The Jiao Tong University Spectroscopic Telescope Project

The Jiao Tong University Spectroscopic Telescope(JUST)is a 4.4-meter f/6.0 segmented-mirror telescope dedicated to spectroscopic observations.The JUST primary mirror is composed of 18 hexagonal segments,each with a diameter of 1.1 m.JUST provides two Nasmyth platforms for placing science instruments.One Nasmyth focus fits a field of view of 10′and the other has an extended field of view of 1.2°with correction optics.A tertiary mirror is used to switch between the two Nasmyth foci.JUST will be installed at a site at Lenghu in Qinghai Province,China,and will conduct spectroscopic observations with three types of instruments to explore the dark universe,trace the dynamic universe,and search for exoplanets:(1)a multi-fiber(2000 fibers)medium-resolution spectrometer(R=4000-5000)to spectroscopically map galaxies and large-scale structure;(2)an integral field unit(IFU)array of 500 optical fibers and/or a long-slit spectrograph dedicated to fast follow-ups of transient sources for multi-messenger astronomy;(3)a high-resolution spectrometer(R~100000)designed to identify Jupiter analogs and Earth-like planets,with the capability to characterize the atmospheres of hot exoplanets.

Skull metastasis revealing a papillary thyroid carcinoma

Although thyroid carcinoma is a relatively common form of malignancy,metastatic spread to the skull is rare.Here,we report a case of papillary thyroid carcinoma with frontal and parietal metastasis.A 61-year-old Chinese woman presented with a one year history of a growing mass on the center of the frontal and parietal bone,initially thought to be meningioma.Biopsy of the skull base mass after intracalvarium excision,indicated a tumor of thyroid origin.One month later the patient underwent a total thyroidectomy.Pathological examination confirmed a diagnosis of papillary thyroid carcinoma with frontal and parietal bone metastasis.Based on this experience,the key to successful management of the skull metastasis of thyroid carcinoma is prompt diagnosis and appropriate treatment.Skull metastasis should be considered at the outset of the clinical course of papillary thyroid cancer.To facilitate this,patients should be meticulously investigated by a multidisciplinary team to improve quality of life.

High expression of GPR160 in prostate cancer is unrelated to CARTp-mediated signaling pathways

To the Editor:G protein-coupled receptors(GPCRs)are the largest group of membrane proteins with over 800 members,characteristic of a seven transmembrane domain1.By playing crucial roles in regulation of various physiological processes,GPCRs have been implicated in many diseases including diabetes,obesity,depression and cancer.To initiate different intracellular responses,GPCRs mainly interact with three families of effector proteins upon agonist binding:the heterotrimeric G proteins,G protein-coupled receptor kinases(GRKs)and arrestins1.

Enhancing electrochemical capacity and interfacial stability of lithium-ion batteries through side reaction modulation with ultrathin carbon nanotube film and optimized lithium cobalt oxide particle size

Lithium cobalt oxide(LCO),the first commercialized cathode active material for lithium-ion batteries,is known for high voltage and capacity.However,its application has been limited by relatively low capacity and stability at high C-rates.Reducing particle size is considered one of the most straightforward and effective strategies to enhance ion transfer,thus increasing the rate performance.However,side reactions are simultaneously enhanced as the specific surface area increases.Herein,we investigate the impact of LCO particles with varying size distributions and optimize the particle size.To modulate the side reactions associated with particle size reduction,an ultrathin carbon nanotube film(UCNF)is introduced to coat the cathode surface.With this simple process and optimized particle size,the rate performance improves significantly,normal commercial LCO achieves 118 mA·h·g^(−1)at 3.0–4.3 V and 20 C(0.72 mA·h·cm^(−2)),corresponding to power density of 8732 W·kg^(−1).This method is applied to high voltage as well,152 mA·h·g^(−1)at 3.0–4.6 V and 20 C(0.99 mA·h·cm^(−2))was achieved with high-voltage LCO(HVLCO),corresponding to power density of 11,552 W·kg^(−1).The cycling stability is also enhanced,with the capacity retention maintaining more than 96%after 100 cycles at 0.1 C.For the first time,UCNF is demonstrated to suppress the excessive decomposition of the electrolytes and solvents by blocking electron injection/extraction between LCO and electrolyte solution.Our findings provide a simple method for improving LCO rate performance,especially at high C-rates.

Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell(cDC1)activation and tumor infiltration

Conventional type 1 dendritic cells(cDC1)are the essential antigen-presenting DC subset in antitumor immunity.Suppressing B-cell lymphoma 9 and B-cell lymphoma 9-like(BCL9/BCL9L)inhibits tumor growth and boosts immune responses against cancer.However,whether oncogenic BCL9/BCL9L impairs antigen presentation in tumors is still not completely understood.Here,we show that targeting BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration into tumor.Pharmacological inhibition of BCL9/BCL9L with a novel inhibitor hsBCL9z96 or Bcl9/Bcl9l knockout mice markedly delayed tumor growth and promoted antitumor CD8^(+)T cell responses.Mechanistically,targeting BCL9/BCL9L promoted antigen presentation in tumors.This is due to the increase of cDC1 activation and tumor infiltration by the XCL1-XCR1 axis.Importantly,using single-cell transcriptomics analysis,we found that Bcl9/Bcl9l deficient cDC1 were superior to wild-type(WT)cDC1 at activation and antigen presentation via NF-κB/IRF1 signaling.Together,we demonstrate that targeting BCL9/BCL9L plays a crucial role in cDC1-modulated antigen presentation of tumor-derived antigens,as well as CD8^(+)T cell activation and tumor infiltration.Targeting BCL9/BCL9L to regulate cDC1 function and directly orchestrate a positive feedback loop necessary for optimal antitumor immunity could serve as a potential strategy to counter immune suppression and enhance cancer immunotherapy.

G protein-coupled receptors: structure- and function-based drug discovery

As one of the most successful therapeutic target families,G protein-coupled receptors(GPCRs)have experienced a transformation from random ligand screening to knowledge-driven drug design.We are eye-witnessing tremendous progresses made recently in the understanding of their structure-function relationships that facilitated drug development at an unprecedented pace.This article intends to provide a comprehensive overview of this important field to a broader readership that shares some common interests in drug discovery.

DeepCPI:A Deep Learning-based Framework for Large-scale in silico Drug Screening

Accurate identification of compound–protein interactions(CPIs)in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development.Conventional similarity-or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled compound and protein data and often limit their usage to relatively small-scale datasets.In the present study,we propose Deep CPI,a novel general and scalable computational framework that combines effective feature embedding(a technique of representation learning)with powerful deep learning methods to accurately predict CPIs at a large scale.Deep CPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unlabeled data.Evaluations of the measured CPIs in large-scale databases,such as Ch EMBL and Binding DB,as well as of the known drug–target interactions from Drug Bank,demonstrated the superior predictive performance of Deep CPI.Furthermore,several interactions among smallmolecule compounds and three G protein-coupled receptor targets(glucagon-like peptide-1 receptor,glucagon receptor,and vasoactive intestinal peptide receptor)predicted using Deep CPI were experimentally validated.The present study suggests that Deep CPI is a useful and powerful tool for drug discovery and repositioning.The source code of Deep CPI can be downloaded from https://github.com/Fangping Wan/Deep CPI.

Modulating effects of RAMPs on signaling profiles of the glucagon receptor family

Receptor activity-modulating proteins(RAMPs)are accessory molecules that form complexes with specific G protein-coupled receptors(GPCRs)and modulate their functions.It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood.In this study,we used a bioluminescence resonance energy transfer(BRET)approach to comprehensively investigate such interactions.In conjunction with c AMP accumulation,Gaqactivation andβ-arrestin1/2 recruitment assays,we not only verified the GPCR-RAMP pairs previously reported,but also identified new patterns of GPCR-RAMP interaction.While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor(GCGR)and glucagon-like peptide-1 receptor(GLP-1 R),and RAMP2 mainly affectedβ-arrestin1/2 recruitment by GCGR,GLP-1 R and glucagon-like peptide-2 receptor,RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways.Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner.Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.

BCL9 regulates CD226 and CD96 checkpoints in CD8^(+)T cells to improve PD-1 response in cancer

To date,the overall response rate of PD-1 blockade remains unsatisfactory,partially due to limited understanding of tumor immune microenvironment(TIME).B-cell lymphoma 9(BCL9),a key transcription co-activator of the Wnt pathway,is highly expressed in cancers.By genetic depletion and pharmacological inhibition of BCL9 in tumors,we found that BCL9 suppression reduced tumor growth.

