Base editing of the HBG promoter induces potent fetal hemoglobin expression with no detectable off-target mutations in human HSCs.

Reactivating silenced γ-globin expression through the disruption of repressive regulatory domains offers a therapeutic strategy for treating β-hemoglobinopathies. Here, we used transformer base editor (tBE), a recently developed cytosine base editor with no detectable off-target mutations, to disrupt transcription-factor-binding motifs in hematopoietic stem cells. By performing functional screening of six motifs with tBE, we found that directly disrupting the BCL11A-binding motif in HBG1/2 promoters triggered the highest γ-globin expression.

DNA topology regulates PAM-Cas9 interaction and DNA unwinding to enable near-PAMless cleavage by thermophilic Cas9.

CRISPR-Cas9-mediated genome editing depends on PAM recognition to initiate DNA unwinding. PAM mutations can abolish Cas9 binding and prohibit editing. Here, we identified a Cas9 from the thermophile Alicyclobacillus tengchongensis for which the PAM interaction can be robustly regulated by DNA topology.

A highly sensitive strain sensor with a sandwich structure composed of two silver nanoparticles layers and one silver nanowires layer for human motion detection.

The fabrication of strain sensors with high sensitivity, large sensing range and excellent stability is highly desirable because of their promising applications in human motion detection, human-machine interface and electric skin, etc. Herein, by introducing a highly conductive silver nanowire (AgNW) layer between two serried silver nanoparticle (AgNP) layers, forming a sandwich structure, a strain sensor with high sensitivity (a large gauge factor of 2.8 × 10), large sensing range (up to 80% strain) and excellent stability (over 1000 cycles) can be achieved.

Pyrrolidinedithiocarbamic Acid Ammonium Salt Inhibits Apoptosis and Phenotypic Transformation of Co-Culture of Myeloma Cells and Renal Tubular Epithelial Cells by Reducing the Secretion of Light Chain Protein.

Background: We investigate the effects of NFϰB inhibitor pyrrolidinedithiocarbamic acid ammonium salt (PDTC) on the viability, apoptosis and cell phenotype of HK-2 cells in the co-culture system of myeloma cells in renal tubular epithelial cells.

Methods: This study was performed in Qiqihar Medical University, from Jun 2018 to Jan 2019. RPMI-8226 cells and HK-2 cells were inoculated in the co-culture chamber and cultured to establish the co-culture system.

Wearable electronics for heating and sensing based on a multifunctional PET/silver nanowire/PDMS yarn.

Stretchable and flexible electronics built from multifunctional fibres are essential for devices in human-machine interactions, human motion monitoring and personal healthcare. However, the combination of stable heating and precision sensing in a single conducting yarn has yet to be achieved. Herein, a yarn comprising poly(ethylene terephthalate) (PET), silver nanowires (AgNWs), and polydimethylsiloxane (PDMS) was designed and prepared.

Follicular Helper T Cell Derived Exosomes Promote B Cell Proliferation and Differentiation in Antibody-Mediated Rejection after Renal Transplantation.

Follicular helper T cells (Tfh cells) are closely related to the occurrence and development of antibody-mediated rejection (AMR) after renal transplantation. Exosomes play a key role in the rejection after organ transplantation. However, whether Tfh-derived exosomes are involved in AMR has not been reported.

Water-Based Purification of Ultrathin Silver Nanowires toward Transparent Conductive Films with a Transmittance Higher than 99.

Ultrathin silver nanowires (UTAgNWs) are indispensable to achieve transparent conductive films (TCFs) with overall optoelectronic performance exceeding that of the state-of-the-art indium tin oxide films. Impurities in raw UTAgNW products severely impair the optical properties of TCFs. Unfortunately, highly effective and environment-friendly approaches for purification of UTAgNWs are still lacking.

Circulating NK cell subsets and NKT‑like cells in renal transplant recipients with acute T‑cell‑mediated renal allograft rejection.

Emerging evidence indicates that natural killer (NK) cells and NKT‑like cells may affect allograft outcomes following solid organ transplantation. However, the roles of these cells in allograft acceptance and dysfunction are controversial. To assess the changes in NK cell and CD3+CD56+ NKT‑like cell frequency and phenotype in renal allograft recipients and to explore their associations with acute T‑cell‑mediated renal allograft rejection (ACR), longitudinal changes in NK and NKT‑like cell frequency and phenotype were characterized using flow cytometry and immunohistochemistry in the peripheral blood and kidney allograft tissues in 142 recipients undergoing kidney transplantation.

Ectopic expression of E3 ubiquitin-protein ligase 2 in glioma and enhances resistance to apoptosis through activating nuclear factor κ-light-chain-enhancer of B cells.

