Stereoselective Synthesis of Chiral β-Fluoro α-Amino Acids via Pd(II)-Catalyzed Fluorination of Unactivated Methylene C(sp(3))-H Bonds: Scope and Mechanistic Studies.

The synthesis of fluorinated complex molecules via direct C(sp(3))-H fluorination is attractive yet remains challenging. Here we describe the Pd(II)-catalyzed fluorination of unactivated methylene C(sp(3))-H bonds by an inner-sphere mechanism. This method allows the site- and diastereoselective fluorination of β-methylene C(sp(3))-H bonds of α-amino acid derivatives.

Long-circulating siRNA nanoparticles for validating Prohibitin1-targeted non-small cell lung cancer treatment.

RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy, we develop a unique nanoparticle (NP) platform composed of a solid polymer/cationic lipid hybrid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery.

MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD.

Rationale: Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-associated protein with death domain (FADD). In addition, microRNAs and long noncoding RNAs have been shown to play important roles in various biological processes recently.

Chlorogenic Acid Activates CFTR-Mediated Cl- Secretion in Mice and Humans: Therapeutic Implications for Chronic Rhinosinusitis.

Objectives: Salubrious effects of the green coffee bean are purportedly secondary to high concentrations of chlorogenic acid. Chlorogenic acid has a molecular structure similar to bioflavonoids that activate transepithelial Cl(-) transport in sinonasal epithelia. In contrast to flavonoids, the drug is freely soluble in water.

Cu(I)-Catalyzed Cross-Coupling of Terminal Alkynes with Trifluoromethyl Ketone N-Tosylhydrazones: Access to 1,1-Difluoro-1,3-enynes.

C-C Bond formation and β-F elimination have been achieved in a Cu(I)-catalyzed cross-coupling reaction of terminal alkynes and trifluoromethyl ketone N-tosylhydrazones. The reaction represents an efficient synthesis of 1,1-difluoro-1,3-enyne derivatives. Mechanistically, the migratory insertion of the copper carbene intermediate leads to the C-C bond formation, which is followed by C-F bond cleavage.

Acute toxicity assessment of ANAMMOX substrates and antibiotics by luminescent bacteria test.

Acute toxicities of anaerobic ammonia oxidation (ANAMMOX) substrates and four antibiotics from pharmaceutical wastewaters on ANAMMOX process were reported. Individual and joint acute toxicity assays were performed using 50% inhibitory concentration (IC50). Results showed that IC50 values and their 95% confidence interval of ammonium chloride (A), sodium nitrite (B), penicillin G-Na (C), polymyxin B sulfate (D), chloramphenicol (E) and kanamycin sulfate (F) were 2708.

A simple base-mediated synthesis of diverse functionalized ring-fluorinated 4H-pyrans via double direct C-F substitutions.

A straightforward and efficient approach to structurally diverse and synthetically useful ring-fluorinated 4H-pyrans via a simple base-mediated cascade reaction of readily available trifluoromethylated alkenes with 1,3-dicarbonyl compounds was developed. The key events of this reaction involve two consecutive C-F substitutions under very mild conditions.

5'-β,γ-CHF-ATP diastereomers: synthesis and fluorine-mediated selective binding by c-Src protein kinase.

The first preparation of the individual β,γ-CHF-ATP stereoisomers 12a and 12b is reported. Configurationally differing solely by the orientation of the C-F fluorine, 12a and 12b have discrete (31)P (202 MHz, pH 10.9, ΔδPα 6 Hz, ΔδPβ 4 Hz) and (19)F NMR (470 MHz, pH 9.

Critical noise of majority-vote model on complex networks.

The majority-vote model with noise is one of the simplest nonequilibrium statistical model that has been extensively studied in the context of complex networks. However, the relationship between the critical noise where the order-disorder phase transition takes place and the topology of the underlying networks is still lacking. In this paper, we use the heterogeneous mean-field theory to derive the rate equation for governing the model's dynamics that can analytically determine the critical noise f(c) in the limit of infinite network size N→∞.

Variation in glucose homeostasis traits associated with P2RX7 polymorphisms in mice and humans.

Context: Extracellular nucleotide receptors are expressed in pancreatic B-cells. Purinergic signaling via these receptors may regulate pancreatic B-cell function.

Objective: We hypothesized that purinergic signaling might influence glucose regulation and sought evidence in human studies of glycemic variation and a mouse model of purinergic signaling dysfunction.

Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the Antarctic environment.

Background: Penguins are flightless aquatic birds widely distributed in the Southern Hemisphere. The distinctive morphological and physiological features of penguins allow them to live an aquatic life, and some of them have successfully adapted to the hostile environments in Antarctica. To study the phylogenetic and population history of penguins and the molecular basis of their adaptations to Antarctica, we sequenced the genomes of the two Antarctic dwelling penguin species, the Adélie penguin [Pygoscelis adeliae] and emperor penguin [Aptenodytes forsteri].

Delayed geochemical hazard: a tool for risk assessment of heavy metal polluted sites and case study.

A concept of delayed geochemical hazard (DGH) was proposed instead of chemical time bomb to represent an ecological and environmental hazard caused by sudden reactivation and release of long-term accumulated pollutants in soil/sediment system due to the change of physicochemical conditions or the decrease of environmental capacity. A DGH model was also established to provide a quantitative tool to assess and predict potential environmental risk caused by heavy metals and especially its dynamic evolutions. A case study of DGH was carried out for a mercury-polluted area in southern China.

