An outbreak of coronavirus disease 2019 (COVID-19)
, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
, has spread globally. Countermeasures are needed to treat and prevent ...further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.
Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to ...treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 10
cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.
A resonant metasurface with high quality factor can not only localize light at the nanoscale but also manipulate the far-field radiation. In this work, we experimentally demonstrate an active ...Fano-resonant metasurface that combines an asymmetric silicon nanorod array with embedded germanium quantum dots. The collective resonance of the nanorods results in strong near-field confinement, and the nanorods also lead to directional emission. This gives rise to 3 orders of magnitude enhancement of the photoluminescence intensity with respect to the unpatterned area. Besides, due to the symmetry-breaking property of the structure, the light emission is of specific polarization. Moreover, by varying the geometric parameters of the nanorods, different resonances are spectrally overlapped, which can be utilized to manipulate the far-field radiation pattern. The metasurface shows enormous potential in manipulating light emission and provides a route for high-directionality, high-efficiency LEDs and potentially functional dielectric metasurface lasers.
Metasurface‐based lenses (metalenses) offer specific conceptual advantages compared to ordinary refractive lenses. For example, it is possible to tune the focal length of a metalens doublet by ...varying the relative angle between the two metalenses while fixing their distance, leading to an extremely compact zoom lens. An improved polarization‐insensitive design based on silicon nanocylinders on silica substrates is presented. This design is realized and characterized experimentally at 1550 nm wavelength. By varying the relative angle between the metalenses in steps of 10°, tuning of the doublet focal length is demonstrated from −54 mm to ±3 mm to +54 mm. This results in a zoom factor of an imaging system varying between 1 and 18. For positive focal lengths, the doublet focusing efficiency has a minimum of 34% and a maximum of 83%. Experiment and theory are in very good agreement.
In this work, experimental results following an optimized design of a zoom metalens doublet are presented, based on rotating two metasurfaces with respect to each other at fixed distance between them, at an operation wavelength of 1550 nm. The focal length could be adjusted from ±3 mm to ±54 mm, corresponding to extremal zoom factors of ±18× at an average focusing efficiency of 54%.
Benzimidazole fungicide residue in food products poses a risk to consumer health. Due to its localized electric-field enhancement and high-quality factor value, the metamaterial sensor is appropriate ...for applications regarding food safety detection. However, the previous detection method based on the metamaterial sensor only considered the resonance dip shift. It neglected other information contained in the spectrum. In this study, we proposed a method for highly sensitive detection of benzimidazole fungicide using a combination of a metamaterial sensor and mean shift machine learning method. The unit cell of the metamaterial sensor contained a cut wire and two split-ring resonances. Mean shift, an unsupervised machine learning method, was employed to analyze the THz spectrum. The experiment results show that our proposed method could detect carbendazim concentrations as low as 0.5 mg/L. The detection sensitivity was enhanced 200 times compared to that achieved using the metamaterial sensor only. Our present work demonstrates a potential application of combining a metamaterial sensor and mean shift in benzimidazole fungicide residue detection.
The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients ...with severe COVID-19, who were recruited in our previous UC-MSC clinical trial.
In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment. The primary endpoint was an altered proportion of whole-lung lesion volumes measured by high-resolution CT. Other imaging outcomes, 6 min walking distance (6-MWD), lung function, plasma biomarkers, and adverse events were also recorded and analyzed. This trial was registered with ClinicalTrials.gov (NCT04288102).
MSC administration improved in whole-lung lesion volume compared with the placebo with a difference of −10.8% (95% CI: −20.7%, −1.5%, p = 0.030) on day 10. MSC also reduced the proportion of solid component lesion volume compared with the placebo at each follow-up point. More interestingly, 17.9% (10/56) of patients in the MSC group had normal CT images at month 12, but none in the placebo group (p = 0.013). The incidence of symptoms was lower in the MSC group than in the placebo group at each follow-up time. Neutralizing antibodies were all positive, with a similar median inhibition rate (61.6% vs. 67.6%) in both groups at month 12. No difference in adverse events at the 1-year follow-up and tumor markers at month 12 were observed between the two groups.
UC-MSC administration achieves a long-term benefit in the recovery of lung lesions and symptoms in COVID-19 patients.
The National Key R&D Program of China, the Innovation Groups of the National Natural Science Foundation of China, and the National Science and Technology Major Project.
