AlphaFold2 in biomedical research: facilitating the development of diagnostic strategies for disease.

Proteins, as the primary executors of physiological activity, serve as a key factor in disease diagnosis and treatment. Research into their structures, functions, and interactions is essential to better understand disease mechanisms and potential therapies. DeepMind's AlphaFold2, a deep-learning protein structure prediction model, has proven to be remarkably accurate, and it is widely employed in various aspects of diagnostic research, such as the study of disease biomarkers, microorganism pathogenicity, antigen-antibody structures, and missense mutations. Thus, AlphaFold2 serves as an exceptional tool to bridge fundamental protein research with breakthroughs in disease diagnosis, developments in diagnostic strategies, and the design of novel therapeutic approaches and enhancements in precision medicine. This review outlines the architecture, highlights, and limitations of AlphaFold2, placing particular emphasis on its applications within diagnostic research grounded in disciplines such as immunology, biochemistry, molecular biology, and microbiology.

Identification of sulfakinin receptor regulating feeding behavior and hemolymph trehalose homeostasis in the silkworm, Bombyx mori.

Feeding behavior, the most fundamental physiological activity, is controlled by two opposing groups of factors, orexigenic and anorexigenic factors. The sulfakinin family, an insect analogue of the mammalian satiety factor cholecystokinin (CCK), has been shown to suppress food intake in various insects. Nevertheless, the mechanisms through which sulfakinin regulates feeding behavior remain a biological question. This study aimed to elucidate the signaling pathway mediated by the anorexigenic peptide sulfakinin in Bombyx mori. We identified the Bombyx mori neuropeptide G protein-coupled receptor A9 (BNGR-A9) as the receptor for sulfakinin through functional assays. Stimulation with sulfakinin triggered a swift increase in intracellular IP3, Ca2+, and a notable enhancement of ERK1/2 phosphorylation, in a manner sensitive to a Gαq-specific inhibitor. Treatment with synthetic sulfakinin resulted in decreased food consumption and average body weight. Additionally, administering synthetic sulfakinin to silkworms significantly elevated hemolymph trehalose levels, an effect markedly reduced by pre-treatment with BNGR-A9 dsRNA. Consequently, our findings establish the sulfakinin/BNGR-A9 signaling pathway as a critical regulator of feeding behavior and hemolymph trehalose homeostasis in Bombyx mori, highlighting its roles in the negative control of food intake and the positive regulation of energy balance.

[Advances in the application of AlphaFold2: a protein structure prediction model].

Protein structure prediction is an important research field in life sciences and medicine, and it is also a key application scenario of artificial intelligence in scientific research. AlphaFold2 is a protein structure prediction system developed by DeepMind based on deep learning, capable of efficiently generating the atomic-scale spatial structure of a protein from the amino acid sequence. It has demonstrated superior performance in the prediction of protein structures since its inception, thus attracting much attention and research. This paper introduces the model architecture, highlights, limitations, and application progress of AlphaFold2. Furthermore, it briefs the capabilities, highlights, and limitations of several other types of protein structure prediction models and prospects the future development direction in this field.

Aggregate assembly of ferrocene functionalized indium-oxo clusters.

In this study, we synthesized multi-nuclear indium oxide clusters (InOCs) using 1,1'-ferrocene dicarboxylic acid (H2FcDCA) as the chelating and surface protection ligand. The obtained clusters include the cubane-type heptanuclear InOCs ([In7]) and the sandwich-type thirteen-nuclear InOCs ([In13]). Notably, [In13] represents the highest nuclear number reported within the InOC family. In addition, the presence of labile coordination sites in these clusters allowed for structural modification and self-assembly. A series of [In7] clusters with adjustable band gaps have been obtained and the self-assembly of [In7] clusters resulted in the formation of an Fe-doped dimer, [Fe2In12], and an imidazole-bridged tetramer, [In28]. Similarly, in the case of [In13] clusters, the coordinated water molecules could be replaced by imidazole, methylimidazole, and even a bridged carboxylic acid, allowing the construction of one-dimensional extended structures. Additionally, part of the H2FcDCA could be substituted by pyrazole. This flexibility in replacing solvent molecules offered diverse possibilities for tailoring the properties and structures of the InOCs to suit specific applications.

Verifying AXL and putative proteins as SARS-CoV-2 receptors by DnaE intein-based rapid cell-cell fusion assay.

As the understanding of the mechanisms of SARS-CoV-2 infection continues to grow, researchers have come to realize that ACE2 and TMPRSS2 receptors are not the only way for the virus to invade the host, and that there are many molecules that may serve as potential receptors or cofactors. The functionality of these numerous receptors, proposed by different research groups, demands a fast, simple, and accurate validation method. To address this issue, we here established a DnaE intein-based cell-cell fusion system, a key result of our study, which enables rapid simulation of SARS-CoV-2 host cell infection. This system allowed us to validate that proteins such as AXL function as SARS-CoV-2 spike protein receptors and synergize with ACE2 for cell invasion, and that proteins like NRP1 act as cofactors, facilitating ACE2-mediated syncytium formation. Our results also suggest that mutations in the NTD of the SARS-CoV-2 Delta variant spike protein show a preferential selection for Spike-AXL interaction over Spike-LDLRAD3. In summary, our system serves as a crucial tool for the rapid and comprehensive verification of potential receptors, screening of SARS-CoV-2-neutralizing antibodies, or targeted drugs, bearing substantial implications for translational clinical applications.