Retarded Translocation of Nucleic Acids through α-Hemolysin Nanopore in the Presence of a Calcium Flux.

Electrophysiological measurement of molecular translocation through a nanopore is the fundamental basis of nanopore sensing. Free translocation of nucleic acids however is normally so fast that the identities of the compounds are not clearly resolvable. Inspired by recent progress in fluorescence imaging based nanopore sensing, we found that during electrophysiology measurements, translocation of nucleic acids is also retarded whenever a calcium flux around the pore vicinity is established.

Development of a Simple and Quick Method to Assess Base Editing in Human Cells.

Base editing is a form of genome editing that can directly convert a single base (C or A) to another base (T or G), which is of great potential in biomedical applications. The broad application of base editing is limited by its low activity and specificity, which still needs to be resolved. To address this, a simple and quick method for the determination of its activity/specificity is highly desired.

Prolyl endopeptidase gene disruption attenuates high fat diet-induced nonalcoholic fatty liver disease in mice by improving hepatic steatosis and inflammation.

Background: Prolyl endopeptidase (PREP) is a serine endopeptidase that regulates inflammatory responses. PREP inhibitors can reduce hepatocyte lipid accumulation and may participate in the progression of nonalcoholic fatty liver disease (NAFLD). We investigated whether disruption of PREP regulates hepatic steatosis and inflammation in mice with NAFLD.

Occurrence and sources of chromophoric organic carbon in fine particulate matter over Xi'an, China.

Understanding the characteristics and sources of atmospheric chromophores is essential to assess their impact on climate change and the quality of atmospheric environment. In this work, the fine particulate matter (PM) samples of Xi'an, China in 2017 were analyzed by excitation-emission matrices and parallel factor analysis (EEM-PARAFAC) method to obtain the species, content, sources and seasonal variation characteristics of atmospheric chromophores. The results showed that humic-like (HULIS) chromophores and polycyclic aromatic hydrocarbons-like (PAHs-like) chromophores were the most abundant chromophores in the samples, accounting for 42% and 33%, respectively.

METTL3 is essential for postnatal development of brown adipose tissue and energy expenditure in mice.

Brown adipose tissue (BAT) undergoes rapid postnatal development and then protects against cold and obesity into adulthood. However, the molecular mechanism that determines postnatal development and maturation of BAT is largely unknown. Here we show that METTL3 (a key RNA methyltransferase) expression increases significantly in interscapular brown adipose tissue (iBAT) after birth and plays an essential role in the postnatal development and maturation of iBAT.

Transcription factor Hap5 induces gsh2 expression to enhance 2-phenylethanol tolerance and production in an industrial yeast Candida glycerinogenes.

2-Phenylethanol (2-PE) is an important flavor compound but also impairs cell growth severely, which in turn blocks its bioproduction. However, the molecular mechanism of 2-PE tolerance is unclear. In this study, a superb 2-PE stress-tolerant and producing yeast, Candida glycerinogenes, was selected to uncover the underlying mechanism of 2-PE tolerance.

Effects of Terminal Motif on the Self-Assembly of Dexamethasone Derivatives.

Tailoring the terminal motif of molecules including drugs might significantly affect their self-assembly tendency in aqueous solution, thus providing a rational strategy to modulate its macroscopic characteristics of supramolecular assembly. A model drug of dexamethasone (Dex) was esterified by different fatty acids [succinic acid (SA), glutaric acid (GA), and adipic acid (AA)] and aromatic acid [phthalic acid (PA)] to generate a series of Dex derivatives. Aqueous solution of Dex-SA, Dex-GA, and Dex-AA turned into hydrogel spontaneously after a period time of incubation (24, 48, and 72 h, respectively) via the auto-hydrolytic strategy, while aqueous solution of Dex-PA did not result in hydrogelation during 3 days of incubation.

Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism.

Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined.

Direct microRNA Sequencing Using Nanopore-Induced Phase-Shift Sequencing.

MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in RNA silencing and post-transcriptional gene regulation. However, direct characterization of miRNA is challenging due to its unique properties such as its low abundance, sequence similarities, and short length. Although urgently needed, single molecule sequencing of miRNA has never been demonstrated, to the best of our knowledge.

Identification of species and sources of atmospheric chromophores by fluorescence excitation-emission matrix with parallel factor analysis.

It is essential to fully understand the physicochemical properties and sources of atmospheric chromophores to evaluate their impacts on environmental quality and global climate. Three-dimensional excitation-emission matrix (EEM) fluorescence spectroscopy is an important method for directly characterizing the occurrences, origins, and chemical behaviors of atmospheric chromophores. However, there is still a lack of adequate information on the sources and chemical structures of EEM-defined chromophores.

Does Epichloë Endophyte Enhance Host Tolerance to Root Hemiparasite?

Epichloë endophytes have been shown to be mutualistic symbionts of cool-season grasses under most environmental conditions. Although pairwise interactions between hemiparasites and their hosts are heavily affected by host-associated symbiotic microorganisms, little attention has been paid to the effects of microbe-plant interactions, particularly endophytic symbiosis, in studies examining the effects of parasitic plants on host performance. In this study, we performed a greenhouse experiment to examine the effects of hereditary Epichloë endophyte symbiosis on the growth of two host grasses (Stipa purpurea and Elymus tangutorum) in the presence or absence of a facultative root hemiparasite (Pedicularis kansuensis Maxim).

Study on the oxidation potential of the water-soluble components of ambient PM over Xi'an, China: Pollution levels, source apportionment and transport pathways.

Reactive oxygen species (ROS) are a class of substances that are of general concern in terms of human health and are used to represent the oxidation potential (OP) of the atmosphere. In this study, the ROS levels in 116 daily fine particulate matter (PM) samples taken over Xi'an in 2017 were measured with the dithiothreitol (DTT) method. The sources of DTTv (volume-based DTT consumption) in PM as well as their contributions were identified by both positive matrix factorization (PMF) and multiple linear regression (MLR) based on the measured chemical species in particulate matter (PM).

Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle.

Background: This study used a genome-wide screen of gene expression to better understand the metabolic and functional differences between commercially valuable intramuscular fat (IMF) and commercially wasteful subcutaneous (SC) fat depots in Bos taurus beef cattle.

Results: We confirmed many findings previously made at the biochemical level and made new discoveries. The fundamental lipogenic machinery, such as ACACA and FASN encoding the rate limiting Acetyl CoA carboxylase and Fatty Acid synthase were expressed at 1.

Impacts of Sources on PM Oxidation Potential during and after the Asia-Pacific Economic Cooperation Conference in Huairou, Beijing.

To illustrate the major sources responsible for the redox activity of ambient fine particles during the 2014 Asia-Pacific Economic Cooperation (APEC) conference in Beijing, 3 months of daytime (8:00-19:30 LST) and nighttime (20:00-7:30 LST) particulate kmatter (PM) was collected in Huairou, Beijing from November 3, 2014 through January 31, 2015. PM compositions were analyzed, including elements, organic carbon, elemental carbon, water-soluble ions, organics, and redox activities measured by both the dithiothreitol and the macrophage reactive oxygen species (ROS) assays. The mass-normalized redox activity was approximately constant during the noncontrol period (NCP) and control period (CP).

Deficiency of core fucosylation activates cellular signaling dependent on FLT3 expression in a Ba/F3 cell system.

Fms-like tyrosine kinase 3 (FLT3) is a glycoprotein, that is a member of the class III receptor tyrosine kinase family. Approximately one-third of acute myeloid leukemia (AML) patients have mutations of this gene, and activation of the FLT3 downstream pathway plays an important role in both normal and malignant hematopoiesis. However, the role of N-glycosylation for FLT3 activation remains unclear.

Pedestrian Dead Reckoning-Assisted Visual Inertial Odometry Integrity Monitoring.

Visual inertial odometers (VIOs) have received increasing attention in the area of indoor positioning due to the universality and convenience of the camera. However, the visual observation of VIO is more susceptible to the environment, and the error of observation affects the final positioning accuracy. To address this issue, we analyzed the causes of visual observation error that occur under different scenarios and their impact on positioning accuracy.

