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Context: Early-rescue intracytoplasmic sperm injection (R-ICSI) can avoid total fertilization failure in conventional in vitro fertilization (IVF). However, the R-ICSI embryos had lower implantation rate than the direct ICSI in the fresh embryo transfer. Aims: To investigate the effect of frozen embryo transfer (FET)after R-ICSI. Methods: This was a retrospective study of the first cycle primary infertility patients with the age ≤ 35 undergoing R-ICSI and ICSI treatment. The clinical pregnancy rate, implantation rate, ectopic pregnancy, abortion rate and live birth rate were analyzed between the R-ICSI and ICSI groups in their first embryo transfer (fresh and FET cycles). Key Results: The average age of patients in fresh and frozen ET of two groups was (29.1±3.1 vs. 29.0±3.2, and 28.9±3.0 vs. 29.1±3.3), respectively (P>0.05). The R-ICSI embryos clinical pregnancy rate, implantation rate and live birth rate were lower than the ICSI embryos in fresh embryo transfer. Whereas there were no significant difference between R-ICSI and ICSI embryos in the FET cycle. Conclusions: R-ICSI embryos with frozen embryo transfer would be an optimal strategy rather than fresh embryo transfers. Implications:early R-ICSI combined with frozen embryo transfer could achieve satisfying clinical outcomes compared with fresh embryo transfers.

To determine whether glutamine consumption is associated with embryo quality and aneuploidy, a retrospective study was conducted in an in vitro fertilization center. Spent embryo culture media from patients undergoing assisted reproduction treatment and preimplantation genetic testing (PGT) were obtained on day 3 of in vitro culture. Embryo quality was assessed for cell number and fragmentation rate. PGT for aneuploidy was performed using whole genome amplification and DNA sequencing. Glutamine levels in spent embryo culture media were analyzed by gas chromatography–mass spectrometry. The results demonstrated that glutamine was a primary contributor to the classification of the good-quality and poor-quality embryos based on the orthogonal partial least-squares discriminant analysis model. Glutamine consumption in the poor-quality embryos was significantly higher than that in the good-quality embryos (P P

Background Heterogeneity of gliomas challenges the neuronavigated biopsy and oncological therapy. Diffusion and perfusion magnetic resonance imaging (MRI) can reveal the cellular and hemodynamic heterogeneity of tumors. Integrated positron emission tomography (PET)/MRI is expected to be a non-invasive imaging approach to characterizing glioma. Purpose To evaluate the value of apparent diffusion coefficient (ADC), cerebral blood volume (CBV), and spatially co-registered maximal standard uptake value (SUVmax) for tissue characterization and glioma grading. Material and Methods Thirty-seven consecutive patients with pathologically confirmed gliomas were retrospectively investigated. The relative minimum ADC (rADCmin), relative maximal ADC (rADCmax), relative maximal rCBV (rCBVmax), the relative minimum rCBV (rCBVmin), and the corresponding relative SUVmax (rSUVmax) were measured. The paired t-test was used to compare the quantitative parameters between different regions to clarify tumor heterogeneity. Imaging parameters between WHO grade IV and grade II/III gliomas were compared by t-test. The diagnostic efficiency of multiparametric PET/MRI was analyzed by receiver operating characteristic (ROC) curve. Results The values of rSUVmax were significantly different between maximal diffusion/perfusion area and minimum diffusion/perfusion area ( P min ( P max ( P = 0.002), and corresponding rSUVmax ( P = 0.001/ P max defined by rADCmin and rCBVmax were 0.89 and 0.91, respectively. Conclusion Diffusion and perfusion MRI can detect glioma heterogeneity with excellent molecular imaging correlations. Regions with rCBVmax suggest tissues with the highest metabolism and malignancy for guiding glioma grading and tissue sampling.

