Molecular characterization of human HSPCs with different cell fates in vivo using single-cell transcriptome analysis and lentiviral barcoding technology.

Hematopoietic stem and progenitor cells (HSPCs) possess the potential to produce all types of blood cells throughout their lives. It is well recognized that HSPCs are heterogeneous, which is of great significance for their clinical applications and the treatment of diseases associated with HSPCs. This study presents a novel technology called Single-Cell transcriptome Analysis and Lentiviral Barcoding (SCALeBa) to investigate the molecular mechanisms underlying the heterogeneity of human HSPCs in vivo.

Intermittent Hypobaric Hypoxia Ameliorates Autistic-Like Phenotypes in Mice.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and stereotyped behaviors. Although major advances in basic research on autism have been achieved in the past decade, and behavioral interventions can mitigate the difficulties that individuals with autism experience, little is known about the many fundamental issues of the interventions, and no specific medication has demonstrated efficiency for the core symptoms of ASD. Intermittent hypobaric hypoxia (IHH) is characterized by repeated exposure to lowered atmospheric pressure and oxygen levels, which triggers multiple physiological adaptations in the body.

A novel computational method enables RNA editome profiling during human hematopoiesis from scRNA-seq data.

RNA editing is a post-transcriptional modification with a cell-specific manner and important biological implications. Although single-cell RNA-seq (scRNA-seq) is an effective method for studying cellular heterogeneity, it is difficult to detect and study RNA editing events from scRNA-seq data because of the low sequencing coverage. To overcome this, we develop a computational method to systematically identify RNA editing sites of cell types from scRNA-seq data.

Suppression of innate and acquired immunity in severe hand foot and mouth disease caused by EV71 infections in children.

Hand, foot, and mouth disease (HFMD) is a common children infectious disease caused by human enteroviruses. Most of the cases have minimal symptoms, however, some patients may develop serious neurological, cardiac complications, or even death. The pathological mechanism leading to severe HFMD is not clearly understood, and the immunological status of the individual patient may play an important role.

Stemness-related genes revealed by single-cell profiling of naïve and stimulated human CD34 cells from CB and mPB.

Background: Hematopoietic stem cells (HSCs) from different sources show varied repopulating capacity, and HSCs lose their stemness after long-time ex vivo culture. A deep understanding of these phenomena may provide helpful insights for HSCs.

Methods: Here, we applied single-cell RNA-seq (scRNA-seq) to analyse the naïve and stimulated human CD34 cells from cord blood (CB) and mobilised peripheral blood (mPB).

Restoration of β-Globin Expression with Optimally Designed Lentiviral Vector for β-Thalassemia Treatment in Chinese Patients.

β-Thalassemia is one of the most prevalent genetic diseases worldwide. The current treatment for β-thalassemia is allogeneic hematopoietic stem cell transplantation, which is limited due to lack of matched donors. Gene therapy has been developed as an alternative therapeutic option for transfusion-dependent β-thalassemia (TDT).

Transcriptome Analyses of β-Thalassemia -28(A>G) Mutation Using Isogenic Cell Models Generated by CRISPR/Cas9 and Asymmetric Single-Stranded Oligodeoxynucleotides (assODNs).

β-thalassemia, caused by mutations in the human hemoglobin β () gene, is one of the most common genetic diseases in the world. The -28(A>G) mutation is one of the five most common mutations in Chinese patients with β-thalassemia. However, few studies have been conducted to understand how this mutation affects the expression of pathogenesis-related genes, including globin genes, due to limited homozygote clinical materials.

DNB-based on-chip motif finding: A high-throughput method to profile different types of protein-DNA interactions.

Here, we report a sensitive DocMF system that uses next-generation sequencing chips to profile protein-DNA interactions. Using DocMF, we successfully identified a variety of endonuclease recognition sites and the protospacer adjacent motif (PAM) sequences of different CRISPR systems. DocMF can simultaneously screen both 5' and 3' PAMs with high coverage.

Selective targeting of the oncogenic G12S mutant allele by CRISPR/Cas9 induces efficient tumor regression.

: is one of the most frequently mutated oncogenes in cancers. The protein's picomolar affinity for GTP/GDP and smooth protein structure resulting in the absence of known allosteric regulatory sites makes its genomic-level activating mutations a difficult but attractive target. : Two CRISPR systems, genome-editing CRISPR/SpCas9 and transcription-regulating dCas9-KRAB, were developed to deplete the G12S mutant allele or repress its transcription, respectively, with the goal of treating -driven cancers.

Serum-Free Culture System for Spontaneous Human Mesenchymal Stem Cell Spheroid Formation.

Human mesenchymal stem cells (hMSCs) are widely used in clinical research because of their multipotential, immunomodulatory, and reparative properties. Previous studies determined that hMSC spheroids from a three-dimensional (3D) culture possess higher therapeutic efficacy than conventional hMSCs from a monolayer (2D) culture. To date, various 3D culture methods have been developed to form hMSC spheroids but most of them used culture medium containing fetal bovine serum (FBS), which is not suitable for further clinical use.

