Low coordinate Zn(II) organocations bearing extremely bulky NHC ligands: structural features, air-/water-tolerance and use in hydrosilylation and hydrogenation catalysis.

This work details the synthesis and characterization of low-coordinate Zn(II)-based organocations [(NHC)Zn(R)]+ incorporating extremely bulky NHCs [ITr] and [IAd] ([ITr] = ([ITr] = [(HCNCPh3)2C:]; [IAd] = [(HCNAd)2C:], Ad = adamantyl)). Their structural features and particularities are thoroughly assessed as well as their air and water tolerance. Neutral ITr and IAd adducts [(ITr)Zn(R)2] (1, R = Me; 2, R = Et) and [(IAd)Zn(R)2] (3, R = Me; 4, R = Et) were synthesized by reaction of carbene [ITr] or [IAd] with a stoichiometric amount of [ZnR2] and isolated in good yields. Despite the steric bulk of [ITr] and [IAd], neutral compounds 1-4 are robust and the solid state structure of adduct 3 was established through X-ray crystallographic studies as a trigonal monomer Zn(II) species. Adducts 1-4 may readily be ionized by [Ph3C][B(C6F5)4] to afford two-coordinate Zn(II) alkyl cations [(ITr)Zn(Me)]+ ([5]+) and [(ITr)Zn(Et)]+ ([6]+), [(IAd)Zn(Me)]+ ([7]+) and [(IAd)Zn(Me)]+ ([8]+), all isolated in high yields (>80%) as [B(C6F5)4]- salts, which were fully characterized. Remarkably, cation [(ITr)Zn(C6F5)]+ ([9]+), prepared by reaction of [5][B(C6F5)4] with [B(C6F5)3], features π-arene interactions with the electrophilic Zn(II), as deduced from solid state data and further completed by DFT-estimated non-covalent interactions (NCI), indicating that [ITr] may provide substantial steric and electrostatic stabilization. The latter certainly explains the remarkable stability of [(ITr)Zn(C6F5)]+ ([9]+) towards hydrolysis at RT, as it only coordinates H2O to afford an unprecedented stable Zn-OH2 organocation [10]+. Also noteworthy, H2O coordination is reversible allowing recovery of [(ITr)Zn(C6F5)]+ cation, even after prolonged air exposure. Yet, controlled hydrolysis of [(ITr)Zn(C6F5)]+ may occur upon heating with selective protonolysis of the Zn-C6F5 bond to afford structurally characterized dication [(ITr)Zn(OH)]22+ [11]2+. Interestingly, despite steric hindrance, the air-/water-tolerant cation [(ITr)Zn(C6F5)]+ is an effective CO2 hydrosilylation catalyst, and was also shown to mediate imine hydrogenation catalysis.

Aged polystyrene microplastics exacerbate alopecia associated with tight junction injuries and apoptosis via oxidative stress pathway in skin.

Microplastics (MPs) are pervasive pollutants in the natural environment and contribute to increased levels of illness in both animals and humans. However, thespecific impacts of MPs on skin damage and alopeciaare not yet well understood. In this study, we have examined the effects of two types of polystyrene MPs (pristine and aged) on skin and hair follicle damage in mice. UV irradiation changed the chemical and physical properties of the aged MPs, including functional groups, surface roughness, and contact angles. In both in vivo and in vitro experiments, skin and cell injuries related to oxidative stress, apoptosis, tight junctions (TJs), alopecia, mitochondrial dysfunction, and other damages were observed. Mechanistically, MPs and aged MPs can induce TJs damage via the oxidative stress pathway and inhibition of antioxidant-related proteins, and this can lead to alopecia. The regulation of cell apoptosis was also observed, and this is involved in the ROS-mediated mitochondrial signaling pathway. Importantly, aged MPs showed exacerbated toxicity, which may be due to their elevated surface irregularities and altered chemical compositions. Collectively, this study suggests a potential therapeutic approach for alopecia and hair follicle damage caused by MPs pollution.

Signaling pathways in hair aging.

