A sensitive red/far-red photoswitch for controllable gene therapy in mouse models of metabolic diseases.

Red light optogenetic systems are in high demand for the precise control of gene expression for gene- and cell-based therapies. Here, we report a red/far-red light-inducible photoswitch (REDLIP) system based on the chimeric photosensory protein FnBphP (Fn-REDLIP) or PnBphP (Pn-REDLIP) and their interaction partner LDB3, which enables efficient dynamic regulation of gene expression with a timescale of seconds without exogenous administration of a chromophore in mammals. We use the REDLIP system to establish the REDLIP-mediated CRISPR-dCas9 (REDLIP) system, enabling optogenetic activation of endogenous target genes in mammalian cells and mice.

Exploring the Genotype-Phenotype Correlations in a Child with Inherited Seizure and Thrombocytopenia by Digenic Network Analysis.

Understanding the correlation between genotype and phenotype remains challenging for modern genetics. Digenic network analysis may provide useful models for understanding complex phenotypes that traditional Mendelian monogenic models cannot explain. Clinical data, whole exome sequencing data, in silico, and machine learning analysis were combined to construct a digenic network that may help unveil the complex genotype-phenotype correlations in a child presenting with inherited seizures and thrombocytopenia.

Clinical features, epidemiology, and treatment of Shwachman-Diamond syndrome: a systematic review.

Background: Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS.

Methods: We searched the WangFang and China National Knowledge Infrastructure databases with the keywords "Shwachman-Diamond syndrome," "SDS," "SBDS gene" and "inherited bone marrow failure" for relevant articles published from January 2002 to October 2022.

Respiratory tract infections in children with allergic asthma on allergen immunotherapy during influenza season.

To describle how respiratory tract infections (RTIs) that occurred in children with allergic asthma (AA) on allergen immunotherapy (AIT) during an influenza season. Data including clinical symptoms and treatment history of children (those with AA on AIT and their siblings under 14 years old), who suffered from RTIs during an influenza season (Dec 1st, 2019-Dec 31st, 2019), were collected (by face to face interview and medical records) and analyzed. Children on AIT were divided into 2 groups: stage 1 (dose increasing stage) and stage 2 (dose maintenance stage).

Single-cell profiles of human bone marrow-derived mesenchymal stromal cells after IFN-γ and TNF-α licensing.

Background: Pre-licensing mesenchymal stromal cells (MSCs) with IFN-γ and TNF-α can empower their immune fate and induce a more effective immune regulation. However, the cellular heterogeneity of MSCs limits our understanding of this inflammatory licensing.

Methods: The publicly available Gene Expression Omnibus single-cell RNA sequencing (scRNA-seq) data of human bone marrow-derived MSCs with or without IFN-γ and TNF-α licensing were analyzed.

Identification of Differentially Expressed lncRNAs and mRNAs in Children with Acquired Aplastic Anemia by RNA Sequencing.

Background: The effects of long noncoding RNAs (lncRNAs) and their related messenger RNAs (mRNAs) remain unknown in children with acquired aplastic anemia (AA). The aim of this study is to screen key lncRNAs and mRNAs and investigate their potential roles in the pathology of acquired AA in children.

Methods: RNA sequencing was performed to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between blood samples of acquired AA children and healthy controls.

Clinical features of dyskeratosis congenita in mainland China: case reports and literature review.

Dyskeratosis congenita (DC) is a rare-inherited bone marrow failure syndrome associated with multi-system disorder. To summarize the clinical features, epidemiology, and treatment of DC in mainland China, we retrospectively reviewed the medical records of two patients diagnosed with DC at our hospital and published reports on other DC patients in mainland China. The clinical features of 82 DC patients were summarized.

GATA6 loss-of-function mutation contributes to congenital bicuspid aortic valve.

Congenital bicuspid aortic valve (BAV), the most common form of birth defect in humans, is associated with substantial morbidity and mortality. Increasing evidence demonstrates that genetic risk factors play a key role in the pathogenesis of BAV. However, BAV is a genetically heterogeneous disease and the genetic determinants underpinning BAV in an overwhelming majority of patients remain unknown.

MEF2C loss-of-function mutation contributes to congenital heart defects.

Congenital heart disease (CHD) is the most common type of developmental abnormality in humans, and is a leading cause for substantially increased morbidity and mortality in affected individuals. Increasing studies demonstrates a pivotal role of genetic defects in the pathogenesis of CHD, and presently mutations in more than 60 genes have been associated with CHD. Nevertheless, CHD is of pronounced genetic heterogeneity, and the genetic basis underpinning CHD in a large proportion of patients remains unclear.

OCH-mediated shift of Th1 and Th2 cytokines by NKT cells in mice with aplastic anemia.

The immune-mediated destruction of bone marrow (BM) is the major cause of aplastic anemia (AA) in most patients. It has been shown that an imbalance of Th1 and Th2 cells is involved in immune-mediated destruction of BM in patients with AA. In the present study, we determined the role of NKT cells in regulating the balance of Th1 and Th2 cytokines.

OCH ameliorates bone marrow failure in mice via downregulation of T-bet expression.

The aim of this study is to evaluate the immune mechanism of OCH in the treatment of AA (also named bone marrow failure, BMF) induced in mice. OCH at a dose of 400 μg/kg was injected intraperitoneally (I.P.