Using the redox‐active tetrathiafulvalene tetrabenzoate (TTFTB4−) as the linker, a series of stable and porous rare‐earth metal–organic frameworks (RE‐MOFs), RE9(μ3‐OH)13(μ3‐O)(H2O)9(TTFTB)3 (1‐RE, ...where RE=Y, Sm, Gd, Tb, Dy, Ho, and Er) were constructed. The RE9(μ3‐OH)13(μ3‐O) (H2O)9(CO2)12 clusters within 1‐RE act as segregated single‐molecule magnets (SMMs) displaying slow relaxation. Interestingly, upon oxidation by I2, the S=0 TTFTB4− linkers of 1‐RE were converted into S=1/2
TTFTB.3− radical linkers which introduced exchange‐coupling between SMMs and modulated the relaxation. Furthermore, the SMM property can be restored by reduction in N,N‐dimethylformamide. These results highlight the advantage of MOFs in the construction of redox‐switchable SMMs.
Redox switchable single‐molecule magnets (SMM) arranged in ordered architectures are valuable objects for use in memory devices. A metal–organic framework is an ideal platform to integrate SMM as nodes and redox‐active organic linkers as switching probes (see figure).
An herbal prescription is usually composed of several herbal medicines. The complex and diverse components bring great challenges to its bioactivity study. To comprehensively analyze the bioactivity ...of an herbal prescription, a new strategy based on peak‐by‐peak cutting and knock‐out chromatography was proposed. In this strategy, active compounds were screened out via peak‐by‐peak cutting from an herbal extract, and the influence of a compound on the overall activity of the herbal extract was evaluated by knock‐out chromatography. Qiliqiangxin capsule is an herbal prescription composed of 11 herbal medicines for the treatment of chronic heart failure. A total of 71 peaks were collected through peak‐by‐peak cutting, and each peak was identified by a high‐resolution mass spectrum. The bioassay against 1,1‐diphenyl‐2‐picrylhydrazyl showed that two types of compounds namely salvianolic acids and caffeoylquinic acids were potent scavengers. Knock‐out chromatography suggested that the removal of one single compound had no obvious influence on the overall activity of the Qiliqiangxin capsule. After all the main peaks in the Qiliqiangxin capsule were knocked out, the remaining part still exhibited a potent activity, indicating high activity stability of the Qiliqiangxin capsule. The proposed strategy is helpful for the comprehensive analysis of the bioactivity of other herbal prescriptions.
In search of multifunctional metal–organic frameworks (MOFs), redox-active donors and acceptors, namely, tetrathiafulvalene (TTF) and 7,7,8,8-tetracyanoquinodimethane (TCNQ), were concomitantly used ...as skeletal components with diamagnetic metal nodes (Cd and Zn) to construct unique framework materials. Six isostructural frameworks were synthesized by diffusion of metal salts, TTF(py)4, and either paramagnetic Li(TCNQ) or diamagnetic H2TCNQ. They were characterized by single-crystal X-ray diffraction and FT-IR and UV–vis–NIR spectroscopy, and their physical properties were studied, including two postsynthetic modifications involving crystal-to-crystal transformations following a solid-solution reaction with I2. The highly colored crystals of two isostructural Zn and Cd frameworks contain undulating Cd-TTF(py)4 layers entwined with TCNQ in a chicken-wire net as part of the skeleton of the MOF as well as TCNQ intercalated within the channels, while nitrate anions are occluded within the cavities formed by the pyridine moieties. Reaction with I2 replaces each intercalated TCNQ•– within the channels with I3 –. The optical properties and the electron paramagnetic resonance (EPR) spectra indicate the presence of only radical TCNQ•– in the parent compounds, while the magnetic susceptibilities enabled an estimation of the amount of TCNQ•– (S = 1/2) leading to almost paramagnetic behavior. Solid-state electrochemistry provides evidence of several one-electron redox states corresponding to the electroactive cores.
Primary failure of tooth eruption (PFE) is a rare autosome genetic disorder that causes open bite. This work aimed to report a small family of PFE(OMIM: # 125,350) with a novel PTH1R variant. One of ...the patients has a rare clinical phenotype of the anterior tooth involved only.
The proband was a 13-year-old young man with an incomplete eruption of the right upper anterior teeth, resulting in a significant open-bite. His left first molar partially erupted. Family history revealed that the proband's 12-year-old brother and father also had teeth eruption disorders. Genetic testing found a novel PTH1R variant (NM_000316.3 c.1325-1336del), which has never been reported before. The diagnosis of PFE was based on clinical and radiographic characteristics and the result of genetic testing. Bioinformatic analysis predicted this variant would result in the truncation of the G protein-coupled receptor encoded by the PTH1R, affecting its structure and function.
