Search

Transient receptor potential canonical 3 (TRPC3) is a nonselective cation channel, and its dysfunction is the basis of many clinical diseases. However, little is known about its possible role in the bladder. The purpose of this study was to explore the function and mechanism of TRPC3 in partial bladder outlet obstruction (PBOO)-induced detrusor overactivity (DO). We studied 31 adult female rats with DO induced by PBOO (the DO group) and 40 sham-operated rats (the control group). Here we report that the expression of TRPC3 in the bladder of DO rats increased significantly. Furthermore, PYR10, which can selectively inhibit the TRPC3 channel, significantly reduced bladder excitability in DO and control rats, but the decrease of the bladder excitability of DO rats was more obvious. PYR10 significantly reduced the intracellular calcium concentration in smooth muscle cells (SMCs) in DO and control rats. Finally, Na+/Ca2+ exchanger 1 (NCX1) colocalizes with TRPC3 and affects its expression and function. Collectively, these results indicate that TRPC3 plays an important role in the pathogenesis of DO through a synergistic effect with NCX1. TRPC3 and NCX1 may be new therapeutic targets for DO. The expression and functional levels of TRPC3, a nonselective cation channel, and NCX1, a Na+/Ca2+ exchanger, are increased in the bladders of rats with partial bladder outlet obstruction-induced detrusor overactivity. The synergistic effects of TRPC3 and NCX1 significantly increase the concentration of Ca2+i in smooth muscle cells, which induces bladder hyperactivity in this animal model of overactive bladder. TRPC3 and NCX1 may be new therapeutic targets for detrusor overactivity.

Qudong Lu,1 Yang Yang,1 Hengshuai Zhang,1 Cheng Chen,2 Jiang Zhao,1 Zhenxing Yang,1 Yi Fan,1 Longkun Li,1 Huan Feng,1 Jingzhen Zhu,1 Shanhong Yi1 1Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 2Department of Burns, First Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Jingzhen Zhu; Shanhong YiDepartment of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of ChinaTel +86 23-68774453Email zhujz1114@163.com; 2644057844@qq.comPurpose: Hyperalgesia and bladder overactivity are two main symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Cannabinoid receptors participate in the modulation of pain and bladder function. GPR18, a member of the cannabinoid receptor family, also participates in the regulation of pain and bladder function, but its underlying mechanisms are unknown. In this work, we sought to study the role of GPR18 in IC/BPS.Methods: A rat model of IC/BPS was established with cyclophosphamide (CYP). Paw withdrawal threshold (PWT) measurement and cystometry were used to evaluate pain and bladder function, respectively. RT-PCR, Western blotting and immunofluorescence were used to assess the expression and distribution of GPR18. The role of GPR18 in pain and bladder function was studied by intrathecal injection of resolvin D2 (RvD2, a GPR18 agonist) and O-1918 (a GPR18 antagonist). Calcium imaging was used to study the relationship between GPR18 and TRPV1.Results: A rat model of IC/BPS, which exhibited a decreased PWT and micturition interval, was successfully established with CYP. The mRNA and protein expression of GPR18 was reduced in the bladder and dorsal root ganglia (DRG) in rats with CYP-induced cystitis. Intrathecal injection of RvD2 increased the PWT and micturition interval. However, O-1918 blocked the therapeutic effect of RvD2. GPR18 was present in bladder afferent nerves and colocalized with TRPV1 in DRG, and RvD2 decreased capsaicin-induced calcium influx in DRG.Conclusion: Activation of GPR18 by RvD2 alleviated hyperalgesia and improved bladder function, possibly by inhibiting TRPV1 in rats with CYP-induced cystitis.Keywords: interstitial cystitis/bladder pain syndrome, GPR18, TRPV1, hyperalgesia, bladder overactivity, resolvin D2, O-1918

Evidence suggests constipation precedes motor dysfunction and is the most common gastrointestinal symptom in Parkinson's disease (PD). 5-HT4 receptor (5-HT4R) agonist prucalopride has been approved to treat chronic constipation. Here, we reported intraperitoneal injection of prucalopride for 7 days increased dopamine and decreased dopamine turnover. Prucalopride administration improved motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mouse models. Prucalopride treatment also ameliorated intestinal barrier impairment and increased IL-6 release in PD model mice. However, prucalopride treatment exerted no impact on JAK2/STAT3 pathway, suggesting that prucalopride may stimulate IL-6 via JAK2/STAT3-independent pathway. In conclusion, prucalopride exerted beneficial effects in MPTP-induced Parkinson's disease mice by attenuating the loss of dopamine, improving motor dysfunction and intestinal barrier.

The effect of binding strength of counterions with the polyelectrolyte chain to the swelling of polyelectrolyte brushes is studied, by investigating the swelling of both the polycation and polyanion in response to the variation of the salt concentration under the change of counterion's identity. Two polyelectrolyte brushes grafted on solid substrates are adopted: the cationic poly [2-(methacryloyloxy)ethyltrimethyl ammonium] (PMETA-X, X = F, Cl, Br, and I) and the anionic polystyrene sulfonate (M-PSS, M = Li, Na, K, and Cs). The swelling change with the salt concentration is investigated by ellipsometry, quartz crystal microbalance with dissipation, and dielectric spectroscopy. It is discovered that although the thickness of PMETA-X brushes is larger than that of M-PSS brushes of similar grafting density, the former has much less solvent incorporated than the latter. Such a difference is attributed to the weaker interaction between the PMETA+ chain and its halide counterions than that between the PSS- chain and its alkali counterions, discovered by dielectric spectroscopy. This makes the original charges on the PMETA-X chain less neutralized and therefore have a higher charge density, compared with the M-PSS chain. The results demonstrate that the stronger binding of the counterions to the polyelectrolytes makes the main chains less charged, resulting in the weaker inter-chain electrostatic repulsion and less swelling of the brushes. Investigations into the effect of ion identity show the following order of binding strength: for the cationic PMETA+ chain, F- < Cl- < Br- < I- and for the anionic PSS- chain, Li+ < Na+ < K+ < Cs+.

The dynamics of adsorption and desorption of counterions on a polyelectrolyte chain in aqueous solution is studied at a single molecular level. The investigation is through the process of fluoresce...

