Knowledge Sharing

GPCRs are key membrane signal-transduction proteins regulating diverse physiological functions. AT1R is critical for blood pressure and cardiovascular health. The activation mechanism of peptide-binding GPCRs like AT1R has long been a bottleneck. Using synthetic nanobodies, researchers resolved this issue, with results published in Cell, advancing GPCR research and drug development.

CD7 is a transmembrane glycoprotein mainly expressed on T cells, NK cells and their precursors. It is highly upregulated in hematologic malignancies including T-ALL and lymphomas. As an immunoglobulin superfamily member, CD7 mediates T-cell activation, adhesion and signaling, and serves as a key marker for T-cell malignancies. Its specific and stable expression makes it an ideal target for novel immunotherapies.

CD8 is a membrane‑bound glycoprotein expressed on cytotoxic T cells, subsets of NK cells and developing thymocytes. As an αβ heterodimer TCR co‑receptor, it binds MHC‑I to strengthen TCR affinity and promote T‑cell activation. Essential for antiviral and antitumor immunity, CD8 serves as a key target in tumor immunotherapy and immune regulation research.

CD8 is a membrane glycoprotein expressed on cytotoxic T cells, some NK cells and developing thymocytes. It acts as a TCR co-receptor, mostly as an αβ heterodimer, binding MHC-I to boost TCR-peptide-MHC affinity, enhance signaling and T-cell activation. Critical for antiviral and antitumor immunity, CD8 is a key target in tumor immunotherapy and immune mechanism studies.

2024 data from China’s National Health Commission shows Chinese adult overweight and obesity rates at 34.3% and 16.4%, meaning over half are overweight. Obesity raises risks of diabetes, cardiovascular diseases, cancers and metabolic syndrome. By 2050, over half of adults worldwide may be affected. Given limited lifestyle intervention efficacy and drug side effects, safe and effective novel anti-obesity strategies are urgently needed.

Psoriatic arthritis (PsA) is a chronic inflammatory disease impairing skin, joints and entheses, severely reducing patients’ quality of life. Conventional DMARDs and monoclonal antibodies show limited efficacy, poor tissue penetration and low synovial drug levels. IL‑17A and IL‑17F jointly drive PsA inflammation, so single‑cytokine inhibition is inadequate. Novel dual‑targeting antibodies with improved tissue penetration are urgently needed to overcome these therapeutic bottlenecks.

T-cell malignancies are aggressive hematologic tumors with high relapse and poor prognosis. CD5, a key marker of malignant T-cells, is also present on normal T-cells, so CD5-targeted CAR-T cannot distinguish tumor from normal cells, causing T-cell depletion and immune deficiency. NK cells are ideal effectors as they kill tumors without prior sensitization and do not express CD5, enabling safe targeting of CD5+ malignant T-cells.

Immune checkpoint inhibitors have revolutionized human cancer therapy, driving demand for comparable treatments in dogs. Canine spontaneous tumors resemble human cancers, making them excellent translational models. Yet specific anti-canine PD-L1 immunotherapies remain scarce. Current antibodies suffer from immunogenicity and high costs. Nanobody-based inhibitors could benefit veterinary oncology and inform human immunotherapy.

In the 1970s, scientists discovered the first incretin hormone, GIP (Glucose-Dependent Insulinotropic Polypeptide), and later identified the second incretin hormone: Glucagon-Like Peptide-1 (GLP-1). GLP-1 is secreted by intestinal L cells in the distal small intestine and proximal colon, encoded by the proglucagon gene, and is a polypeptide consisting of 30 amino acids[1-3].

Herpes Simplex Virus comprises HSV‑1 and HSV‑2, causing oral and genital herpes respectively. Both can lead to severe complications. Current drugs such as acyclovir only inhibit replication but not latency or recurrence. Conformational changes in gB also drive increasing drug resistance.

Chemokines are a class of small cytokines or signaling proteins secreted by cells. They are so named because of their ability to induce directional chemotaxis of nearby responsive cells. All their receptors belong to the G protein - coupled receptor (GPCR) family with 7 - transmembrane domains, and are mainly expressed in cells such as neutrophils, macrophages, epithelial cells, smooth muscle cells, and fibroblasts [1].

Brain disorders linked to NMDA receptor hypofunction, such as schizophrenia and GRIN1-related diseases, lack effective treatments. Traditional drugs lack selectivity and antibodies fail to cross the BBB. An international team developed bispecific nanobody DN13-DN1, which crosses the BBB, enhances mGlu2 activity, and improves cognitive and sensorimotor deficits in mouse models with stable efficacy and no obvious side effects, published in Nature.