Hair follicle (HF) homeostasis is regulated by various signaling pathways. Disruption of such homeostasis leads to HF disorders, such as alopecia, pigment loss, and hair aging, which is causing severe health problems and aesthetic concerns. Among these disorders, hair aging is characterized by hair graying, hair loss, hair follicle miniaturization (HFM), and structural changes to the hair shaft. Hair aging occurs under physiological conditions, while premature hair aging is often associated with certain pathological conditions. Numerous investigations have been made to determine the mechanisms and explore treatments to prevent hair aging. The most well-known hypotheses about hair aging include oxidative stress, hormonal disorders, inflammation, as well as DNA damage and repair defects. Ultimately, these factors pose threats to HF cells, especially stem cells such as hair follicle stem cells, melanocyte stem cells, and mesenchymal stem cells, which hamper hair regeneration and pigmentation. Here, we summarize previous studies investigating the above mechanisms and the existing therapeutic methods for hair aging. We also provide insights into hair aging research and discuss the limitations and outlook.

Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways.

Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.

Cooperation of TGF-ß and FGF signalling pathways in skin development.

The skin is a multi-layered structure composed of the epidermis, dermis and hypodermis. The epidermis originates entirely from the ectoderm, whereas the dermis originates from various germ layers depending on its anatomical location; thus, there are different developmental patterns of the skin. Although the regulatory mechanisms of epidermal formation are well understood, mechanisms regulating dermis development are not clear owing to the complex origin. It has been shown that several morphogenetic pathways regulate dermis development. Of these, transforming growth factor-ß (TGF-ß) and fibroblast growth factor (FGF) signalling pathways are the main modulators regulating skin cell induction, fate decision, migration and differentiation. Recently, the successful generation of human skin by modulating TGF-ß and FGF signals further demonstrated the irreplaceable roles of these pathways in skin regeneration. This review provides evidence of the role of TGF-ß and FGF signalling pathways in the development of different skin layers, especially the disparate dermis of different body regions. This review also provides new perspectives on the distinct developmental patterns of skin and explores new ideas for clinical applications in the future.

Combinational Growth Factor and Gas Delivery for Thrombosis Prevention.

Cardiovascular stents enable the rapid re-endothelialization of endothelial cells (ECs), and the constant suppression of smooth muscle cell (SMC) proliferation has been proved to effectively prevent thrombosis. However, the development and application of such stents are still insufficient due the delayed re-endothelialization progress, as well as the poor durability of the SMC inhibition. In this paper, we developed a mussel-inspired coating with the ability for the dual delivery of both growth factor (e.g., platelet-derived growth factor, PDGF) and therapeutic gas (e.g., nitric oxide, NO) for thrombosis prevention. We firstly synthesized the mussel-inspired co-polymer (DMHM) of dopamine methacrylamide (DMA) and hydroxyethyl methacrylate (HEMA) and then coated the DMHM on 316L SS stents combined with CuII. Afterwards, we immobilized the PDGF on the DMHM-coated stent and found that the PDGF could be released in the first 3 days to enhance the recruitment, proliferation, and migration of human umbilical vein endothelial cells (HUVECs) to promote re-endothelialization. The CuII could be "sealed" in the DMHM coating, with extended durability (2 months), with the capacity for catalyzed NO generation for up to 2 months to suppress the proliferation of SMCs. Such a stent surface modification strategy could enhance the development of the cardiovascular stents for thrombosis prevention.

Exploring the Temporal Correlation of Sarcopenia with Bone Mineral Density and the Effects of Osteoblast-Derived Exosomes on Myoblasts through an Oxidative Stress-Related Gene.

Sarcopenia is an age-related accelerated loss of muscle strength and mass. Bone and muscle are closely related as they are physically adjacent, and bone can influence muscle. However, the temporal association between bone mineral density (BMD) and muscle mass in different regions of the body after adjustment for potential indicators and the mechanisms by which bone influences muscle in sarcopenia remain unclear. Therefore, this study aimed to explore the temporal association between muscle mass and BMD in different regions of the body and mechanisms by which bone regulates muscle in sarcopenia. Here, cross-lagged models were utilized to analyze the temporal association between BMD and muscle mass. We found that low-density lipoprotein (LDL-C) positively predicted appendicular lean mass. Mean whole-body BMD (WBTOT BMD), lumbar spine BMD (LS BMD), and pelvic BMD (PELV BMD) temporally and positively predicted appendicular lean mass, and appendicular lean mass temporally and positively predicted WBTOT BMD, LS BMD, and PELV BMD. Moreover, this study revealed that primary mice femur osteoblasts, but not primary mice skull osteoblasts, induced differentiation of C2C12 myoblasts through exosomes. Furthermore, the level of long noncoding RNA (lncRNA) taurine upregulated 1 (TUG1) was decreased, and the level of lncRNA differentiation antagonizing nonprotein coding RNA (DANCR) was increased in skull osteoblast-derived exosomes, the opposite of femur osteoblast-secreted exosomes. In addition, lncRNA TUG1 enhanced and lncRNA DANCR suppressed the differentiation of myoblasts through regulating the transcription of oxidative stress-related myogenin (Myog) gene by modifying the binding of myogenic factor 5 (Myf5) to the Myog gene promoter via affecting the nuclear translocation of Myf5. The results of the present study may provide novel diagnostic biomarkers and therapeutic targets for sarcopenia.

