Immunomagnetic microscopy of tumor tissues using quantum sensors in diamond.

Histological imaging is essential for the biomedical research and clinical diagnosis of human cancer. Although optical microscopy provides a standard method, it is a persistent goal to develop new imaging methods for more precise histological examination. Here, we use nitrogen-vacancy centers in diamond as quantum sensors and demonstrate micrometer-resolution immunomagnetic microscopy (IMM) for human tumor tissues. We immunomagnetically labeled cancer biomarkers in tumor tissues with magnetic nanoparticles and imaged them in a 400-nm resolution diamond-based magnetic microscope. There is barely magnetic background in tissues, and the IMM can resist the impact of a light background. The distribution of biomarkers in the high-contrast magnetic images was reconstructed as that of the magnetic moment of magnetic nanoparticles by employing deep-learning algorithms. In the reconstructed magnetic images, the expression intensity of the biomarkers was quantified with the absolute magnetic signal. The IMM has excellent signal stability, and the magnetic signal in our samples had not changed after more than 1.5 y under ambient conditions. Furthermore, we realized multimodal imaging of tumor tissues by combining IMM with hematoxylin-eosin staining, immunohistochemistry, or immunofluorescence microscopy in the same tissue section. Overall, our study provides a different histological method for both molecular mechanism research and accurate diagnosis of human cancer.

Direct Formation of Amide-Linked C-Glycosyl Amino Acids and Peptides via Photoredox/Nickel Dual Catalysis.

Glycoproteins account for numerous biological processes including those associated with diseases and infections. The advancement of glycopeptides has emerged as a promising strategy for unraveling biological pathways and discovering novel medicines. In this arena, a key challenge arises from the absence of efficient synthetic strategies to access glycopeptides and glycoproteins. Here, we present a highly concise approach to bridging saccharides with amino acids and peptides through an amide linkage. Our amide-linked C-glycosyl amino acids and peptides are synthesized through cooperative Ni-catalyzed and photoredox processes. The catalytic process generates a glycosyl radical and an amide carbonyl radical, which subsequently combine to yield the C-glycosyl products. The saccharide reaction partners encompass mono-, di-, and trisaccharides. All 20 natural amino acids, peptides, and their derivatives can efficiently undergo glycosylations with yields ranging from acceptable to high, demonstrating excellent stereoselectivities. As a substantial expansion of applications, we have shown that simple C-glycosyl amino acids can function as versatile building units for constructing C-glycopeptides with intricate spatial complexities.

Field-programmable gate array and deep neural network-accelerated spatial-spectral interferometry for rapid optical dispersion analysis.

Spatial-spectral interferometry (SSI) is a technique used to reconstruct the electrical field of an ultrafast laser. By analyzing the spectral phase distribution, SSI provides valuable information about the optical dispersion affecting the spectral phase, which is related to the energy distribution of the laser pulses. SSI is a single-shot measurement process and has a low laser power requirement. However, the reconstruction algorithm involves numerous Fourier transform and filtering operations, which limits the applicability of SSI for real-time dispersion analysis. To address this issue, this Letter proposes a field-programmable gate array (FPGA)-based deep neural network to accelerate the spectral phase reconstruction and dispersion estimation process. The results show that the analysis time is improved from 124 to 9.27 ms, which represents a 13.4-fold improvement on the standard Fourier transform-based reconstruction algorithm.

New Constraints on Exotic Spin-Spin-Velocity-Dependent Interactions with Solid-State Quantum Sensors.

We report new experimental results on exotic spin-spin-velocity-dependent interactions between electron spins. We designed an elaborate setup that is equipped with two nitrogen-vacancy (NV) ensembles in diamonds. One of the NV ensembles serves as the spin source, while the other functions as the spin sensor. By coherently manipulating the quantum states of two NV ensembles and their relative velocity at the micrometer scale, we are able to scrutinize exotic spin-spin-velocity-dependent interactions at short force ranges. For a T-violating interaction, V_{6}, new limits on the corresponding coupling coefficient, f_{6}, have been established for the force range shorter than 1 cm. For a P,T-violating interaction, V_{14}, new constraints on the corresponding coupling coefficient, f_{14}, have been obtained for the force range shorter than 1 km.

Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization.

BACKGROUND: Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels. METHODS: We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses. RESULTS: The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features. CONCLUSIONS: The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.

Noise Prediction and Reduction of Single Electron Spin by Deep-Learning-Enhanced Feedforward Control.

Noise-induced control imperfection is an important problem in applications of diamond-based nanoscale sensing, where measurement-based strategies are generally utilized to correct low-frequency noises in realtime. However, the spin-state readout requires a long time due to the low photon-detection efficiency. This inevitably introduces a delay in the noise-reduction process and limits its performance. Here we introduce the deep learning approach to relax this restriction by predicting the trend of noise and compensating for the delay. We experimentally implement feedforward quantum control of the nitrogen-vacancy center in diamond to protect its spin coherence and improve the sensing performance against noise. The new approach effectively enhances the decoherence time of the electron spin, which enables exploration of more physics from its resonant spectroscopy. A theoretical model is provided to explain the improvement. This scheme could be applied in general sensing schemes and extended to other quantum systems.

Fabrication of Janus Composite Membranes with a Gradient Pore Structure Based on Melt Electrowriting and Solution Electrospinning for Directional Water Transport.

As a functional textile, the directional water transport textile has been widely used in daily life due to the ability of excellent moisture absorption and quick drying. However, it is still a great challenge to construct a textile that ensures water to transport rapidly from the skin to the outer environment (positive direction) and prevents the skin from being rewetted effectively in the reverse direction. Herein, this study aims to improve the ability of the hydrophobic layer in moisture management using melt electrowriting (MEW) to fabricate gradient pore structures precisely. The pore sizes in different layers can be tailored by altering the collector speed, and thus, the configuration of the pore structure dominates the process of water transportation. The unique multilayered structure achieves the directional water transport effects by improving the permeability with large pores and hindering the transport with small pores in the reverse direction. Meanwhile, we use solution electrospinning (SE) technology to fabricate the hydrophilic layer. The constructed composite membranes exhibit excellent performance with a one-way transport index R up to 1281% and a desired overall moisture management capacity (OMMC) of 0.87. This research outlines an approach to fabricating Janus membranes to enhance its directional water transport performance, facilitating the MEW technique to be applied on the more expanded field for directional water transport textiles.

Immobilization of Actinobacillus succinogenes on nano- and micro-fiber membranes for efficient and robust production of succinic acid.

This work aimed to study the efficiency of nano- and micro- fiber membranes in immobilizing Actinobacillus succinogenes CCTCC M2012036 for succinic acid production. Among the four kinds of electrospun nanofiber membranes of cellulose acetate, chitosan, poly(vinyl alcohol) (PVA) and chitosan-PVA, the cellulose acetate nanofiber membrane-immobilized cells performed the best with a succinic acid concentration and yield to be 27.3 ± 3.5 g/L and 70.9 ± 5.8%. The cell-immobilized viscose microfiber membrane presented good reuse stability, and 17 batches of fermentation without activity loss were realized with the highest succinic acid yield of 83.20%. A microfiber membrane bioreactor was further constructed with the cell-immobilized viscose microfiber membrane to perform fermentation on a larger scale, and the concentration, yield and productivity of succinic acid were 73.20 g/L, 86.50% and 1.49 g/(L⋅h) using a fed-batch strategy, which were 124.30%, 127.60% and 124.2% of those obtained in the traditional fermenter. This study provided an approach for improving the practicality of biological succinic acid production.

Excited-State Spectroscopy of Spin Defects in Hexagonal Boron Nitride.

