Silencing TRIM8 alleviates allergic asthma and suppressing Th2 differentiation through inhibiting NF-κB/NLRP3 signaling pathway.

Background And Aim: Allergic asthma is a primary type of asthma and characterized by T helper 2 (Th2) cells -mediated inflammation. Tripartite motif containing 8 (TRIM8) protein is involved in immunoreaction and inflammatory response in many diseases. However, its role in allergic asthma remains unclear.

Peptide Drug Design Using Alchemical Free Energy Calculation: An Application and Validation on Agonists of Ghrelin Receptor.

With recent large-scale applications and validations, the relative binding free energy (RBFE) calculated using alchemical free energy methods has been proven to be an accurate measure to probe the binding of small-molecule drug candidates. On the other hand, given the flexibility of peptides, it is of great interest to find out whether sufficient sampling could be achieved within the typical time scale of such calculation, and a similar level of accuracy could be reached for peptide drugs. However, the systematic evaluation of such calculations on protein-peptide systems has been less reported.

Fe-N hollow mesoporous carbon spheres with high oxidase-like activity for sensitive detection of alkaline phosphatase.

Due to the vital role of alkaline phosphatase (ALP) in clinical diagnoses and biomedical research, a sensitive and selective detection method for ALP activity is of considerable importance. Herein, a facile and sensitive colorimetric assay for the detection of ALP activity was developed based on Fe-N hollow mesoporous carbon spheres (Fe-N HMCS). Fe-N HMCS were synthesized by a practical one-pot method with aminophenol/formaldehyde (APF) resin as the carbon/nitrogen precursor, silica as the template and iron phthalocyanine (FePC) as the iron source.

TRIM32 biallelic defects cause limb-girdle muscular dystrophy R8: identification of two novel mutations and investigation of genotype-phenotype correlation.

Background: Limb-girdle muscular dystrophy R8 (LGMD R8) is a rare autosomal recessive muscle disease caused by TRIM32 gene biallelic defects. The genotype-phenotype correlation of this disease has been reported poorly. Here, we report a Chinese family with two female LGMD R8 patients.

Dearomative [4 + 2] Annulation of Electron-Poor N-Heteroarenes with Azoalkenes for Access to Polycyclic Tetrahydro-1,2,4-triazines.

A direct dearomative [4 + 2] annulation of electron-poor N-heteroarenes with azoalkenes generated in situ from α-halogeno hydrazones was developed under mild conditions. Accordingly, a series of fused polycyclic tetrahydro-1,2,4-triazines with potential biological activity were obtained in up to 96% yield. Various α-halogeno hydrazones and N-heteroarenes, such as pyridines, quinolines, isoquinolines, phenanthridine, and benzothiazole, were tolerated by this reaction.

Reduced mitochondrial size in hippocampus and psychiatric behavioral changes in the mutant mice with homologous mutation of .

Background: Deafness-dystonia-optic neuronopathy (DDON) syndrome, a condition that predominantly affects males, is caused by mutations in () () gene and characterized by progressive deafness coupled with other neurological abnormalities. In a previous study, we demonstrated the phenotype of male mice carrying the hemizygous mutation of . In a follow-up to that study, this study aimed to observe the behavioral changes in the female mutant (MUT) mice with homologous mutation of and to elucidate the underlying mechanism for the behavioral changes.

Photo-induced catalytic halopyridylation of alkenes.

The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here we report an atom-economical cross-coupling of halopyridines and unactivated alkenes under photoredox catalysis to afford a series of alkene halopyridylation products. This protocol with mild and redox neutral conditions contributes broad substrate scope.

Charcot-Marie-Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy.

A 29-year-old female experienced chronic progressive peripheral neuropathy since childhood and was diagnosed with Charcot-Marie-Tooth disease (CMT) at age 15. She developed recurrent, fever-induced rhabdomyolysis (RM) at age 24. EMG studies showed decreased amplitude of compound muscle action potential, declined motor conductive velocity, and absence of sensor nerve action potential.

The serendipitous effect of KF in Ritter reaction: Photo-induced amino-alkylation of alkenes.