Comprehensive evaluation of cobalt incorporated cryptomelane-type manganese oxide molecular sieve as an efficient adsorbent for enhanced removal of europium from wastewater systems.

Extraction of radionuclide contaminants from wastewater systems has recently drawn widespread attention, and then developing a novel and green extracting technology has also become an enormous challenge. Herein, a facile hydrothermal method was employed to fabricate cobalt-incorporated cryptomelane-type manganese oxide molecular sieve (Co-OMS-2) for extraction Eu(III) from wastewater under diverse experimental conditions. All kinds of characterized techniques, such as SEM, TEM, XRD, FTIR, BET, EDS and XPS had verified the qualified synthesis process and splendid structural features of the Co-OMS-2. The maximum adsorption capacity of Co-OMS-2 was 7.62 × 10-4 mol/g for Eu(III) at 298 K, which was superior than primarily traditional materials reported previous literatures. The high adsorption capacity of Eu(III) onto Co-OMS-2 was primarily attributed to high specific surface area and abundant surface functional groups, and the interactions were mainly contributed to strong surface complexation and electrostatic attraction. Under the condition of low pH, the outer-sphere surface complexation and cation exchange were primary mechanisms to Eu(III) adsorption onto Co-OMS-2 composites, while inner-sphere surface complexation was mainly assigned to Eu(III) adsorption onto Co-OMS-2 under the high pH sections. The Co-OMS-2 composite achieved equilibrium in a relatively short time, and this excellent performance was conducive to the treatment of Eu(III) under the extreme emergency conditions. In view of the extraordinary adsorption capacity and recycled reusability, the Co-OMS-2 composites can be as prospective adsorbents adopted for the extraction of Eu(III) in real wastewater management.

Cellular Heterogeneity and Plasticity of Skin Epithelial Cells in Wound Healing and Tumorigenesis.

Cellular differentiation, the fundamental hallmark of cells, plays a critical role in homeostasis. And stem cells not only regulate the process where embryonic stem cells develop into a complete organism, but also replace ageing or damaged cells by proliferation, differentiation and migration. In characterizing distinct subpopulations of skin epithelial cells, stem cells show large heterogeneity and plasticity for homeostasis, wound healing and tumorigenesis. Epithelial stem cells and committed progenitors replenish each other or by themselves owing to the remarkable plasticity and heterogeneity of epidermal cells under certain circumstance. The development of new assay methods, including single-cell RNA sequence, lineage tracing assay, intravital microscopy systems and photon-ablation assay, highlight the plasticity of epidermal stem cells in response to injure and tumorigenesis. However, the critical mechanisms and key factors that regulate cellular plasticity still need for further exploration. In this review, we discuss the recent insights about the heterogeneity and plasticity of epithelial stem cells in homeostasis, wound healing and skin tumorigenesis. Understanding how stem cells collaborate together to repair injury and initiate tumor will offer new solutions for relevant diseases. Schematic abstract of cellular heterogeneity and plasticity of skin epithelial cells in wound healing and tumorigenesis.

Nanosized CuO encapsulated Ni/Co bimetal Prussian blue with high anti-interference and stability for electrochemical non-enzymatic glucose detection.

