Superelongation of Liquid Metal.

The ability to control interfacial tension electrochemically is uniquely available for liquid metals (LMs), in particular gallium-based LM alloys. This imparts them with excellent locomotion and deformation capabilities and enables diverse applications. However, electrochemical oxidation of LM is a highly dynamic process, which often induces Marangoni instabilities that make it almost impossible to elongate LM and manipulate its morphology directly and precisely on a 2D plane without the assistance of other patterning methods. To overcome these limitations, this study investigates the use of an LM-iron (Fe) particle mixture that is capable of suppressing instabilities during the electrochemical oxidation process, thereby allowing for superelongation of the LM core of the mixture to form a thin wire that is tens of times of its original length. More importantly, the elongated LM core can be manipulated freely on a 2D plane to form complex patterns. Eliminating Marangoni instabilities also allows for the effective spreading and filling of the LM-Fe mixture into molds with complex structures and small features. Harnessing these excellent abilities, a channel-less patterning method for fabricating elastomeric wearable sensors is demonstrated to detect motions. This study shows the potential for developing functional and flexible structures of LM with superior performance.

Comparison of lncRNA Expression in the Uterus between Periods of Embryo Implantation and Labor in Mice.

Uterine function during pregnancy is regulated mainly by progesterone (P4) and estrogen (E2). Serum P4 levels are known to fluctuate significantly over the course of pregnancy, especially during embryo implantation and labor. In this study, pregnant mice at E0.5, E4.5, E15.5, and E18.5 (n = 3/E) were used for an RNA-Seq-based analysis of mRNA and lncRNA expression. In this analysis, 1971 differentially expressed (DE) mRNAs, 493 known DE lncRNAs, and 1041 novel DE lncRNAs were found between E0.5 and E4.5 at the embryo implantation stage, while 1149 DE mRNAs, 192 known DE lncRNAs, and 218 novel DE lncRNAs were found between E15.5 and E18.5 at the labor stage. The expression level of lncRNA-MMP11 was significantly downregulated by P4 treatment on MSM cells, while lncRNA-ANKRD37 was significantly upregulated. Notably, 117 DE mRNAs, 19 known DE lncRNAs, and 31 novel DE lncRNAs were commonly expressed between the two stages, indicating that these mRNAs and lncRNAs may be directly or indirectly regulated by P4.

Programmable Digital Liquid Metal Droplets in Reconfigurable Magnetic Fields.

Gallium-based liquid metals exhibit excellent locomotion and deformation capabilities under external stimuli and has potential in developing intelligent robots. Programing the locomotion and morphology of the Liquid metal (LM) to endow it with functionalities and intelligence as robots is charming but remains challenging. In this study, we develop a programmable digital LM (PDLM) control platform that can realize versatile locomotion and morphological manipulation of magnetic LM (MLM) droplets using arrays of electromagnets. We demonstrate on-demand transportation, deformation, breakup, and merging of multiple MLM droplets simultaneously and precisely. We find that the intriguing behaviors of MLM under a magnetic field are due to the interplay of surface tension and magnetic forces. Furthermore, we present a functional cooperative droplet robot by equipping the MLM droplets with three-dimensionally printed microtool modules. We show that both the position and orientation of a rod-shaped object can be precisely manipulated by the cooperation of the MLM droplet robots. More interestingly, we explore the capability of the MLM droplet robots for cooperatively handling a copper wire to connect and disconnect electronic circuits. Finally, we demonstrate that the PDLM control platform is capable of programing a group of MLM droplets to accomplish a digital display task. We believe that the PDLM control system presents a promising potential in developing LM-based reconfigurable circuits, digital display systems, and biomimetic soft robotic systems with high controllability, multifunctionalities, and intelligence.

SETD7 promotes TNF-α-induced proliferation and migration of airway smooth muscle cells in vitro through enhancing NF-κB/CD38 signaling.

