Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species. It is widely distributed in the gut and central nervous system. Peripheral activities of NMU include stimulation of smooth muscle, increase of blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. An NMU receptor has not been molecularly identified. Here we show that the previously described orphan G-protein-coupled receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting. Intracerebroventricular administration of NMU markedly suppresses food intake in rats. These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.

Autologous chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have high efficacy in large B-cell lymphomas (LBCL), but long-term remissions are observed in less than half the patients and treatment-associated adverse events such as immune effector cell-associated neurotoxicity syndrome (ICANS) are a clinical challenge. We performed single-cell RNA sequencing with capture-based cell identification on autologous axicabtagene ciloleucel (axi-cel) anti-CD19 CAR T-cell infusion products to identify transcriptomic features associated with efficacy and toxicity in 24 patients with LBCL. Patients that achieved a complete response by PET/CT at their 3-month follow-up had 3-fold higher frequencies of CD8 T-cells expressing memory signatures compared to patients with partial response or progressive disease. Molecular response measured by cell-free DNA (cfDNA) sequencing at day 7 post-infusion was significantly associated with clinical response (p=0.008), and a signature of CD8 T-cell exhaustion was associated (q=2.8×10 −149 ) with a poor molecular response. Furthermore, a rare cell population *

The two mammalian neuropeptides NPFF and NPAF have been shown to have important roles in nociception, anxiety, learning and memory, and cardiovascular reflex. Two receptors (FF1 and FF2) have been molecularly identified for NPFF and NPAF. We have now characterized a novel gene designated NPVF that encodes two neuropeptides highly similar to NPFF. NPVF mRNA was detected specifically in a region between the dorsomedial and ventromedial hypothalamic nuclei. NPVFderived peptides displayed higher affinity for FF1 than NPFF-derived peptides, but showed poor agonist activity for FF2. Following intracerebral ventricular administration, a NPVF-derived peptide blocked morphineinduced analgesia more potently than NPFF in both acute and inflammatory models of pain. In situ hybridization analysis revealed distinct expression patterns of FF1 and FF2 in the rat central nervous system. FF1 was broadly distributed, with the highest levels found in specific regions of the limbic system and the brainstem where NPVF-producing neurons were shown to project. FF2, in contrast, was mostly expressed in the spinal cord and some regions of the thalamus. These results indicate that the endogenous ligands for FF1 and FF2 are NPVFand NPFF-derived peptides, respectively, and suggest that the NPVF/FF1 system may be an important part of endogenous anti-opioid mechanism.

This paper introduces the development of a practical brain-computer interface at Tsinghua University. The system uses frequency-coded steady-state visual evoked potentials to determine the gaze direction of the user. To ensure more universal applicability of the system, approaches for reducing user variation on system performance have been proposed. The information transfer rate (ITR) has been evaluated both in the laboratory and at the Rehabilitation Center of China, respectively. The system has been proved to be applicable to > 90% of people with a high ITR in living environments.

Facial expression is temporally dynamic event which can be decomposed into a set of muscle motions occurring in different facial regions over various time intervals.For dynamic expression recognition, two key issues, temporal alignment and semantics-aware dynamic representation, must be taken into account. In this paper, we attempt to solve both problems via manifold modeling of videos based on a novel mid-level representation, i.e. expressionlet. Specifically, our method contains three key components: 1) each expression video clip is modeled as a spatiotemporal manifold (STM) formed by dense low-level features; 2) a Universal Manifold Model (UMM) is learned over all low-level features and represented as a set of local ST modes to statistically unify all the STMs. 3) the local modes on each STM can be instantiated by fitting to UM-M, and the corresponding expressionlet is constructed by modeling the variations in each local ST mode. With above strategy, expression videos are naturally aligned both spatially and temporally. To enhance the discriminative power, the expressionlet-based STM representation is further processed with discriminant embedding. Our method is evaluated on four public expression databases, CK+, MMI, Oulu-CASIA, and AFEW. In all cases, our method reports results better than the known state-of-the-art.