Non-enzymatic glucose sensors based on metal oxides are receiving remarkable attention owing to their outstanding characteristics of being easy-to use, low cost, and reusability. However, the disadvantage of weak anti-interference associated with poor selectivity significantly restricts their applicability. Herein, we report a two-step in situ fabrication of nanosized CuO encapsulated Ni/Co bimetal Prussian blue (PB) with a typical core-shell structure, which can be efficiently used for non-enzymatic glucose detection, ascribing to the permeability and abundant active sites of out-shelled crystalline porous Ni/Co PB and the high catalytic activity and conductivity of embedded CuO nanoparticles, afforded by their mutual synergistic interactions. The glassy carbon electrode modified with the hybrid of the CuO-encapsulated Ni/Co PB (simplified as the Ni/Co-PB/CuO/GCE electrode) exhibited a high glucose sensitivity of 600 µA mM-1 cm-2 with a low detection limit of 0.69 µM (S/N = 3), a fast response time (less than 3 s), and excellent long-term stability. In addition, the CuO-encapsulated Ni/Co PB showed favorable anti-interference ability in the presence of ascorbic acid (AA), L-lysine (Lys), dopamine (DA), cysteine (Cys), dopamine (DA), and KCl interferences. The reusability and long-term stability, as well as the practicability of the Ni/Co-PB/CuO/GCE sensing electrode verified by testing real serum samples were also investigated, and the experimental results demonstrated the applicability of the core-shell NiCo-PB/CuO based flexible electrochemical sensor for non-enzymatic glucose sensing in practical applications.

A hierarchical hollow Ni/Co-functionalized MoS2 architecture with highly sensitive non-enzymatic glucose sensing activity.

A hierarchical hollow Ni/Co-codoped MoS2 architecture was successfully prepared using a Ni/Co Prussian Blue analogue as the precursor followed by the solvothermal-assisted insertion of MoS42- and extraction of [Co(CN)6]3- at 200 °C for 32 h. The obtained Ni/Co-codoped MoS2 composite exhibited a hollow microcubic structural characteristic, and the morphology, structure, and chemical compositions were carefully characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS), respectively. The Ni/Co-codoped MoS2 composite used as an electrode material featured excellent glucose sensing activity and a high sensitivity of 2546 µA mM-1 cm-2 with a relatively low detection limit of 0.69 µM (S/N = 3). In addition, the Ni/Co-codoped MoS2 composite showed good anti-interference sensing performance in the presence of ascorbic acid (AA), lysine (Lys), cysteine (Cys), urea, H2O2, KCl, and other interferents. These experimental results revealed that the composite is a promising electrode material for enzyme-free glucose sensing, and the feasible synthetic strategy may provide an effective and controlled route to prepare other multi-metal substituted sulfide-based hierarchical structures with high electrochemical sensing performance.

SPTBN1 Prevents Primary Osteoporosis by Modulating Osteoblasts Proliferation and Differentiation and Blood Vessels Formation in Bone.

Osteoporosis is a common systemic skeletal disorder that leads to increased bone fragility and increased risk of fracture. Although ßII-Spectrin (SPTBN1) has been reported to be involved in the development of various human cancers, the function and underlying molecular mechanisms of SPTBN1 in primary osteoporosis remain unclear. In this study, we first established a primary osteoporosis mouse model of senile osteoporosis and postmenopausal osteoporosis. The results showed that the expression of SPTBN1 was significantly downregulated in primary osteoporosis mice model compared with the control group. Furthermore, silencing of SPTBN1 led to a decrease in bone density, a small number of trabecular bones, wider gap, decreased blood volume fraction and number of blood vessels, as well as downregulation of runt-related transcription factor 2 (Runx2), Osterix (Osx), Osteocalcin (Ocn), and vascular endothelial growth factor (VEGF) in primary osteoporosis mice model compared with the control group. Besides, the silencing of SPTBN1 inhibited the growth and induced apoptosis of mouse pre-osteoblast MC3T3-E1 cells compared with the negative control group. Moreover, the silencing of SPTBN1 significantly increased the expression of TGF-ß, Cxcl9, and the phosphorylation level STAT1 and Smad3 in MC3T3-E1 cells compared with the control group. As expected, overexpression of SPTBN1 reversed the effect of SPTBN1 silencing in the progression of primary osteoporosis both in vitro and in vivo. Taken together, these results suggested that SPTBN1 suppressed primary osteoporosis by facilitating the proliferation, differentiation, and inhibition of apoptosis in osteoblasts via the TGF-ß/Smad3 and STAT1/Cxcl9 pathways. Besides, overexpression of SPTBN1 promoted the formation of blood vessels in bone by regulating the expression of VEGF. This study, therefore, provided SPTBN1 as a novel therapeutic target for osteoporosis.

