Tsingke has delivered high-quality biotechnology services and products to nearly 300,000 users globally. The number of high-level academic papers published using Tsingke's products and services has grown steadily year after year, continuously driving the advancement of life science research.
We have selected five high-impact papers, published in prestigious journals such as Cell and Signal Transduction and Targeted Therapy, spanning a range of fields from gene function to immunotherapy and beyond.
Compilation of High-Impact Literature
1.
Title: Transport mechanism and pharmacology of the human GlyT1
DOI: 10.1016/j.cell.2024.02.026
Journal: Cell
Impact Factor: 64.5
Summary:
Research has shown that Glycine Transporter 1 (GlyT1) plays a key role in regulating both inhibitory and excitatory neurotransmission by removing glycine from the synaptic cleft. Due to its close association with the glutamate/glycine co-activated NMDA receptors (NMDARs), GlyT1 has become a central target for the treatment of schizophrenia related to NMDA receptor dysfunction. This study explored the cryo-EM structures of GlyT1 in complex with its substrate glycine and the drugs ALX-5407, SSR504734, and PF-03463275, revealing three fundamental states of the transport cycle: the outward-open, closed, and inward-open states, providing a detailed depiction of the conformational changes associated with glycine reuptake. Furthermore, the study identified three specific pockets for drug binding, offering a structural basis for their inhibitory mechanisms and selectivity. Together, these structures provide important insights into the transport mechanism of GlyT1 and the recognition of substrates and antipsychotic drugs, thus laying the foundation for the design of small molecule drugs for treating schizophrenia.
2.
Title: Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer
DOI: 10.1038/s41392-024-01772-w
Journal: Signal Transduction and Targeted Therapy
Impact Factor: 39.3
Summary:
Despite the success of immune checkpoint therapies, resistance and relapse remain common in lung cancer. Cancer stem cells (CSCs) are an important factor in immune therapy resistance. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, has shown synergistic effects with immunotherapy. This study shows that the key rate-limiting enzyme CPT1A in fatty acid oxidation, together with L-carnitine from tumor-associated macrophages, drives ferroptosis resistance and CD8+ T cell dysfunction in lung cancer. Mechanistically, CPT1A inhibits the ubiquitination and degradation of c-Myc, which transcriptionally activates CPT1A expression. The CPT1A/c-Myc positive feedback loop enhances the NRF2/GPX4 system and reduces the quantity of phospholipid polyunsaturated fatty acids, boosting cellular antioxidant capacity and suppressing ferroptosis in CSCs. Importantly, targeting CPT1A enhances anti-tumor immunity and ferroptosis in immune checkpoint blockade therapy in tumor-bearing mice. These results present a metabolic vulnerability-targeting approach to improve lung cancer immunotherapy efficacy.
3.
Title: CircPPAP2B controls metastasis of clear cell renal cell carcinoma via HNRNPC-dependent alternative splicing and targeting the miR-182-5p/CYP1B1 axis
DOI: 10.1186/s12943-023-01912-w
Journal: Molecular Cancer
Impact Factor: 37.3
Summary:
This study explores the role and regulatory mechanism of circular RNA circPPAP2B in clear cell renal cell carcinoma (ccRCC). Renal cell carcinoma (RCC) is one of the most common malignant tumors worldwide, with metastasis being the leading cause of RCC-related death. Circular RNA (circRNA) plays a significant regulatory role in cancer metastasis, but its function and mechanisms in RCC remain unclear. The study found that circPPAP2B is highly expressed in highly invasive ccRCC cells and metastatic ccRCC tissues, and its expression is associated with poor prognosis. Functional experiments showed that circPPAP2B promotes ccRCC cell proliferation and metastasis. Mechanistic studies revealed that circPPAP2B interacts with HNRNPC in an m6A-dependent manner, promoting its nuclear translocation, and regulates the interaction between HNRNPC and splicing factors PTBP1 and HNRNPK, affecting the selective splicing of pre-mRNA. Additionally, circPPAP2B acts as a miRNA sponge, binding to miR-182-5p and increasing the expression of CYP1B1. The study reveals that circPPAP2B promotes ccRCC proliferation and metastasis through HNRNPC-dependent selective splicing and the miR-182-5p/CYP1B1 axis, highlighting the potential of circPPAP2B as a therapeutic target for ccRCC.
4.
Title:Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma
DOI: 10.1016/j.cmet.2023.11.019
Journal: Cell Metabolism
Impact Factor: 29
Summary:
This study reveals that the gut microbiota plays a key role in the treatment of multiple myeloma (MM), which is still considered incurable due to its resistance. Nitrogen cycle bacteria in the gut were found to be enriched in MM patients. However, the role of these bacteria in MM relapse remains unclear. The study highlights the specific enrichment of Citrobacter freundii (C. freundii) in relapsed MM patients. Through fecal microbiota transplantation experiments, it was demonstrated that C. freundii plays a critical role in inducing resistance in MM by increasing circulating ammonia levels. Ammonia enters MM cells via the transmembrane channel protein SLC12A2, stabilizing NEK2 protein, which promotes chromosomal instability and resistance. The study also found that the loop diuretic furosemide sodium can downregulate SLC12A2, inhibit ammonia uptake in MM cells, and improve progression-free survival and treatment efficacy scores. These findings provide new therapeutic targets and strategies for intervening in MM progression and resistance.
5.
Title: CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation
DOI: 10.1038/s41423-023-01103-z
Journal: Cell Mol Immunol
Impact Factor: 24.1
Summary:
This study found that the G protein-coupled receptor ADGRE5 (CD97) can bind to various metabolites that play important regulatory roles in metabolism. However, its function in antiviral innate immune responses has not been fully defined. The study reports that CD97 inhibits virus-induced type I interferon (IFN-I) release and enhances RNA virus replication in both cells and mice. CD97 was identified as a novel negative regulator of the innate immune receptor RIG-I, with the degradation of RIG-I leading to the suppression of the IFN-I signaling pathway. Additionally, overexpression of CD97 promoted the ubiquitination of RIG-I, leading to its degradation, but did not affect the expression of its mRNA. Mechanistically, CD97 induces the expression of RNF125, which mediates K48-linked ubiquitination at the Lys181 site of RIG-I after RNA virus infection, leading to its degradation. Most importantly, compared to wild-type mice, CD97-deficient mice were more resistant to RNA virus infection. The study found that CD97 inhibition mediated by berberine effectively blocked the replication of VSV and SARS-CoV-2. These findings elucidate the unknown mechanism by which CD97 negatively regulates RIG-I in antiviral innate immune responses and provide a molecular basis for the development of new therapeutic strategies and the design of targeted antiviral drugs.
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