Hypoxia-inducible factor-1α inhibitor promotes non-alcoholic steatohepatitis development and increases hepatocellular lipid accumulation via TSKU upregulation.

Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD) which is the most common chronic liver disease worldwide. Hypoxia-inducible factor-1α (HIF1α) inhibitor is emerging as a promising therapeutic strategy for diseases. However, the role of HIF1α inhibitor in NASH is still unclear.

A novel genetic mouse model of osteoporosis with double heterozygosity of Irx3 and Irx5 characterizes sex-dependent phenotypes in bone homeostasis.

Iroquois homeobox gene 3 (Irx3) and Irx5 encode transcription factors that play crucial roles in limb development and bone formation. Previous studies using knockout mice have revealed a role of Irx3 and Irx5 in osteogenesis in young adult mice. However, whether these genes are also essential for bone homeostasis in adulthood and contribute to bone diseases remain poorly understood.

A single diiron enzyme catalyses the oxidative rearrangement of tryptophan to indole nitrile.

Nitriles are uncommon in nature and are typically constructed from oximes through the oxidative decarboxylation of amino acid substrates or from the derivatization of carboxylic acids. Here we report a third nitrile biosynthesis strategy featuring the cyanobacterial nitrile synthase AetD. During the biosynthesis of the eagle-killing neurotoxin, aetokthonotoxin, AetD transforms the 2-aminopropionate portion of 5,7-dibromo-L-tryptophan to a nitrile.

NK-92 cells labeled with FeO-PEG-CD56/Avastin@Ce6 nanoprobes for the targeted treatment and noninvasive therapeutic evaluation of breast cancer.

Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors.

Why •CFH is nucleophilic but •CF is electrophilic in reactions with heterocycles.

Radical substitution is a useful method to functionalize heterocycles, as in the venerable Minisci reaction. Empirically observed regiochemistries indicate that the CFH radical has a nucleophilic character similar to alkyl radicals, but the CF radical is electrophilic. While the difference between •CH and •CF is well understood, the reason that one and two Fs make little difference but the third has a large effect is puzzling.

Organocatalytic aromatization-promoted umpolung reaction of imines.

The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Strong nucleophiles are often required to react with the N-electrophiles without catalytic and stereochemical control. Here we show an effective strategy to realize umpolung of imines promoted by organocatalytic aromatization.

Visible-light optical coherence tomography platform for the characterization of the skin barrier.

We demonstrate a free-space, trolley-mountable Fourier domain visible-light optical coherence tomography (OCT) system for studying the stratum corneum in non-palmar human skin. An axial resolution of 1 µm in tissue and at least -75 dB sensitivity have been achieved. High-quality B-scans, containing 1600 A-scans, are acquired at a rate of 39 Hz.

Discovery of a Thioxanthone-TfOH Complex as a Photoredox Catalyst for Hydrogenation of Alkenes Using p-Xylene as both Electron and Hydrogen Sources.

Hydrogenation of alkenes is one of the most fundamental transformations in organic synthesis, and widely used in the petrochemical, pharmaceutical, and food industries. Although numerous hydrogenation methods have been developed, novel types of catalysis with new mechanisms and new hydrogen sources are still desirable. Thioxanthone (TX) is widely used in energy-transfer photoreactions, but rarely in photoredox processes.

LncRNA and mRNA expression profiles in brown adipose tissue of obesity-prone and obesity-resistant mice.

Obesity-prone or obesity-resistant phenotypes can exist in individuals who consume the same diet type. Brown adipose tissue functions to dissipate energy in response to cold exposure or overfeeding. Long noncoding RNAs play important roles in a wide range of biological processes.

Unusual Enantiodivergence in Chiral Brønsted Acid-Catalyzed Asymmetric Allylation with β-Alkenyl Allylic Boronates.

We report herein a rare example of enantiodivergent aldehyde addition with β-alkenyl allylic boronates via chiral Brønsted acid catalysis. 2,6-Di-9-anthracenyl-substituted chiral phosphoric acid-catalyzed asymmetric allylation using β-vinyl substituted allylic boronate gave alcohols with R absolute configuration. The sense of asymmetric induction of the catalyst in these reactions is opposite to those in prior reports.

Organocatalytic discrimination of non-directing aryl and heteroaryl groups: enantioselective synthesis of bioactive indole-containing triarylmethanes.

Despite the enormous developments in asymmetric catalysis, the basis for asymmetric induction is largely limited to the spatial interaction between the substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between two aryl groups without a directing group or electronic manipulation.

Mitochondrial apolipoprotein A-I binding protein alleviates atherosclerosis by regulating mitophagy and macrophage polarization.

Apolipoprotein A-I binding protein (AIBP), a secreted protein, has been shown to play a pivotal role in the development of atherosclerosis. The function of intracellular AIBP, however, is not yet well characterized. Here, we found that AIBP is abundantly expressed within human and mouse atherosclerotic lesions and exhibits a distinct localization in the inner membrane of mitochondria in macrophages.