A negatively charged boron vacancy (VB-) color center in hexagonal boron nitride has recently been proposed as a promising quantum sensor due to its excellent properties. However, the spin level structure of the VB- color center is still unclear, especially for the excited state. Here we measured and confirmed the excited-state spin transitions of VB- using an optically detected magnetic resonance (ODMR) technique. The zero-field splitting of the excited state is 2.06 GHz, the transverse splitting is 93.1 MHz, and the g factor is 2.04. Moreover, negative peaks in fluorescence intensity and ODMR contrast at the level anticrossing point were observed, and they further confirmed that the spin transitions we measured came from the excited state. Our work deepens the understanding of the excited-state structure of VB- and promotes VB--based quantum sensing applications.

Trajectories of De Ritis ratio with risk of hepatocellular carcinoma and liver-related mortality following direct-acting antivirals for HCV: a retrospective longitudinal study up to 10 years.

The De Ritis ratio has good diagnostic accuracy in patients with chronic viral liver disease. However, its prognostic utility has remained controversial. This study was to identify different trajectories of De Ritis ratio in those hepatitis C patients cured and analyze the relationship between trajectory groups and risk of hepatocellular carcinoma (HCC) with liver-related mortality by the retrospective cohort study. This retrospective longitudinal cohort included 1241 patients with hepatitis C who underwent antiviral therapy since follow-up in 2012. De Ritis ratio trajectories were identified by the latent class growth mixed model. Patients were grouped into subgroups by De Ritis ratio according to longitudinal trajectories. The endpoints were HCC and liver-related mortality. Three distinct trajectory groups were characterized for serum De Ritis ratio: low-stable, middle-stable and high-rising. Fifty-one HCC and 11 liver-related mortality were recorded and tracked. Compared to the low-stable group, the adjusted hazard ratios (HRs) and 95% confidence interval (CI) associated with HCC and liver-related mortality were 2.02 (1.12 to 3.63), 9.36 (3.61 to 24.29), for the middle-stable, and high-rising group, respectively. Notably, the high-rising trajectory group still had prognostic significance after adjusting for preoperative levels. Likewise, for the high-rising trajectory group of sustained virological response, the HRs (95% CI) were 2.85 (1.03 to 10.75) for HCC and liver-related mortality, and in patients with cirrhosis, the HRs (95% CI) were 3.44 (1.64 to 7.19) and 4.35 (1.27 to 14.84) in the middle-stable trajectory group and the high-rising trajectory group, respectively. The dynamic measurements of De Ritis ratio are recommended to monitor the prognosis of Hepatitis C patients.

Experimental Investigation of Quantum Correlations in a Two-Qutrit Spin System.

We report an experimental investigation of quantum correlations in a two-qutrit spin system in a single nitrogen-vacancy center in diamond at room temperatures. Quantum entanglement between two qutrits was observed at room temperature, and the existence of nonclassical correlations beyond entanglement in the qutrit case has been revealed. Our work demonstrates the potential of the NV centers as the multiqutrit system to execute quantum information tasks and provides a powerful experimental platform for studying the fundamental physics of high-dimensional quantum systems in the future.

Asymmetric Transfer Hydrogenation of α-Substituted-ß-Keto Carbonitriles via Dynamic Kinetic Resolution.

A catalytic protocol for the enantio- and diastereoselective reduction of α-substituted-ß-keto carbonitriles is described. The reaction involves a DKR-ATH process with the simultaneous construction of ß-hydroxy carbonitrile scaffolds with two contiguous stereogenic centers. A wide range of α-substituted-ß-keto carbonitriles were obtained in high yields (94%-98%) and excellent enantio- and diastereoselectivities (up to >99% ee, up to >99:1 dr). The origin of the diastereoselectivity was also rationalized by DFT calculations. Furthermore, this methodology offers rapid access to the pharmaceutical intermediates of Ipenoxazone and Tapentadol.

Publisher Correction: Single-DNA electron spin resonance spectroscopy in aqueous solutions.

In the version of this paper originally published online, the ORCID ID for Peter Z. Qin was incorrectly assigned to Zhuoyang Qin. In addition, the ORCID for Fazhan Shi was omitted. These errors have been corrected in the print, PDF, and HTML versions of the paper.

