Role of pyruvate kinase M2-mediated metabolic reprogramming during podocyte differentiation.

Podocytes, a type of highly specialized epithelial cells, require substantial levels of energy to maintain glomerular integrity and function, but little is known on the regulation of podocytes' energetics. Lack of metabolic analysis during podocyte development led us to explore the distribution of mitochondrial oxidative phosphorylation and glycolysis, the two major pathways of cell metabolism, in cultured podocytes during in vitro differentiation. Unexpectedly, we observed a stronger glycolytic profile, accompanied by an increased mitochondrial complexity in differentiated podocytes, indicating that mature podocytes boost both glycolysis and mitochondrial metabolism to meet their augmented energy demands. In addition, we found a shift of predominant energy source from anaerobic glycolysis in immature podocyte to oxidative phosphorylation during the differentiation process. Furthermore, we identified a crucial metabolic regulator for podocyte development, pyruvate kinase M2. Pkm2-knockdown podocytes showed dramatic reduction of energy metabolism, resulting in defects of cell differentiation. Meanwhile, podocyte-specific Pkm2-knockout (KO) mice developed worse albuminuria and podocyte injury after adriamycin treatment. We identified mammalian target of rapamycin (mTOR) as a critical regulator of PKM2 during podocyte development. Pharmacological inhibition of mTOR potently abrogated PKM2 expression and disrupted cell differentiation, indicating the existence of metabolic checkpoint that need to be satisfied in order to allow podocyte differentiation.

The feedback loop between miR-21, PDCD4 and AP-1 functions as a driving force for renal fibrogenesis.

Renal fibrosis is a final common pathway of chronic kidney disease. Sustained activation of fibroblasts is considered to play a key role in perpetuating renal fibrosis but the driving force in the perpetuation stage is only partially understood. To date, some investigations have specifically identified overexpression of microRNA 21 (miR-21) in the progression of kidney fibrosis. Nevertheless, the precise role of miR-21 in fibroblast activation remains largely unknown. In this study, we found that miR-21 was significantly upregulated in activated fibroblasts and that it maintained itself at constant high levels by employing an auto-regulatory loop between miR-21, PDCD4 and AP-1. Persistently upregulated miR-21 suppressed protein expression of Smad7 and, eventually, enhanced the TGF-ß1/Smad pathway to promote fibroblast activation. More importantly, we found miR-21 sequestration with miR-21 antagomir or AP-1 inhibitors attenuated unilateral ureteral obstruction (UUO)-induced renal fibrosis. miR-21-knockout mice also suffered far less interstitial fibrosis in response to kidney injury. Altogether, these data suggest that miR-21 is a main driving force of fibroblast activation and keeps its high expression level by employing a double negative autoregulatory loop. Targeting this aberrantly activated feedback loop may provide new therapeutic strategy in treating fibrotic kidneys.

Catalytic arylsulfonyl radical-triggered 1,5-enyne-bicyclizations and hydrosulfonylation of α,ß-conjugates.

A catalytic bicyclization reaction of 1,5-enynes anchored by α,ß-conjugates with arylsulfonyl radicals generated in situ from sulfonyl hydrazides has been established using TBAI (20 mol%) and Cu(OAc)2 (5 mol%) as co-catalysts under convenient conditions. In addition, the use of benzoyl peroxide (BPO) as the oxidant and pivalic acid (PivOH) as an additive was proven to be necessary for this reaction. The reactions occurred through 5-exo-dig/6-endo-trig bicyclizations and homolytic aromatic substitution (HAS) cascade mechanisms to give benzo[b]fluorens regioselectively. A similar catalytic process was developed for the synthesis of γ-ketosulfones. These reactions feature readily accessible starting materials and simple one-pot operation.

Strong interaction effects and criticality of bosons in shaken optical lattices.

We study the quantum phase transitions and identify a tricritical point between a normal Bose superfluid, a superfluid that breaks additional Z(2) Ising symmetry, and a Mott insulator in a recent shaken optical lattice experiment. We show that near the transition between normal and Z(2) symmetry breaking superfluids, bosons can condense into a momentum state with high or even locally maximum kinetic energies due to the interaction effect. We present a general low-energy effective field theory that treats both the superfluid transition and the Ising transition in a uniform framework. Using the perturbative renormalization group method, we find that the critical behavior of the quantum phase transition belongs to a universality class different from that of a dilute Bose gas.

[Relationship between body fat distribution and insulin resistance, islet ß cell function and metabolic disorders in adults].

OBJECTIVE: To explore the relationship between body fat distribution, insulin resistance, islet ß cell function and metabolic disorders in adult population. METHODS: From February to November 2012, a total of 174 subjects aged 20-68 years were recruited. Their anthropometric parameters, blood biochemical indices and the results of oral glucose tolerance test (OGTT) and insulin releasing test (IRT) were collected. Body fat distribution was measured with dual energy X-ray absorptiometry (DEXA). RESULTS: The values of trunk/total fat mass (T/B) and android/gynoid fat mass ratio (A/G) were positively correlated with blood pressure, blood lipid, plasma glucose, insulin resistance index (HOMA-IR) and high-sensitivity C-reactive protein. Compared with the group of normal metabolism, the group of metabolic disorders had higher T/B and A/G (P < 0.05). After multiple stepwise regression analysis, the main influencing factors of lnHOMA-IR and lnHOMA-ß were T/B and Grespectively.Logistic regression showed that A (OR = 3.01, 95%CI 1.86-8.17) was a risk factor for diabetes and A/G (OR = 2.71, 95%CI 1.75-6.56) a risk factor for dyslipidemia. CONCLUSIONS: Trunk and android fat deposition aggravates insulin resistance, metabolic disorders. And the main influencing factors of insulin resistance and islet ß cell function are trunk and gynoid fat respectively. Android fat mass is a major risk factor for glycolipid metabolism.

Spin-orbit coupled degenerate Fermi gases.

In this Letter, we report the first experimental realization and investigation of a spin-orbit coupled Fermi gas. Both spin dephasing in spin dynamics and momentum distribution asymmetry of the equilibrium state are observed as hallmarks of spin-orbit coupling in a Fermi gas. The single particle dispersion is mapped out by using momentum-resolved radio-frequency spectroscopy. From momentum distribution and momentum-resolved radio-frequency spectroscopy, we observe the change of fermion population in different helicity branches consistent with a finite temperature calculation, which indicates that a Lifshitz transition of the Fermi surface topology change can be found by further cooling the system.

Highly sensitive surface-enhanced Raman scattering substrate made from superaligned carbon nanotubes.

Surface-enhanced Raman scattering (SERS) has attracted wide attention because it can enhance normally weak Raman signal by several orders of magnitude and facilitate the sensitive detection of molecules. Conventional SERS substrates are constructed by placing metal nanoparticles on a planar surface. Here we show that, if the planar surface was substituted by a unique nanoporous surface, the enhancement effect can be dramatically improved. The nanoporous surface can be easily fabricated in batches and at low costs by cross stacking superaligned carbon nanotube films. The as-prepared transparent and freestanding SERS substrate is capable of detecting ambient trinitrotoluene vapor, showing much higher Raman enhancement than ordinary planar substrates because of the extremely large surface area and the unique zero-dimensional at one-dimensional nanostructure. These results not only provide a new approach to ultrasensitive SERS substrates, but also are helpful for improving the fundamental understanding of SERS phenomena.