus mechanically loaded intact globe under pressure), collagen may experience different structural changes after CXL. In addition, the extent of the CXL effects may vary at different depths away from the surface.Understanding the CXL effects on collagen structure may be important in optimizing the scleral crosslinking protocol for future clinical applications such as preventing myopic progression.

In this study, we focused on the plant-growth-promoting properties of two strains isolated from Codonopsis pilosula, and the effect of inoculation with different strain treatments on physiological and metabolite accumulation of C. pilosula. The strains RHBA19 and RHBA17 were isolated and identified as Geobacillu sp. and Pseudomonas fluorescens, respectively. The two strains produced indole acetic acid (IAA), siderophore, biofilm, and various exoenzymes. Based on the pot experiments, inoculation of RHBA19 (G group) and the two mixed bacteria (M group) significantly improved the growth, root development, and photosynthesis of C. pilosula. Compared with the no-inoculation group (CK), the total polysaccharide content of root in the G and M groups was dramatically enhanced by 59.27% and 96.07%, and the lobetyolin (root) improved by 58.4% and 66.0%, respectively. After inoculation with bacteria agents, the activities of antioxidant enzymes (CAT, POD, SOD) of C. pilosula increased differentially. Inoculation with two types of bacterial agents significantly increased the activities of sucrose synthase (SS) and sucrose phosphate synthase (SPS) in root, and phenylalanine ammonia lyase (PAL) in leaf of C. pilosula. In addition, the content of signaling molecules (NO and H

Liquid superlubricity results in a near-frictionless lubrication state, which can greatly reduce friction and wear under aqueous conditions. However, during the running-in process, a large number of abrasive particles are generated, and because these may lead to a breakdown in superlubricity performance, they should be effectively removed. In this paper, the morphology, size, and composition of abrasive particles were verified using scanning electron microscopy with energy-dispersive X-ray spectroscopy, and their influence on liquid superlubricity was explored through friction tests. Subsequently, different solvents were used to remove the abrasive particles, and the optimal cleaning process was determined by macroscopic tribo-tests and microscopic analysis. Finally, droplet-spreading experiments and a force-curve analysis were carried out to understand the abrasive-particle removal mechanism by different solvents. We found that SiO2 was the main component in the abrasive particles, and micron-sized SiO2 particles resulted in random "wave peaks" in the coefficient of friction and, thus, the superlubricity. Absolute ethanol + ultrapure water was determined to be the optimal solvent for effectively removing abrasive particles from friction-pair surfaces and helped the lubricant in exhibiting an ultralow friction coefficient for long periods of time. We proposed a "wedge" and "wrap" model to explain the abrasive-particle removal mechanism of different solvents. The SiO2 removal mechanism outlined in this study can be applied under aqueous conditions to improve the stability and durability of liquid superlubricity in practical engineering applications.

Cervical cancer primarily results from persistent infection with high-risk types of human papillomavirus (HPV). HPV type 58 (HPV58) is an important causative agent, especially in Asia., Human papillomavirus type 58 (HPV58) is associated with cervical cancer and poses a significant health burden worldwide. Although the commercial 9-valent HPV vaccine covers HPV58, the structural and molecular-level neutralization sites of the HPV58 complete virion are not fully understood. Here, we report the high-resolution (∼3.5-Å) structure of the complete HPV58 pseudovirus (PsV58), determined by using cryo-electron microscopy (cryo-EM). Three representative neutralizing monoclonal antibodies (nAbs 5G9, 2H3, and A4B4) were selected through clustering from a panel of nAbs against HPV58. Bypassing the steric hindrance and symmetry mismatch in the HPV Fab-capsid immune complex, we present three different neutralizing epitopes in the PsV58 and show that, despite differences in binding, these nAbs share a neutralization mechanism. These results offer insight into HPV58 genotype specificity and broaden our understanding of HPV58 neutralization sites for antiviral research. IMPORTANCE Cervical cancer primarily results from persistent infection with high-risk types of human papillomavirus (HPV). HPV type 58 (HPV58) is an important causative agent, especially in Asia. Despite this, we still have limited data pertaining to the structural and neutralizing epitopes of HPV58, and this encumbers our in-depth understanding of the virus’ mode of infection. Here, we show that representative nAbs (5G9, 10B11, 2H3, 5H2, and A4B4) from three different groups share a neutralization mechanism that appears to prohibit the virus from associating with the extracellular matrix and cell surface. Furthermore, we determined that the nAbs engage via three different binding patterns: top-center binding (5G9 and 10B11), top-fringe binding (2H3 and 5H2), and fringe binding (A4B4). Our work shows that, despite differences in the pattern in binding, nAbs against HPV58 share a neutralization mechanism. These results provide new insight into HPV58 infection.

Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization.

Abstract Cigarette smoke has been identified as a major risk factor for the development of age-related macular degeneration (AMD). As an alternative to conventional cigarettes (C-cigarette), electronic cigarettes (E-cigarette) have been globally promoted and are currently widely used. The increasing usage of E-cigarettes raises concerns with regard to short- (2 weeks), medium- (3 months), and long- (8 months) term consequences related to retinal tissue. In this report, a controlled study in mouse models was conducted to probe the comprehensive effects of E-cigarette vapor on retina, retinal pigmented epithelium (RPE), and choroidal tissues by (1) comparing the effects of C-cigarette smoke and E-cigarette vapor on retina separately and (2) determining the effects of E-cigarette vapor on the RPE and analyzing the changes with regard to inflammatory (IL-1β, TNFα, iNOS) and angiogenic (VEGF, PEDF) mediators in retina/RPE/choroid by ELISA assays. The data showed that C-cigarette smoke exposure promoted an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor developed inflammatory and angiogenic reactions more pronounced in RPE and choroid as compared to retinal tissue, while nicotine-containing E-cigarette vapor caused even a more serious reaction. Both inflammatory and pro-angiogenic reactions increased with the extension of exposure time. These results demonstrate that exposure to C-cigarette smoke is harmful to the retina. Likewise, the exposure to E-cigarette vapor (with or without nicotine) increases the occurrence and progression of inflammatory and angiogenic stimuli in the retina, which might also be related to the onset of wet AMD in humans. Key messages C-cigarette smoke exposure promotes an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor develop inflammatory and angiogenic reactions more pronounced in RPE and choroid compared to retinal tissue, while nicotine-containing E-cigarette vapor causes even a more serious reaction. Both inflammatory and pro-angiogenic reactions increase with the extension of E-cigarette vapor exposure time.

Nano/microparticle-based formulations are attracting more and more attention in the drug and vaccine formulation field. Analytical methodologies are needed for analyzing the function of the protein molecules before and after their adsorption onto particles. Here, we report a fluorescence imaging-based high content analysis (HCA) for analyzing bimolecular interactions on the particle surface. Subtle conformational alteration of antigen epitope overlapping were shown to be feasible using this microplate-based HCA method. This HCA is highly amenable for automation, making it a method of choice for early formulation development as well as for stability test of products in late stage development.

Understanding various phenomena in non-equilibrium dynamics of closed quantum many-body systems, such as quantum thermalization, information scrambling, and nonergodic dynamics, is a crucial for modern physics. Using a ladder-type superconducting quantum processor, we perform analog quantum simulations of both the $XX$ ladder and one-dimensional (1D) $XX$ model. By measuring the dynamics of local observables, entanglement entropy and tripartite mutual information, we signal quantum thermalization and information scrambling in the $XX$ ladder. In contrast, we show that the $XX$ chain, as free fermions on a 1D lattice, fails to thermalize, and local information does not scramble in the integrable channel. Our experiments reveal ergodicity and scrambling in the controllable qubit ladder, and opens the door to further investigations on the thermodynamics and chaos in quantum many-body systems., Comment: 5 pages, 4 figures, and supplementary materials with 10 pages, 3 tables and 14 figures

The rapid emergence of Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) as a pandemic that presents an urgent human health crisis. Many SARS-CoV-2 neutralizing antibodies (NAbs) were developed with efficient therapeutic potential. NAbs-based therapeutics against SARS-CoV-2 are being expedited to preclinical and clinical studies with two antibody drugs, LY3819253 (LY-CoV555) and REGN-COV2 (REGN10933 and REGN10987), approved by the US Food and Drug Administration for emergency use authorization for treating COVID-19. In this review, we provide a systemic overview of SARS-CoV-2 specific or cross-reactive NAbs and discuss their structures, functions and neutralization mechanisms. We provide insight into how these NAbs specific recognize the spike protein of SARS-CoV-2 or cross-react to other CoVs. We also summarize the challenges of NAbs therapeutics such as antibody-dependent enhancement and viral escape mutations. Such evidence is urgently needed to the development of antibody therapeutic interventions that are likely required to reduce the global burden of COVID-19.