Surface coating can greatly enhance the lifetime of cold extrusion die. It is a significant issue to evaluate the performance of coatings and even predict the lifetime of cold extrusion die. In this work, the titanium-based nitride coatings including TiN, TiAlN, and TiAlCrN were, respectively, deposited on the surface of high-speed steel substrate W6Mo5Cr4V2 (M2) by the physical vapor deposition technology. The hardness test, scratch test, Rockwell adhesion test, and pin-on-disc (POD) wear test were carried out aiming to investigate the performances of the three coatings including hardness, adhesion strength, and wear resistance. The results show that the TiAlCrN coating exhibits the highest hardness of 3,033 HV in comparison with TiN coating (1,222 HV) and TiAlN coating (1,916 HV), while it possesses poor adhesion strength and inferior wear resistance. Furthermore, the TiAlN coating presents the highest resistance to wear and spalling from the substrate. In addition, the Archard wear model of the coatings was solved and applied in the finite element model of cold extrusion to calculate the wear depth and lifetime of the cold extrusion dies. The results suggest that TiAlN coating is the optimal option for cold extrusion die as compared with TiAlCrN and TiN coatings. TiAlN coating can prolong the lifetime of the substrate die up to 260%.

Extracellular plaque deposits of β-amyloid peptide (Aβ) are one of the main pathological features of Alzheimer's disease (AD). The aggregation of Aβ42 species, especially Aβ42 oligomers, is still an active research field in AD pathogenesis. Secretory clusterin protein (sCLU), an extracellular chaperone, plays an important role in AD pathogenesis. Although sCLU interacts directly with Aβ42 in vitro and in vivo, the mechanism is not clear. In this paper, His-tagged sCLU (sCLU-His) was cloned, expressed and purified, and we applied florescence resonance energy transfer-fluorescence correlation spectroscopy (FRET-FCS) to investigate the direct interaction of sCLU-His and Aβ42 at the single-molecule fluorescence level in vitro. Here, we chose four different fluorescently labeled Aβ42 oligomers to form two different groups of aggregation models, easy or difficult to aggregate. The results showed that sCLU-His could form complexes with both aggregation models, and sCLU-His inhibited the aggregation of Aβ42/RB ~ Aβ42/Atto647 (easy to aggregate model). The complexes were produced as the Aβ42/Label adhered to the sCLU-His, which is similar to a "strawberry model," as strawberry seeds are dotted on the outer surface of strawberries. This work provided additional insight into the interaction mechanism of sCLU and Aβ42 .

Chondroitin sulfate (CS) is a kind of linear polysaccharide that is covalently linked to proteins to form proteoglycans. Chondroitin sulfate proteoglycans (CSPGs) consist of a core protein, with one or more CS chains covalently attached. CSPGs are precisely regulated and they exert a variety of physiological functions by binding to adhesion molecules and growth factors. Widely distributed in the nervous system in human body, CSPGs contribute to the major component of extracellular matrix (ECM), where they play an important role in the development and maturation of the nervous system, as well as in the pathophysiological response to damage to the central nervous system (CNS). While there are more than 30 types of CSPGs, this review covers the roles of the most important ones, including versican, aggrecan, neurocan and NG2 in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The updated reports of the treatment of neurodegenerative diseases are involving CSPGs.

Reportedly, long non-coding RNA (lncRNA) are crucial modulators in neurodegenerative diseases. Herein, we investigated the role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in Parkinson’s disease (PD). In-vitro PD model was established based on SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). NEAT1, microRNA (miR) −124-3p and phosphodiesterase 4B (PDE4B) expression levels were examined by qRT-PCR. CCK-8 assay and LDH release assay were adopted to delve into the cell viability and cytotoxicity, respectively. Besides, western blot was utilized to determine mTOR, p-mTOR and PDE4B expression levels. ELISA was executed to detect the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Dual-luciferase reporter assay and RIP assay were used to probe the relationship between miR-124-3p and NEAT1 or PDE4B. We demonstrated that, in SH-SY5Y cells treated with MPP+, NEAT1 and PDE4B expression levels were raised, while miR-124-3p expression was repressed; NEAT1 depletion or miR-124-3p overexpression increased the cell viability and suppressed cell injury. Besides, miR-124-3p was confirmed as the direct target of NEAT1, and its down-regulation counteracted the impact of NEAT1 depletion on SH-SY5Y cells. PDE4B was as the downstream target of miR-124-3p, and its overexpression weakens the impact of miR-124-3p on SH-SY5Y cells. Additionally, NEAT1 decoyed miR-124-3p to modulate PDE4B expression. Collectively, in MPP+-induced SH-SY5Y cells, NEAT1 depletion increases cell viability, represses cytotoxicity and reduces inflammatory response by regulating miR-124-3p and PDE4B expression levels, suggesting that NEAT1 may be a promising target for treating PD.

Polymer electrolytes are essential for next-generation lithium batteries because of their excellent safety record. However, low ionic conductivity is the main obstacle restricting their commercial application. Composites with nanoparticles are a promising route to overcome this obstacle. In this work, lithium polystyrene sulfonate brushes (LiPSS) is anchored to silicon dioxide nanoparticles with chemical bonding using atom transfer radial polymerization (SI-ATRP). The composite polymer electrolytes are made by mixing vinylene carbonate and nanoparticles via a facile in situ polymerization process. The ionic conductivity of composite polymer electrolytes is improved to 7.2 × 10−4 S/cm at room temperature, which is attributed to the low degree of crystallinity of polymer electrolyte and the fast ion transport on the surfaces of polymer brush layers that act as a conductive network. The composite polymer electrolytes show a wide electrochemical window of approximately 4.5 V vs. Li+/Li and excellent cycling performance retention of approximately 95% after 100 cycles at ambient temperature. The results also prove that surface groups of ceramic nanoparticles are an important way to increase the electrochemical properties of composite polymer electrolytes.

