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......

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 inv......

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 membran......

The introduction of antibiotics into clinical use was arguably the greatest medical breakthrough of the 20th century. In addition to treating infectious diseases, antibiotics made many modern medical procedures possible, including surgery and organ transplantation. However, misuse of these valuable compounds has resulted in the rapid rise of antimicrobial resistance (AMR) with some infections now effectively untreatable.Most antibiotics used in the clinic originate from natural product scaffolds that were discovered by screening soil dwelling bacteria. However, to date, traditional screening sources seem overmined because they tend to yield previously known compounds. Because the drug ......

Fertility and reproductive lifespan in humans decrease dramatically with age. Prospective female parents of advanced age may experience increased risk of infertility, spontaneous miscarriages, perinatal mortality and congenital anomaly. Although assisted reproductive technologies can compensate for human suboptimal reproductive outcome to some extent, the success rate of assisted reproductive technology cycles declines with advanced age as well. This tendency is mainly associated with age-related deterioration of ovarian reserve and oocyte quality, along with a higher aneuploidy rate.On October 16, 2023,Bo Xiong, College of Animal Science and Technology, Nanjing Agricultural University......

Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are life threatening, inflammatory disease syndromes of the lung in which its function is critically compromised. ALI is characterized by an acute onset of respiratory distress, edema formation and severe hypoxemia associated with high mortality despite improved treatment regimen, and is normally caused by direct or indirect injury to the lung (i.e., infections, trauma, pneumonia, hemorrhagic shock, among others).Once the lung is injured, there is significant upregulation of proinflammatory pathways, with marked recruitment of neutrophils, and significant secretion of proinflammatory cytok......