ObjectivesThe biological characteristics of plasma circulating cell-free DNA (cfDNA) are related to the pathogenesis of lupus nephritis (LN). The aim of this study was to explore the biological characteristics of cfDNA in patients with LN in terms of serology, fragment omics, and epigenetics, and to discuss the possibility of liquid biopsy for cfDNA as an alternative to conventional tissue biopsy.MethodscfDNA was extracted from plasma samples of 127 patients with systemic lupus erythematosus (64 with LN, 63 without LN). The cfDNA concentration was determined using the Qubit method. Next-generation sequencing cfDNA methylation profiling was performed for three LN patients and six non-LN patients. The methylation panel was designed based on data from The Cancer Genome Atlas cohort. The fragmentation index, motif score, and DELFI score were calculated to explore the fragmentation profile of cfDNA in patients with LN. Statistical and machine learning methods were used to select features to calculate the methylation scores of the samples.ResultsPatients with LN had significantly lower cfDNA concentrations (P = 0.0347) than those without LN. This may be associated with the presence of anti-double-stranded DNA antibodies (r = –0.4189; P = 0.0296). The mean DELFI score (proportion of short fragments of cfDNA) in patients with LN was significantly higher than that in patients without LN (P = 0.0238). Based on the pan-cancer data, 73, 66, 8, and 10 features were selected and used to calculate the methylation scores. The mean methylation scores of these features in patients with LN differed significantly from those in patients without LN (P = 0.0238).ConclusionsThe specificity of cfDNA in patients with LN was identified using serological, fragmentomic, and epigenetic analyses. The findings may have implications for the development of new molecular markers of LN.

The morphology of a polymer brush is of great importance in determining surface properties, such as lubrication. In light of this, we systematically study the morphologies of ring polyelectrolyte b...

Background The use of donated oocytes (DO) for in vitro fertilization(IVF) treatment in patients with infertility is generally recognized, and women with polycystic ovarian syndrome (PCOS) are able to participate in oocyte donation programs as donor patients. However, the pregnancy outcomes and follow-up of offspring of PCOS receptor is unclear. Objective Comparing the pregnancy outcomes and follow-up of offspring in PCOS and non-PCOS receptor. Design : Retrospective cohort study. Methods A total of 62 patients who had undergoing oocyte reception program were separated into two groups: Group I, PCOS oocyte receptor (𝑛=30); Group II, non-PCOS receptors (𝑛=32). Medical records were reviewed and rates of fertilization, cleavage, high quality embryos and blastocysts were compared between PCOS and non-PCOS receptors. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, multiple pregnancy, and offspring outcome were calculated in first single vitrified-warmed blastocyst transfer (SVBT) were analyzed between PCOS and non-PCOS receptors. Results The average recipient age from PCOS and non-PCOS patients were 36.3 ± 2.6 and 36.2 ± 2.8, respectively. Rates of fertilization, cleavage, high quality embryos and blastocysts were not significantly different. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, and multiple pregnancy were not significantly different in SVBT between PCOS and non-PCOS receptors. The incidences for complications such as PIH, or gestational diabetes between PCOS and non-PCOS receptors were similar (11.8% vs.11.1%, 5.9% vs.5.5%; P > 0.05). Preterm birth were similar (11.8% vs.16.7%, P > 0.05). Donor oocytes were more likely to deliver by caesarean section (80.0% vs. 86.7%: P > 0.05). And the mean gestational age, as well as the birth weight, and height were comparable for both groups in full-term delivery. Conclusions There was no difference in the pregnancy outcomes and follow-up of offspring between PCOS and non-PCOS receptor.