Therapeutic effects of nerve leachate-treated adipose-derived mesenchymal stem cells on rat sciatic nerve injury.

Peripheral nerve injury (PNI) is a common condition, often resulting from physical nerve injury and trauma. Successful repair of the peripheral nerve is dependent on the regenerative activity of Schwann cells (SCs). Application of SC-like adipose-derived mesenchymal stem cells (ADSCs) may be a suitable cell-based therapy for PNI.

Correlation of serum amyloid A levels, clinical manifestations, treatment, and disease activity in patients with acute anterior uveitis.

Purpose: To investigate the association between serum amyloid A (SAA) protein and the clinical features of acute anterior uveitis (AAU), and to evaluate the disease activity and treatment effect in relation to SAA levels.

Methods: AAU patients and healthy individuals were recruited from October 2016 to August 2017 at the Department of Uveitis, in the Eye Hospital of Wenzhou Medical University. Related demographic, clinical characteristics, and therapeutic data were analyzed.

Sterolomics in biology, biochemistry, medicine.

In mammalian systems "sterolomics" can be regarded as the quantitative or semi-quantitative profiling of all metabolites derived from cholesterol and its cyclic precursors. The system can be further complicated by metabolites derived from ingested phytosterols or pharmaceuticals, but this is beyond the scope of this article. "Sterolomics" can be performed on either an unbiased global format, or more usually, exploiting a targeted format.

Mucoadhesive dexamethasone-glycol chitosan nanoparticles for ophthalmic drug delivery.

Self-assembly of drug-polysacrrides conjugates forming nanostructures provides a simple and promising strategy for the extension of precorneal retention and enhancement of corneal permeability. In the present study, a series of dexamethasone-glycol chitosan (Dex-GCS) conjugates were synthesized and thoroughly characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and ultraviolet-visible (UV-Vis) spectroscopy. The resulting Dex-GCS conjugates were able to self-assemble into nanoparticles spontaneously with particle sizes in the range of 277-289 nm and a positive charge of approximately +15 mV.

Giant single molecule chemistry events observed from a tetrachloroaurate(III) embedded Mycobacterium smegmatis porin A nanopore.

Biological nanopores are capable of resolving small analytes down to a monoatomic ion. In this research, tetrachloroaurate(III), a polyatomic ion, is discovered to bind to the methionine residue (M113) of a wild-type α-hemolysin by reversible Au(III)-thioether coordination. However, the cylindrical pore geometry of α-hemolysin generates shallow ionic binding events (~5-6 pA) and may have introduced other undesired interactions.

Single molecule observation of hard-soft-acid-base (HSAB) interaction in engineered porin A (MspA) nanopores.

In the formation of coordination interactions between metal ions and amino acids in natural metalloproteins, the bound metal ion is critical either for the stabilization of the protein structure or as an enzyme co-factor. Though extremely small in size, metal ions, when bound to the restricted environment of an engineered biological nanopore, result in detectable perturbations during single channel recordings. All reported work of this kind was performed with engineered α-hemolysin nanopores and the observed events appear to be extremely small in amplitude (∼1-3 pA).

Celastrol exerts anti-inflammatory effect in liver fibrosis via activation of AMPK-SIRT3 signalling.

Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver-related diseases. However, the anti-inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti-inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol-induced anti-inflammatory effects with a focus on AMPK-SIRT3 signalling.

Oxysterols as lipid mediators: Their biosynthetic genes, enzymes and metabolites.

There is growing evidence that oxysterols are more than simple metabolites in the pathway from cholesterol to bile acids. Recent data has shown oxysterols to be ligands to nuclear receptors and to G protein-coupled receptors, modulators of N-methyl-d-aspartate receptors and regulators of cholesterol biosynthesis. In this mini-review we will discuss the biosynthetic mechanisms for the formation of different oxysterols and the implication of disruption of these mechanisms in health and disease.