Synthesis and biological evaluation of water-soluble derivatives of chiral gossypol as HIV fusion inhibitors targeting gp41.

A series of novel or known water-soluble derivatives of chiral gossypol were synthesized and screened in vitro for their anti-HIV-1 activity. (-)-gossypol derivative was more active against HIV-1 than the corresponding (+)-gossypol derivative, respectively. Among these derivatives, d-glucosamine derivative of (-)-gossypol, oligopeptide derivative of (-)-gossypol and taurine derivative of (-)-gossypol, such as compounds 1a, 3a and 14a, showed significant inhibitory activities against HIV-1 replication, HIV-1 mediated cell-cell fusion and HIV gp41 6-helix bundle formation as some amino acid derivatives of (-)-gossypol.

Enantioselective inhibition of reverse transcriptase (RT) of HIV-1 by non-racemic indole-based trifluoropropanoates developed by asymmetric catalysis using recyclable organocatalysts.

Herein, we report the development of efficient inhibitors of reverse transcriptase (RT) of HIV-1 based on indole-alkyl trifluoropyruvate derivatives by a TZM-bl cell assay. The inhibitory activities of the two enantiomers and the corresponding racemic mixture have been compared. TZM-bl cells exhibited strong enantioselective discrimination for the (R)-configuration, among these indole derivatives, the most active compound R-12, with a 5-NO2 substituent, gave the best result when tested in the TZM-bl cells on HIV virus type HIV-1IIIB, with an EC50 value of 0.

The potent human immunodeficiency virus type 1 (HIV-1) entry inhibitor HR212 blocks formation of the envelope glycoprotein gp41 six-helix bundle.

HR212, a recombinant protein composed of the heptad repeat, is a rationally designed human immunodeficiency virus type 1 (HIV-1) fusion inhibitor. This protein can be easily produced by Escherichia coli at a low cost. Previously, studies indicated that HR212 can efficiently inhibit the entry and replication of both laboratory and clinical HIV-1 strains, and this protein is more stable and less sensitive to proteinases than T20.

Amino acid derivatives of the (-) enantiomer of gossypol are effective fusion inhibitors of human immunodeficiency virus type 1.

T20 and maraviroc are the only two currently available entry inhibitors that have shown efficacy in treating HIV-1-infected individuals who have failed to respond to first-line antiretroviral drugs. Gossypol is a polyphenolic aldehyde extracted from cotton plants. By modifying the (-) enantiomer of gossypol with a series of small molecules, we have found that neutral amino acids with aliphatic group derivatives of (-) gossypol show the strongest inhibitory activity and the lowest cytotoxicity in vitro among all the derivatives tested.

Correlating electronic transport to atomic structures in self-assembled quantum wires.

Quantum wires, as a smallest electronic conductor, are expected to be a fundamental component in all quantum architectures. The electronic conductance in quantum wires, however, is often dictated by structural instabilities and electron localization at the atomic scale. Here we report on the evolutions of electronic transport as a function of temperature and interwire coupling as the quantum wires of GdSi(2) are self-assembled on Si(100) wire-by-wire.

Synthesis and antiviral activities of novel gossypol derivatives.

In this study, a series of novel gossypol derivatives were synthesized and screened in vitro for their anti-HIV-1 and anti-H(5)N(1) activities, respectively. Replacing the aldehyde groups of gossypol with some amino acids not only reduced the cytotoxicity but also enhanced the activities against HIV-1 and H(5)N(1). Compounds 13-17 showed more potent activities against HIV-1 and H(5)N(1) than the other gossypol derivatives.

Structural and chemical properties of gold rare earth disilicide core-shell nanowires.

Clear understanding of the relationship between electronic structure and chemical activity will aid in the rational design of nanocatalysts. Core-shell Au-coated dysprosium and yttrium disilicide nanowires provide a model atomic scale system to understand how charges that transfer across interfaces affect other electronic properties and in turn surface activities toward adsorbates. Scanning tunneling microscopy data demonstrate self-organized growth of Au-coated DySi₂ nanowires with a nanometer feature size on Si(001), and Kelvin probe force microscopy data measure a reduction of work function that is explained in terms of charge transfer.

The route of inoculation determines the tissue tropism of modified vaccinia Tiantan expressing the spike glycoprotein of SARS-CoV in mice.

The live replication-competent modified vaccinia virus Tiantan (MVTT) is an attractive vaccine vector, yet little is known about its tissue tropism and pathology in vivo. Recently, we demonstrated that a recombinant MVTT expressing the spike glycoprotein of SARS-CoV (namely MVTT-S) is superior to the non-replicating modified vaccinia Ankara (MVA-S) for inducing high level of neutralizing antibodies through mucosal vaccination. In this study, we further determined the tissue tropism and safety of MVTT-S after the vaccine was administrated through various routes including: intramuscular (i.