Human urine-derived stem cells (hUSCs) show multipotential differentiation ability and can differentiate into mesodermal cell lineages. Interstitial cells of Cajal-like cells (ICC-LCs) are crucial for the pace-making function of spontaneous contraction in the bladder. However, the mechanisms by which hUSCs generate ICC-LCs have not been elucidated. In this study, we developed a strategy for directional differentiation of hUSCs into ICC-LCs. hUSCs were transfected with lentiviral vectors encoding c-Kit, stem cell factor (SCF), hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4), and 5-azacytidine induced 2 (AZI2) genes, and the cells were cultured for an additional 7 days in specific medium. The expression of the surface marker c-Kit on ICC-LCs was determined at 7 days after transfection. hUSCs were successfully expanded and transfected with the four lentiviral vectors. hUSCs transfected with lentiviral-c-Kit, lentiviral-HCN4, and lentiviral-AZI2 showed higher expression of c-Kit 7 days after transfection, but only the lentiviral-HCN4-transfected cells showed morphological alterations in ICC-LCs. These cells also displayed visible HCN current amplitude and density. This approach may provide a new strategy for the treatment of underactive bladder.

Lateral diffusion of polymer molecules at the interfaces between immiscible oil and water is investigated at the single molecular level. The interfaces between water and alkanes are chosen as the model systems and polyethylene oxide (PEO) is the model polymer. Fluorescence correlation spectroscopy is used to measure the interfacial diffusion of fluorescence-labeled PEO with its molecular weight ranging over more than an order of magnitude. It is discovered that the interfacial diffusion coefficient scales with the molecular weight by the exponent of -0.5. Detailed analysis shows that the PEO chain takes an ideal two-dimensional random coil conformation at these fluidic interfaces and the bigger contribution from water's hydrodynamic friction is discovered.

An original flexible enzyme-free glucose amperometric biosensor based on Cu nanoparticles anchored on laser-induced graphene (Cu NPs-LIG) composite is successfully developed by a simple substrate-assisted electroless deposition (SAED) technique. The as-prepared Cu NPs-LIG sensor demonstrates an excellent glucose sensitivity of 495 μA mM−1 cm−2, ultrafast response time less than 0.5 s and the prominently low detection limit of 0.39 μM. Besides, the sensor shows extraordinary reproducibility, stability and selectivity in glucose sensing. Finally, a possible mechanism of the Cu NPs-LIG sensor for glucose sensing is proposed. Due to the simplicity preparation and performance reliability, the novel flexible Cu NPs-LIG sensor is an attractive candidate for next generation wearable and implantable non-enzymatic glucose diagnostic devices.

The thiazole unit can exhibit both electron-deficient and electron-rich features, which provides more possibilities for shaping the photophysical and electroluminescence (EL) properties of the Ir(III) complex emitters. Herein, a series of cyclometalated Ir(III) complexes were synthesized from the 2-phenylthiazole-type ligands bearing fluorinated benzenesulfonyl moieties. Their thermal stabilities, photophysical and electrochemical properties and EL performances were fully studied. They can emit intense orange phosphorescence with peaks ranging from 577 to 590 nm, and the phosphorescence quantum yield (Φp) can be up to 0.89. Interestingly, when the number of fluorine atoms on the phenyl ring of the benzenesulfonyl moiety increases, their absorption and emission maxima both show red-shift effects, which were interpreted by the related theoretical calculation results. Besides, their LUMO levels follow a decreasing trend as the fluorine atoms increase, leading to good electron injection/transporting (EI/ET) properties. Finally, their EL performances were characterized by their solution processed OLEDs, which achieve the best EL efficiencies with a maximal current efficiency (ηL) of 27.5 cd A−1, a maximal power efficiency (ηp) of 17.3 lm W−1 and a maximal external quantum efficiency (ηext) of 12.3%, these results can outcompete the EL efficiencies of the reported solution processed OLEDs built by the thiazole-based Ir(III) complexes. All the concerned results should offer inspirations for Ir(III) complex functionalizations and reveal the great potential of 2-phenylthiazole ligands with fluoro-benzenesulfonyl moieties in developing high performance emitters.

The dense medium modulates the molecular structure and bioreactions in living cells via both noncovalent interactions and macromolecular crowding and confinement effects. However, the interplay between the volume effect and noncovalent interactions remains unclear. In this work, we studied in detail on how electrostatic interactions influence the crowding and confinement effect by comparing the formation and elongation of DNA nanotubes in branched dextran and charged hyaluronic acid (HA) solution of a broad concentration range, with and without 150 mM NaCl. In all the studied cases, three concentration regimes are identified: a crowding regime, a double-effect regime, and a confinement regime. In the crowding and double-effect regimes, the addition of 150 mM NaCl enhances the assembly of DNA tiles by screening the electrostatic repulsion, and a higher dextran solution is required to confine the DNA assembly into nanotubes. However, the screening effect on the HA network is more than that on the DNA assembly, so DNA tubes formed in HA solution at much lower concentrations. In the confinement regime, the electrostatic interaction exhibits a negligible effect on the DNA assembly in both dextran medium and HA medium. Our study demonstrates that the volume effect and noncovalent interactions are system specific and concentration dependent. Their interplay governs the living processes in crowded cells.

Background Controlling the blood glucose level is an effective method to reduce type 2 diabetes and prevent diabetes-related complications. Ursolic acid is a plant extract that can reduce postprandial hyperglycemia effectively. This study aimed to explore the inhibitory effect and interaction mechanism of ursolic acid against α-amylase and α-glucosidase. Results In this study, the effect of ursolic acid on glycosidase was studied in vitro, in vivo, and in silico. The half-maximal inhibitory concentration (IC50 ) of ursolic acid on α-amylase and α-glucosidase was 0.482 ± 0.12 mg mL-1 and 0.213 ± 0.042 mg mL-1 , respectively. The results of enzymatic kinetics showed that ursolic acid inhibited α-amylase and α-glucosidase activity in a non-competitive manner. The fluorescence spectrum showed that the combination of ursolic acid and glycosidase caused the intrinsic fluorescence quenching of glycosidase. The observation of starch granules revealed that the activity of α-amylase was inhibited and the hydrolysis of starch granules was prevented in the presence of ursolic acid. Molecular docking results showed that ursolic acid bound to the inactive site of α-amylase and α-glucosidase through the formation of ursolic acid-glucosidase complex. Ursolic acid interacted with α-amylase and α-glucosidase mainly through hydrogen bonding. The postprandial hypoglycemic effect of ursolic acid in C57BL/6J mice showed that the high concentration of ursolic acid could quickly reduce postprandial blood glucose level. Conclusion Ursolic acid can be considered as a natural ingredient in functional foods to control postprandial blood glucose levels and prevent diabetes by delaying the digestion of starch in foods. © 2019 Society of Chemical Industry.