A novel PTH1R variant identified through whole-exome sequencing further expands the mutation spectrum of PFE. Patients in this family have different phenotypes, which reflects the characteristics of variable phenotypic expression of PFE.
Narrow therapeutic window limits treatments with thrombolysis and neuroprotection for most stroke patients. Widening therapeutic window remains a critical challenge. Understanding the key mechanisms ...underlying the pathophysiological events in the peri-infarct area where secondary injury coexists with neuroplasticity over days to weeks may offer an opportunity for expanding the therapeutic window. Here we show that ischemia-induced histone deacetylase 2 (HDAC2) upregulation from 5 to 7 d after stroke plays a crucial role. In this window phase, suppressing HDAC2 in the peri-infarct cortex of rodents by HDAC inhibitors, knockdown or knock-out of
promoted recovery of motor function from stroke via epigenetically enhancing cells survival and neuroplasticity of surviving neurons as well as reducing neuroinflammation, whereas overexpressing HDAC2 worsened stroke-induced functional impairment of both WT and
conditional knock-out mice. More importantly, inhibiting other isoforms of HDACs had no effect. Thus, the intervention by precisely targeting HDAC2 in this window phase is a novel strategy for the functional recovery of stroke survivors.
Narrow time window phase impedes current therapies for stroke patients. Understanding the key mechanisms underlying secondary injury may open a new window for pharmacological interventions to promote recovery from stroke. Our study indicates that ischemia-induced histone deacetylase 2 upregulation from 5 to 7 d after stroke mediates the secondary functional loss by reducing survival and neuroplasticity of peri-infarct neurons as well as augmenting neuroinflammation. Thus, precisely targeting histone deacetylase 2 in the window phase provides a novel therapeutic strategy for stroke recovery.
Presbycusis is the cumulative effect of aging on hearing. Recent studies have shown that common mitochondrial gene deletions are closely related to deafness caused by degenerative changes in the ...auditory system, and some of these nuclear factors are proposed to participate in the regulation of mitochondrial function. However, the detailed mechanisms involved in age-related degeneration of the auditory systems have not yet been fully elucidated. In this study, we found that FOXG1 plays an important role in the auditory degeneration process through regulation of macroautophagy/autophagy. Inhibition of FOXG1 decreased the autophagy activity and led to the accumulation of reactive oxygen species and subsequent apoptosis of cochlear hair cells. Recent clinical studies have found that aspirin plays important roles in the prevention and treatment of various diseases by regulating autophagy and mitochondria function. In this study, we found that aspirin increased the expression of FOXG1, which further activated autophagy and reduced the production of reactive oxygen species and inhibited apoptosis, and thus promoted the survival of mimetic aging HCs and HC-like OC-1 cells. This study demonstrates the regulatory function of the FOXG1 transcription factor through the autophagy pathway during hair cell degeneration in presbycusis, and it provides a new molecular approach for the treatment of age-related hearing loss.
Abbreviations: AHL: age-related hearing loss; baf: bafilomycin A1; CD: common deletion; D-gal: D-galactose; GO: glucose oxidase; HC: hair cells; mtDNA: mitochondrial DNA; RAP: rapamycin; ROS: reactive oxygen species; TMRE: tetramethylrhodamine, ethyl ester
Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes ...of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.
Display omitted
•Six high-quality ixodid tick genomes and 678 re-sequenced tick specimens•Insights into the genetic basis of tick hematophagy and related phenotypes•Population structure and genetic diversity of six tick species•Tick-borne pathogen composition and distribution by metagenome analyses
The high-quality genomes of six ixodid tick species and resequencing of 678 tick specimens are a resource to understand the genetic diversity, population structure, and pathogen distribution of ticks with implications for control of ticks and tick-borne diseases.