The inflammation-induced the excessive proliferation and migration of airway smooth muscle (ASM) cells in the airway wall contribute to airway remodeling in asthma pathogenesis. SET domain-containing lysine methyltransferase 7 (SETD7) has emerged as one of the key regulators of inflammation. Yet, the function of SETD7 in regulating inflammation-induced ASM cell proliferation and invasion remains unclear. In the present study, we aimed to investigate the function of SETD7 in regulating ASM cell proliferation and invasion induced by tumor necrosis factor (TNF)-α in vitro. Our results showed that SETD7 expression was upregulated in ASM cells stimulated with TNF-α. Silencing SETD7 significantly decreased TNF-α-induced ASM cell proliferation and migration, while SETD7 overexpression exhibited the opposite effect. Notably, silencing SETD7 decreased the activation of nuclear factor (NF)-κB and reduced the expression of CD38 induced by TNF-α. Blocking NF-κB activation significantly abrogated the promotional effect of SETD7 overexpression on CD38 expression. Moreover, overexpression of CD38 partially reversed the inhibitory effect of SETD7 silencing on TNF-α-induced ASM cell proliferation and migration. Overall, these results demonstrate that SETD7 regulates TNF-α-induced ASM cell proliferation and migration through modulation of NF-κB/CD38 signaling, suggesting a potential role of SETD7 in asthma airway remodeling.

Serum cystatin C as a potential biomarker for the evaluation COPD.

BACKGROUND: Imbalance between protease-antiprotease plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cystatin C in circulating blood is a cysteine protease inhibitor and contributes to elastolysis and tissue destruction. OBJECTIVES: The aims of the present study were to investigate whether cystatin C was a promising biomarker for the evaluation and follow-up of patients with COPD. METHODS: Serum cystatin C level was determined in groups of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (n = 93), stable COPD (SCOPD) (n = 299) and healthy controls (n = 151). The influences of smoking on the level of serum cystatin C and the correlation of cystatin C with lung functional parameters were further analyzed. RESULTS: Serum cystatin C level was significantly higher in COPD patients than that of healthy controls. Smoking increased serum cystatin C level in patients with SCOPD but not in AECOPD and control. In SCOPD group, serum cystatin C level was positively correlated with RV%TLC and negatively correlations with FEV1% predicted, FEV1%FVC, MMEF75/25% predicted, MVV% predicted and DLco% predicted. In multiple line analysis, FEV1% predicted and age were found to be independent predictors of serum cystatin C levels, but not smoking statue, sex and BMI. CONCLUSIONS: COPD had a higher level of serum cystatin C, smoking only increased cystatin C level in SCOPD. Serum cystatin C level was negatively correlated with FEV1% predicted. These results suggest that cystatin C might be a potential biomarker for lung tissue destruction and severity of COPD.

Combination therapy with losartan and pioglitazone additively reduces renal oxidative and nitrative stress induced by chronic high fat, sucrose, and sodium intake.

We recently showed that combination therapy with losartan and pioglitazone provided synergistic effects compared with monotherapy in improving lesions of renal structure and function in Sprague-Dawley rats fed with a high-fat, high-sodium diet and 20% sucrose solution. This study was designed to explore the underlying mechanisms of additive renoprotection provided by combination therapy. Losartan, pioglitazone, and their combination were orally administered for 8 weeks. The increased level of renal malondialdehyde and expression of nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) and nitrotyrosine as well as the decreased total superoxide dismutase activity and copper, zinc-superoxide dismutase expression were tangible evidence for the presence of oxidative and nitrative stress in the kidney of model rats. Treatment with both drugs, individually and in combination, improved these abnormal changes. Combination therapy showed synergistic effects in reducing malondialdehyde level, p47(phox), and nitrotyrosine expression to almost the normal level compared with monotherapy. All these results suggest that the additive renoprotection provided by combination therapy might be attributed to a further reduction of oxidative and nitrative stress.

Losartan and pioglitazone ameliorate nephropathy in experimental metabolic syndrome rats.

