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The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants., Introduction Since the start of the pandemic in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has led to over 660 million cases of coronavirus disease 2019 [...]

Cell hashing, a nucleotide barcode-based method that allows users to pool multiple samples and demultiplex in downstream analysis, has gained widespread popularity in single-cell sequencing due to its compatibility, simplicity, and cost-effectiveness. Despite these advantages, the performance of this method remains unsatisfactory under certain circumstances, especially in experiments that have imbalanced sample sizes or use many hashtag antibodies. Here, we introduce a hybrid demultiplexing strategy that increases accuracy and cell recovery in multi-sample single-cell experiments. This approach correlates the results of cell hashing and genetic variant clustering, enabling precise and efficient cell identity determination without additional experimental costs or efforts. In addition, we developed HTOreader, a demultiplexing tool for cell hashing that improves the accuracy of cut-off calling by avoiding the dominance of negative signals in experiments with many hashtags or imbalanced sample sizes. When compared to existing methods using real-world datasets, this hybrid approach and HTOreader consistently generate reliable results with increased accuracy and cell recovery. [ABSTRACT FROM AUTHOR]

The construction of deep foundation pits that are adjacent to an operating subway tunnel can cause significant disturbance to the surrounding soil and tunnel structure. Assessing the stability of the soil in the security area of the tunnel is key to controlling the displacement of the tunnel structure. Assuming that the soil behind the wall is in the elastic stage of small deformation, the unloading stress distribution law of the soil on the excavation surface of the side wall is inversely calculated using the horizontal displacement curve of the retaining structure. Based on the analytical solutions for the horizontal displacement and surface settlement of the soil behind the wall proposed in this paper, the spatial distribution characteristics of the deformation transfer of the soil in the security area are obtained. Considering the interaction between the soil in the security area and the tunnel structure, by simplifying the soil in the security area to a Pasternak foundation model, the tunnel displacement that is caused by deformation transfer can be obtained. The correctness of the theoretical model is verified by comparing it with the measured data for the soil displacement behind the wall and the tunnel structure in project cases of foundation pit excavation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effect of Apocynin on compressive force‐induced apoptosis and autophagy in periodontal ligament stem cells (PDLSCs). Materials and Methods: Periodontal ligament stem cells were subjected to a uniform compressive force of 2.0 g/cm2 for 24 h, without and with addition of 50, 100 and 200 μM Apocynin. Beclin‐1 was overexpressed in PDLSCs. Flow cytometry was used to assess apoptosis and transmission electron microscopy was used to evaluate ultrastructural features of PDLSCs. Immunofluorescence was used to assess the levels of microtubule‐associated protein 1 light chain 3 (LC3). The protein levels of B‐cell lymphoma‐2 (Bcl‐2), Bcl‐2 associated X (Bax), Caspase‐3, LC3, and Beclin were determined by Western blot analysis. Results: Compressive force of PDLSCs significantly increased apoptosis, Bax, Caspase‐3, the number of autophagosome or autolysosomes, Beclin‐1, the ratio of LC3 II/LC3 I, and decreased Bcl‐2. Apocynin was shown to inhibit apoptosis and Beclin‐1‐mediated autophagy. Over‐expression of Beclin‐1 increased apoptosis and autophagy. Conclusions: Application of Apocynin attenuated long‐term compressive force‐induced apoptosis by regulating Beclin‐1‐mediated autophagy in PDLSCs. These results provide an alternative approach to improve orthodontic treatment outcomes for patients. [ABSTRACT FROM AUTHOR]

With the acceleration of urbanization, the distance between the underground structure and the aboveground structure is becoming smaller and smaller, and the mutual influence between them during earthquake is worthy of attention. In this study, a three-dimensional (3D) finite element (FE) analysis procedure was verified based on shaking table test data firstly. Subsequently, the validated FE analysis procedure was used to carry out an extended parameter analysis to study general seismic response of more complex aboveground structure-soil-underground structure systems. The key parameters, such as the height and number of aboveground structures, earthquake type, and distance between underground and aboveground structures, were considered. It was found that the tunnel-soil-aboveground structure interaction could effectively affect the acceleration and deformation response of both the ground and underground structures. With the increasing height and number of aboveground structures and the decreasing distance between underground and aboveground structures, the deformation of the underground structure tended to become larger. On the other hand, the existence of underground structure could effectively reduce the response of aboveground structure, and the influencing effect was found to be considerably affected by the distance between underground and aboveground structures. The findings obtained from this study could provide useful references for the seismic design of both aboveground and underground structures in urban areas. [ABSTRACT FROM AUTHOR]