MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas.

Uterine leiomyomas cause heavy menstrual bleeding, anemia, and pregnancy loss in millions of women worldwide. Driver mutations in the transcriptional mediator complex subunit 12 (MED12) gene in uterine myometrial cells initiate 70% of leiomyomas that grow in a progesterone-dependent manner. We showed a distinct chromatin occupancy landscape of MED12 in mutant MED12 (mut-MED12) versus WT-MED12 leiomyomas. Integration of cistromic and transcriptomics data identified tryptophan 2,3-dioxygenase (TDO2) as the top mut-MED12 target gene that was significantly upregulated in mut-MED12 leiomyomas when compared with adjacent myometrium and WT-MED12 leiomyomas. TDO2 catalyzes the conversion of tryptophan to kynurenine, an aryl hydrocarbon receptor (AHR) ligand that we confirmed to be significantly elevated in mut-MED12 leiomyomas. Treatment of primary mut-MED12 leiomyoma cells with tryptophan or kynurenine stimulated AHR nuclear translocation, increased proliferation, inhibited apoptosis, and induced AHR-target gene expression, whereas blocking the TDO2/kynurenine/AHR pathway by siRNA or pharmacological treatment abolished these effects. Progesterone receptors regulated the expression of AHR and its target genes. In vivo, TDO2 expression positively correlated with the expression of genes crucial for leiomyoma growth. In summary, activation of the TDO2/kynurenine/AHR pathway selectively in mut-MED12 leiomyomas promoted tumor growth and may inform the future development of targeted treatments and precision medicine.

Effects of a postural cueing for head and neck posture on lumbar lordosis angles in healthy young and older adults: a preliminary study.

BACKGROUND: Postural rehabilitation plays an important role in the treatment of non-specific low back pain. Although pelvic inclination has been widely used to improve lumbar lordosis, the effect of cervical anterior inclination on lumbar lordosis in young and older adults in sitting and standing posture is still unclear. This preliminary study was designed to examine the influence of changing the cervical anterior angle on the lumbar lordosis angle, through alterations of the head position under the natural sitting and standing conditions, aiming to provide a basis for establishing a new postural rehabilitation strategy. METHODS: Thirty-six young (24.0 ± 2.2 years, 14 females and 22 males) and 38 older (68.4 ± 5.9 years, 36 females and 2 males) healthy adults participated in this study. The four spinal regional angles-cervical anterior angle, thoracic kyphosis angle, lumbar lordosis angle, and pelvic forward inclination angle, were measured in standing and relaxed sitting postures to determine the effects of a postural cueing for the head and neck posture, "inclining head backward and performing chin tuck," on lumbar lordosis angle. RESULTS: In the standing posture, the pelvic forward inclination angle in the older adult group was significantly smaller (P < 0.001, by ANOVA) than that in the young adult group and increased significantly (P < 0.001) in response to the postural cueing. In addition, the thoracic kyphosis angle in the standing (P = 0.001) and sitting (P = 0.003) positions was significantly reduced in response to the postural cueing. However, the lumbar lordosis angle in response to the postural cueing increased significantly in both the standing position (P < 0.001) and sitting position (P < 0.001). CONCLUSION: The results suggest that increasing the cervical anterior angle can increase the lumbar lordosis angle, and the cervical anterior inclination can be used as an alternative to pelvic forward inclination to improve the lumbar lordosis angle. Furthermore, the change in head and neck posture can reduce the thoracic kyphosis angle, making it possible to establish a new noninvasive body posture rehabilitation strategy.

Polypyrrole Hollow Microspheres with Boosted Hydrophilic Properties for Enhanced Hydrogen Evolution Water Dissociation Kinetics.

The water dissociation step (H2O + M + e- → M - Hads + OH-) is a crucial one toward achieving high-performance hydrogen evolution reaction (HER). The application of electronic conducting polymers (ECPs), such as polypyrrole (PPy), as the electrocatalyst for HER is rarely reported because of their poor adsorption energy per water molecule, which hinders the Volmer step. Herein, we strongly enrich PPy hollow microspheres (PPy-HMS) with attractive HER activity by enhancing their hydrophilic properties through hybridization with good water affinity SiO2. The as-prepared PPy-coated SiO2 (PPy@SiO2-HMS) achieves a current density of 10 mA cm-2 at -123 mV, which is lower than that of pristine PPy-HMS (-192 mV). Raman and X-ray photospectroscopy analyses reveal that the enhanced HER catalytic capability can be attributed to the strong electronic couplings between PPy and SiO2, and this improves the adsorption energy per water molecule and in turn accelerates the water dissociation kinetics on PPy. This work highlights the potential application of low-cost ECPs as promising electrocatalysts for water electrolysis.