The longitudinal associations between bone mineral density and appendicular skeletal muscle mass in Chinese community-dwelling middle aged and elderly men.

BACKGROUND: The present study aimed to investigate longitudinal associations between bone mineral densities (BMDs) and appendicular skeletal muscle (ASM) mass in different regions of the body using three different indicators, in Chinese community-dwelling middle-aged and elderly men. METHODS: A total of 1,343 men aged ≥ 40 years from a Chinese community were assessed at baseline (2014-2016), one-year follow-up (2016-2017; n = 648), two-year follow-up (2017-2018; n = 407), and three-year follow up (2018-2019; n = 208). At all the four time-points, measurements included ASM mass and BMDs for all regions of the body using dual-energy X-ray absorptiometry. A questionnaire was completed by patients and biochemical markers were assessed. We applied three different indicators to define ASM mass or lean mass respectively, including the appendicular skeletal muscle index (ASM adjusted by height, ASMI, according to the Asian Working Group for Sarcopenia), skeletal muscle index (ASM adjusted by weight, SMI, according to the International Working Group on Sarcopenia), and the appendicular skeletal muscle/body mass index (ratio of ASM and Body mass index (BMI), ASM/BMI, according to the Foundation for the National Institutes of Health). After adjusting for potential confounders, the generalized additive mixed model (GAMM) was used to analyze the trend in ASM mass over time, and to test the association between ASM mass and regional and whole-body BMDs. RESULTS: The incidence of low lean mass was 8.2% defined by ASMI, 16.3% defined by SMI, and 8.3% defined by ASM/BMI. There was a linear relationship between BMDs and ASM mass, and ASMI, ASM/BMI, and SMI gradually decreased with time. After adjusting for covariances, GAMM analysis determined longitudinal associations between BMDs and ASM mass by three indicators respectively: the skull BMD was negatively associated with ASM mass. For each unit increase in skull BMD, ASMI decreased by 0.28 kg/m2 (95% confidence interval (CI) [-0.39 to -0.16]), ASM/BMI decreased by 0.02 m2 (95% CI [-0.03 to -0.00]), and SMI decreased by 0.01% (95% CI[-0.01 to -0.00]). The remaining parameters (including whole-body mean BMD, thoracic spinal BMD, lumbar spinal BMD, hip BMD, femoral neck BMD, pelvic BMD, left arm BMD, right arm BMD, left leg BMD, right leg BMD) were positively correlated with ASM mass. The ASMI increased by 3.07 kg/m2for each unit increase in the femoral neck BMD (95% CI [2.31-3.84]). The ASM/BMI increased by 0.22 m2for each unit increase in the left arm BMD (95% CI [0.12-0.33]), and the SMI increased by 0.05% per unit increase in the left arm BMD (95% CI [0.02-0.08]). CONCLUSIONS: Compared to ASMI and ASM/BMI, SMI was more sensitive to screen for the low lean mass. Skull BMD was negatively associated with ASM mass, while BMDs throughout the rest of the body were positively correlated with ASM mass among the middle-aged and elderly Chinese men.

Synthesis of potential Ca-Mg-Al layered double hydroxides coated graphene oxide composites for simultaneous uptake of europium and fulvic acid from wastewater systems.