Nuclear factor κ-light-chain-enhancer of B cells (NF-κB) is one of the most important tumorigenic factors. Although it has been established that NF-κB is overly activated in human glioma cells, the molecular mechanisms that lead to the signal transduction to NF-κB and thereby the induction of resistance to apoptosis remain poorly understood. The present study demonstrated that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples.

Prucalopride inhibits the glioma cells proliferation and induces autophagy via AKT-mTOR pathway.

Backgrounds: Glioma is the most fatal primary brain glioma in central nervous system mainly attributed to its high invasion. Prucalopride, a Serotonin-4 (5-HT4) receptor agonist, has been reported to regulate neurodevelopment. This study aimed to investigate the influence of the Prucalopride on glioma cells and unveil underlying mechanism.

Exosome-Modified Tissue Engineered Blood Vessel for Endothelial Progenitor Cell Capture and Targeted siRNA Delivery.

Instability and poor targeting causes the long-term patency of RNA-modified tissue engineering blood vessels (TEBVs) remaining unsatisfactory. RNA can be enriched in exosome and then delivered into targeted cells while whether exosome-modified TEBVs achieve RNA targeted delivery is unclear. Here, to promote the expression of klotho protein on the mesenchymal stem cell (MSC)-derived exosomes, klotho plasmids are first transfected into MSCs, and adenosine kinase (ADK) siRNA is then loaded into exosome (klotho/ADK siRNA-exosome) using electrotransfection.

Low proportion of follicular regulatory T cell in renal transplant patients with chronic antibody-mediated rejection.

Follicular regulatory T (Tfr) cell can effectively regulate humoral immunity, but its function and mechanism in antibody-mediated rejection (AMR) after organ transplantation remains unclear. Here we detected follicular helper T (Tfh) cell subsets in 88 renal transplant patients with chronic renal allograft dysfunction (40 with AMR and 48 without AMR). The ratio of Tfr cells in renal graft tissues and peripheral blood of AMR patients significantly decreased, while the ratio of IL-21-producing Tfh cells (Tfh2 and Tfh17) significantly increased, compared to non-AMR patients.

Genetic polymorphisms in ERCC1 and ERCC2 genes are associated with response to chemotherapy in osteosarcoma patients among Chinese population: a meta-analysis.

Background: There existed controversies about the association between the response to chemotherapy for osteosarcoma (OS) patients and the genetic polymorphisms in excision repair cross-complementation group (ERCC1 and ERCC2) genes. We aimed to perform a meta-analysis to comprehensively evaluate the association.

Method: We searched multiple databases for literature retrieval including the PubMED (1966 ∼ 2017), Embase (1980 ∼ 2017), and the Web of science (1945 ∼ 2017).

Toll-like receptor 4 confers inflammatory response to Suilysin.

Streptococcus suis serotype 2 (SS2) is an emerging human pathogen worldwide. A large outbreak occurred in the summer of 2005 in China. Serum samples from this outbreak revealed that levels of the main proinflammatory cytokines were significantly higher in patients with streptococcal toxic-shock-like syndrome (STSLS) than in patients with meningitis only.

Disturbance of hippocampal H2S generation contributes to CUMS-induced depression-like behavior: involvement in endoplasmic reticulum stress of hippocampus.

The chronic unpredictable mild stress (CUMS) model is a widely used experimental model of depression. Exogenous stress-induced neuronal cell death in the hippocampus is closely associated with the pathogenesis of depression. Excessive and prolonged endoplasmic reticulum (ER) stress triggers cell death.

Increased production of suilysin contributes to invasive infection of the Streptococcus suis strain 05ZYH33.

Streptococcus suis serotype 2 (SS2) is widely recognized in the veterinary world as the cause of rapidly progressive and fatal sepsis in infant pigs, manifested with meningitis, polyarthritis and pneumonia. It has evolved into a highly infectious strain, and caused two large-scale outbreaks of human epidemic in China, characterized bytypical toxic-shock syndrome and invasive infection. However, the molecular basis of virulence of this emerging zoonotic pathogen is still largely unknown.

[Purification and biological activities analysis of streptococcus suis Serotype 2 suilysin].

Aim: To explore the purification methods of wild-type and recombinant suilysin and to evaluate their biological activities.

Methods: Wild-type suilysin was purified by ammonium sulfate precipitation, anion-exchange chromatography and hydrophobic chromatography in turn, while recombinant suilysin was first refolded and purified by immobilized metal ion affinity chromatography, and further purified by Thiopropyl Sepharose 6B. The biological activities were evaluated by hemolysis test, cytotoxicity assay.