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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
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Function: formatAIDetailSummary
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Line: 260
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Line: 316
Function: require_once
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Filename: controllers/Detail.php
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857409 | PMC |
http://dx.doi.org/10.1126/science.abe3255 | DOI Listing |
bioRxiv
December 2024
Bioengineering Graduate Group, University of Pennsylvania, PA 19104.
Cells contain membrane-bound and membraneless organelles that operate as spatially distinct biochemical niches. However, these subcellular reaction centers lose fidelity with aging and as a result of disease. A grand challenge for biomedicine is restoring or augmenting cellular functionalities.
View Article and Find Full Text PDFNature
January 2025
Department of Genetics, Stanford University, Stanford, CA, USA.
Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery and basic research. However, established technologies such as chimeric antigen receptors can only detect immobilized antigens, have limited output scope and lack built-in drug control. Here we engineer synthetic G-protein-coupled receptors (GPCRs) that are capable of driving a wide range of native or non-native cellular processes in response to a user-defined antigen.
View Article and Find Full Text PDFACS Synth Biol
December 2024
School of Life Sciences, Anhui University, Hefei 230601, China.
Microbial cell factories provide a nontoxic, economical way for the synthesis of various chemicals and drugs, garnering significant attention from researchers. However, excessive dispersion of enzymes and accumulation of intermediate metabolites in the production process will weaken the reaction efficiency of the pathway enzyme. In this study, a cellular compartment was constructed to isolate the enzyme reaction space and optimize the modular metabolic synthesis.
View Article and Find Full Text PDFVet Sci
November 2024
Jiangsu Key Laboratory for High-Tech Research and Development of Veterinary Biopharmaceuticals, Engineering Technology Research Center for Modern Animal Science and Novel Veterinary Pharmaceutic Development, Jiangsu Agri-Animal Husbandry Vocational College, Taizhou 225300, China.
Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that infect pigs' intestinal epithelial cells, causing high morbidity and mortality. Due to the rapid mutation of PEDV, vaccine efficacy is uncertain, prompting exploration of alternative treatments. Nanobodies, also known as variable heavy chain domains of heavy chain-only antibodies (VHHs), offer significant potential in biomedical applications due to their small size and high specificity.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518055, China.
The recent advancements on membrane protein degraders (MPDs) have broadened the applicability of proteolysis-targeting chimeras (PROTACs) beyond intracellular proteins to include the previously "undruggable" cell-surface targets. However, the potential toxicity of MPDs caused by undesired off-target degradation poses a significant challenge to clinical deployment, mirroring concerns associated with PROTACs. Here, we introduce a conditionally activatable membrane protein degrader (Pro-MPD), which leverages the specificity and high affinity of biparatopic nanobodies combined with a tumor microenvironment-activated cell-penetrating peptide (Pro-CPP) to achieve on-target activated internalization and degradation of PD-L1 within tumor sites.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!