Since the first member of the Wnt family was identified in 1982, studies on Wnt signalling have been steadily increasing. The Wnt signalling pathways include noncanonical and canonical pathways. The noncanonical Wnt pathways are independent of β-catenin-T-cell factor/lymphoid enhancer-binding factor (TCF/LEF). The canonical Wnt pathway, also known as the Wnt/β-catenin pathway, involves the nuclear translocation of β-catenin and activation of target genes via TCF/LEF transcription factors. The canonical Wnt pathway mainly controls cell proliferation, whereas the noncanonical Wnt pathways regulate cell polarity and migration, and the two main pathways form a network of mutual regulati......2023-12-18

Osteochondral lesions and defects in joints are prevalent and pose a significant health concern, resulting in knee joint pain, dysfunction, and, ultimately, disability.While bone tissue is vascularized and possesses intrinsic regenerative capabilities, cartilage is avascular, aneural, and alymphatic, which limits its capacity for self-repair.Traditional clinical therapeutic approaches, such as microfracture, osteochondral grafts, and autologous cell transplantation, do not successfully improve the structure and function of the affected areas. Tissue engineering, which involves creating a scaffold that mimics tissue, offers a flexible solution for osteochondral regeneration. However, th......2023-12-15

Respiratory syncytial virus (RSV) is a negative single-stranded RNA virus of the Pneumoviridae family (order Mononegavirales) with a seasonal epidemic transmission pattern. RSV is highly contagious and a major cause of respiratory infections worldwide. Although disease is mild in most of the cases, vulnerable populations like very young infants, adults with chronic heart or lung disease, with weakened immune system, or over 65 years of age can experience a more severe disease course.Consistent with the massive disease burden that is posed by RSV infection, there is a large body of information that has been elucidated on RSV replication, pathogenesis, and transmission. Despite all that ......2023-12-11

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second bi......2023-11-29

Bladder cancer (BCa) is one of the most common tumors in urinary system. Approximately 90% of bladder cancers are uroepithelial cancers. According to the depth of invasion, BCa can be classified into nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). The overall 5-year survival rate of MIBC is approximately 60%-70%. About 10% of newonset MIBC is metastasized, and the 5-year survival rate is 5%-30%. The primary treatment for BCa is surgery and platinum-based chemotherapy. Although surgical or chemotherapeutic treatment is evolving, tumors still frequently relapse, significantly impacting patients’ quality of life and survival.Therefore, more indepth i......2023-11-24

Schizophrenia is a severe psychiatric disorder, significantly affecting individuals’ well-being and imposing a substantial societal health burden.Its diagnosis primarily relies on subjective assessments of clinical symptomatology. However, this approach is prone to misdiagnosis due to symptom overlap with other severe mental disorders. Meanwhile, there is high heterogeneity of response to antipsychotic drugs among patients. These clinical issues lead to delayed or inappropriate treatment for schizophrenia. Consequently, reliable and objective biomarkers that can guide clinicians towards precise diagnoses and treatment is urgently needed. Extracellular vesicles (EVs) are bilayer membr......2023-11-23