Catalytic -Alkylation of (Hetero)Aromatic Amines and Tandem Annulation Reactions.

A general and practical approach for -alkylation of heteroaromatic amines with heteroaromatic alcohols is always challenging and rarely reported. Here, we designed and synthesized phosphine-free, robust, and efficient N,N-bidentate-Co(II) complexes for a universal -alkylation of amines strategy. This present catalytic methodology can be applied to a wide range of substrates by varying alcohols, including aryl, aliphatic, acyclic, and cyclic groups, with heteroaromatic amines such as aminopyridine, 2-aminopyrimidine, and aminoquinoline to provide diverse monoalkylated organonitrogen compounds in good to excellent yields (108 examples).

The loss of OPA1 accelerates intervertebral disc degeneration and osteoarthritis in aged mice.

NP cells of the intervertebral disc and articular chondrocytes reside in avascular and hypoxic tissue niches. As a consequence of these environmental constraints the cells are primarily glycolytic in nature and were long thought to have a minimal reliance on mitochondrial function. Recent studies have challenged this long-held view and highlighted the increasingly important role of mitochondria in the physiology of these tissues.

OPA1 protects intervertebral disc and knee joint health in aged mice by maintaining the structure and metabolic functions of mitochondria.

Unlabelled: Due to their glycolytic nature and limited vascularity, nucleus pulposus (NP) cells of the intervertebral disc and articular chondrocytes were long thought to have minimal reliance on mitochondrial function. Recent studies have challenged this long-held view and highlighted the increasingly important role of mitochondria in the physiology of these tissues. We investigated the role of mitochondrial fusion protein OPA1 in maintaining the spine and knee joint health in aging mice.

GLUT1 is redundant in hypoxic and glycolytic nucleus pulposus cells of the intervertebral disc.

Glycolysis is central to homeostasis of nucleus pulposus (NP) cells in the avascular intervertebral disc. Since the glucose transporter, GLUT1, is a highly enriched phenotypic marker of NP cells, we hypothesized that it is vital for the development and postnatal maintenance of the disc. Surprisingly, primary NP cells treated with 2 well-characterized GLUT1 inhibitors maintained normal rates of glycolysis and ATP production, indicating intrinsic compensatory mechanisms.

The mitophagy receptor BNIP3 is critical for the regulation of metabolic homeostasis and mitochondrial function in the nucleus pulposus cells of the intervertebral disc.

The contribution of mitochondria to the metabolic function of hypoxic NP cells has been overlooked. We have shown that NP cells contain networked mitochondria and that mitochondrial translocation of BNIP3 mediates hypoxia-induced mitophagy. However, whether BNIP3 also plays a role in governing mitochondrial function and metabolism in hypoxic NP cells is not known.

Conditional Deletion of HIF-2α in Mouse Nucleus Pulposus Reduces Fibrosis and Provides Mild and Transient Protection From Age-Dependent Structural Changes in Intervertebral Disc.

Hypoxia-inducible factors (HIFs) are critical to the development and homeostasis of hypoxic tissues. Although HIF-2α, one of the main HIF-α isoforms, is expressed in nucleus pulposus (NP) cells, its functions remain unknown. We deleted HIF-2α in the NP tissue using a notochord-specific FoxA2 allele to study HIF-2α function in the adult intervertebral disc.

A new-fangled horizon in leather process to sidestep toxic chrome and formaldehyde using hyperbranched polymer.

A novel chrome-free tanning and formaldehyde-free post tanning process with PEG-melamine base hyperbranched polymer by complexing aluminum (Al) present in aluminum sulfate for eco-friendly tanning applications. The hyperbranched polymers PEGM-400-C-Al and PEGM-600-C-Al were synthesized and characterized by FT-IR, NMR, UV, and XRD. The molecular weight of polymers was assessed by GPC and subjected to the leather process.

Null Mice-a Model for Mineralization Disorder PXE Shows Vertebral Osteopenia Without Enhanced Intervertebral Disc Calcification With Aging.

Chronic low back pain is a highly prevalent health condition intricately linked to intervertebral disc degeneration. One of the prominent features of disc degeneration that is commonly observed with aging is dystrophic calcification. ATP-binding cassette sub-family C member 6 (ABCC6), a presumed ATP efflux transporter, is a key regulator of systemic levels of the mineralization inhibitor pyrophosphate (PPi).

Current evidence on potential of adipose derived stem cells to enhance bone regeneration and future projection.

Injuries to the postnatal skeleton are naturally repaired through successive steps involving specific cell types in a process collectively termed "bone regeneration". Although complex, bone regeneration occurs through a series of well-orchestrated stages wherein endogenous bone stem cells play a central role. In most situations, bone regeneration is successful; however, there are instances when it fails and creates non-healing injuries or fracture nonunion requiring surgical or therapeutic interventions.