A Simple and Scalable Approach To Remarkably Boost the Overall Water Splitting Activity of Stainless Steel Electrocatalysts.

The stainless steel mesh (SSM) has received growing consideration as an electrocatalyst for efficient hydrogen and oxygen evolution reactions. Recently, the application of SSM as an oxygen evolution reaction (OER) electrocatalyst has been more promising, while its hydrogen evolution reaction (HER) catalytic activity is very low, which definitely affects its overall water splitting activity. Herein, a simple chemical bath deposition (CBD) method followed by phosphorization is employed to significantly boost the overall water splitting performance of SSM. The CBD method could allow the voids between the SSM fibers to be filled with Ni and P. Electrocatalytic studies show that the CBD-treated and phosphorized stainless steel (denoted SSM-Ni-P) exhibits an HER overpotential of 149 mV, while the phosphorization-free CBD-treated SSM (denoted as SSM-Ni) delivers an OER overpotential of 223 mV, both at a current density of 10 mA cm-2. An asymmetric alkaline electrolyzer assembled based on the SSM-Ni-P cathode (HER) and SSM-Ni anode (OER) achieved an onset and 10 mA cm-2 current densities at an overall potential of 1.62 V, granting more prospects for the application of inexpensive and highly active electrocatalysts for electrocatalytic water splitting reactions.

Enhanced lithium storage performance of porous exfoliated carbon fibers via anchored nickel nanoparticles.

Herein, flexible carbon fiber cloth (CFC) is modified by embedding Ni nanoparticles via a thermal reduction strategy, and it is used as a suitable anode material for lithium-ion batteries. Benefitting from the elemental interaction between Ni and carbon, the Ni-embedded CFC displayed higher lithium storage properties than pristine CFC and Ni-free porous CFC.

Enhanced Photoelectrochemical Oxygen Evolution Reaction Ability of Iron-Derived Hematite Photoanode with Titanium Modification.

A facile fabrication route towards a titanium-modified hematite photoanode has been developed, and the photoelectrochemical properties of this anode have been evaluated. Compared to pristine hematite, the activity of the modified photoanode in this work delivered almost twofold higher photocurrent under Air Mass 1.5G illumination. Further research revealed that the enhanced performance of the hematite photoanode with a titanium-modified surface resulted from the dominant impact of heterojunction formation and suppressed surface recombination, supplemented by a slightly improved light-harnessing ability.

Ruthenium (II) complexes interact with human serum albumin and induce apoptosis of tumor cells.

The interaction of ruthenium (II) complex [Ru(bpy)2(mal)](2+) (RBM) and [Ru(phen)2(mal)](2+) (RPM) (bpy = 2, 2-bipyridine, phen = 1,10-phenanthroline, mal = malonyl carboxylate) with human serum albumin (HSA) has been investigated by using fluorescence, UV absorption and circular dichroism (CD) spectroscopy approaches. A strong fluorescence quenching reaction of complexes to HSA was observed and the quenching mechanism was suggested as static quenching according to the Stern-Volmer (S-V) equation. The number of binding sites n and observed binding constant Kb was measured by fluorescence quenching method. The thermodynamic parameters ΔH, ΔS, and ΔG at different temperatures were calculated and the results indicate the binding reaction is mainly entropy-driven and Vander Waals force played a major role in the reaction. The result of CD showed that the secondary structure of HSA molecules was changed in the presence of the ruthenium (II) complexes. Furthermore, the cell viability of ruthenium (II) complexes was evaluated by MTT and complex RPM has shown significant higher anticancer potency than RBM against all the cell lines screened. RPM showed a significant antitumor activity through induction of apoptosis in A549 cells.

Ruthenium (II) polypyridyl complexes stabilize the bcl-2 promoter quadruplex and induce apoptosis of Hela tumor cells.