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

Synthetic two-dimensional polymorphs of boron, or borophene, have attracted attention because of their anisotropic metallicity, correlated-electron phenomena, and diverse superlattice structures. Although borophene heterostructures have been realized, ordered chemical modification of borophene has not yet been reported. Here, we synthesize "borophane" polymorphs by hydrogenating borophene with atomic hydrogen in ultrahigh vacuum. Through atomic-scale imaging, spectroscopy, and first-principles calculations, the most prevalent borophane polymorph is shown to possess a combination of two-center-two-electron boron-hydrogen and three-center-two-electron boron-hydrogen-boron bonds. Borophane polymorphs are metallic with modified local work functions and can be reversibly returned to pristine borophene through thermal desorption of hydrogen. Hydrogenation also provides chemical passivation because borophane reduces oxidation rates by more than two orders of magnitude after ambient exposure.

Emerging evidence suggested that epigenetic regulators can exhibit both activator and repressor activities in gene transcriptional regulation and disease development, such as cancer. However, how these dual activities are regulated and coordinated in specific cellular contexts remains elusive. Here, it is reported that KDM5C, a repressive histone demethylase, unexpectedly activates estrogen receptor alpha (ERα)‐target genes, and meanwhile suppresses type I interferons (IFNs) and IFN‐stimulated genes (ISGs) to promote ERα‐positive breast cancer cell growth and tumorigenesis. KDM5C‐interacting protein, ZMYND8, is found to be involved in both processes. Mechanistically, KDM5C binds to active enhancers and recruits the P‐TEFb complex to activate ERα‐target genes, while inhibits TBK1 phosphorylation in the cytosol to repress type I IFNs and ISGs. Pharmacological inhibition of both ERα and KDM5C is effective in inhibiting cell growth and tumorigenesis. Taken together, it is revealed that the dual activator and repressor nature of an epigenetic regulator together contributes to cancer development., A histone demethylase named KDM5C activates estrogen/estrogen receptor alpha‐target genes to promote cancer cell growth, while suppresses type I interferons and interferon‐stimulated genes to escape from immune surveillance. The dual activator and repressor nature of KDM5C together contributes to cancer development.

Safe and efficient interaction with other moving vehicles is crucial for autonomous vehicles. Speed planning affects the safety and smoothness of autonomous vehicles in dynamic environments, and is still an open problem. This paper focuses on how to avoid colliding with around moving vehicles by planning the speed of autonomous vehicles when its driving path is determined. The proposed method combines a heuristic search algorithm and a quadratic optimization algorithm to generate a safe and smooth speed profile for autonomous vehicles. In the interactions with other dynamic vehicles, the planning speed of the autonomous vehicles is adaptive to the changing environments. Finally, the feasibility and flexibility of the proposed method have been validated by the simulation results in two typical interaction scenarios by using Prescan Software.

We report the analog simulation of an ergodic-localized junction by using an array of 12 coupled superconducting qubits. To perform the simulation, we fabricated a superconducting quantum processor that is divided into two domains: one is a driven domain representing an ergodic system, while the second is localized under the effect of disorder. Because of the overlap between localized and delocalized states, for a small disorder there is a proximity effect and localization is destroyed. To experimentally investigate this, we prepare a microwave excitation in the driven domain and explore how deep it can penetrate the disordered region by probing its dynamics. Furthermore, we perform an ensemble average over 50 realizations of disorder, which clearly shows the proximity effect. Our work opens a new avenue to build quantum simulators of driven-disordered systems with applications in condensed matter physics and material science.

Fungal endophytes from medicinal plants have the potential to promote plant growth and the accumulation of active ingredients via different mechanisms. In this study, an endophytic fungus was isolated from the roots of Codonopsis pilosula, and was identified as Trichoderma strain RHTA01 based on morphological analysis, fatty acid composition, Fourier infrared spectroscopy and molecular analysis. The strain exhibited good plant growth promoting capacity. In C. pilosula plants inoculated with Trichoderma strain RHTA01, the plant defense system, total chlorophyll content and root activity were enhanced, and levels of antioxidant enzymes, non-enzymatic ingredients and single molecules including nitric oxide (NO), jasmonic acid (JA), salicylic acid (SA) and hydrogen peroxide (H2O2) were up-regulated in different tissues (Root, Stem and Leave). Activities of enzymes involved in polysaccharide and Lobetyolin biosynthesis were up-regulated, thus increasing their accumulation in C. pilosula plants. The function of endophytic fungi was further clarified by structural equation modeling (SEM). Overall, our results provide a strong foundation for further investigation of the interaction between endophytic fungi and plants.