A high-speed and high-sensitivity avalanche photodetector (APD) is a critical component of a high-data-rate and low-power optical-communication link. In this paper, we study a high-speed and ...high-efficiency Ge/Si heterostructure APD. First, we numerically study the speed performance of the APD by analyzing frequency response. An optimized epitaxial structure of the high-speed APD is designed. In the absence of RC time effects, the APD exhibits a fast pulse response (full-width at half-maximum) of 10 ps and a high 3 dB bandwidth of 33 GHz at a high-gain value of 10. Taking device size and the corresponding RC time effects into account, the APD still achieves a high 3 dB bandwidth of 29 GHz at a gain value of 10. Moreover, a novel subwavelength periodic hole array is designed on the normal-incidence APD for enhancing light absorption without sacrificing speed performance. Near-perfect absorption is almost achieved by an infinite-period hole array due to the coupling of dual-resonance modes. A high-absorption efficiency of 64% is obtained by a limited-sized hole array in the high-speed APD. This work provides a promising method to design high-speed and high-efficiency normal-incidence Ge/Si heterostructure APDs for optical interconnect systems.
High-efficiency and high-speed photodetectors with broadband responses are playing pivotal roles for wavelength-division multiplexing optical communications. Germanium photodetectors on silicon ...platforms exhibit potential cost advantage due to the compatibility for monolithic integration with silicon-based electronic circuits for signal amplification and processing. In this article, we report a normal incidence, germanium photodetector enabled by guided-mode resonances in photonic crystal, which successfully resolved the compromise between quantum efficiency, wavelength coverage and bandwidth requirement, a drawback usually faced by conventional photodetectors operating at normal incidence. The resonant photonic crystal structure is designed to support multiple resonances in the target wavelength range. With an intrinsic absorption layer thickness of 350 nm, the device achieved a high external quantum efficiency of 50% at 1550 nm, along with an enhancement around 300% for the entire C-band. Using a mesa diameter of 14 μm, the fabricated device exhibited a 3-dB bandwidth of 33 GHz and obtained clear eye diagrams at bit rate up to 56 Gbps. This work provides a promising method to design high-efficiency, high-speed, normal incidence germanium photodetectors for optical interconnect systems.
Background
The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples ...from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections.
Methods
In this real‐world study, we enrolled 143 COVID‐19‐vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti‐spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4‐BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed.
Results
Patients with liver cancer receiving booster doses had higher levels of anti‐spike RBD IgG against circulating omicron (BA.4‐BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4‐BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti‐spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti‐spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients.
Conclusion
Our study found that there may be differences in vaccine response and protective effect against COVID‐19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID‐19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.
Background
The gut is an important site for human immunodeficiency virus (HIV) infection and immune responses. The role of gut mucosal immune cells in immune restoration in patients infected with HIV ...undergoing antiretroviral therapy remains unclear.
Methods
Ileocytes, including 54 475 immune cells, were obtained from colonoscopic biopsies of five HIV‐negative controls, nine immunological responders (IRs), and three immunological non‐responders (INRs) and were analyzed using single‐cell RNA sequencing. Immunohistochemical assays were performed for validation. The 16S rRNA gene was amplified using PCR in faecal samples to analyze faecal microbiota. Flow cytometry was used to analyze CD4+ T‐cell counts and the activation of T cells.
Results
This study presents a global transcriptomic profile of the gut mucosal immune cells in patients infected with HIV. Compared with the IRs, the INRs exhibited a lower proportion of gut plasma cells, especially the IGKC+IgA+ plasma cell subpopulation. IGKC+IgA+ plasma cells were negatively associated with enriched f. Prevotellaceae the INRs and negatively correlated with the overactivation of T cells, but they were positively correlated with CD4+ T‐cell counts. The INRs exhibited a higher proportion of B cells than the IRs. Follicular and memory B cells were significantly higher in the INRs. Reduced potential was observed in the differentiation of follicular or memory B cells into gut plasma cells in INRs. In addition, the receptor‐ligand pairs CD74_MIF and CD74_COPA of memory B/ follicular helper T cells were significantly reduced in the INRs, which may hinder the differentiation of memory and follicular B cells into plasma cells.
Conclusions
Our study shows that plasma cells are dysregulated in INRs and provides an extensive resource for deciphering the immune pathogenesis of HIV in INRs.
Key points
An investigation was carried out at the single‐cell‐level to analyze gut mucosal immune cells alterations in PLWH after ART.
B cells were significantly increased and plasma cells were significantly decreased in the INRs compared to the IRs and NCs.
There are gaps in the transition from gut follicular or memory B cellsinto plasma cells in INRs.
(1) An investigation was carried out at the single‐cell level to analyse gut mucosal immune cell alterations in PLWH after ART. (2) B cells were significantly increased and plasma cells were significantly decreased in the INRs compared to the IRs and NCs. (3) There are gaps in the transition from gut follicular or memory B cells into plasma cells in INRs.
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