Background The use of donated oocytes (DO) for in vitro fertilization(IVF) treatment in patients with infertility is generally recognized, and females with polycystic ovarian syndrome (PCOS) can participate in oocyte donation programs as donor patients. However, the pregnancy outcomes and offspring follow-up in patients with PCOS as the recipients are unclear. This study was to compare the pregnancy outcomes and follow-up of offspring in PCOS and non-PCOS receptor. Methods This was a retrospective cohort study of 62 patients undergoing the oocyte reception program were separated into 2 groups: Group I, PCOS oocyte recipients (n = 30); Group II, non-PCOS recipients (n = 32). Medical records were reviewed, and rates of fertilization, cleavage, high-quality embryos and blastocysts were compared between PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, multiple pregnancies, and offspring outcomes were calculated using the first single vitrified-warmed blastocyst transfer (SVBT) analysis between the groups. Results The average recipient age and body mass index (BMI) of PCOS and non-PCOS patients was (36.3 ± 2.6 vs. 36.2 ± 2.8, and 23.4 ± 3.9 vs. 23.7 ± 4.0), respectively (P > 0.05). The fertilization, cleavage, high-quality embryos and blastocyst rates were not significantly different between the PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, and multiple pregnancies were not significantly different in SVBT between the PCOS and non-PCOS groups. The incidence of complications, such as pre-eclampsia or gestational diabetes, between PCOS and non-PCOS groups was similar (11.8% vs.11.1%, 5.9% vs.5.5%; P > 0.05). Preterm births were also similar (11.8% vs.16.7%, P > 0.05). Donor oocytes are more likely to be delivered via cesarean Sect. (80.0% vs. 86.7%: P > 0.05). The mean gestational age, birth weight, and height were comparable between the 2 groups during full-term delivery. Conclusion There was no difference in the pregnancy outcomes and follow-up of the offspring between the PCOS and non-PCOS groups.

Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder that leads to severe joint deformities, negatively affecting the patient's quality of life. Extracellular vesicles (EVs), which include exosomes and ectosomes, act as intercellular communication mediators in several physiological and pathological processes in various diseases including RA. In contrast, EVs secreted by mesenchymal stem cells perform an immunomodulatory function and stimulate cartilage repair, showing promising therapeutic results in animal models of RA. EVs from other sources, including dendritic cells, neutrophils and myeloid-derived suppressor cells, also influence the biological function of immune and joint cells. This review describes the role of EVs in the pathogenesis of RA and presents evidence supporting future studies on the therapeutic potential of EVs from different sources. This information will contribute to a better understanding of RA development, as well as a starting point for exploring cell-free-based therapies for RA.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease associated with impaired organ functions that can seriously affect the daily life of patients. Recent SLE therapies frequently elicit adverse reactions and side effects in patients, and clinical heterogeneity is considerable. Mesenchymal stromal cells (MSCs) have anti-inflammatory, tissue repair, and immunomodulatory properties. Their ability to treat autoimmune diseases largely depends on secreted extracellular vesicles, especially exosomes. The effects of exosomes and microRNAs (miRNAs) on SLE have recently attracted interest. This review summarizes the applications of MSCs derived from bone marrow, adipocyte tissue, umbilical cord, synovial membrane, and gingival tissue, as well as exosomes to treating SLE and the key roles of miRNAs. The efficacy of MSCs infusion in SLE patients with impaired autologous MSCs are reviewed, and the potential of exosomes and their contents as drug delivery vectors for treating SLE and other autoimmune diseases in the future are briefly described.

Objective: Vascular smooth muscle cells (VSMCs) undergo the phenotypic changes from contractile to synthetic state during vascular remodeling after ischemia. SIRT1 protects against stress-induced vascular remodeling via maintaining VSMC differentiated phenotype. However, the effect of smooth muscle SIRT1 on the functions of endothelial cells (ECs) has not been well clarified. Here, we explored the role of smooth muscle SIRT1 in endothelial angiogenesis after ischemia and the underlying mechanisms. Methods: We performed a femoral artery ligation model using VSMC specific human SIRT1 transgenic (SIRT1-Tg) and knockout (KO) mice. Angiogenesis was assessed in in vivo by quantification of the total number of capillaries, wound healing and matrigel plug assays, and in vitro ECs by tube formation, proliferation and migration assays. The interaction of HIF1α with circRNA was examined by using RNA immunoprecipitation, RNA pull-down and in situ hybridization assays. Results: The blood flow recovery was significantly attenuated in SIRT1-Tg mice, and markedly improved in SIRT1-Tg mice treated with SIRT1 inhibitor EX527 and in SIRT1-KO mice. The density of capillaries significantly decreased in the ischemic gastrocnemius of SIRT1-Tg mice compared with SIRT1-KO and WT mice, with reduced expression of VEGFA, which resulted in decreased number of arterioles. We identified that the phenotypic switching of SIRT1-Tg VSMCs was attenuated in response to hypoxia, with high levels of contractile proteins and reduced expression of the synthetic markers and NG2, compared with SIRT1-KO and WT VSMCs. Mechanistically, SIRT1-Tg VSMCs inhibited endothelial angiogenic activity induced by hypoxia via the exosome cZFP609. The cZFP609 was delivered into ECs, and detained HIF1α in the cytoplasm via its interaction with HIF1α, thereby inhibiting VEGFA expression and endothelial angiogenic functions. Meantime, the high cZFP609 expression was observed in the plasma of the patients with atherosclerotic or diabetic lower extremity peripheral artery disease, associated with reduced ankle-brachial index. Knockdown of cZFP609 improved blood flow recovery after hindlimb ischemia in SIRT1-Tg mice. Conclusions: Our findings demonstrate that SIRT1 may impair the plasticity of VSMCs. cZFP609 mediates VSMCs to reprogram endothelial functions, and serves as a valuable indicator to assess the prognosis and clinical outcomes of ischemic diseases.