Comparative Evaluation of Efficacy of Kefir Milk Probiotic Curd and Probiotic Drink on in 8-12-year-old Children: An Study.

Aim And Objective: To compare the effect of probiotic products in reducing the levels of salivary before and after their consumption.

Materials And Methods: Eighty school children with initial carious lesions in the age group of 8-12 years were selected and divided into four groups. Children in group I (control) were undergone with restorations without supplementation of probiotics.

Hypoxia and Hypoxia-Inducible Factor-1α Regulate Endoplasmic Reticulum Stress in Nucleus Pulposus Cells: Implications of Endoplasmic Reticulum Stress for Extracellular Matrix Secretion.

Endoplasmic reticulum (ER) stress is shown to promote nucleus pulposus (NP) cell apoptosis and intervertebral disc degeneration. However, little is known about ER stress regulation by the hypoxic disc microenvironment and its contribution to extracellular matrix homeostasis. NP cells were cultured under hypoxia (1% partial pressure of oxygen) to assess ER stress status, and gain-of-function and loss-of-function approaches were used to assess the role of hypoxia-inducible factor (HIF)-1α in this pathway.

Role of autophagy in intervertebral disc and cartilage function: implications in health and disease.

The intervertebral disc and cartilage are specialized, extracellular matrix-rich tissues critical for absorbing mechanical loads, providing flexibility to the joints, and longitudinal growth in the case of growth plate cartilage. Specialized niche conditions in these tissues, such as hypoxia, are critical in regulating cellular activities including autophagy, a lysosomal degradation pathway that promotes cell survival. Mounting evidence suggests that dysregulation of autophagic pathways underscores many skeletal pathologies affecting the spinal column, articular and growth plate cartilages.

Hypoxic Regulation of Mitochondrial Metabolism and Mitophagy in Nucleus Pulposus Cells Is Dependent on HIF-1α-BNIP3 Axis.

Nucleus pulposus (NP) cells reside in an avascular and hypoxic microenvironment of the intervertebral disc and are predominantly glycolytic due to robust HIF-1 activity. It is generally thought that NP cells contain few functional mitochondria compared with cells that rely on oxidative metabolism. Consequently, the contribution of mitochondria to NP cell metabolism and the role of hypoxia and HIF-1 in mitochondrial homeostasis is poorly understood.

Nucleus pulposus primary cilia alter their length in response to changes in extracellular osmolarity but do not control TonEBP-mediated osmoregulation.

The nucleus pulposus (NP) cells adapt to their physiologically hyperosmotic microenvironment through Tonicity-responsive enhancer binding protein (TonEBP/nuclear factor of activated T-cell5 [NFAT5])-mediated osmoregulation. Primary cilia in different organs serve diverse roles including osmosensing, but its contribution to NP cell osmoadaptive response is unknown. A high percentage of cultured primary NP cells possessed primary cilia that changed length in response to osmotic stimuli.

Reversible Thermochromism of Nickel(II) Complexes and Single-Crystal-to-Single-Crystal Transformation.

A molecular Ni(II)-NNN pincer complex () exhibited unprecedented reversible single-crystal-to-single-crystal transformation and color change upon heating and cooling due to a subtle change in the N-Ni(II) bond length and ligand conformation. UV-vis, thermogravimetric, differential scanning calorimetry, single-crystal structural data, temperature-dependent powder X-ray diffraction, and Raman and computational studies supported the structural change of the Ni(II) complex with temperature.

NFAT5/TonEBP controls early acquisition of notochord phenotypic markers, collagen composition, and sonic hedgehog signaling during mouse intervertebral disc embryogenesis.

High osmolarity, bound water, and hydrostatic pressure contribute to notochord mechanics and its morphogenesis into the nucleus pulposus (NP) compartment of the intervertebral disc. Indeed, the osmoadaptive transcription factor, nuclear factor of activated T-cells 5 (NFAT5 aka TonEBP), is robustly expressed by resident cells of the notochord and NP. Nevertheless, the molecular mechanisms that drive notochord osmoregulation and the functions of NFAT5 in disc embryogenesis remain largely unexplored.

Correction: BMP-Non-Responsive Sca1+CD73+CD44+ Mouse Bone Marrow Derived Osteoprogenitor Cells Respond to Combination of VEGF and BMP-6 to Display Enhanced Osteoblastic Differentiation and Ectopic Bone Formation.

[This corrects the article DOI: 10.1371/journal.pone.

Assessment of Hedgehog Signaling Pathway Activation for Craniofacial Bone Regeneration in a Critical-Sized Rat Mandibular Defect.

