Phenylalanine diminishes M1 macrophage inflammation

Emerging evidence suggests that amino acids dictate the effector functions of immune cells; however, whether and how phenylalanine(Phe) orchestrates the polarization of macrophages is not understood. Here, we determined that Phe attenuated lipopolysaccharide(LPS) and P. multocida serotype A strain CQ2(PmCQ2) infection-induced inflammation in vivo. Furthermore, we demonstrated that Phe inhibited the production of interleukin(IL)-1β and tumor necrosis factor(TNF)-α in proinflammatory(M1) macrophag...     

A novel reporter mouse line for studying alveolar macrophages

Alveolar macrophages(AMs) are self-maintained immune cells that play vital roles in lung homeostasis and immunity. Although reporter mice and culture systems have been established for studying macrophages, an accurate and specific reporter line for alveolar macrophage study is still not available. Here we reported a novel Rspo1-td Tomato gene reporter mouse line that could specifically label mouse AMs in a cell-intrinsic manner. Using this reporter system, we visualized the dynamics of alveolar ...     

Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia

Aplastic anemia(AA) is a life-threatening disease characterized by bone marrow(BM) failure and pancytopenia. As an important component of the BM microenvironment, endothelial cells(ECs) play a crucial role in supporting hematopoiesis and regulating immunity. However, whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown. In this study, a classical AA mouse model and VE-cadherin blocking antibod...     

Machine learning-aided scoring of synthesis difficulties for designer chromosomes

Designer chromosomes are artificially synthesized chromosomes. Nowadays, these chromosomes have numerous applications ranging from medical research to the development of biofuels. However, some chromosome fragments can interfere with the chemical synthesis of designer chromosomes and eventually limit the widespread use of this technology. To address this issue,this study aimed to develop an interpretable machine learning framework to predict and quantify the synthesis difficulties of designer ch...     

AIWW: a new nutrition-screening tool for the oncologic population

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named a...     

A shared role of the myocardin-family transcriptional coactivators in cardiomyocyte maturation

<正>Dear Editor,In development, after cells make a commitment to their fates,they undergo a continuous and adaptive maturation process to eventually reach their terminal states. Cell maturity often decays during aging and pathogenesis. The immature phenotypes of stem cell-differentiated cells deposit a major bottleneck in regenerative medicine.     

Computer-aided engineering of CRISPR-Cas proteins for enhanced human genome editing

<正>Dear editor.The remarkably diversified CRISPR-Cas systems in nature have provided unlimited valuable resources to develop genome editing tools that are revolutionizing the fields of biotechnology and medicine.However,due to their microbial origin,the activity of most naturally occurring CRISPR-Cas nucleases is relatively poor in mammalian cells (Ran et al.,2015).Thus,improving the mammalian genome editing efficiency becomes the priority for harnessing more CRISPRCas systems for widespre...     

Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently

CD19 chimeric antigen receptor(CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL), but compromising result in chronic lymphoblastic leukemia(CLL) and non-Hodgkin’s lymphoma(NHL).CD19-relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome.CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure. Previous studies have established variant structures of bispecific CAR-T wh...     

HIV encephalopathy is contributed by macrophages and microglia

<正>Dear Editor,Acquired immunodeficiency syndrome(AIDS), characterized by a significant decrease in the number of CD4+T cells,causes a defective T cell immune response, which subsequently leads to various conditional pathogenic infections and tumors(Calmy et al., 2018; Seligmann et al., 1987). Neurological disorders have been reported in 70%–80% of patients with AIDS(Saylor et al., 2016),     

The burgeoning importance of PIWI-interacting RNAs in cancer progression

PIWI-interacting RNAs(pi RNAs) are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells. Recent studies have found that pi RNAs, as tissue-specific molecules, both play oncogenic and tumor suppressive roles in cancer progression, including cancer cell proliferation, metastasis, chemoresistance and stemness. Additionally, the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a ...     

Glucocorticoid and glycolysis inhibitors cooperatively abrogate acute graft-versus-host disease

Although glucorticosteroids(GCs) are the standard first-line therapy for acute graft-versus-host disease(a Gv HD), nearly 50% of a Gv HD patients have no response to GCs. The role of T cell metabolism in murine a Gv HD was recently reported. However,whether GCs and metabolism regulators could cooperatively suppress T cell alloreactivity and ameliorate a Gv HD remains to be elucidated. Increased glycolysis, characterized by elevated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3),an...     