Using molecular dynamics simulations, the flexible ring polyelectrolyte chains tethered to a planar substrate and immersed in good solvents are investigated systematically. Two sets of simulations are performed to explore the effects of grafting density and charge fraction, respectively. Both the monovalent and trivalent counterions are considered. The height of the brush H follows a scaling relation with grafting density (~σgν) and charge fraction (~fν). The values of the exponents are different from those of the linear counterparts. Through a careful analysis on the distributions of monomers and counterions, pair correlation functions of monomer-monomer and monomer-counterion, as well as the fractions of trivalent counterions in four states, the equilibrium structures of the ring PE brushes are examined in detail. Furthermore, a brief comparison with the ‘equivalent’ linear brush is carried out. Also, our results can serve as a guide for improving the performance of ring polyelectrolyte brushes as unique surface modifiers.

In order to fulfill the functions of comprehensive perception, real time interconnection, analysis and decision making, autonomous learning, dynamic prediction and cooperative control, an overall framework of Digital Twin Smart Mining Workface was established. Firstly, the digital twin smart mining face system was divided into 3 levels, and the functions and characteristics of each level were given. Secondly, based on the physical domain entities contained in the intelligent mining face, the data perception models of coal shearer, scraper conveyor, stage loader, crusher, hydraulic support, belt conveyor support, emulsion pump station and environment in the digital twin working face system were expounded in detail, and the collaborative constraint relationship among shearer, hydraulic support, coal flow transportation system, workface environment and equipment was analyzed in depth. Finally, the application scheme of the digital twin intelligent mining face system was designed. Based on the digital twin intelligent mining face system, the virtual real mapping and real time interaction between physical mine entities and digital mine twins could be realized, and the intelligent perception and cooperative control of digital twins could be performed, which provides a basis for improving the intelligent level of coal mining face.

Long noncoding RNAs are a group of more than 200 nt, nonprotein coding RNAs, some of which are dysregulated in many pathophysiological processes including endometriosis. This study aims to clarify the roles of dysregulated growth arrest‐specific 5 (GAS5) in patients with endometriosis, and unveil the underlying mechanisms. We obtained endometrium samples from 37 patients with endometriosis and 23 controls without endometriosis. Primary endometrial stromal cells (ESCs) and endothelial cells were separated from the endometrium. Levels of GAS5 were quantified using quantitative real‐time polymerase chain reaction, and levels of p27, cleaved caspase‐3, cleaved poly (ADP‐Ribose) polymerase 1, vascular endothelial growth factor A, tissue inhibitor of metalloproteinases 3 (TIMP3), and trypsin‐modified soy protein 10 were assessed by immunoblotting. Cell viability was examined using MTT assays, and the cell cycle and apoptosis were analyzed by flow cytometry. Endothelial cell tube formation capacity was assayed in vitro. GAS5 and p27 levels were found lower in the endometrium samples from patients with endometriosis. Primary ESCs from patients with endometriosis had increased viability, reduced apoptosis, and a relatively uncontrolled cell cycle. Gain‐ and loss‐of‐function studies confirmed that GAS5 regulated p27 expression in ESCs. Furthermore, GAS5 level was relatively low in primary endothelial cells from patients with endometriosis and GAS5 acted as an angiogenesis inhibitor by regulating the miR‐181c‐TIMP3 axis. Thus, lower GAS5 level in endometrium might be related to endometriosis by regulating cell proliferation, apoptosis, cell cycle, and angiogenesis.