Single-DNA electron spin resonance spectroscopy in aqueous solutions.

Magnetic resonance spectroscopy of single biomolecules under near-physiological conditions could substantially advance understanding of their biological function, but this approach remains very challenging. Here we used nitrogen-vacancy centers in diamonds to detect electron spin resonance spectra of individual, tethered DNA duplexes labeled with a nitroxide spin label in aqueous buffer solutions at ambient temperatures. This work paves the way for magnetic resonance studies on single biomolecules and their intermolecular interactions in native-like environments.

Polymorphisms of RIG-I-like receptor influence HBV clearance in Chinese Han population.

Retinoic acid-inducible gene I-like receptors (RLRs) play an essential role in human innate immune, which may influence the spontaneous clearance of hepatitis B virus (HBV) infection. We aimed to investigate whether the SNPs in RLR family were associated with HBV spontaneous clearance. The current study included 82 participants with spontaneous clearance, 601 asymptomatic hepatitis B surface antigen (HBsAg) carriers, and 168 participants with chronic hepatitis B (CHB). Six SNPs (DDX58 rs3824456, rs3205166, DHX58 rs2074160, rs2074158, IFIH1 rs2111485, rs3747517) were genotyped to explore their association with HBV spontaneous clearance. Patients carrying the mutant allele C at rs3824456 or A at rs2074160 were more likely to achieve spontaneous clearance compared with asymptomatic HBsAg carriers (additive model: odds ratio [OR] = 0.69, 95% confidence interval [CI] = 0.49-0.97; dominant model: OR = 0.54, 95% CI = 0.31-0.95, respectively). In addition, patients carrying the mutant allele G at rs2111485 were more likely to achieve spontaneous clearance compared with CHB (dominant model: OR = 0.47, 95% CI = 0.25-0.87). The mutations were protective factors for HBV spontaneous clearance. These results suggest the DDX58 rs3824456, DHX58 s2074160, IFIH1 rs2111485 were associated with spontaneous clearance of HBV, which may be predictive markers in the Chinese Han population of HBV.

Telomerase detection using a DNA-PAINT strategy.

Telomerase plays an important role in maintaining the length of telomere during cell division and is recognized as a new kind of biomarkers for cancer diagnosis. In this work, we present a brand new telomerase detection strategy based on a DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) like strategy. With an extraordinary spatial resolution (∼10 nm), the DNA-PAINT based strategy offers several advantages. First, it avoids complicated polymerase chain reaction and electrophoresis procedures. Second, it enables super resolution imaging of the reaction products with a high signal-to-noise ratio and facilitates the location of telomeric elongation sites on the single particle level, which results in a high sensitivity. Third, the detection scheme of the DNA-PAINT strategy allows directin situvisualization of the telomeric elongation process, which has never been achieved before. All these advantages make the DNA-PAINT telomerase detection strategy significant for dynamic investigation of telomerase related physiological processes as well as cancer diagnosis.

Effectiveness of ombitasvir/paritaprevir/ritonavir, dasabuvir for HCV in HIV/HCV coinfected subjects: a comprehensive analysis.

BACKGROUND: Data on the treatment of patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) coinfection remains limited. A comprehensive analysis was performed to evaluate the efficacy and safety of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir(r) ± dasabuvir (DSV) ± ribavirin (RBV) for treatment in HCV/HIV coinfected patients. METHODS: We systematically searched and included studies that enrolled patients with HIV/HCV coinfection using the OBV/PTV/r ± DSV ± RBV regimens and reported sustained virological response after 12 weeks (SVR12) end-of-treatment. Heterogeneity of results was assessed and pooled SVR rates were computed with 95% confidence intervals (95%CI). Subgroup analysis and assessment of publication bias through Egger's test were further performed. RESULTS: Ten studies containing 1358 coinfected patients were included in this study. The pooled estimate of SVR12 was 96.3% (95%CI: 95.1-97.4). Subgroup analysis showed that pooled SVR12 rate was 96.2% (95% CI: 94.8-97.4) for patients with genotype (GT) 1 and 98.8% (95% CI: 95.1-100.0) for those with GT4. The SVR12 rates for the treatment-naïve (TN) and treatment-experienced (TE) patients were 96.8% (95% CI, 94.8-98.5) and 98.9% (95% CI, 96.4-100.0), respectively. Pooled SVR12 rate was 97.8(95%CI: 94.6-99.8) for patients with cirrhosis and 96.7% (95%CI: 95.3-97.8) without cirrhosis. The pooled incidence of any adverse events (AEs) and serious adverse events (SAEs) was 73.9% (95%CI: 38.1-97.6) and 2.7% (95%CI: 0.0-9.5). Publication bias did not exist in this study. CONCLUSIONS: The comprehensive analysis showed high efficacy for the OBV/PTV/r ± DSV ± RBV regimen in patients coinfected with HIV and HCV, regardless of genotypes, history of treatment and the presence or absence of cirrhosis.

