Herein, we present a stable water‐soluble cobalt complex supported by a dianionic 2,2′‐(2,2′‐bipyridine‐6,6′‐diyl)bis(propan‐2‐ol) ligand scaffold, which is a rare example of a high‐oxidation ...species, as demonstrated by structural, spectroscopic and theoretical data. Electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements revealed that the CoIV center of the mononuclear complex in the solid state resides in the high spin state (sextet, S=5/2). The complex can effectively catalyze water oxidation via a single‐site water nucleophilic attack pathway with an overpotential of only 360 mV in a phosphate buffer with a pH of 6. The key intermediate toward water oxidation was speculated based on theoretical calculations and was identified by in situ spectroelectrochemical experiments. The results are important regarding the accessibility of high‐oxidation state metal species in synthetic models for achieving robust and reactive oxidation catalysis.
A stable water‐soluble cobalt(IV) complex supported by a dianionic 2,2′‐(2,2′‐bipyridine‐6,6′‐diyl)bis(propan‐2‐ol) ligand scaffold is very active in the catalysis of water oxidation at an overpotential of only 360 mV at pH=6.
Viral infection is a significant risk factor for fertility issues. Here, we demonstrated that infection by neurotropic alphaherpesviruses, such as pseudorabies virus (PRV), could impair female ...fertility by disrupting the hypothalamus-pituitary-ovary axis (HPOA), reducing progesterone (P4) levels, and consequently lowering pregnancy rates. Our study revealed that PRV exploited the transient receptor potential mucolipin 1 (TRPML1) and its lipid activator, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), to facilitate viral entry through lysosomal cholesterol and Ca2+. P4 antagonized this process by inducing lysosomal storage disorders and promoting the proteasomal degradation of TRPML1 via murine double minute 2 (MDM2)-mediated polyubiquitination. Overall, the study identifies a novel mechanism by which PRV hijacks the lysosomal pathway to evade P4-mediated antiviral defense and impair female fertility. This mechanism may be common among alphaherpesviruses and could contribute significantly to their impact on female reproductive health, providing new insights for the development of antiviral therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There are many differences in brain structure and function between males and females. However, how these differences were manifested during development and maintained through adulthood are still ...unclear. Here we present a time series analyses of genome-wide transcription profiles of the human brain, and we identified genes showing sex biased expression at major developmental stages (prenatal time, early childhood, puberty time and adulthood). We observed a great number of genes (>2,000 genes) showing between-sex expression divergence at all developmental stages with the greatest number (4,164 genes) at puberty time. However, there are little overlap of sex-biased genes among the major developmental stages, an indication of dynamic expression regulation of the sex-biased genes in the brain during development. Notably, the male biased genes are highly enriched for genes involved in neurological and psychiatric disorders like schizophrenia, bipolar disorder, Alzheimer's disease and autism, while no such pattern was seen for the female-biased genes, suggesting that the differences in brain disorder susceptibility between males and females are likely rooted from the sex-biased gene expression regulation during brain development. Collectively, these analyses reveal an important role of sex biased genes in brain development and neurodevelopmental disorders.
Introduction
This study tested the self‐reported sleep characteristics associated with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in cognitively intact older adults.
Methods
The ...linear and non‐linear regression analyses were conducted in 736 cognitively normal participants (mean standard deviation; SD age, 62.3 10.5 years, range 40 to 88 years, 59% female) who had measurements of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tTau proteins and sleep characteristics, after adjusting for age, gender, education, apolipoprotein E gene (APOE) ε4 status, and general cognition.
Results
Greater daytime sleepiness was associated with higher CSF indicators of amyloid deposition in female patients. No significant associations were revealed for CSF tTau proteins after Bonferroni correction. A U‐shaped relationship was revealed for nocturnal sleep habits, such that those with insufficient or excessive nocturnal sleep duration had greater CSF biomarkers of amyloid deposition (the reflection range: bedtime: around 10:00 p.m. and sleep duration: 6.0 to 6.5 hours).
Discussion
These findings consolidated the close relationship between sleep and AD.
Since the observables at particular time instants in a temporal sequence exhibit dependencies, they are not independent samples. Thus, it is not plausible to apply i.i.d. assumption-based ...dimensionality reduction methods to sequence data. This paper presents a novel supervised dimensionality reduction approach for sequence data, called Linear Sequence Discriminant Analysis (LSDA). It learns a linear discriminative projection of the feature vectors in sequences to a lower-dimensional subspace by maximizing the separability of the sequence classes such that the entire sequences are holistically discriminated. The sequence class separability is constructed based on the sequence statistics, and the use of different statistics produces different LSDA methods. This paper presents and compares two novel LSDA methods, namely M-LSDA and D-LSDA. M-LSDA extracts model-based statistics by exploiting the dynamical structure of the sequence classes, and D-LSDA extracts the distance-based statistics by computing the pairwise similarity of samples from the same sequence class. Extensive experiments on several different tasks have demonstrated the effectiveness and the general applicability of the proposed methods.
Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. ...Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate mechanisms and altered pathways of gypenoside against carbon tetrachloride (CCl4)-induced liver fibrosis based on integrative analysis of proteomics and metabolomics data.
CCl4-induced ...liver fibrosis rats were administrated gypenoside. The anti-fibrosis effects were evaluated by histomorphology and liver hydroxyproline (Hyp) content. Protein profiling and metabolite profiling of rats liver tissues were examined by isobaric tags for relative and absolute quantitation (iTRAQ) approach and gas chromatography-mass spectrometer (GC-MS) technology. Altered pathways and pivotal proteins and metabolites were searched by integrative analysis of proteomics and metabolomics data. The levels of some key proteins in altered pathways were determined by western blot.
Histopathological changes and Hyp content in gypenoside group had significant improvements (P<0.05). Compared to liver fibrosis model group, we found 301 up-regulated and 296 down-regulated proteins, and 9 up-regulated and 8 down-regulated metabolites in gypenoside group. According to integrative analysis, some important pathways were found, including glycolysis or gluconeogenesis, fructose and mannose metabolism, glycine, serine and threonine metabolism, lysine degradation, arginine and proline metabolism, glutathione metabolism, and sulfur metabolism. Furthermore, the levels of ALDH1B1, ALDH2 and ALDH7A1 were found increased and restored to normal levels after gypenoside treated (P<0.05).
Gypenoside inhibited CCl4-induced liver fibrosis, which may be involved in the alteration of glycolysis metabolism and the protection against the damage of aldehydes and lipid peroxidation by up-regulating ALDH.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In situ modulation of surface reaction is a powerful approach to drive high-yield H2O2 electrosynthesis on metal-free carbon. Here, we discover that cationic surfactants can work efficiently as an in ...situ kinetic promoter for the oxygen-to-peroxide reaction on a carbon black electrode, achieving a peroxide yield above 90% (up to 95.2%) across a >0.8 V window in alkaline media, the best among reported H2O2 electrocatalysts. Our characterizations and kinetic model analysis show that the high peroxide selectivity is attributable to surface carboxylates (–COO−) with weak peroxide binding under a Coulombic pull imposed by an adsorbed cationic layer. Although surface carbonyls (–C=O) also participate in the peroxide synthesis, they exhibit strong binding to peroxide and promote on-site reduction at moderate-to-high overpotential. At only a minute amount of cationic surfactant, a chronoamperometry experiment with a carbonyl-free system can deliver a peroxide production at a sustainably high selectivity (∼96%) over 10 h.
Display omitted
•>95% H2O2 selectivity attained across 0.80 V in a metal-free electrosynthesis system•In situ engineering with cationic surfactant promotes H2O2 selectivity on carbon•Surface COO− groups are main active sites with weak binding to surface peroxides•Surface C=O groups deteriorates selectivity by the strong binding with peroxides
Electrosynthesis via two-electron oxygen reduction reactions is one of the most feasible ways for on-demand production of H2O2, which has aroused enormous research interest in chemistry and material science. However, severe problems, such as the low selectivity to H2O2, use of rare noble metal catalysts, and high energy demand, still exist and seriously restrict the applications of this process. Here, we demonstrate that an in situ modulation of peroxide selectivity by charged surfactants on metal-free carbon surface can achieve the best catalytic performance ever reported at >90% (up to 95.2%) peroxide selectivity across a wide potential window. Besides the sustainably high activity, which promises potential applications of the interface reaction system, the results also reveal that the surface oxygen groups act as peroxide generation sites with differential functionality, shedding light on a new discipline in interfacial design for highly selective H2O2 electrosynthesis.
Wu et al. demonstrate that a >95% H2O2 selectivity can simply be achieved in an electrosynthesis by using a positively charged surfactant on metal-free carbon electrode without needing sophisticated material design. Under the oxygen reduction reaction, the positively charged promoter pulls off adsorbed peroxide as formed, promoting the release of peroxide while protecting carbon surface from corrosion. It works well with surface carboxylates with weak binding, whereas carbonyl groups hold on to peroxides strongly and thus hinder the desorption and release.
Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance, but the mechanisms regulating the stability and function of Treg cells have not been fully elucidated. Here ...we show SUMO-specific protease 3 (SENP3) is a pivotal regulator of Treg cells that functions by controlling the SUMOylation and nuclear localization of BACH2. Treg cell-specific deletion of Senp3 results in T cell activation, autoimmune symptoms and enhanced antitumor T cell responses. SENP3-mediated BACH2 deSUMOylation prevents the nuclear export of BACH2, thereby repressing the genes associated with CD4
T effector cell differentiation and stabilizing Treg cell-specific gene signatures. Notably, SENP3 accumulation triggered by reactive oxygen species (ROS) is involved in Treg cell-mediated tumor immunosuppression. Our results not only establish the role of SENP3 in the maintenance of Treg cell stability and function via BACH2 deSUMOylation but also clarify the function of SENP3 in the regulation of ROS-induced immune tolerance.
PDF