High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway

Interferons(IFNs) are cytokines with fundamental roles in resistance to infections, cancer and other diseases. Type-I IFNs, interferon α(IFN-α) and interferon β(IFN-β), act through a shared receptor complex(IFNAR) comprised of IFNAR1 and IFNAR2 subunits. Binding of type-I IFN to IFNAR1 will robustly activate Janus activated kinase-signal transducer and activator of transcription(JAK-STAT)signaling pathway. Aberrant activation of the type-I IFN response results in a spectrum of disorders called interferonopathies. The purpose of this research is to develop an assay for high-throughput screening(HTS) of small molecule inhibitors of the type-I IFN signaling pathway. Inhibition of type-I IFN signaling can be beneficial in terms of therapeutic use and understanding the underlying mechanism of action. We report here a HTS campaign with the secreted embryonic alkaline phosphatase(SEAP) reporter gene assay against 32,000 compounds which yielded 25 confirmed hits. These compounds were subsequently characterized for their cytotoxicity, effects on STAT phosphorylation and activities in IFN regulatory factor(IRF) transcription.

GPR160 is a potential biomarker associated with prostate cancer

Dear Editor,Prostate cancer(PC)is one of the most common noncutaneous cancers among men worldwide with a relatively higher incidence and mortality rate.1 Conventional screening for prostate cancer relies on prostate-specific antigen(PSA),a valuable biomarker but has some deficiencies.Radical prostatectomy,androgen ablation,and radiotherapy are still commonly used treatments for localized prostate cancer.

Orthogonal assays for the identification of inhibitors of the single-stranded nucleic acid binding protein YB-1

We have previously shown that high expression of the nucleic acid binding factor YB-1 is strongly associated with poor prognosis in a variety of cancer types. The 3-dimensional protein structure of YB-1 has yet to be determined and its role in transcriptional regulation remains elusive. Drug targeting of transcription factors is often thought to be difficult and there are very few published high-throughput screening approaches. YB-1 predominantly binds to single-stranded nucleic acids, adding further difficulty to drug discovery. Therefore, we have developed two novel screening assays to detect compounds that interfere with the transcriptional activation properties of YB-1, both of which may be generalizable to screen for inhibitors of other nucleic acid binding molecules. The first approach is a cell-based luciferase reporter gene assay that measures the level of activation of a fragment of the E2 F1 promoter by YB-1. The second approach is a novel application of the Alpha Screen system, to detect interference of YB-1 interaction with a single-stranded DNA binding site. These complementary assays examine YB-1 binding to two discrete nucleic acid sequences using two different luminescent signal outputs and were employed sequentially to screen 7360 small molecule compounds leading to the identification of three putative YB-1 inhibitors.

Quantitative analysis of the intertube coupling effect on the photoluminescence characteristics of distinct(n,m)carbon nanotubes dispersed in solution

In this work,we quantitatively studied the intertube coupling of different(n,m)-sorted semiconducting single-wall carbon nanotubes(SWCNTs)on their photoluminescence(PL)efficiencies by precisely tuning the ratio of(9,4)and(6,5)SWCNTs in the mixture.A significant decrease in the PL intensity of(9,4)SWCNTs was observed after mixing with(6,5)species when fixing the(9,4)concentration,which was confirmed to be caused by the absorption of incident photons and reabsorption of the emitted photons by the added(6,5)species.By contrast,a similar decrease in the PL intensity of(6,5)SWCNTs was also observed after mixing with the larger-diameter(9,4)species.Different from that of(9,4)SWCNTs,the PL decrease of(6,5)SWCNTs was found to originate not only from photon absorption and reabsorption by the(9,4)species but also from one-way exciton energy transfer(EET)from the(6,5)SWCNTs to the larger-diameter(9,4)SWCNTs.Both the experimental results and numerical simulations further demonstrated that increasing the concentration of mixed(9,4)SWCNTs would enhance the effects of photon absorption and reabsorption and EET on the PL intensity of(6,5)SWCNTs quantified by the decrease ratio of the(6,5)PL intensity.Meanwhile,the influence of EET was found to be always weaker than that of photon absorption and reabsorption.We proposed that the observed EET between isolated SWCNTs in a surfactant solution is derived from their proximity due to Brownian motion.