High background electrolyte and natural organic matter are favorable to migration of hazardous radionuclides in geochemical repository. Herein, Ca-Mg-Al layered double hydroxide coated onto graphene oxide (Ca-Mg-Al LDH/GO) composites were successfully synthesized, characterized and adopted to decontaminate Eu(III) and fulvic acid (FA) under diverse experimental conditions. Diverse concentration gradients and different addition sequences on Eu(III) and FA were also obtained, which revealed different interaction mechanisms. The experimental results displayed that the coexistence of FA and Eu(III) respectively promoted adsorption performance of Eu(III) and FA under the ternary systems. The acquired Ca-Mg-Al LDH/GO composites were adopted to remove Eu(III) and FA, which further illustrated excellent chemo-physical stability and adsorption capacity of 1.12 × 10-3 mol/g and 3.54 × 10-4 mol/g, respectively. The remarkable adsorption performances of Ca-Mg-Al LDH/GO were confirmed through kinetic procedures and depending-temperature isotherms, illustrating that the kinetics processes were simulated using pseudo-second-order pattern, and the adsorption isotherms were splendidly simulated using Langmuir pattern. XPS spectrum analysis revealed that these containing oxygen groups took significant part in the restricting of Eu(III) and FA onto the surfaces of Ca-Mg-Al LDH/GO composites. In view of experimental results, the Ca-Mg-Al LDH/GO composites can be as potential adsorbents with availably recycled reusability for the decontamination of Eu(III) and FA from nuclear fuel partition or nuclear wastewater systems.

Vascular endothelial growth factor gene polymorphisms and hypertensive disorder of pregnancy: A meta-analysis.

BACKGROUND: Whether vascular endothelial growth factor (VEGF) polymorphisms affect individual susceptibility to hypertensive disorder of pregnancy remain controversial. Therefore, we performed this meta-analysis to better evaluate associations between VEGF polymorphisms and hypertensive disorder of pregnancy in a larger pooled population. METHODS: Pubmed, Web of Science, Embase and CNKI were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Totally 24 studies were eligible for analyses. In overall analyses, a significant association with hypertensive disorder of pregnancy was observed for rs3025039 polymorphism in dominant (p = 0.01, OR = 0.66, 95%CI 0.48-0.91), recessive (p = 0.002, OR = 1.79, 95%CI 1.25-2.58), overdominant (p = 0.04, OR = 1.35, 95%CI 1.01-1.80) and allele (p = 0.01, OR = 0.72, 95%CI 0.56-0.93) comparisons. But we did not observe any significant associations with hypertensive disorder of pregnancy for other VEGF polymorphisms in overall analyses. Further subgroup analyses by ethnicity showed that rs2010963 polymorphism was significantly associated with hypertensive disorder of pregnancy in Caucasians (dominant and recessive models) and Africans (allele model), whereas rs3025039 polymorphism was significantly associated with hypertensive disorder of pregnancy in Asians (recessive model). CONCLUSIONS: In summary, our findings indicated that rs2010963 and rs3025039 polymorphisms were both significantly associated with the susceptibility to hypertensive disorder of pregnancy in certain populations.

Liraglutide regulates the viability of pancreatic α-cells and pancreatic ß-cells through cAMP-PKA signal pathway.

AIMS: As a glucagon-like peptide-1 receptor agonist, liraglutide could effectively increase insulin secretion from pancreatic ß-cells and suppress glucagon secretion from pancreatic α-cells in the treatment of hyperglycemia in type 2 diabetes patients. However, the mechanisms for the different regulation of pancreatic α-cells and ß-cells are still unclear. In this study, we mainly explored the different effects of liraglutide on mouse pancreatic α-cell line and ß-cell line in vitro. MAIN METHODS: Herein, mouse pancreatic α-cell line, α-TC1-6, and mouse pancreatic ß-cell line, ß-TC-tet, were used to analyze the biological effects of liraglutide in different concentrations. Cell proliferation, cell apoptosis and cell secretion ability were detected in different groups. Besides, the level of miR-375 and cAMP-PKA signal pathway were further evaluated using qPCR and western blot. KEY FINDINGS: The results indicated that liraglutide could increase the level of miR-375 and cell apoptosis in pancreatic α-cells through inhibiting the cAMP-PKA signal pathway, but activate cAMP-PKA signal pathway in pancreatic ß-cells, and further lead to the down-regulation of miR-375 and improve cell viability. Therefore, the treatment with liraglutide could down-regulate the glucagon secretion ability of α-TC1-6 cells, and the insulin secretion ability of ß-TC-tet cells was enhanced with the liraglutide treatment in a dose-dependent manner. SIGNIFICANCE: In conclusion, we mainly found that liraglutide could regulate the viability of pancreatic α-cells and pancreatic ß-cells through inhibiting and activating cAMP-PKA signal pathway respectively. The better understanding of the mechanism could help us to develop more novel therapy methods for diabetes in the future.

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients.