In the present study, the interaction between GC-rich sequence of bcl-2 gene P1 promoter (Pu39) and two ruthenium (II) polypyridyl complexes, [Ru(bpy)2(tip)]²âº (1) and [Ru(phen)2(tip)]²âº (2), was investigated by UV-Visible, fluorescence spectroscopy, circular dichroism, fluorescence resonance energy transfer melting assay and polymerase chain reaction stop assay. Those experimental results indicated that the two complexes can effectively stabilize the G-quadruplex of Pu39. It was found that the complex 2 exhibited greater cytotoxic activity than 1 against human Hela cells and can enter into Hela cells in a short period of time to effectively induce apoptosis of cells. Further experiments found that complexes 1 and 2 had as potent inhibitory effects on ECV-304 cell migration as suramin. Those noteworthy results provide new insights into the development of anticancer agents for targeting G-quadruplex DNA.

[The role of gap-junction in suspended animation for hemorrhagic shock with brain injury: experiment with rats].

OBJECTIVE: To investigate the role of gap-junction in suspended animation for hemorrhagic shock with brain injury. METHODS: Twenty-four SD rats were made into models of uncontrolled hemorrhagic shock and occlusion of bilateral common carotid arteries and randomly divided into 3 equal groups: traditional resuscitation group (Group I) undergoing traditional resuscitation, hypothermy resuscitation group (Group II) undergoing temperature lowering by ice-cap, and carbenoxolone resuscitation group (Group III) undergoing injection of carbenoxolone 50 microg/200 g. The process was divided into 3 periods: traumatic hemorrhagic period (30 min), pre-hospital treatment period (60 min), and in-hospital cardiopulmonary resuscitation period (60 min). The levels of left ventricular systolic pressure (LVSP), maximum change rate of left ventricular pressure rise and fall (+/- dp/dt(max)), mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) were recorded at the beginning and the end of traumatic hemorrhagic period (T1 and T2), the end of pre-hospital treatment period (T3), and the end of in-hospital cardiopulmonary resuscitation period (T4). The survival time was recorded after in-hospital cardiopulmonary resuscitation period. Then the left brain was taken out and the hippocampal neurons apoptosis was observed by flow cytometry, chemiluminescence was used to detect the ATP, and IL-6 and tumor necrosis factor (TNF)-alpha were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: The survival time of Groups II and III were (2.9 +/- 0.6) h and (2.6 +/- 1.0) h respectively, both significantly longer than that of Group I [(1.4 +/- 0.3) h, both P < 0.01]. The apoptotic rates of hippocampal neurons of Groups II and III were (72 +/- 6)% and (75 +/- 9)% respectively, both significantly lower than that of Group [83 +/- 5)% P < 0.05]. The ATP levels in hippocampus of Groups II and III were (2.0 +/- 0.3) and (1.9 +/- 0.4) pg/g respectively, both significantly higher than that of Group I [(1.4 +/- 0.5 pg/g, both P < 0.05). The TNF-alpha and IL-6 levels of Groups II were (1.7 +/- 0.3) pg/g and (19 +/- 3) pg/g respectively, both significantly lower than those of Group I [(2.2 +/- 0.6) and (24 +/- 3) pg/g respectively, both P < 0.05]. The IL-6 level of Group III was (26 +/- 4) pg/g, significantly higher than that of Group II (P < 0. 01). There were no significant difference between Groups II and III in the values of survival time, hippocampal neuron apoptosis, dissipation of ATP, and liberation of TNF-alpha (all P > 0.05), but there was significant difference in IL-6 (P < 0.01). CONCLUSION: Both hypothermy resuscitation and carbenoxolone resuscitation protect the brain of cerebral ischemia on hemorrhagic shock with brain injury, and suggest that Gap junctions play an important role in suspended animation to treat hemorrhagic shock with brain injury.

[Preparation of the spin trapping probe, N-tert-butyl-alpha-phenylnitrone, nanoparticle and its affinity to hepatoma cells].

This article describes the preparation of the N-tert-butyl-alpha-phenylnitrone (PBN) liposomes and their related characteristics. The PBN liposomes were prepared by film dispersion-supersonic method and the formula of liposomes was optimized by orthogonal uniform design. RP-HPLC was used to qualify the amount of PBN that entered into the hepatoma cells. Necrosis rate was also investigated by fluorescence activated cell sorter (FACS) after PBN liposomes transfection. Result showed that the mean particle size, entrapment efficiency, and polydispersity of the resulting PBN-liposome were 137.5 nm, 71.52% and 0.286, respectively. PBN liposomes can enter into the tumor cell stably and they have higher affinity to hepatoma cell compared with free PBN resulting in a higher necrosis rate after transfection. These results provide a potential method for early diagnosis and treatment of cancer using specific spin trapping probe targeting tumor cells.