Background17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by a mutation in the CYP17A1 gene is characterized by hypertension, hypokalemia, and abnormal development of the genitalia. The ...majority of CYP17A1 mutations are located in the coding sequence, and several intronic splicing site mutations have been reported.ObjectiveA 2.5-year-old girl with 46,XY disordered sex development exhibited a nearly normal basal cortisol level and reduced sexual steroids. This study is aimed to explore the molecular basis and analyze its possible influence on the phenotype of the patient.Methods and resultsMutation analysis revealed compound heterozygous CYP17A1 mutations, with c.985_987delinsAA in one allele and a synonymous substitution (c.1263G>A) in another allele. In vitro expression analysis of the allelic minigene showed that the novel nucleotide variation located in exon 8 induces a splicing signal, which results in an aberrant splicing of CYP17A1 mRNA and a missing portion of exon 8. The translation product includes the deletion of six or seven amino acids from residue position 415 without causing a frameshift. Consistent with the result of molecular modeling, functional studies in transiently transfected HEK-293T cells with the aberrantly spliced enzyme proteins showed that the deleted proteins completely abolished the enzyme activity. However, RT-PCR indicated the existence of a small fraction of normal, functionally intact enzyme, which may explain the partial masculinization of this patient.ConclusionThis is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17OHD phenotype. It also demonstrates the importance of studying synonymous change in such patients with less severe phenotype.
Abstract
Rutile TiO
2
nanorod arrays vertically aligned on conductive fluorine-doped tin oxide glass are optimized for photocatalysis in terms of the density and diameter of nanorods by tuning the ...concentration of Ti precursor and reaction time during the hydrothermal process. Quantum dots (QDs) of V
2
VI
3
( V = Bi; VI = Se, Te) topographic insulators are then employed as sensitizers to enhance the visible-light response of TiO
2
. Electrochemical measurements show that the decoration of Bi
2
Se
3
or Bi
2
Te
3
significantly increases the photocurrent due to the enhanced light harvesting properties and the charge carrier separation capability mediated by the topographic isolation effect of V
2
VI
3
QDs. Photoelectrocatalytic (PEC) activity evaluation is conducted towards the decoloration of azo dyes, including methyl orange and methylene blue under the sunlight irradiation. The elaborated Bi
2
Se
3
/TiO
2
nanorod array exhibits the superior PEC performances, presenting shows great potentials in environmental remediation.
The strategical integration of membrane water filtration with semiconductor photocatalysis presents a frontier in deep purification with a self-cleaning capability. However, the membrane fouling ...caused by the cake layer of the reclaimed TiO
nanoparticles is a key obstacle. Herein, mesoporous WO
/TiO
spheres (∼450 nm in diameter) consisting of numerous self-assembled WO
-decoated anatase TiO
nanocrystallites are successfully prepared via a facile wet-chemistry route. The decoration of monolayered WO
significantly affects the surface, photocatalytic, and optical properties of original mesoporous TiO
spheres. XRD and Raman analyses show the presence of monolayered WO
suppresses the crystal growth of TiO
during the calcination process, significantly improves the surface acidity, and causes an obvious red shift in absorption edge. These favorable textural properties, coupling the enhanced interfacial charge carrier separation, render mesoporous WO
/TiO
spheres with a superior photocatalytic activity in degradation of methylene blue under UV, visible, and solar light irradiations. The optimal molar ratio of W/Ti is examined to 6%. The synthesized mesoporous WO
/TiO
spheres also show much higher flux during membrane filtration in both dead-end and cross-flow modes, suggesting a promising photocatalyst for concurrent membrane filtration and solar photocatalysis.
A theoretical inverse relationship exists between osteogenic (bone forming) and adipogenic (fat forming) mesenchymal stem cell (MSC) differentiation. This inverse relationship in theory partially ...underlies the clinical entity of osteoporosis, in which marrow MSCs have a preference for adipose differentiation that increases with age. Two pro-osteogenic cytokines have been recently studied that each also possesses antiadipogenic properties: Sonic Hedgehog (SHH) and NELL-1 proteins. In the present study, we assayed the potential additive effects of the biologically active N-terminus of SHH (SHH-N) and NELL-1 protein on osteogenic and adipogenic differentiation of human primary adipose-derived stromal cell (hASCs). We observed that both recombinant SHH-N and NELL-1 protein significantly enhanced osteogenic differentiation and reduced adipose differentiation across all markers examined (alkaline phosphatase, Alizarin red and Oil red O staining, and osteogenic gene expression). Moreover, SHH-N and NELL-1 directed signaling produced additive effects on the pro-osteogenic and antiadipogenic differentiation of hASCs. NELL-1 treatment increased Hedgehog signaling pathway expression; coapplication of the Smoothened antagonist Cyclopamine reversed the pro-osteogenic effect of NELL-1. In summary, Hedgehog and Nell-1 signaling exert additive effects on the pro-osteogenic and antiadipogenic differentiation of ASCs. These studies suggest that the combination cytokines SHH-N+NELL-1 may represent a viable future technique for inducing the osteogenic differentiation of MSCs.