Ritter reaction has been recognized as an elegant strategy to construct the C-N bond. Its key feature is forming the carbocation for nucleophilic attack by nitriles. Herein, we report a complementary visible-light-induced three-component Ritter reaction of alkenes, nitriles, and -bromo nitriles/esters, thereby providing mild and rapid access to various -amino nitriles/acids.

Visible Light Induced Bifunctional Rhodium Catalysis for Decarbonylative Coupling of Imides with Alkynes.

Transition metal catalyzed decarbonylation offers a distinct synthetic strategy for new chemical bond formation. However, the π-backbonding between CO π* orbitals and metal center d-orbitals impedes ligand dissociation to regenerate the catalyst under mild reaction conditions. Developed here is visible light induced rhodium catalysis for decarbonylative coupling of imides with alkynes under ambient conditions.

Frameshift mutation of gene in mouse leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment.

Background: Deafness-dystonia-optic neuronopathy (DDON) syndrome is a progressive X-linked recessive disorder characterised by deafness, dystonia, ataxia and reduced visual acuity. The causative gene deafness/dystonia protein 1 ()translocase of the inner membrane 8A () encodes a mitochondrial intermembrane space chaperon. The molecular mechanism of DDON remains unclear, and detailed information on animal models has not been reported yet.

Phosphatidylserine-exposing blood cells, microparticles and neutrophil extracellular traps increase procoagulant activity in patients with pancreatic cancer.

Patients with pancreatic cancer (PC) are at increased risk of venous thrombosis, but the precise mechanisms of hypercoagulable state in PC remain unclear. We aimed to identify how phosphatidylserine positive (PS) blood cells (BCs), PS microparticles (MPs) and neutrophil extracellular traps (NETs) regulate procoagulant activity (PCA) in PC, and to assess the relationship between PCA and PC staging. A total of 83 PC patients with different stages of disease were compared to 30 healthy controls, with confocal microscopy and flow cytometry used to assess MP and cellular PS exposure.

Rhodium-catalyzed asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds.

A highly enantioselective hydrogenation of exocyclic α,β-unsaturated carbonyl compounds catalyzed by Rh/bisphosphine-thiourea (ZhaoPhos) has been developed, giving the corresponding α-chiral cyclic lactones, lactams and ketones with high yields and excellent enantioselectivities (up to 99% yield and 99% ee). Remarkably, the hydrogen bond between the substrate and the catalyst plays a critical role in this transformation. The synthetic utility of this protocol has been demonstrated by efficient synthesis of chiral 3-(4-fluorobenzyl)piperidine, a key chiral fragment of bioactive molecules.

Enantioselective Rhodium-Catalyzed Cycloisomerization of 1,6-Allenynes to access 5/6-Fused Bicycle[4.3.0]nonadienes.

Transition-metal-catalyzed cycloisomerization of 1,n-allenynes represents a powerful synthetic tool to rapidly assemble complex polycyclic skeletons from simple linear substrates. Nevertheless, there are no reports of the asymmetric version of these reactions. Moreover, most of these reactions proceed through a 6-endo-dig cyclization pathway, which preferentially delivers the distal product (via 5/5 rhodacyclic intermediate) rather than the proximal one (via 6/5 rhodacyclic intermediate).

A cheap metal for a challenging task: nickel-catalyzed highly diastereo- and enantioselective hydrogenation of tetrasubstituted fluorinated enamides.

Nickel-catalyzed asymmetric hydrogenation of challenging tetrasubstituted fluorinated enamides has been achieved, affording chiral α-fluoro-β-amino esters in high yields with excellent diastereo- and enantioselectivities (up to 98% yield, >99 : 1 dr, up to >99% ee). Deuterium-labeling experiments and control experiments were conducted to probe the mechanism, and the results indicated that the acidity of the solvent plays a critical role in the control of diastereoselectivity by trapping the adduct of nickel hydride to C[double bond, length as m-dash]C bonds protonolysis, giving the hydrogenation product with stereospecific -selectivity. This protocol provides efficient access to chiral α-fluoro-β-amino esters which have important potential applications in organic synthesis and medicinal chemistry.

Iridium-Catalyzed Asymmetric Hydrogenation of Tetrasubstituted α-Fluoro-β-enamino Esters: Efficient Access to Chiral α-Fluoro-β-amino Esters with Two Adjacent Tertiary Stereocenters.