Importance: Osseous craniofacial defects are currently reconstructed with bone grafting, rigid fixation, free tissue transfer, and/or recombinant human bone morphogenetic protein 2. Although these treatment options often have good outcomes, they are associated with substantial morbidity, and many patients are not candidates for free tissue transfer.

Objective: To assess whether polysaccharide-based scaffold (PS) constructs that are cross-linked with smoothened agonist (SAG), vascular endothelial growth factor (VEGF), and bone morphogenetic protein 6 (BMP-6) would substantially increase bone regeneration.

Ni-Catalyzed α-Alkylation of Unactivated Amides and Esters with Alcohols by Hydrogen Auto-Transfer Strategy.

A transition-metal-catalyzed borrowing hydrogen/hydrogen auto-transfer strategy allows the utilization of feedstock alcohols as an alkylating partner, which avoids the formation of stoichiometric salt waste and enables a direct and benign approach for the construction of C-N and C-C bonds. In this study, a nickel-catalyzed α-alkylation of unactivated amides and ester (tert-butyl acetate) is carried out by using primary alcohols under mild conditions. This C-C bond-forming reaction is catalyzed by a new, molecularly defined nickel(II) NNN-pincer complex (0.

RNA binding protein HuR regulates extracellular matrix gene expression and pH homeostasis independent of controlling HIF-1α signaling in nucleus pulposus cells.

Nucleus pulposus (NP) cells reside in the hypoxic niche of the intervertebral disc. Studies have demonstrated that RNA-binding protein HuR modulates hypoxic signaling in several cancers, however, its function in the disc is unknown. HuR did not show cytoplasmic translocation in hypoxia and its silencing did not alter levels of Hif-1α or HIF-targets in NP cells.

An Organic Receptor Isolated in an Unusual Intermediate Conformation: Computation, Crystallography, and Hirshfeld Surface Analysis.

1,1″-1,4-Phenylene-bis(methylene)bis-4,4'-bipyridinium cation [CHN] (c), an organic receptor that generally crystallizes in its anti conformation, has recently been shown to be isolated in its syn conformation in an ion-paired compound [CHN][Zn(dmit)]·2DMF (dmit = 1,3-dithiole-2-thione-4,5-dithiolate; DMF = dimethylformamide). In this article, we demonstrated that the same receptor [CHN] (c) can also be stabilized in an unusual intermediate conformation (neither syn nor anti) with PF anion in compound [CHN](PF)·(1,4-dioxane) (1·(1,4-dioxane)). The energetically favored anti conformation has been described in its nitrate salt [CHN](NO)·2HO (2·2HO).

Bay Functionalized Perylenediimide with Pyridine Positional Isomers: NIR Absorption and Selective Colorimetric/Fluorescent Sensing of Fe and Al Ions.

Bay functionalized perylene diimide substituted with pyridine isomers, (2-pyridine (2HMP-PDI), 3-pyridine (3-HMP-PDI) and 4-pyridine (4-HMP-PDI)) have been synthesized and explored for selective coloro/fluorimetric sensing of heavy transition metal ions. HMP-PDIs showed strong NIR absorption (760-765 nm) in DMF. The absorption and fluorescence of HMP-PDIs have been tuned by make use of pyridine isomers.

Mastication Frequency and Postprandial Blood Sugar Levels in Normoglycaemic and Dysglycaemic Individuals: A Cross- Sectional Comparative Study.

Introduction: Mastication has potential to affect postprandial blood glucose levels by affecting cephalic phase of insulin release. However, limited number of studies done in this regard has yielded conflicting results.

Aim: To evaluate effects of mastication on postprandial blood glucose levels.

Radionuclide Esophageal Transit Scintigraphy in Primary Hypothyroidism.

Background/aims: Esophageal dysmotility is associated with gastrointestinal dysmotility in various systemic and neuroregulatory disorders. Hypothyroidism has been reported to be associated with impaired motor function in esophagus due to accumulation of glycosaminoglycan hyaluronic acid in its soft tissues, leading to changes in various contraction and relaxation parameters of esophagus, particularly in the lower esophageal sphincter. In this study we evaluated esophageal transit times in patients of primary hypothyroidism using the technique of radionuclide esophageal transit scintigraphy.

Respiratory variation in aortic flow peak velocity and inferior vena cava distensibility as indices of fluid responsiveness in anaesthetised and mechanically ventilated children.

Background And Aims: Dynamic parameters such as the respiratory variation in aortic flow peak velocity (ΔVpeak) and inferior vena cava distensibility index (dIVC) are accurate indices of fluid responsiveness in adults. Little is known about their utility in children. We studied the ability of these indices to predict fluid responsiveness in anaesthetised and mechanically ventilated children.