Proton resonance frequency chemical shift thermometry: experimental design and validation toward high-resolution noninvasive temperature monitoring and in vivo experience in a nonhuman primate model of acute ischemic stroke.

Background And Purpose: Applications for noninvasive biologic temperature monitoring are widespread in biomedicine and of particular interest in the context of brain temperature regulation, where traditionally costly and invasive monitoring schemes limit their applicability in many settings. Brain thermal regulation, therefore, remains controversial, motivating the development of noninvasive approaches such as temperature-sensitive nuclear MR phenomena. The purpose of this work was to compare the utility of competing approaches to MR thermometry by using proton resonance frequency chemical shift.

Dysfunction in the βII spectrin-dependent cytoskeleton underlies human arrhythmia.

Background: The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked to cardiac pathologies, including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction and cardiac electric activity is not well understood and often overlooked in the cardiac arrhythmia field.

Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China.

Context: The WHO Technical Consultation recommends urinary iodine concentrations (UIC) from 250 to 499 μg/L as more-than-adequate iodine intake and UIC ≥ 500 μg/L as excessive iodine for pregnant and lactating women, but scientific evidence for this is weak.

Objective: We investigated optimal and safe ranges of iodine intake during early pregnancy in an iodine-sufficient region of China.

Method: Seven thousand one hundred ninety pregnant women at 4-8 weeks gestation were investigated and their UIC, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroglobulin (Tg) were measured.

Iron deficiency, an independent risk factor for isolated hypothyroxinemia in pregnant and nonpregnant women of childbearing age in China.

Context: Isolated hypothyroxinemia during early pregnancy may irreversibly damage the neurodevelopment of offspring. However, the causes are not well clarified.

Objective: To explore the association of iron deficiency (ID) with hypothyroid function of women in early pregnancy and nonpregnant women.

Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance.

Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists.

Complete mineralization of perfluorooctanoic acid (PFOA) by γ-irradiation in aqueous solution.

Decomposition of perfluorooctanoic acid (C7F15COOH, PFOA) has been gaining increasing interests because it is a ubiquitous environmental contaminant and resistant to the most conventional treatment processes. In this work, the rapid and complete mineralization of PFOA and simultaneous defluorination were achieved by γ-ray irradiation with a (60)Co source. The degradation rate of PFOA by γ-ray irradiation would be high, and a pseudo-first-order kinetic rate constant of 0.

[99mTc]cFLFLF for Early Diagnosis and Therapeutic Evaluation in a Rat Model of Acute Osteomyelitis.

Purpose: Early diagnosis and therapeutic monitoring of acute osteomyelitis (AO) is challenging. Here, we use a polyethylene glycol (PEG)ylated chemotactic peptide cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF) conjugated with hydrazinonicotinamide (HYNIC) and labeled with Tc-99m ([(99m)Tc]cFLFLF) to image AO in a rat model and to validate its efficacy in early diagnosis and therapeutic evaluation of AO.

Procedures: Forty rats were divided into eight groups of five each.

Changes of major tea polyphenols and production of four new B-ring fission metabolites of catechins from post-fermented Jing-Wei Fu brick tea.

HPLC analysis of samples from four major fermentation procedures of Jing-Wei Fu brick tea showed that the level of major tea catechins epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) dropped increasingly to about 1/3 in the final product. Phytochemical study of the final product led to the discovery of four new B-ring fission metabolites of catechins (BRFCs) Fuzhuanin C-F (1-4) together with three known BRFCs (5-7), six known catechins (8-13), five simple phenols (14-18), seven flavones and flavone glycosides (19-25), two alkaloids (26, 27), three triterpenoids (28-30) and one steroid (31). The structures were elucidated by spectroscopic methods including 1D and 2D NMR, LC-HR-ESI-MS, IR, and CD spectra.

Studying regioisomer formation in the Pd-catalyzed fluorination of aryl triflates by deuterium labeling.

Isotopic labeling has been used to determine that a portion of the desired product in the Pd-catalyzed fluorination of electron-rich, non-ortho-substituted aryl triflates results from direct C-F cross-coupling. In some cases, formation of a Pd-aryne intermediate is responsible for producing undesired regioisomers. The generation of the Pd-aryne intermediate occurs primarily via ortho-deprotonation of a L·Pd(Ar)OTf (L = biaryl monophosphine) species by CsF and thus competes directly with the transmetalation step of the catalytic cycle.

New phenylpropanoid-substituted flavan-3-ols from Pu-er ripe tea.

Pu-er ripe tea is a special microbial post-fermented tea made from Pu-er raw tea, a kind of green tea produced from the leaves of Camellia sinensis var. assamica. It is one of the most consumed teas in the past two decades in China, due to its special flavor, taste, and beneficial effects.

Nanoparticles containing a liver X receptor agonist inhibit inflammation and atherosclerosis.

Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer.

CD82 restrains pathological angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells.

Background: Angiogenesis is crucial for many pathological processes and becomes a therapeutic strategy against diseases ranging from inflammation to cancer. The regulatory mechanism of angiogenesis remains unclear. Although tetraspanin CD82 is widely expressed in various endothelial cells (ECs), its vascular function is unknown.