A paternal protein facilitates sperm RNA delivery to regulate zygotic development

Sperm contributes essential paternal factors, including the paternal genome, centrosome, and oocyte-activation signals, to sexual reproduction. However, it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development. Here, we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize. We reconstitute an SPE-11 liquid...     

Developmental dynamics of the single nucleus regulatory landscape of pig hippocampus

The hippocampus is a brain region associated with memory, learning and spatial navigation, its aging-related dysfunction is a common sign of Alzheimer’s disease. Pig is a good model for human neurodegenerative disease, but our understanding of the regulatory program of the pig hippocampus and its cross-species conservation in humans remains limited. Here, we profiled chromatin accessibility in 33,409 high-quality nuclei and gene expression in 8,122 high-quality nuclei of the pig hippocampus at f...     

Global patterns of phylogenetic diversity and transmission of bat coronavirus

Bats are reservoirs for multiple coronaviruses(Co Vs). However, the phylogenetic diversity and transmission of global bat-borne Co Vs remain poorly understood. Here, we performed a Bayesian phylogeographic analysis based on 3,594 bat Co V Rd Rp gene sequences to study the phylogenetic diversity and transmission of bat-borne Co Vs and the underlying driving factors. We found that host-switching events occurred more frequently for α-Co Vs than for β-Co Vs, and the latter was highly constrained by ...     

Cross-species binding spectrum of ACE2 to SARS-CoV-2 RBD

<正>Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCo V-2) is the cause of COVID-19, which has posed a massive threat to human health, economy, and security worldwide(Bai et al., 2022). Genomic analysis of SARS-Co V-2 and related coronaviruses revealed that SARS-Co V and SARS-Co V-2likely had ancestors(Xu et al., 2020), which might originate in bats, followed by subsequent spread within intermediate hosts(spillover hosts) and then transmission to humans(Wang et al., 2021).     

Mechanism of iron on the intestinal epithelium development in suckling piglets

This study aimed to investigate the mechanism of iron on intestinal epithelium development of suckling piglets. Compared with newborn piglets, 7-day-old and 21-day-old piglets showed changes in the morphology of the jejunum, increased proliferation,differentiated epithelial cells, and expanded enteroids. Intestinal epithelium maturation markers and iron metabolism genes were significantly changed. These results suggest that lactation is a critical stage in intestinal epithelial development, acco...     

An iron-dependent form of non-canonical ferroptosis induced by labile iron

Ferroptosis is a recently identified iron-dependent form of nonapoptotic cell death characterized by reactive oxygen species(ROS) generation and lipid peroxidation. Here, we report a novel iron-dependent form of ferroptosis induced by labile iron and investigate the mechanism underlying this process. We find that labile iron-induced ferroptosis is distinct from canonical ferroptosis and is linked to the mitochondrial pathway. Specifically, the mitochondrial calcium uniporter mediates the ferropt...     

Complicated target recognition by archaeal box C/D guide RNAs

Box C/D RNAs guide the site-specific formation of 2′-O-methylated nucleotides(Nm) of RNAs in eukaryotes and archaea. Although C/D RNAs have been profiled in several archaea, their targets have not been experimentally determined. Here, we mapped Nm in r RNAs, t RNAs, and abundant small RNAs(s RNAs) and profiled C/D RNAs in the crenarchaeon Sulfolobus islandicus. The targets of C/D RNAs were assigned by analysis of base-pairing interactions, in vitro modification assays, and gene deletion experime...     

PanGu Drug Model: learn a molecule like a human

<正>Dear Editor,Recent achievements in large-scale pre-trained models like GPT-3 and PanGu-α have demonstrated astounding performances in many downstream tasks of natural language processing (NLP),confirming AI to be user-oriented for even industrial applications.Deep learning has been recognized as the most promising technology for pharmaceuticals,a powerful molecule pre-trained model that could economize researchers’tons of time.For the strategic application of AI capabilities to the drug...