It is well known that metabolic syndrome (MS) is a risk factor for proteinuria and chronic kidney disease. Losartan (angiotensin II receptor blocker, ARB) and pioglitazone (peroxisome proliferator-activated receptor-γ, PPARγ agonist) have been shown to confer renoprotection. However, to date, whether or not an ARB and a PPARγ agonist have synergistic renoprotective effects remains controversial. Thus, the present study was designed to evaluate a combined treatment with losartan and pioglitazone in Sprague-Dawley rats fed with a high-fat, high-salt (HFS) diet and 20% sucrose solution for 16 weeks, an animal model of MS accompanying with renal lesions. Losartan, pioglitazone, and their combination were orally administered in the MS rats from 8 weeks to the end of this study. At 16 weeks, the MS rats showed the elevation in systolic blood pressure (SBP), urinary albumin excretion (UAE), and glomerulosclerosis (GS) score, but creatinine clearance, urinary protein excretion, and score of tubulointerstitial damage were not affected. Renal vascular endothelial growth factor (VEGF) protein level, mRNA and protein expression, which were respectively measured by enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis, were obviously decreased in the MS rats. Treatment with the combination of losartan and pioglitazone provided synergistic effects in reducing the SBP, UAE, and GS score when compared with monotherapy. These effects were not associated with ameliorated the downregulation of renal VEGF expression. Our data suggest that combined treatment with losartan and pioglitazone may offer additional advantages in treating MS nephropathy.

Role of adenylate and guanylate cyclases in beta1-, beta2-, and beta3-adrenoceptor-mediated relaxation of internal anal sphincter smooth muscle.

The purpose of the present study was to ascertain the role of adenylate (AC) versus guanylate cyclase (GC) signaling pathways in the internal anal sphincter (IAS) smooth muscle relaxation by beta(1)-, beta(2)-, and beta(3)-adrenoceptor (AR) activation by xamoterol, procaterol, and disodium 5-[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino)propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316243), respectively. The above-mentioned agonists produced concentration-dependent relaxation of the smooth muscle strips. Both the selective G(i/o)alpha and G(s)alpha antagonists 8,8'-(carbonylbis(imino-3,1-phenylene))bis-(1,3,5-naphthalene trisulfonic acid) (NF 023) and 4,4',4",4"'-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid (NF 449), respectively, inhibited the relaxation induced by procaterol. However, only NF 023 inhibited the relaxation induced by xamoterol and CL 316243. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, a soluble GC inhibitor, significantly inhibited the relaxation induced by different agonists. In contrast, the selective AC inhibitor [9-(tetrahydro-2'-furyl)adenine] (SQ 22536) inhibited only the relaxation induced by procaterol. (9R,10S,12S)-2,3,9,10,11,12-Hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg: 3',2',1'-kl]pyrrolo[3,4-l][1,6]benzodiazocine-10-carboxylic acid, hexyl ester (KT 5720), a cAMP-dependent protein kinase inhibitor, attenuated the relaxation by procaterol, whereas (9S,10R,12R)-2,3,9,10,11,12, hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9.12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-I][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT 5823), a selective cGMP-dependent protein kinase (PKG) inhibitor, attenuated the relaxation induced by xamoterol and CL 316243. Xamoterol produced significant increase in cGMP levels, whereas only procaterol enhanced the cAMP levels. Western blot analysis confirmed the presence of beta(1), beta(2), and beta(3)-AR subtypes in the IAS. In summary, beta(2)-AR activates both G(s)alpha and G(i/o)alpha-protein subunits and induces relaxation in the rat IAS via both cAMP/cGMP pathways. In contrast, the beta(1)/beta(3)-ARs activation causes the smooth muscle relaxation via G(i/o)alpha-protein subunit/GC/GMP/PKG pathway. These studies are important for the understanding of intracellular mechanisms underlying IAS smooth muscle relaxation and in turn the pathophysiology of certain anorectal motility disorders.