In-fiber fluid instability can be harnessed to realize scalable microparticles fabrication with tunable sizes and multifunctional characteristics making it competitive in comparison to conventional microparticles fabrication methods. However, since in-fiber fluid instability has to be induced via thermal annealing and the resulting microparticles can only be collected after dissolving the fiber cladding, obtaining contamination-free particles for high-temperature incompatible materials remains great challenge. Herein, confinement-free fluid instability is demonstrated to fabricate polymeric microparticles in a facile manner induced by the ultralow surface energy of the superamphiphobic surface. The polymer solution columns break up into uniform droplets then form spherical particles spontaneously in seconds at ambient temperature. This method can be applied to a variety of polymers spanning an exceptionally wide range of sizes: from 1 mm down to 1 µm. With the aid of microfluidic spinning instrument, a large quantity of microparticles can be obtained, making this method promising for scaling up production. Notably, through simple modification of the feed solution configuration, composite/structured micromaterials can also be produced, including quantum-dots-labeled fluorescent particles, magnetic particles, core-shell particles, microcapsules, and necklace-like microfibers. This method, with general applicability and facile control, is envisioned to have great prospects in the field of polymer microprocessing.

BackgroundAbnormal renal metabolism is closely related to the development of chronic kidney disease. It is well known that renal inflammation plays an important role in the occurrence and development of tubulointerstitial damage in the renal tubules. The purpose of the experiment was to observe the bioactivity ofAlpina oxyphyllaextract (AOE) on renal injury in diabetic nephropathy (DN) rats induced by streptozotocin (STZ).MethodsThirty male Wistar rats were randomly divided into five group (n = 6): (1) intact control (non-diabetic, ND); (2) intact diabetic (STZ), (3) diabetic rats treated with gliclazide 5 mg/kg (STZ-gli), (4) diabetic rats treated with AOE 400 mg/kg (AOE 400), (5) diabetic rats treated with AOE 800 mg/kg (AOE 800). The diabetic nephropathy rat model was established by single intraperitoneal injected 50 mg/kg STZ. Fasting blood glucose (FBG) and body weight was observed at 1、3、6 weeks. After 6 weeks, the renal function parameters of five groups and 24 h urinary protein were detected. Expression of transforming growth factor-beta1 (TGF-β1) and myeloid differentiation factor 88 (MyD88) were assessed by Western Blot.ResultsThe STZ group showed hyperglycemia, proteinuria, renal function damage, and the levels of 24 h urinary protein, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Scr), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and interleukin-6 (IL-6) in the STZ group increased significantly compared with the ND group. The expression of TGF-β1 in STZ group was increase (p p ConclusionsAOE can effectively protect kidney tissues of diabetic nephropathy, and probably through regulating level of TGF-β1/MyD88.

We study the morphologies of a polyelectrolyte brush grafted onto a surface of cubic geometry under good solvent conditions in the presence of trivalent counterions, using molecular dynamics simulations. The electrostatic correlation effect and excluded volume effect on the morphologies are studied through varying the charge fraction and grafting density, respectively. Combining snapshots of surface morphologies, brush height, distribution profiles of polymer monomers, and monomer-monomer/counterion pair correlation functions, it is clearly shown that the electrostatic correlation effect, represented by the trivalent-counterion-mediated bridging effect, can induce lateral microphase separation of the cubic polyelectrolyte brush, resulting in the formation of pinned patches. These structures then lead to multi-scale ordering in the brush system and, thereby, a non-monotonic dependence of the brush height, corresponding to a collapse-to-swell transition, on the grafting density. Our simulation results demonstrate that, with the sequence of surface morphologies responsive to adjusting external parameters, the cubic polyelectrolyte brush can serve as a candidate system for the manufacturing of smart stimuli-responsive materials.