Aneuploidy is one of the main causes of fetal and embryonic mortality in mammals. Nonetheless, its incidence in domestic ruminants has been investigated little. Indeed, no incidence data have ever ...been reported for water buffalo. To establish the incidence of aneuploidy in this species, we analysed in vitro matured metaphase II (MII) oocytes with corresponding first polar bodies (I PB) of the river (2n = 50) and swamp (2n = 48) buffaloes. For the first time, six river type probes (corresponding to chromosomes 1-5 and heterosome X), were tested on swamp buffalo metaphases using Multicolor-Fluorescent In Situ Hybridization (M-FISH) before their use on oocytes MII metaphases. Of the 120 total Cumulus Oocyte Complexes (COCs, 60 for each buffalo type) subjected to in vitro maturation, 104 reached the MII stage and were analysed by M-FISH. Haploid chromosome arrangement and visible I PB were observed in 89 of the oocytes (45 in river and 44 in swamp type). In the river type, the analysis revealed one oocyte was disomic for the chromosome X (2.22%). In the swamp type, one oocyte was found to be nullisomic for chromosome X (2.27%); another was found to be nullisomic for chromosome 5 (2.27%). We also observed one oocyte affected by a premature separation of sister chromatids (PSSC) on the chromosome X (2.27%). In both buffalo types, no abnormalities were detected in other investigated chromosomes. Based on merged data, the overall aneuploidy rate for the species was 3.37%. Oocytes with unreduced chromosomes averaged 1.92% across the two types, with 1.96% in river and 1.88% in swamp. The interspecies comparison between these data and cattle and pig published data revealed substantial difference in both total aneuploidy and diploidy rates. Reducing the negative impact of the meiotic segregation errors on the fertility is key to more sustainable breeding, an efficient embryo transfer industry and ex-situ bio-conservation. In this respect, additional M-FISH studies are needed on oocytes of domestic species using larger sets of probes and/or applying next generation sequencing technologies.
Objective
Maternal vitamin D deficiency is associated with glucose and lipid metabolism in the mother and offspring. Meanwhile, it can also lead to adverse pregnancy outcomes. The aim of this ...case‐control study was to document maternal, umbilical arterial glucose and lipid metabolic levels and correlations in pregnancies with or without vitamin D deficiency, while also investigating adverse pregnancy outcomes.
Design/Participants/Measurements
A total of 425 pregnant women who received antenatal care and delivered at Wenzhou People's Hospital were enrolled. According to their serum 25‐hydroxyvitamin D 25(OH)D level, the pregnant women were divided into the vitamin D deficiency group 25(OH)D < 20 ng/mL, 185 participants and the control group 25(OH)D ≥ 20 ng/mL, 240 participants. Maternal blood samples were collected at 24‐28 weeks of gestation and delivery for 75‐g oral glucose tolerance test (OGTT), and measurements of glucose and lipid metabolite levels and 25(OH)D levels. Umbilical arterial samples were collected during delivery (33.57‐41.43 gestational weeks).
Results
Compared with control participants, vitamin D deficiency women had significantly higher concentrations of fasting blood‐glucose (P < .01), 1‐h OGTT plasma glucose (P < .01), 2‐h OGTT plasma glucose (P < .01), insulin (P < .01), HOMA‐IR (P < .01), LDL (P < .01) and triglycerides (P = .02) and lower concentrations of HOMA‐S (P < .01). Compared with the control group, vitamin D deficiency women had higher concentrations of triglycerides (P < .01) and lower concentrations of HDL‐C (P < .01) and HOMA‐β (P = .01) in infant umbilical arterial blood. Pearson's correlation analysis demonstrated that the maternal 25(OH)D level was negatively correlated with maternal plasma glucose, insulin, LDL‐C, cholesterol, triglyceride and HOMA‐IR (r = −.38, −.27, −.2, −.11, −.11, −.33 and .11; P < .01, <.01, <.01, <.05, <.05 and <.01, respectively), while there was a positive correlation between maternal serum 25(OH)D and HOMA‐S (r = .11, P < .05). The triglyceride level in the umbilical artery was negatively correlated with maternal serum 25(OH)D concentration (r = −.286, P < .01), while the HDL‐C and HOMA‐β in umbilical artery were positively related (r = .154, .103, P < .01). Compared with the control group, the incidences of pre‐eclampsia 4.8% (9/185) vs 1.25% (3/240), P = .03, gestational diabetes mellitus 19.45% (36/185) vs 12.08% (29/240), P = .04 and premature rupture of membranes 15.68% (29/185) vs 5.42% (13/240), P < .01 were higher in the vitamin D deficiency group.
Conclusion
Vitamin D deficiency during pregnancy is associated with maternal glucose and lipid metabolism and pregnancy outcomes. Therefore, it is worth recommending to maintain vitamin D status at an optimal level in pregnant women to prevent metabolic disorders and pregnancy complications.
PDF