The concept that catalytic enzymes can act as molecular machines transducing chemical activity into motion has conceptual and experimental support, but much of the claimed support comes from experimental conditions where the substrate concentration is higher than biologically relevant and accordingly exceeds kM, the Michaelis-Menten constant. Moreover, many of the enzymes studied experimentally to date are oligomeric. Urease, a hexamer of subunits, has been considered to be the gold standard demonstrating enhanced diffusion. Here we show that urease and certain other oligomeric enzymes of high catalytic activity above kM dissociate into their smaller subunit fragments that diffuse more rapidly, thus providing a simple physical mechanism of enhanced diffusion in this regime of concentrations. Mindful that this conclusion may be controversial, our findings are sup-ported by four independent analytical techniques, static light scattering, dynamic light scattering (DLS), size-exclusion chroma-tography (SEC), and fluorescence correlation spectroscopy (FCS). Data for urease are presented in the main text and the con-clusion is validated for hexokinase and acetylcholinesterase with data presented in supplementary information. For substrate concentration regimes below kM at which these enzymes do not dissociate, our findings from both FCS and DLS validate that enzymatic catalysis does lead to the enhanced diffusion phenomenon. INTRODUCT

Inhibition the activity of glycosidase is an effective method for the treatment and prevention of diabetes. In this study, enzymatic kinetics, fluorescence spectrum experiment, starch granule digestion, molecular docking studies and animal's studies were used to investigate the interaction mechanism of carnosic acid against two glycosidase (α-amylase and α-glucosidase). Enzymatic kinetics showed that carnosic acid inhibited α-amylase activity in a competitive manner and α-glucosidase activity in a non-competitive manner. The half inhibitory concentrations (IC50) of carnosic acid to α-amylase and α- glucosidase were (1.12 ± 0.31) and (0.08 ± 0.17), respectively. The fluorescence quenching experiments showed that the intrinsic fluorescence of α-amylase or α-glucosidase was quenched by forming a complex with carnosic acid, and there was only one binding site between carnosic acid and glycosidase. The starch granules were no longer hydrolyzed by α-amylase after the addition of carnosic acid, which indicated that carnosic acid inhibited the activity of α-amylase. Molecular docking study showed that carnosic acid binds to the amino acid residues of glycosidase through hydrogen bond and van der Waals force, which leads to the change of the molecular conformation of glycosidase and thus reduces the activity of glycosidase. The experiment on mice showed that carnosic acid could effectively reduce postprandial blood glucose in mice.

Melatonin (MT) increases oocyte maturation by reducing reactive oxygen species level and enhancing oocyte antioxidant capacity. However, the mechanisms via which MT works are still poorly understood. In the present study, the effects of MT on the maturation rate and development ability of bovine oocytes were investigated. Then, the transcriptome of oocytes treated by MT was sequenced. Finally, the expression of gap junction protein alpha 4 (GJA4) protein and cAMP level were detected in bovine oocytes, and isoprenaline (enhancer of gap junctional intercellular communication (GJIC)) and heptanol (inhibitor of GJIC) were used to investigate the effect of MT on GJIC activity in bovine oocytes. Our results showed that MT significantly improved the maturation, developmental ability and mRNA expression of GJA4 of bovine oocytes. Meanwhile, MT significantly increased GJA4 protein level and cAMP level in bovine oocytes. In contrast to heptanol, both isoproterenol and MT significantly increased GJIC activity, nuclear maturation and the development ability of bovine oocytes. However, MT significantly restored the nuclear maturation and developmental ability of oocytes treated by heptanol. In conclusion, our results showed that MT improves the maturation and developmental ability of bovine oocytes by enhancing GJIC activity via up-regulating GJA4 protein expression in IVM progress.

Aryl Hydrocarbon Receptor (AHR) is a ligand-activated transcription factor expressed in various brain regions. However, little is known about the role of AHR during neuroinflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Here, mice were sacrificed at day 4, day 6 and day 8 respectively after MPTP or saline treatment. Behavioral tests, Tyrosine hydroxylase (TH) expression, glial reaction, and AHR expression and activation were then assayed. As expected, mice treated with MPTP showed apparent behavioral dysfunctions and significantly reduced TH content. Immunofluorescence (IF) labeling showed an increased trend of phosphorylated AHR activation in the Substantia Nigra pars compacta (SNpc) and striatum after MPTP treatment. Western blot analysis demonstrated that MPTP treatment induced a significantly increased level of AHR at each time point tested, with the highest level observed at day 6 in the striatum. To determine exactly the AHR activation in relation to changes of glial cell reactivity, double IF labeling was performed for either IBA1 (microglia marker) and p-AHR, or GFAP (astrocyte marker) and p-AHR. The results demonstrated that MPTP treatment not only increases the number of p-AHR-positive IBA1-expressing cells in the striatum and the SNpc, but also increases that of p-AHR-positive GFAP-expressing cells in the striatum. Intriguingly, the increase of the number of cells co-expressing both p-AHR and IBA1 was highest at day 4 in response to MPTP in the striatum and at day 8 in the SNpc. The number of cells co-expressing both p-AHR and GFAP was increased at days 4, 6 and 8 in the striatum. In conclusion, our study suggests that AHR activation may facilitate PD diagnosis and serve as a target for the treatment of PD.