To study the clinical value of combined measurement of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and serum ferritin (SF) in the etiological ...diagnosis of fever of unknown origin (FUO) in children.
The clinical data of 154 hospitalized children who had FUO for at least two weeks were retrospectively analyzed, and they were classified into infection (n=54), rheumatism (n=67), and tumor (n=33) groups according to the diagnosis at discharge. The levels of CRP, ESR, LDH, and SF were compared between the three groups, and the diagnostic values of the four indices alone or together were analyzed using the receiver operating characteristic (ROC) curve.
Serum CRP and ESR levels were elevated in all the three groups, and increased most significantly in the rheumatism group. Serum LDH level was increased most significantly in the tumor group. SF level was significantly increased in the rheumatism and tumor groups. The area under the ROC curve (AUC) of LDH for diagnosing
•Two molecular solids containing Ni(mnt)2− monoanion were prepared and characterized.•The Ni(mnt)2− anions in 1 form a non-uniform 1D chain with the Ni⋯Ni distances of 3.443, 3.935 and 3.968Å.•The ...Ni(mnt)2− anions in 2 form a uniform 1D magnetic chain with a Ni⋯Ni distance of 4.148Å.•Compound 1 exhibits a characteristic of spin-gap around 86K upon the temperature is lowed.
Two molecular metals, 2F4BrBzTPPNi(mnt)2·H2O (1) and 2Br4FBzTPPNi(mnt)2 (2) (2F4BrBzTPP+=1-(2′-fluoro-4′-bromobenzyltriphenylphosphonium, 2Br4FBzTPP+=1-(2′-bromo-4′-fluorobenzyltriphenylphosphonium, mnt2−=maleonitriledithiolate), have been synthesized and structurally characterized by single crystal X-ray diffraction. Compound 1 crystallizes in the triclinic space group P−1, while 2 does in the monoclinic space group P21/c. The Ni(III) ions from Ni(mnt)2− anion of 1 form a 1D non-uniform chain through Ni⋯S, Ni⋯Ni and π⋯π interactions with the Ni⋯Ni distances of 3.443, 3.935 and 3.968Å, as well as CH⋯F, CH⋯N, CH⋯π, and π⋯π weak interactions exist in 1. The anions and cations in 2 stack into segregated structure, and the anions give rise to a 1D uniform column with a Ni⋯Ni distance of 4.148Å. Magnetic measurements have shown that 1 exhibits a characteristic of spin-gap (Δ/kb=267.5K) around 86K, while 2 shows an antiferromagnetic coupling feature with J=−15.4cm−1 upon the temperature is lowed.
Background
Home oxygen therapy (HOT) is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia (BPD). There is a lack of evidence-based consensus on the indication ...for HOT among these infants. Because wide variation in the institutional use of HOT exists, little is known about the role of regional social-economic level in the wide variation of HOT.
Methods
This was a secondary analysis of Chinese Neonatal Network (CHNN) data from January 1, 2019 to December 31, 2019. Infants at gestational ages < 32 weeks, with a birth weight < 1500 g, and with moderate or severe BPD who survived to discharge from tertiary hospitals located in 25 provinces were included in this study. Infants with major congenital anomalies and those who were discharged against medical advice were excluded.
Results
Of 1768 preterm infants with BPD, 474 infants (26.8%) were discharged to home with oxygen. The proportion of HOT use in participating member hospitals varied from 0 to 89%, with five of 52 hospitals’ observing proportions of HOT use that were significantly greater than expected, with 14 hospitals with observing proportions significantly less than expected, and with 33 hospitals with appropriate proportions. We noted a negative correlation between different performance groups of HOT and median GDP per capita (
P
= 0.04).
Conclusions
The use of HOT varied across China and was negatively correlated with the levels of provincial economic levels. A local HOT guideline is needed to address the wide variation in HOT use with respect to different regional economic levels in countries like China.
Display omitted
One-third of patients with autoimmune hepatitis (AIH) have cirrhosis at the time of diagnosis. The relevance of these variables, although unknown, is believed to be critical in AIH ...because of suspected interactions between the gut microbiome and genetic factors. Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor (pIgR) levels have been observed in both patients and mouse models. Moreover, there is a direct relationship between pIgR expression and transaminase levels in patients with AIH. In this study, we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta (Reg3b) and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH. Reg3b expression was reduced in pIgR gene (Pigr)-knockout mice compared to that in wild-type mice, leading to increased microbiota disruption. Conversely, exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis. RNA sequencing revealed the participation of the interleukin (IL)-17 signaling pathway in the regulation of Reg3b through pIgR. Furthermore, the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH, and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3 (STAT3). In this study, pIgR facilitated the upregulation of Reg3b via the STAT3 pathway, which plays a crucial role in preserving the balance of the intestinal microbiota in AIH. Through this research, we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.
PDF