An iridium-catalyzed highly efficient asymmetric hydrogenation of challenging tetrasubstituted α-fluoro-β-enamino esters was successfully developed using bisphosphine-thiourea (ZhaoPhos) as the ligand, which prepared a series of chiral α-fluoro-β-amino esters containing two adjacent tertiary stereocenters with high yields and excellent diastereoselectivities/enantioselectivities (73%-99% yields, >25:1 dr, 91%->99% ee, and turnover number (TON) values up to 8600), and no defluorinate byproduct was detected.

Nickel-Catalyzed Highly Enantioselective Hydrogenation of β-Acetylamino Vinylsulfones: Access to Chiral β-Amido Sulfones.

The nickel/( S)-Binapine complex was found to be an efficient catalyst for asymmetric hydrogenation of β-acetylamino vinylsulfones to afford chiral β-Amido sulfones with excellent yields and enantioselectivities (up to 95% yields and >99% ee). This protocol has good compatibility with a series of substituted ( Z)-β-acetylamino vinylsulfones or Z/ E isomeric mixtures. A gram-scale reaction has also been achieved in the presence of a 0.

Rhodium-catalyzed asymmetric hydrogenation of tetrasubstituted β-acetoxy-α-enamido esters and efficient synthesis of droxidopa.

A rhodium-catalyzed asymmetric hydrogenation of challenging tetrasubstituted β-acetoxy-α-enamido esters was developed, giving chiral β-acetoxy-α-amido esters in high yields with excellent enantioselectivities (up to >99% ee). The products could be easily transformed to β-hydroxy-α-amino acid derivatives which are valuable chiral building blocks and a novel route for the synthesis of droxidopa was also developed.

Enantioselective Rhodium-Catalyzed Cycloisomerization of (E)-1,6-Enynes.

An enantioselective rhodium(I)-catalyzed cycloisomerization reaction of challenging (E)-1,6-enynes is reported. This novel process enables (E)-1,6-enynes with a wide range of functionalities, including nitrogen-, oxygen-, and carbon-tethered (E)-1,6-enynes, to undergo cycloisomerization with excellent enantioselectivity, in a high-yielding and operationally simple manner. Moreover, this Rh(I) -diphosphane catalytic system also exhibited superior reactivity and enantioselectivity for (Z)-1,6-enynes.

Adiponectin Upregulates MiR-133a in Cardiac Hypertrophy through AMPK Activation and Reduced ERK1/2 Phosphorylation.

Adiponectin and miR-133a are key regulators in cardiac hypertrophy. However, whether APN has a potential effect on miR-133a remains unclear. In this study, we aimed to investigate whether APN could regulate miR-133a expression in Angiotensin II (Ang II) induced cardiac hypertrophy in vivo and in vitro.

Influence of diabetes on cardiac resynchronization therapy in heart failure patients: a meta-analysis.

Background: Diabetes mellitus is an independent risk factor of increased morbidity and mortality in patients with heart failure. Cardiac resynchronization therapy (CRT), a pacemaker-based therapy for dyssynchronous heart failure, improves cardiac performance and quality of life, but its effect on mortality in patients with diabetes is uncertain.

Methods: We performed a meta-analysis of results from randomized controlled trials (RCTs) of the long-term outcome of cardiac resynchronization therapy for heart failure in diabetic and non-diabetic patients.

Unilateral symptomatic intracranial arterial stenosis and myopathy in an adolescent with Graves disease: a case report of an high-resolution magnetic resonance imaging study.

Vascular and muscular involvements in Graves disease (GD) are rare. Here, we report a case of a 17-year-old patient with unilateral symptomatic middle cerebral artery stenosis concurrent with GD and myopathy. He presented with a 1-day history of acute severe right-sided hemiparesis and aphasia and a 3-week history of high metabolic syndrome.

[Comparison of clinical and physiological characteristics between Kennedy disease and amyotrophic lateral sclerosis].

Objective: To study the clinical presentations of Kennedy disease (KD) and compare the neurophysiological features between KD and amyotrophic lateral sclerosis(ALS).

Methods: Nine patients with KD, 13 patients with ALS and 26 normal control subjects were recruited. The clinical presentations of KD were analyzed, and the results of nerve conduction studies and electromyography were compared among the 3 groups.