Parkinson's disease (PD), the second most prevalent age-related neurodegenerative disease, occurs as a result of the loss of dopaminergic neurons in the substantia nigra. Long non-coding RNA-p21 (lnc-p21) has been demonstrated to be upregulated in PD. However, its role in PD is unknown. Here, the results showed that lnc-p21 was highly expressed in human neuroblastoma SH-SY5Y cells treated with MPP+. Knockdown of lnc-p21 attenuated the cytotoxicity and cell apoptosis induced by MPP+ as shown by enhanced cell viability, decreased LDH release and cell apoptosis rate, accompanying with reduction of caspase-3 activity and Bax expression, and enhancement of Bcl-2 expression. Furthermore, knockdown of lnc-p21 mitigated MPP+-induced oxidative stress and neuroinflammation, as evidenced by the decrease in ROS generation, increase in SOD activity and decline in TNF-α, IL-1β and IL-6 levels. Conversely, overexpression of lnc-p21 resulted in the opposite effect. miR-625 was identified as a target of lnc-p21. lnc-p21 overturned the inhibitory effect of miR-625 on MPP+-induced neuronal injury in SH-SY5Y cells. Additionally, lnc-p21 positively regulated TRPM2 expression by targeting miR-625, and knockdown of TRPM2 inhibited MPP+-induced neuronal injury. Overall, our study identified a new lnc-p21-miR-625-TRPM2 regulatory network that lnc-p21 regulated MPP + -induced neuronal injury by sponging miR-625 and upregulating TRPM2 in SH-SY5Y cells, which provide a better understanding for the pathogenesis of PD.

Nitrilase-mediated biocatalysis reactions have been continuously arousing wide interests by scholars and entrepreneurs in organic synthesis over the past six decades. Since regioselective nitrilases could hydrolyze only one cyano group of dinitriles into corresponding cyanocarboxylic acids, which are virtually impossible by chemical hydrolysis and of interest for a variety of applications, it becomes particularly appealing to synthetic chemists. The aim of the current review is to summarize the recent advancements on regioselective nitrilases concerning their fundamental researches and applications in synthesis of a series of high-value fine chemicals and pharmaceuticals. Carbon chain lengths and substituent group positions of substrates are found to be two crucial factors in affecting regioselectivity of nitrilase. Practical applications of regioselective nitrilases in synthesis of 1,5-dimethyl-2-piperidone (1,5-DMPD), atorvastatin, gabapentin, (R)-baclofen, and (S)-pregabalin were systematically reviewed. Future perspectives clearly elucidating the mechanism of regioselectivity and further molecular modifications of regioselective nitrilases integrating within silico technology for industrial applications were discussed.

Among numerous research studies focusing on macromolecular crowding and confinement, few are concerned with the medium at a broad range of concentrations, let alone the interplay between the crowdi...

Plants glycerol-3-phosphate dehydrogenase (GPDH) catalyzes the formation of glycerol-3-phosphate, and plays an essential role in glycerolipid metabolism and stress responses. In the present study, the knock-out mutants of cytosolic GPDH (AtGPDHc2) and wild-type Arabidopsis plants were treated with 0, 50, 100, and 150 mmol L−1 NaCl to reveal the effects of AtGPDHc2 deficiency on salinity stress responses. The fluctuation in redox status, reactive oxygen species (ROS) and antioxidant enzymes as well as the transcripts of genes involved in the relevant processes were measured. In the presence of 100 and 150 mmol L−1 NaCl treatments, AtGPDHc2-deficient plants exhibited a pronounced reduction in germination rate, fresh weight, root length, and overall biomass. Furthermore, loss of AtGPDHc2 resulted in a significant perturbation in cellular redox state (NADH/NAD+ and AsA/DHA) and consequent elevation of ROS and thiobarbituric acid-reactive substances (TBARS) content. The elevated ROS level triggered substantial increases in ROS-scavenging enzymes activities, and the up-regulated transcripts of the genes (CSD1, sAPX and PER33) encoding the antioxidant enzymes were also observed. In addition, the transcript levels of COX15, AOX1A and GLDH in gpdhc2 mutants decreased in comparison to wild-type plants, which demonstrated that the deficiency of AtGPDHc2 might also has impact on mitochondrial respiration under salt stress. Together, this work provides some new evidences on illustrating the roles of AtGPDHc2 playing in response to salinity stress by regulating cellular redox homeostasis, ROS metabolism and mitochondrial respiration.

Supramolecular polymerization is influenced by many factors, especially the stiffness of the polymers, which is directly related to cyclization of the polymers. We have proposed a supramolecular “ring opening” polymerization system with DNA molecules to study the ring-chain equilibrium of supramolecular polymerization. The molecular weight of the supramolecular polymers was characterized by Asymmetric Flow Field Flow Fractionation, and the diffusion coefficient of the supramolecular polymers was characterized by Fluorescent Correlation Spectra. Tuning the ratio of the “ring opening” strand, the length of the DNA monomers and temperature could change the ring-chain equilibrium, thus influence the molecular weight and diffusion coefficient. This strategy has offered us a useful platform to dig into the kinetic mechanism of supramolecular polymerization.

In this study, we modified the well-known photothermal polydopamine nanoparticles with the poly[(2-methacryloyloxy)ethyl phosphorylcholine-b-(2-dimethylamino)ethyl methacrylate] (PMPC-b-PDMAEMA) diblock copolymers, containing both biocompatible cell membrane phosphorylcholine zwitterions segments and pH-responsive dimethylaminoethyl units on the polymer chains, to achieve both the photothermal property and pH-responsive release behavior. The results showed that the obtained nanoparticles had a narrow size distribution with the diameter about 220 nm. Besides, the modified polydopamine nanoparticles showed enhanced colloidal stability, pH-sensitive drug release behavior, excellent biocompatibility and remarkable near-infrared photothermal property. Thus, it is highly anticipated that PMPC-b-PDMAEMA modified polydopamine nanoparticles can serve as a powerful drug delivery system for combined pH-sensitive drug release and near-infrared photothermal therapeutic.

A self-healing hydrogel was synthesized via the multi-component reaction of azobenzene-methacrylamide, β-CD and 3-methacrylamido phenylboronic acid. The orthogonal method was applied to analyze the influence of host–guest inclusion complexation, cross-linker and phenylboronic acid monomers content on mechanical properties and healing efficiency of the hydrogel. The results indicated that hydrogel showed autonomic self-healing behavior. The hydrogel demonstrated light-switchable self-healing ability and pH-sensitive swelling ratio. It was found that hydrogel showed high elongation, excellent resilience and low elastic hysteresis. The design of the combined host–guest interactions and boronate esters on the hydrogel showed advantage for improving the mechanical, self-healing and recovery properties simultaneously.

