Transcriptomic and Metabolomic Signatures of Acute Circadian Misalignment in Mice.

Acute circadian misalignment, such as that induced by a single episode of jet lag, can leave molecular traces even after behavioral rhythms appear to recover. Here, we applied an integrated multi-omics approach-combining liver transcriptomics and plasma metabolomics-to characterize residual signatures on the 7th day after a single 6-h phase advance in male mice. Our data revealed significant alterations, particularly in the core clock genes Bmal1 and Cry1, and the metabolites l-arginine and SM(d18:1/18:1(11Z)), with notable differences at Zeitgeber Time 0 (ZT0).

[Liver X receptor attenuates renal ischemia-reperfusion injury in mice].

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mechanism incompletely clarified. The liver X receptors (LXRs), including LXRα and LXRβ, are members of the nuclear receptor superfamily.

Identification of four TTN variants in three families with fetal akinesia deformation sequence.

Background: TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset.

Expression and localization of HSD17B13 along mouse urinary tract.

17β-Hydroxysteroid dehydrogenase-13 (HSD17B13), a newly identified lipid droplet-associated protein, plays an important role in the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Emerging evidence demonstrates that NASH is an independent risk factor for chronic kidney disease, which is frequently accompanied by renal lipid accumulation. In addition, the HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven NAFLD.

A large-scale production of mesenchymal stem cells and their exosomes for an efficient treatment against lung inflammation.

Mesenchymal stem cells (MSCs) and their produced exosomes have demonstrated inherent capabilities of inflammation-guided targeting and inflammatory modulation, inspiring their potential applications as biologic agents for inflammatory treatments. However, the clinical applications of stem cell therapies are currently restricted by several challenges, and one of them is the mass production of stem cells to satisfy the therapeutic demands in the clinical bench. Herein, a production of human amnion-derived MSCs (hMSCs) at a scale of over 1 × 10 cells per batch was reported using a three-dimensional (3D) culture technology based on microcarriers coupled with a spinner bioreactor system.

Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/β-catenin signaling.

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with various etiologies, which seriously affects the structure and function of the kidney. Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily and plays a critical role in regulating the genes related to xenobiotic and endobiotic metabolism in mammals. Previous studies show that PXR is expressed in the kidney and has protective effect against acute kidney injury (AKI).

Case report: Prenatal diagnosis of fetal intracranial hemorrhage due to compound mutations in the gene.

Intracranial hemorrhage is a common complication in preterm infants but occasionally occurs in fetuses. Disruptions of the genes, such as the and genes are common genetic causes identified in fetal intracranial hemorrhage; however, the disruptions of the gene are rarely reported. In the current investigation, fetal intracranial hemorrhage and dilated lateral ventricles were observed in three consecutive siblings in a pedigree.

Germline intergenic duplications at Xq26.1 underlie Bazex-Dupré-Christol basal cell carcinoma susceptibility syndrome.

Background: Bazex-Dupré-Christol syndrome (BDCS; MIM301845) is a rare X-linked dominant genodermatosis characterized by follicular atrophoderma, congenital hypotrichosis and multiple basal cell carcinomas (BCCs). Previous studies have linked BDCS to an 11·4-Mb interval on chromosome Xq25-q27.1.

Impact of Time-Restricted Feeding on Adaptation to a 6-Hour Delay Phase Shift or a 12-Hour Phase Shift in Mice.

Nowadays, more and more people are suffering from circadian disruption. However, there is no well-accepted treatment. Recently, time-restricted feeding (TRF) was proposed as a potential non-drug intervention to alleviate jet lag in mice, especially in mice treated with a 6-h advanced phase shift.

Nuclear receptors in renal health and disease.

As a major social and economic burden for the healthcare system, kidney diseases contribute to the constant increase of worldwide deaths. A deeper understanding of the underlying mechanisms governing the etiology, development and progression of kidney diseases may help to identify potential therapeutic targets. As a superfamily of ligand-dependent transcription factors, nuclear receptors (NRs) are critical for the maintenance of normal renal function and their dysfunction is associated with a variety of kidney diseases.

Identification of of a PAX2 mutation from maternal mosaicism causes recurrent renal disorder in siblings.

Background: PAX2-related disorder is an autosomal dominant disorder characterized by renal and eye abnormalities. Some patients may present with isolated renal abnormalities without obvious ocular abnormalities. It is associated with mutations in paired box gene 2 (PAX2), which is one of the families of paired box transcription factor genes.

[Genetic Study and Prenatal Diagnosis of a Family with Thrombocytopenia-Absent Radius (TAR) Syndrome].

Objective: To analyze the potential genetic cause of thrombocytopenia-absent radius (TAR) syndrome in a family and provide prenatal diagnosis for them.

Methods: Genetic mutation analysis of the sporadic family with TAR syndrome was performed with chromosome microarray analysis (CMA), quantitative polymerase chain reaction (qPCR) and Sanger sequencing. DNA samples were collected from 4 members of the family, including the proband, her parents and her sister.

Lack of MECP2 gene transcription on the duplicated alleles of two related asymptomatic females with Xq28 duplications and opposite X-chromosome inactivation skewing.

Xq28 duplication syndrome (MIM# 300815) is a severe neurodevelopmental disorder in males due to MeCP2 overexpression. Most females with MECP2 duplication are asymptomatic carriers, but there are phenotypic heterogeneities. Skewed X-chromosome inactivation (XCI) can protect females from exhibiting clinical phenotypes.

Generation of the human induced pluripotent stem cell line (ZJUi005-A) from a patient with Pelizaeus-Merzbacher disease (PMD) carrying a novel hemizygous mutation in PLP1 gene.

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked leukodystrophy caused by mutations in the proteolipid protein 1 gene (PLP1) which is specifically expressed on the myelin sheath of oligodendrocytes. We established an induced pluripotent stem cell (iPSC) line (ZJUi005-A) from peripheral blood mononuclear cells of an 18-year-old male PMD patient with a novel hemizygous c.437T>C mutation in PLP1 gene using episomal reprogramming plasmids.

[Genetic study of a family of neuronal ceroid lipofuscinosis caused by a heterozygous mutation of gene].

Objective: To analyze the genetic cause of a family with autosomal recessive neuronal ceroid lipofuscinoses (NCL).

Methods: The proband was screened for mutations within the coding region of the candidate genes through high-throughput targeted sequencing. Potential causative mutations were verified by PCR and Sanger sequencing in the proband and his parents.

[Genetic analysis and prenatal diagnosis of a sporadic family with neurofibromatosis type 1].

Objective: To identify pathogenic mutation for a family with neurofibromatosis type 1(NF1) and provide prenatal diagnosis for them.

Methods: Mutation analysis of the sporadic family with NF1 was performed with target captured next generation sequencing and Sanger sequencing. RNA samples were extracted from the lymphocytes of NF1 patient and her parents.

Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression.

Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in γ-secretase component genes. We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice.

The application of NIPT using combinatorial probe-anchor synthesis to identify sex chromosomal aneuploidies (SCAs) in a cohort of 570 pregnancies.

Background: Non-invasive prenatal testing (NIPT) as alternative screening method had been proven to have very high sensitivity and specificity for detecting common aneuploidies such as T21, T18, and T13, with low false positive and false negative rates. Unfortunately, recent studies suggested that the NIPT achieved lower accuracy in sex chromosomal aneuploidies (SCAs) detection than autosomal aneuploidies detection. BGISEQ-500 powered by Combinatorial Probe-Anchor Synthesis (CPAS) and DNA Nanoballs (DNBs) technology that combined linear amplification and rolling circle replication to reduce the error rate while enhancing the signal.

Mutation Screening of the EDA Gene in Seven Chinese Families with X-Linked Hypohidrotic Ectodermal Dysplasia.

Background: As the most common form of ectodermal dysplasia (ED), X-linked hypohidrotic ED (XLHED) is characterized by the triad of hypohidrosis, hypotrichosis, and anodontia in male patients. The gene responsible for XLHED is EDA. To date, more than 300 mutations have been identified in this gene, including point mutations, deletions, and insertions.