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.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study used electroencephalogram measurements to investigate the effects of aging on oscillatory theta modulation during an audiovisual discrimination task. By a wavelet-based time-frequency ...analysis, age-related theta oscillation response differences were observed within a relatively restricted time range (0-500 ms) over frontal-central regions. Older adults showed stronger theta spectral power during visual and audiovisual stimuli in the left frontal regions; however, young adults showed stronger theta spectral power during auditory and audiovisual stimuli in the central regions. These findings suggest that multisensory oscillatory theta responses differ according to age, which further proves that the left frontal regions play an important role in audiovisual integration.
Recent studies have attempted to demonstrate the importance of the characteristics of directional cues and observers’ traits in attentional orienting. This study investigated how attentional ...orienting is influenced by target processing. Two experiments showed the critical role played by target processing in attentional orienting that relies on eye-gaze and arrow cues. In Experiment
1
, stronger attentional orienting was observed under the object-target condition compared with the scrambled-display condition, irrespective of whether gaze or arrow cues were used. The results indicated that meaningful targets produced stronger attentional orienting than did meaningless targets, regardless of the social characteristics of the target. Experiment
2
, which investigated whether attentional orienting was influenced by differences in the meaningfulness of targets regardless of their perceptual features, used participants’ own faces and the faces of others as target stimuli; one’s own face is typically more meaningful than the face of another. The results showed stronger attentional orienting in response to one’s own face than in response to another’s face under both gaze and arrow conditions. These findings suggest that the use of task-irrelevant meaningful information as targets may be effective in enhancing attention, regardless of perceptual features.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and purpose: With the increasing sensitivity of axillary imaging and ultrasound guided biopsy, some clinically axillary negative patients were upstaged to axillary positive (cN1) and ...received axillary lymph node dissection (ALND). This study aimed to assess the feasibility of sentinel lymph node (SLN) biopsy (SLNB) in patients with axilla negative evaluation by physical examination but suspicious lymph nodes finding on preoperative imaging and metastasis confirmed with a fine-needle aspiration cytology/core-needle biopsy pathology (FNAC/CNBP). Methods: This retrospective cohort study included patients with early breast cancer who had axilla negative evaluation by physical examination but suspicious lymph nodes finding on preoperative imaging and metastasis confirmed with a FNAC/CNBP from October 2015 to December 2022 in the Breast Cancer Centre of Shandong Cancer Hospital and Institute. All patients received ALND. The data were analyzed by using SPSS version 27.0 statistical software, and P<0.05 was considered statistically significant. Results: A total of 158 patients were identified to have axilla negative evaluation by physical examination but one to two suspicious lymph nodes finding on preoperative imaging and metastasis confirmed with FNAC/CNBP, 43.7% (69/158) of them had only one ALN metastasis after ALND, 15.2% (24/158) had only two ALNs metastases after ALND, and 41.1% (65/158) had more than two ALNs metastases after ALND. Among these cases, 65 patients received SLNB followed by ALND, and the false negative rate of SLNB was 0%. Positive non-SLN metastasis rate was 0 in the 61.5% (40/65) patients with 1-2 positive SLNs metastasis. One, two, three and more than three non-SLN metastasis rates were 10.8% (7/65), 4.6% (3/65), 6.2% (4/65) and 16.9% (11/65), respectively (P=0.042). Conclusion: SLNB was safe and feasible in patients with axilla negative evaluation by physical examination but one to two suspicious lymph nodes finding on preoperative imaging and metastasis confirmed with a FNAC/CNBP. In these patients, the axillary lymph node tumor burden was high, and exhaustive radiotherapy and systematic treatment were needed to control reginal disease.
The classification of electroencephalogram (EEG) motor imagery signals has emerged as a prominent research focus within the realm of brain-computer interfaces. Nevertheless, the conventional, limited ...categories (typically just two or four) offered by brain-computer interfaces fail to provide an extensive array of control modes. To address this challenge, we propose the Time-Spatial Parallel Network (TSPNet) for recognizing six distinct categories of upper limb motor imagery. Within TSPNet, temporal and spatial features are extracted separately, with the time dimension feature extractor and spatial dimension feature extractor performing their respective functions. Following this, the Time-Spatial Parallel Feature Extractor is employed to decouple the connection between temporal and spatial features, thus diminishing feature redundancy. The Time-Spatial Parallel Feature Extractor deploys a gating mechanism to optimize weight distribution and parallelize time-spatial features. Additionally, we introduce a feature visualization algorithm based on signal occlusion frequency to facilitate a qualitative analysis of TSPNet. In a six-category scenario, TSPNet achieved an accuracy of 49.1% ± 0.043 on our dataset and 49.7% ± 0.029 on a public dataset. Experimental results conclusively establish that TSPNet outperforms other deep learning methods in classifying data from these two datasets. Moreover, visualization results vividly illustrate that our proposed framework can generate distinctive classifier patterns for multiple categories of upper limb motor imagery, discerned through signals of varying frequencies. These findings underscore that, in comparison to other deep learning methods, TSPNet excels in intention recognition, which bears immense significance for non-invasive brain-computer interfaces.
Ionic protein-lipid interactions are critical for the structure and function of membrane receptors, ion channels, integrins and many other proteins. However, the regulatory mechanism of these ...interactions is largely unknown. Here we show that Ca(2+) can bind directly to anionic phospholipids and thus modulate membrane protein function. The activation of T-cell antigen receptor-CD3 complex (TCR), a key membrane receptor for adaptive immunity, is regulated by ionic interactions between positively charged CD3ε/ζ cytoplasmic domains (CD3(CD)) and negatively charged phospholipids in the plasma membrane. Crucial tyrosines are buried in the membrane and are largely protected from phosphorylation in resting T cells. It is not clear how CD3(CD) dissociates from the membrane in antigen-stimulated T cells. The antigen engagement of even a single TCR triggers a Ca(2+) influx and TCR-proximal Ca(2+) concentration is higher than the average cytosolic Ca(2+) concentration. Our biochemical, live-cell fluorescence resonance energy transfer and NMR experiments showed that an increase in Ca(2+) concentration induced the dissociation of CD3(CD) from the membrane and the solvent exposure of tyrosine residues. As a consequence, CD3 tyrosine phosphorylation was significantly enhanced by Ca(2+) influx. Moreover, when compared with wild-type cells, Ca(2+) channel-deficient T cells had substantially lower levels of CD3 phosphorylation after stimulation. The effect of Ca(2+) on facilitating CD3 phosphorylation is primarily due to the charge of this ion, as demonstrated by the fact that replacing Ca(2+) with the non-physiological ion Sr(2+) resulted in the same feedback effect. Finally, (31)P NMR spectroscopy showed that Ca(2+) bound to the phosphate group in anionic phospholipids at physiological concentrations, thus neutralizing the negative charge of phospholipids. Rather than initiating CD3 phosphorylation, this regulatory pathway of Ca(2+) has a positive feedback effect on amplifying and sustaining CD3 phosphorylation and should enhance T-cell sensitivity to foreign antigens. Our study thus provides a new regulatory mechanism of Ca(2+) to T-cell activation involving direct lipid manipulation.
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IJS, KISLJ, NUK, UL, UM, UPUK
A new silver-promoted 3+2 cycloaddition of azomethine ylides with isocyanides has been described. The methodology provides an efficient and modular approach to 1,2,4-trisubstituted imidazoles of ...vital bioactive molecules and atypical antipsychotics analogues.
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