The hydroformylation of long chain alkenes catalyzed by a water soluble Rh/TPPTS complex (TPPTS: sodium salt of sulfonated triphenylphosphine) in methanol was investigated. The mixture of rhodium precursor HRh(CO)(TPPTS)3, ligand TPPTS, methanol and a long chain alkene becomes a single phase under reaction conditions, which make the hydroformylation reaction proceed homogeneously. Both the conversion of long chain alkene and the selectivity to aldehydes (including the aldehydes forming methylacetals) could reach up to 97.8% and 97.6%, respectively, with 3323 h−1 of TOF (TOF: turnover frequency is defined as the moles of converted alkene per mole of Rh per hour). After the solvent methanol was removed under the reaction temperature, two phases were formed automatically. The colourless product phase could be efficiently separated from the precipitate rhodium catalyst phase by centrifuge. The catalyst was reused for five times without obvious loss of rhodium and the catalytic activity. The rhodium leaching in product mixture was less than 0.03% of the total rhodium.

Liquid chromatography coupled with mass spectrometry has been used as metabolomics profiling tool to discover and identify the metabolites in metabolic diseases. Osteoporosis (OP) syndrome is a chronic metabolic disease characterized by bone mass reduction and changes in bone microstructure. Psoralea corylifolia Linn. seeds (PCS) have a therapeutic effect on osteoporosis, but their action mechanism and therapeutic target are still unclear. This study aims to explore the metabolic changes of the urine profile in glucocorticoid-induced OP model rats and the therapeutic effect of PCS. High-throughput metabolomics based on the liquid chromatography coupled with mass spectrometry quadrupole time-of-flight mass spectrometry and multivariate data analysis were used to analyze the urine metabolites. The results showed that has an obvious separation between model and control groups. OPLS-DA was used to further analyze and discover substances that contributed to the separation. 42 potential biomarkers and 12 related metabolic pathways were identified in combination with network databases. After the intervention of PCS, 24 biomarkers were significantly regulated, mainly with glycone, serine and threonine metabolism, glutathione metabolism and purine metabolism and other metabolic pathways are related and discovered. This study has proved that PCS has therapeutic effect against OP by regulating that metabolic pathways disturbed in the OP. It provided a basis for the research and future development of new drugs for OP treatment.

The widespread adoption of genetically modified, glyphosate-tolerant corn and soybean varieties in US crop production has led to a dramatic increase in glyphosate usage. Though present at or below regulatory limits currently set for human foodstuffs, the concentration of glyphosate in companion animal feed is currently unknown. In the present study, 18 commercial companion animal feeds from eight manufacturers were analyzed for glyphosate residues using ELISA. Every product contained detectable glyphosate residues in the range of 7.83 × 101–2.14 × 103 μg kg−1 dry weight, with the average and medians being 3.57 × 102 and 1.98 × 102 μg kg−1 respectively. Three products were tested for within-bag variation and six were tested for lot to lot variation. Little within-bag variation was found, but the concentration of glyphosate varied by lot in half of the products tested. Glyphosate concentration was significantly correlated with crude fiber content, but not crude fat or crude protein. Average daily intakes by animals consuming feeds containing the median glyphosate concentration are estimated to result in exposures that are 0.68–2.5% of the Allowable Daily Intake (ADI) for humans in the US and EU, which are 1750 and 500 μg kg−1 respectively. Consumption of the most contaminated feed, however, would result in exposure to 7.3% and 25% of the above ADIs, though the relevance of such an exposure to companion animals is currently unknown. Companion animal feeds contained 7.83 × 101–2.14 × 103 μg kg−1 glyphosate which is likely to result in pet exposure that is 4–12 times higher than that of humans on a per Kg basis.

The thermal and mechanical properties of the chemically imidized polyimide (CIPI) films and thermally imidized polyimide (TIPI) films were investigated systematically. Experimental results indicated that the CIPI films show dramatically enhanced tensile strength and modulus with obviously reduced coefficient of thermal expansion (CTE) in comparison with TIPI films. These enhancements results from the high in-plane orientation and close packing of the CIPI backbones. Compared with thermal imidization which starts at about 140 °C, the chemical imidization activated by acetic anhydride and isoquinoline initiates the cyclization even at room temperature. The resulting imide rings restrict the mobility of polymer chains and lead to the in-plane orientation with solvent evaporation. Additionally, fewer small molecules remain in the films after treated at 120 °C by chemical imidization than by thermal imidization. The polymer chain plasticization caused by the evaporation of small molecules at high temperature is obviously restricted. Moreover, the partially imidized polymer inhibits the decomposition of mainchains that occurs at subsequent high temperature process, being beneficial to the formation of high molecular weight PI films. Hence, chemical imidization pathway shows apparent advantage to produce PI films with great combined properties, including high modulus, strength and toughness, as well as high thermal dimension stability etc.

Mammalian gametes and embryos are particularly vulnerable to oxidative stress-induced damage, which is mainly caused by reactive oxygen species (ROS) originating from normal metabolism and/or the external environment. Several researchers have implicated the role of oxidative stress in the activation of apoptosis, causing peroxidative damage to sperms/oocytes and inducing embryo fragmentation, arrest, or demise. Melatonin is a tryptophan derivative that is known for its powerful free radical-scavenging activity and broad-spectrum antioxidant property. Numerous studies have shown that melatonin and its metabolic derivatives can sequentially detoxify ROS in an antioxidant cascade, and modulate various antioxidant enzymes via its receptors to prevent radical-mediated damage. The identification of melatonin receptors in cumulus/granulosa cells, oocytes, and epididymal tissues implies that melatonin has protective actions on gametes and embryos. Enriching the semen extender or culture medium with melatonin significantly benefits sperm characteristics, improves oocyte maturation potential and quality, and enhances the developmental competence of preimplantation embryos. Certainly, further comparative studies are needed to show the unique antioxidant role and the advantage of melatonin in this field. This review summarizes the harmful effects of ROS and the beneficial role of melatonin against oxidative damage of gametes and embryos.

Xiaobin Luo,1 Bin Zhao,2 Baoxia Chen,2 Hongyu Chen,1 Tao Han,1 Najeeb Bassam Najeeb Bsoul,1 Hede Yan1 1Department of Orthopedics (Division of Hand Surgery), The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Key Laboratory of Orthopedics of Zhejiang Province, The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Department of Post Anaesthesia Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People’s Republic of ChinaCorrespondence: Hede YanDepartment of Orthopaedics (Division of Hand Surgery), The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, West Xueyuan Road 109#, Wenzhou, 325027, Zhejiang Province, People’s Republic of ChinaEmail yanhede@hotmail.comBackground: The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Trans-cinnamaldehyde has antibacterial, anticancer, and antioxidant properties. In this study, we aimed to investigate the effect of trans-cinnamaldehyde on skin flap survival and its possible mechanism regarding nitric oxide.Materials and Methods: One hundred forty male Sprague-Dawley rats were randomly divided into seven groups (n = 20 each group). After the dorsal flap was raised, different doses of trans-cinnamaldehyde (10, 20, and 30 mg/kg) were immediately given by oral gavage in the three different groups. To assess the possible involvement of the nitric oxide system, NG-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used in this study. All flap samples were incised on postoperative day 7.Results: Our results showed that flap survival was increased significantly in the 20 mg/kg (P < 0.001) trans-cinnamaldehyde (TC) group compared to the control group or 30 mg/kg TC group. This protective function was restrained by coadministration of L-NAME with 20 mg/kg TC. The results of histopathology, laser Doppler, arteriography mediated with oxide–gelatine, and fluorescent staining all showed a significant increase in capillary count, collagen deposition, angiogenesis, and flap perfusion. Immunohistochemistry results revealed a significant increase in the expression of CD34, eNOS, and VEGF.Conclusion: Trans-cinnamaldehyde increased flap survival through the nitric oxide synthase pathway and contributed to angiogenesis. A concentration of 20 mg/kg trans-cinnamaldehyde was recommended in this study.Keywords: random pattern flap, flap necrosis, trans-cinnamaldehyde, angiogenesis, flap perfusion

This study investigated the influence of the exogenous application of vitamin B2 (VB2), B12 (VB12), biotin (VH), and nicotinic acid (VPP) on oxygen production in maize (Zea mays L.) seedlings at 5 °C for day 1, 3, 5 and 7. The seeds were soaked in VB2, VB12, VH, and VPP solutions for 24 h at the concentration of 100 mg/L, and control was soaked in distilled water. A total of 50 seeds were used for each treatment in germination boxes was repeated three times. The germination box was placed in a hypothermic incubator for 1, 3, 5, and 7 days in the dark at 5 °C, then moved to a plant growth room and kept for seven days. Compared with the VH and VPP treatments, the VB2 and VB12 treatments had higher thiobarbituric acid reactive substances, proline, and soluble sugars. The VB2 and VB12 treatments also increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) than other treatments. The VB2 and VB12 treatments reduced the contents of hydrogen peroxide (H2O2–), superoxide anion (O2–), and the damage of reactive oxygen species (ROS) to cells, increased the stability of the cell membrane and the content of cell osmoregulation substances. Moreover, VB2 and VB12 had higher seedling growth, germination rate, and index. Treatments VB2 and VB12 could promote maize seed germination and growth under low-temperature stress. Exogenous vitamins in crop production can be a valuable tool for protecting plants against low-temperature stress.

It is well documented that conventional methods such as dynamic light scattering have encountered difficulties in characterizing charged macromolecules and, therefore, it is desirable that new methods and techniques are introduced. With the ultra-high sensitivity, single molecule fluorescence spectroscopy has successfully lowered the detection limit considerably and enabled measurement under extreme dilution conditions—around the concentration of 10−9M—at which the effect of inter-chain electrostatic repulsion is suppressed. Furthermore, the excellent spatial and temporal resolution as well as the capacity of molecular recognition of these methods help in obtaining rich information of charged macromolecules. This paper summarizes the applications of single molecule fluorescence spectroscopy, especially fluorescence correlation spectroscopy and photon counting histogram, in the studies on charged macromolecules in aqueous solutions and plenty of new information has been revealed on the molecular conformation, counterion distribution, and a few important governing factors. The powerfulness and effectiveness of single molecule fluorescence spectroscopy make it promising in the investigations of charged macromolecules.

Many experiments show that vitrification significantly reduces the fertilization capacity of mammalian oocytes, restricting the application of vitrified oocytes. It has been proven that the JUNO protein plays a vital role in mammalian oocytes fertilization. However, little information is available about the effects of vitrification on the JUNO protein and the procedure to protect it in bovine oocytes. Here, the present study was designed to investigate the effect of vitrification on the JUNO protein level in bovine oocytes. In this study, MII oocytes were treated with cholesterol-loaded methyl-β-cyclodextrin (CLC; 0, 10, 15, 20 mM) for 45 min before vitrification and methyl-β-cyclodextrin (MβCD; 0, 2.25, 4.25, 6.25 mM) for 45 min after thawing (38-39°C). Then, the expression level and function of JUNO protein, cholesterol level in the membrane, the externalization of phosphatidylserine, sperm binding capacity and the developmental ability of vitrified bovine oocytes were examined. Our results showed that vitrification significantly decreased the JUNO protein level, cholesterol level, sperm binding capacity, development ability, and increased the promoter methylation level of the JUNO gene and apoptosis level of bovine oocytes. Furthermore, 15 mM CLC + 4.25 mM MβCD treatment significantly improved the cholesterol level and increased sperm binding and development ability of vitrified bovine oocytes. In conclusion, the combination treatment of cholesterol-loaded methyl-β-cyclodextrin and methyl-β-cyclodextrin significantly improves the fertilization capacity of vitrified bovine oocytes by protecting fertilization protein JUNO.

The helicopter transmission system generally employs oil injection lubrication, while the tooth surface often operates under mixed lubrication. In the case of mixed lubrication, the relationship among the fluid flow, rough contact, and material wear renders it quite difficult to establish a predictive model for wear and lubrication coupling. The present study involved, in consideration of the effect of tooth surface micro-morphology, establishing a coupling analysis model for the wear characteristics of involute gear mixed lubrication. The effects of the mixture of squalane base oil and 15% (by weight) polyisoprene(SQL+PIP), polyalphaolefin oil (PAO6) and mineral SN100 on the distribution of lubrication performance parameters and the wear characteristics were analyzed. The results revealed that the film thickness of SQL+PIP was higher than that of PAO6 and SN100, and the coefficient of friction is lower. In addition, the increase in lubricant viscosity was conducive to reducing the contact area and load ratios of direct rough contact, which was, in turn, beneficial to reducing wear.

In this study, a novel, high surface area iron phosphonate (IP) for highly efficient adsorption of uranyl ion in acidic medium was described. The as-prepared IP was amorphous with its specific surface area and total pore volume as high as 268 m2/g and 1.04 cm3/g, respectively. Particularly, the as-prepared IP with ferrous ions and oxygen, nitrogen-bearing functional groups prove excellent U(VI) adsorption capacity (154.6 mg/g) as compared to that of amorphous FePO4 (67.3 mg/g) and Fe3(PO4)2(H2O)8 (33.8 mg/g). Surprising, the saturation adsorption capacity could achieve up to 353.9 mg/g. Besides, the IP also had a fast adsorption rate for attaining adsorption equilibrium within 20 min, and followed pseudo-second-order kinetic and Freundlich models. Moreover, both the Dubinin-Radushkevich isotherm adsorption model and the value of enthalpy indicated a chemisorption process. Otherwise, the Na+-independent U(VI) adsorption on IP and the adsorption-desorption isotherm studies revealed that inner-layer surface complexation is the control step for U(VI) adsorption process, and the adsorbent featured an irreversible adsorption process. The structure and functional groups of the adsorbent remained unchanged after capture of U(VI). Further, X-ray photoelectron spectra (XPS) analysis demonstrated that the capture mechanism of U(VI) on IP from acidic aqueous solution was due to not only redox reaction, but also ascribed to the coordinated chemical adsorption.

This study aims to investigate the expression and function of absent, small, or homeotic 1-like (ASH1L) methyltransferase in bovine cumulus cells in order to reveal by which mechanisms ASH1L regulates epigenetic modification and apoptosis in cumulus cells. The location of ASH1L and the methylation pattern of H3K36 were detected using immunofluorescence staining in cumulus cells. Quantitative PCR (qPCR) and western blotting were used to screen for effective siRNA targeting the ASH1L gene. Also, the mRNA expression levels of apoptosis-related genes and polycomb inhibitory complex genes were estimated by qPCR after knocking down the ASH1L gene in bovine cumulus cells. Cell proliferation and apoptosis were measured with the CCK-8 method and Annexin V-FITC by flow cytometry, respectively. The results of immunofluorescence analysis showed that ASH1L is located in the nucleus of bovine cumulus cells and is distributed in a dotted pattern. ASH1L knockdown in cumulus cells induced a decrease in the levels of H3K36me1/2/3 methylation (P 0.05). Additionally, ASH1L knockdown inhibited cell proliferation, increased the apoptosis rate, and upregulated the expression of apoptosis genes CASPASE-3, BAX and BAX/BCL-2 ratio (P 0.05). Meanwhile, the mRNA expression levels of EZH2 and SUZ12, two subunits of PRC2 protein, were increased in cells with ASH1L knockdown (P 0.05). Therefore, the expression of ASH1L methyltransferase and its function in on the apoptosis of bovine cumulus cells were first studied. The mechanism by which ASH1L regulates the histone methylation and apoptosis in cumulus cells was also revealed.

The structural parameters of 23 ionic liquids were calculated by the Hartree–Fock ab initio method. The relationship between the antiwear properties of ionic liquids dissolved in dimethyl sulfoxide and the structural parameters of the ionic liquids was studied using multiple linear regression analysis. A quantitative structure tribo-ability relationship model with good fitting and prediction ability was established. The results show that entropy is the most important structural parameter affecting the antiwear performance of ionic liquid-dimethyl sulfoxide systems. The entropy of the ionic liquid is related to the hydrogen bonding in the system, and an orderly arrangement of this hydrogen bonding is beneficial in terms of improving antiwear performance.

In this paper two Nb-silicide-based alloys with nominal compositions (at.%) Nb-12Ti-18Si-6Ta-2.5W-1Hf-2Sn-2Ge (JZ1) and Nb-12Ti-18Si-6Ta-2.5W-1Hf-5Sn-5Ge (JZ2) were studied. The alloys were designed using the alloy design methodology NICE to meet specific research objectives. The cast microstructures of both alloys were sensitive to solidification conditions. There was macro-segregation of Si in JZ1 and JZ2. In both alloys the &beta, Nb5Si3 was the primary phase and the Nbss was stable. The A15-Nb3X (X = Ge,Si,Sn) was stable only in JZ2. The Nbss+&beta, Nb5Si3 eutectic in both alloys was not stable as was the Nb3Si silicide that formed only in JZ1. At 800 &deg, C both alloys followed linear oxidation kinetics and were vulnerable to pesting. At 1200 &deg, C both alloys exhibited parabolic oxidation kinetics in the early stages and linear kinetics at longer times. The adhesion of the scale that formed on JZ2 at 1200 &deg, C and consisted of Nb and Ti-rich oxides, silica and HfO2 was better than that of JZ1. The microstructure of JZ2 was contaminated by oxygen to a depth of about 200 &mu, m. There was no Ge or Sn present in the scale. The substrate below the scale was richer in Ge and Sn where the NbGe2, Nb5(Si1-xGex)3, W-rich Nb5(Si1-xGex)3, and A15-Nb3X compounds (X = Ge,Si,Sn) were formed in JZ2. The better oxidation behavior of JZ2 compared with JZ1 correlated well with the decrease in VEC and increase in &delta, parameter values, in agreement with NICE. For both alloys the experimental data for Si macrosegregation, vol.% Nbss, chemical composition of Nbss and Nb5Si3, and weight gains at 800 and 1200 &deg, C was compared with the calculations (predictions) of NICE. The agreement was very good. The calculated creep rates of both alloys at 1200 &deg, C and 170 MPa were lower than that of the Ni-based superalloy CMSX-4 for the same conditions but higher than 10&minus, 7 s&minus, 1.