BACKGROUND/AIMS: Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. METHODS: AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. RESULTS: In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). CONCLUSION: Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed.

Predictors of Long-Term Mortality in Patients With Acute Heart Failure.

To investigate parameters which were related with long-term mortality in patients hospitalized for acute heart failure (AHF).A total of 287 patients with AHF presenting to the First Affiliated Hospital of Nanjing Medical University were enrolled into the registry from April 2012 to January 2015. The primary endpoint was all-cause mortality within 1 year; the association between variables and prognosis was assessed after 1 year.Among the 287 patients, 17 did not continue follow-up and 47 (17.4%) passed away. Baseline NT-proBNP and sST2 concentrations were higher amongst deceased than among survivors (P < 0.001). Serum sodium concentrations of patients who died were lower (P < 0.001). In receiver operator characteristics (ROC) analyses, the area under the curve (AUC) values for NT-proBNP, sST2, and serum sodium to predict 1-year mortality were 0.699 (95%CI 0.639-0.755), 0.692, (95%CI 0.634-0.747), and 0.694 (95%CI 0.634-0.750), respectively. The optimal cut-off points for NT-proBNP, sST2, and serum sodium were 2137.0 ng/L, 35.711 ng/mL, and 136.6 mmol/L, respectively. In Cox regression analysis, ln-transformed NT-proBNP (HR 1.546, P = 0.039), ln-transformed sST2 (HR1.542, P = 0.049), and serum sodium (HR 0.880, P = 0.000) values reliably predicted long-term mortality after multivariable adjustment.In patients with acute heart failure, NT-proBNP, sST2 and serum sodium are potential predictors of 1-year mortality.

Circulating miR-30d Predicts Survival in Patients with Acute Heart Failure.

BACKGROUND/AIMS: Identification of novel biomarkers to identify acute heart failure (AHF) patients at high risk of mortality is an area of unmet clinical need. Recently, we reported that the baseline level of circulating miR-30d was associated with left ventricular remodeling in response to cardiac resynchronization therapy in advanced chronic heart failure patients. However, the role of circulating miR-30d as a prognostic marker of survival in patients with AHF has not been explored. METHODS: Patients clinically diagnosed with AHF were enrolled and followed up for 1 year. Quantitative reverse transcription polymerase chain reactions were used to determine serum miR-30d levels. The univariate logistic regression analysis and multivariate logistic regression analysis were used to determine the predictors for all-cause mortality in AHF patients. Kaplan-Meier survival analysis was used to analyze the role of miR-30d in prediction of survival. RESULTS: A total of 96 AHF patients were enrolled and followed up for 1 year. Serum miR-30d was significantly lower in AHF patients who expired in the one year follow-up period compared to those who survived. Univariate logistic regression analysis yielded 18 variables that were associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 4 variables including heart rate, hemoglobin, serum sodium, and serum miR-30d level associated with mortality. ROC curve analysis showed that hemoglobin, heart rate and serum sodium displayed poor prognostic value for AHF (AUCs not higher than 0.700) compared to miR-30d level (AUC = 0.806). Kaplan-Meier survival analysis confirmed that patients with higher serum miR-30d levels had significantly lower mortality (P=0.001). CONCLUSION: In conclusion, this study shows evidence for the predictive value of circulating miR-30d as 1-year all-cause mortality in AHF patients. Large multicentre studies are further needed to validate our findings and accelerate the transition to clinical utilization.

Interaction of Droplets Separated by an Elastic Film.

The Laplace pressure of a droplet placed on one side of an elastic thin film can cause significant deformation in the form of a bulge on its opposite side. Here, we show that this deformation can be detected by other droplets suspended on the opposite side of the film, leading to interaction between droplets separated by the solid (but deformable) film. The interaction is repulsive when the drops have a large overlap and attractive when they have a small overlap. Thus, if two identical droplets are placed right on top of each other (one on either side of the thin film), they tend to repel each other, eventually reaching an equilibrium configuration where there is a small overlap. This observation can be explained by analyzing the energy landscape of the droplets interacting via an elastically deformed film. We further demonstrate this idea by designing a pattern comprising a big central drop with satellite droplets. This phenomenon can lead to techniques for directed motion of droplets confined to one side of a thin elastic membrane by manipulations on the other side.