Experimental Demonstration of Uncertainty Relations for the Triple Components of Angular Momentum.

The uncertainty principle is considered to be one of the most striking features in quantum mechanics. In the textbook literature, uncertainty relations usually refer to the preparation uncertainty which imposes a limitation on the spread of measurement outcomes for a pair of noncommuting observables. In this work, we study the preparation uncertainty for the angular momentum, especially for spin-1/2. We derive uncertainty relations encompassing the triple components of angular momentum and show that, compared with the relations involving only two components, a triple constant 2/sqrt[3] often arises. Intriguingly, this constant is the same for the position and momentum case. Experimental verification is carried out on a single spin in diamond, and the results confirm the triple constant in a wide range of experimental parameters.

Experimental Adiabatic Quantum Factorization under Ambient Conditions Based on a Solid-State Single Spin System.

The adiabatic quantum computation is a universal and robust method of quantum computing. In this architecture, the problem can be solved by adiabatically evolving the quantum processor from the ground state of a simple initial Hamiltonian to that of a final one, which encodes the solution of the problem. Adiabatic quantum computation has been proved to be a compatible candidate for scalable quantum computation. In this Letter, we report on the experimental realization of an adiabatic quantum algorithm on a single solid spin system under ambient conditions. All elements of adiabatic quantum computation, including initial state preparation, adiabatic evolution (simulated by optimal control), and final state read-out, are realized experimentally. As an example, we found the ground state of the problem Hamiltonian S_{z}I_{z} on our adiabatic quantum processor, which can be mapped to the factorization of 35 into its prime factors 5 and 7.

Integrating single-cell RNA sequencing data to genome-wide association analysis data identifies significant cell types in influenza A virus infection and COVID-19.

With the global pandemic of COVID-19, the research on influenza virus has entered a new stage, but it is difficult to elucidate the pathogenesis of influenza disease. Genome-wide association studies (GWASs) have greatly shed light on the role of host genetic background in influenza pathogenesis and prognosis, whereas single-cell RNA sequencing (scRNA-seq) has enabled unprecedented resolution of cellular diversity and in vivo following influenza disease. Here, we performed a comprehensive analysis of influenza GWAS and scRNA-seq data to reveal cell types associated with influenza disease and provide clues to understanding pathogenesis. We downloaded two GWAS summary data, two scRNA-seq data on influenza disease. After defining cell types for each scRNA-seq data, we used RolyPoly and LDSC-cts to integrate GWAS and scRNA-seq. Furthermore, we analyzed scRNA-seq data from the peripheral blood mononuclear cells (PBMCs) of a healthy population to validate and compare our results. After processing the scRNA-seq data, we obtained approximately 70 000 cells and identified up to 13 cell types. For the European population analysis, we determined an association between neutrophils and influenza disease. For the East Asian population analysis, we identified an association between monocytes and influenza disease. In addition, we also identified monocytes as a significantly related cell type in a dataset of healthy human PBMCs. In this comprehensive analysis, we identified neutrophils and monocytes as influenza disease-associated cell types. More attention and validation should be given in future studies.