Hydrogen Abstraction by Alkoxyl Radicals: Computational Studies of Thermodynamic and Polarity Effects on Reactivities and Selectivities.

Density functional theory calculations (ωB97X-D) are reported for the reactions of methoxy, -butoxy, trichloroethoxy, and trifluoroethoxy radicals with a series of 26 C-H bonds in different environments characteristic of a variety of hydrocarbons and substituted derivatives. The variations in activation barriers are analyzed with modified Evans-Polanyi treatments to account for polarity and unsaturation effects. The treatments by Roberts and Steel and by Mayer have inspired the development of a simple treatment involving the thermodynamics of reactions, the difference between the reactant radical and product radical electronegativities, and the absence or presence of α-unsaturation.

Sphingosine-1-phosphate in mitochondrial function and metabolic diseases.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite. The past decade has witnessed exponential growth in the field of S1P research, partly attributed to drugs targeting its receptors or kinases. Accumulating evidence indicates that changes in the S1P axis (i.

Anlotinib Suppresses Oral Squamous Cell Carcinoma Growth and Metastasis by Targeting the RAS Protein to Inhibit the PI3K/Akt Signalling Pathway.

Oral squamous cell carcinoma (OSCC) is a malignant tumour originating from the mucosal lining of the oral cavity. Its characteristics include hidden onset, high recurrence, and distant metastasis after operation. At present, clinical treatment usually includes surgery, chemotherapy, radiotherapy, or the joint use of these modalities.

Chiral Phosphoric Acid Catalyzed Conversion of Epoxides into Thiiranes: Mechanism, Stereochemical Model, and New Catalyst Design.

Computations and experiments leading to new chiral phosphoric acids (CPAs) for epoxide thionations are reported. Density functional theory calculations reveal the mechanism and origin of the enantioselectivity of such CPA-catalyzed epoxide thionations. The calculated mechanistic information was used to design new efficient CPAs that were tested experimentally and found to be highly effective.

Stereochemical Control via Chirality Pairing: Stereodivergent Syntheses of Enantioenriched Homoallylic Alcohols.

We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α-CH Bpin-substituted crotylboronate. Chiral phosphoric acid (S)-A-catalyzed asymmetric allyl addition with the reagent gave Z-anti-homoallylic alcohols with excellent enantioselectivities and Z-selectivities. When the enantiomeric acid catalyst (R)-A was utilized, the stereoselectivity was completely reversed and E-anti-homoallylic alcohols were obtained with high E-selectivities and excellent enantioselectivities.

High Site Selectivity in Electrophilic Aromatic Substitutions: Mechanism of C-H Thianthrenation.

The introduction of thianthrene as a linchpin has proven to be a versatile strategy for the C-H functionalization of aromatic compounds, featuring a broad scope and fast diversification. The synthesis of aryl thianthrenium salts has displayed an unusually high regioselectivity, notably superior to those observed in halogenation or borylation reactions for various substrates. We report an experimental and computational study on the mechanism of aromatic C-H thianthrenation reactions, with an emphasis on the elucidation of the reactive species and the nature of the exquisite site selectivity.

Fas signaling in adipocytes promotes low-grade inflammation and lung metastasis of colorectal cancer through interaction with Bmx.

Obesity is a global public health issue. Obesity-related chronic low-grade inflammation (meta-inflammation) can lead to aberrant adipokine release and promote cardiometabolic diseases and obesity-related tumors. However, the mechanisms involved in the initiation of inflammatory responses in obesity and obesity-related tumors as well as metastasis are not fully understood.

Organocatalytic enantioselective dearomatization of thiophenes by 1,10-conjugate addition of indole imine methides.

Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. This work reports an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition. By suitable stabilization of the thiophenyl carbocation with an indole motif in the form of indole imine methide, excellent remote chemo-, regio-, and stereocontrol in the nucleophilic addition can be achieved with chiral phosphoric acid catalysis under mild conditions.

Is there a relationship between psoriasis and hepatitis C? A meta-analysis and bioinformatics investigation.

Background: The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection.

Methods: We conducted a systematic review of the case-control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein-protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis.

Deciphering Reactivity and Selectivity Patterns in Aliphatic C-H Bond Oxygenation of Cyclopentane and Cyclohexane Derivatives.

A kinetic, product, and computational study on the reactions of the cumyloxyl radical with monosubstituted cyclopentanes and cyclohexanes has been carried out. HAT rates, site-selectivities for C-H bond oxidation, and DFT computations provide quantitative information and theoretical models to explain the observed patterns. Cyclopentanes functionalize predominantly at C-1, and tertiary C-H bond activation barriers decrease on going from methyl- and -butylcyclopentane to phenylcyclopentane, in line with the computed C-H BDEs.

Early postnatal irradiation-induced age-dependent changes in adult mouse brain: MRI based characterization.

Background: Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients.