The cyclization reactions of propargylic alcohols and propargylic amines with CO2 are important in industrial applications, but it was a great challenge that non‐noble‐metal catalysts catalyzed both ...reactions under mild conditions. Herein, the catalyst Cu2O@ZIF‐8 was prepared by encapsulating Cu2O nanoparticles into robust ZIF‐8, and it can effectively catalyze the cyclization of both propargylic alcohols and propargylic amines with CO2 into valuable α‐alkylidene cyclic carbonates and oxazolidinones with turnover numbers (TONs) of 12.1 and 19.6, which can be recycled at least five times. The mechanisms were further uncovered by NMR, FTIR, 13C isotope‐labeling experiments and DFT calculations, in which Cu2O and DBU can synergistically activate the C≡C bond and the hydroxy/amino group of substrates. Importantly, it is the first example of a noble‐metal‐free catalyst that can catalyze both propargylic alcohols and propargylic amines with CO2 simultaneously.
The noble‐metal‐free catalyst Cu2O@ZIF‐8 with a yolk–shell structure was synthesized, and it represents the first noble‐metal‐free catalyst that can effectively catalyze both propargylic alcohols and propargylic amines with CO2 under mild conditions.
The development of efficient enzyme immobilization to promote their recyclability and activity is highly desirable. Zeolitic imidazolate framework‐8 (ZIF‐8) has been proved to be an effective ...platform for enzyme immobilization due to its easy preparation and biocompatibility. However, the intrinsic hydrophobic characteristic hinders its further development in this filed. Herein, a facile synthesis approach was developed to immobilize pepsin (PEP) on the ZIF‐8 carrier by using Ni2+ ions as anchor (ZIF‐8@PEP‐Ni). By contrast, the direct coating of PEP on the surface of ZIF‐8 (ZIF‐8@PEP) generated significant conformational changes. Electrochemical oxygen evolution reaction (OER) was employed to study the catalytic activity of immobilized PEP. The ZIF‐8@PEP‐Ni composite attains remarkable OER performance with an ultralow overpotential of only 127 mV at 10 mA cm−2, which is much lower than the 690 and 919 mV overpotential values of ZIF‐8@PEP and PEP, respectively.
A facile synthesis approach was developed to immobilize enzyme on the ZIF‐8 carrier by using Ni2+ ions as anchor, which can significantly promote the recyclability and activity of the enzyme.
Alterations in microRNAs (miRNAs) have been considered to have diagnostic implications in most diseases, but few studies have reported dysregulated miRNAs in schizophrenia (SCZ). In order to observe ...an association between miRNAs and SCZ, this study was designed to investigate expression profiling of miRNAs in peripheral blood mononuclear cells (PBMCs). miRNA microarray technology was employed to compare the expression of miRNAs in PBMCs from SCZ patients (n=105) and normal controls (n=130), and real-time quantitative polymerase chain reaction (QPCR) was used to analyze the results. Several important miRNA levels were examined before and after antipsychotic treatment in first-onset SCZ patients. In addition, an SCZ-like rat model was established using dizocilpine (MK-801), and miR-132 expression in PBMCs and whole-brain tissue from SCZ-like rats was studied using QPCR. In humans, dysregulated miRNAs were observed before treatment and QPCR verified that miR-132, miR-134, miR-1271, miR-664⁎, miR-200c and miR-432 levels were significantly decreased (P<0.01 for all) in PBMCs of SCZ patients compared with healthy controls. After antipsychotic treatment there was a marked increase in miR-132 (P<0.01), miR-664⁎ (P<0.05) and miR-1271 (P<0.05) levels in SCZ patients compared with the levels before treatment. In the animal assays, miR-132 levels declined in PBMCs and whole-brain tissues (both P<0.05) of the SCZ-like rats compared to controls. For the first time, our results suggest that miR-132 is a potential and superior biomarker in peripheral blood that will allow discrimination of SCZ patients from healthy controls.
•miR-132, miR-134, miR-1271, miR-664*, miR-200c and miR-432 were significantly decreased in PBMCs of SCZ patients•miR-132, miR-664* and miR-1271 increased in PMCSs upon anti-psychotic treatment of SCZ patients•miR-132 showed a trend for decline in PBMCs and whole-brain tissue of SCZ-like rats
Background
Premature ovarian insufficiency (POI) is one major cause of female infertility, minichromosome maintenance complex component 8 (MCM8) has been reported to be responsible for POI.
Methods
...Whole‐exome sequencing was performed to identify the genetic variants of women with POI. Sanger sequencing was used to validate the variants in all the family members. Various bioinformatic software was used for the pathogenicity assessment. Reverse transcription polymerase chain reaction (RT‐PCR), real‐time quantitative PCR, and a chromosomal instability study induced by mitomycin C were performed to analyze the functional effects of the variant.
Results
A novel homozygous frameshift mutation (NM_032485.4:c.351_354delAAAG) of MCM8 gene was identified in the patients, segregated with POI in this family. This mutation is predicted to produce truncated MCM8 protein and to be pathogenic. Reverse transcription polymerase chain reaction revealed that the frameshift mutation led to a remarkably reduced level of MCM8 transcript products, and chromosomal instability study showed that the ability of mutant MCM8 to repair DNA breaks was impaired.
Conclusion
We identified a novel homozygous frameshift mutation in the MCM8 gene in two affected sisters with POI, and functional analysis revealed that this mutation is pathogenic. Our findings enrich the MCM8 mutation spectrum and might help clinicians to make a precise diagnosis, thereby allowing better family planning and genetic counseling.
In our study, a novel homozygous frameshift mutation in the MCM8 gene was identified in a consanguineous Han Chinese family by whole‐exome sequencing, which segregates with POI in this family. Furthermore, functional characterization revealed that this frameshift mutation is pathogenic.
Premature ovarian insufficiency (POI) is a severe clinical syndrome defined by ovarian dysfunction in women less than 40 years old who generally manifest with infertility, menstrual disturbance, ...elevated gonadotrophins, and low estradiol levels.
is considered a genetic aetiology of POI, which facilitates entry of REC8 into the nucleus of a cell and plays an essential role in gametogenesis. At present, only six truncated variants associated with POI have been reported; there have been no reports of an in-frame variant of
causing POI. In this study, two novel homozygous in-frame variants (c.877_885del, p.293_295del; c.891_893dupTGA, p.297_298insAsp) in
were identified in two sisters with POI from a five-generation consanguineous Han Chinese family. To evaluate the effects of these two variants, we performed fluorescence localization and co-immunoprecipitation analyses using
cell model. The two variants were shown to be pathogenic, as neither STAG3 nor REC8 entered nuclei, and interactions between mutant STAG3 and REC8 or SMC1A were absent. To the best of our knowledge, this is the first report on in-frame variants of
that cause POI. This finding extends the spectrum of variants in
and sheds new light on the genetic origins of POI.
Objective
To predict the risk of dystrophinopathy in fetal carriers of dystrophin gene (DMD) mutations.
Methods
Twenty‐three pregnant women, with a total of 25 female fetuses carrying DMD mutations, ...were recruited. Among them, 13 pregnant women who participated in this study were only used to analyse the incidence of induced abortion after fetuses were diagnosed as dystrophinopathy carriers. Eleven fetal carriers from 10 pregnant women were tested to analyse X‐chromosome inactivation (XCI) using amniocytes to assess the risk of dystrophinopathy. Follow‐ups were conducted on all cases.
Results
Approximately one‐third of fetuses were aborted before assessing the risk of dystrophinopathy. XCI analysis of amniocytes showed that 10 fetuses had random XCI patterns, and one fetus exhibited a highly skewed XCI pattern (100:0) with primary expression of the maternal X chromosome that carried the mutant allele. These 11 fetal carriers were born, and follow‐up showed that the girl who showed the skewed XCI pattern as a fetus was diagnosed with Duchenne muscular dystrophy (DMD) at the age of four. The others did not present with dystrophinopathy‐associated symptoms.
Conclusions
XCI was significantly implicated in symptomatic female carriers of dystrophinopathies, and XCI pattern analysis of amniocytes may be useful in predicting the risk of dystrophinopathy in fetal carriers.
The control of temporal networks is of paramount importance to complex systems in diverse fields. Recent studies showed that temporal networks are more controllable than their static counterparts, in ...terms of control time, cost, and trajectory length. However, the underlying mechanism of this intriguing phenomenon remains elusive, partly due to the fact that multiple properties of a temporal network simultaneously change over time. Here, we explore a general model of temporal networks, and prove that the weight variation of a link is equivalent to attaching a virtual driver node to that link. Consequently, the random variation of link weights can significantly increase the dimension of controllable space and remarkably reduce control cost, which unveils the fundamental mechanism for the advantages of temporal networks in controllability. The finding of this mechanism leads to a graphic criterion that allows us to further discover that, degree-heterogeneous networks are more advantageous for enhancing controllability by link weight variation, and the favorable positions of weight variation are the incoming links of the nodes with a high outdegree and a low indegree. Our results are validated in both synthetic and empirical network data, together deepening the understanding of network temporality and shedding light on the long-standing problem of establishing graphic criteria for the controllability of general dynamic systems.
Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in ...Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE
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mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE
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mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE
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mice were randomly divided into the model group, OPD group, and simvastatin group (
n
= 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites.
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