We study surface morphologies of a spherical polyelectrolyte brush in the presence of trivalent counterions using molecular dynamics simulations. Solvent quality and electrostatic interaction strength are varied to generate a series of structures. Through a careful analysis on snapshots of morphologies, shape factor of tethered chains, and monomer–monomer pair correlation function we find a nonmonotonic dependence of surface morphology on electrostatic strength, which represents clearly the electrostatic correlation effect mediated by the multivalent counterions. Due to the very importance of counterions, we further study the correlation effect by classifying counterions into four states, calculating the monomer–counterion pair correlation function and diffusion coefficient of counterions. Our simulation results clearly demonstrate that ordered patterns can be induced by the electrostatic correlation effect in the presence of trivalent counterions, which is absent in the system with monovalent ions. Also,...

Two new iron(II) complexes with 1D chain and 2D network structures have been successfully synthesized and characterized. One of the complexes exhibits a pressure-induced spin-crossover property with a reversible color change from white to purple at room temperature. The special property makes it a suitable candidate as a pressure sensor.

Objective— Smooth muscle (SM) 22α, an actin-binding protein, displays an upregulated expression as a marker during cellular senescence. However, the causal relationship between SM22α and senescence is poorly understood. This study aimed to investigate the role of SM22α in angiotensin II (Ang II)–induced senescence of vascular smooth muscle cells (VSMCs). Approach and Results— We prepared a model of VSMC senescence induced by Ang II and found that the expression of SM22α in VSMCs was increased in response to chronic Ang II treatment. Overexpression of SM22α promoted Ang II–induced VSMC senescence, whereas knockdown of SM22α suppressed this process. Moreover, this effect of SM22α was p53 dependent. Increased SM22α protein obstructed ubiquitination and degradation of p53 and subsequently improved its stability. Furthermore, SM22α inhibited phosphorylation of Mdm2 (mouse double minute 2 homolog), an E3 ubiquitin-protein ligase, accompanied by a decreased interaction between Mdm2 and p53. Using LY294002, a PI3K/Akt inhibitor, we found that PI3K/Akt-mediated Mdm2 phosphorylation and activation was inhibited in senescent or SM22α-overexpressed VSMCs, in parallel with decreased p53 ubiquitination. We further found that SM22α inhibited activation of PI3K/Akt/Mdm2 pathway via strengthening actin cytoskeleton. In the in vivo study, we showed that the disruption of SM22α reduced the increase of blood pressure induced by Ang II, associated with decreased VSMC senescence through a mechanism similar to that in VSMCs in vitro. Conclusions— In conclusion, these findings suggest that the accumulation of SM22α promotes Ang II–induced senescence via the suppression of Mdm2-mediated ubiquitination and degradation of p53 in VSMCs in vitro and in vivo.

Background Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. Objective To identify and prospectively validate asthma clusters in a Chinese population. Methods Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k -means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Results Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03–1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07–3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26–40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02–4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95–69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission ( P Conclusion We identified 3 clinical clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries.

Aims Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-κB) activity in response to the inflammatory cytokine tumour necrosis factor alpha (TNF-α). Smooth muscle (SM) 22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signalling cascades in vascular smooth muscle cells (VSMCs). Sm22α knockout results in increased expression of pro-inflammatory genes in the aortas which are controlled by NF-κB. This study aimed to investigate the relationship between SM22α and SIRT1 in the control of vascular inflammation. Methods and results The ligation injury model of Sirt1-Tg/Sm22α-/- mice displayed an increased level of the inflammatory molecules in the carotid arteries compared with Sirt1-Tg mice, accompanied with aggravating neointimal hyperplasia. In the in vitro study, on the one hand, we showed that TNF-α induced the epigenetic silencing of SM22α transcription via EZH2-mediated H3K27 methylation in the SM22α promoter region, contributing to inflammatory response. On the other hand, TNF-α simultaneously induced SIRT1 phosphorylation via CKII and thereby protected against inflammation. Phosphorylated SIRT1 interacted with and deacetylated EZH2 and, subsequently, promoted SM22α transcription by inhibiting EZH2 activity. Increased SM22α in turn facilitated the phosphorylation and activation of SIRT1 via recruitment of CKII to SIRT1, which amplified the anti-inflammatory effect of SIRT1. Conclusion Our findings demonstrate that, in response to TNF-α stimulation, CKII-SIRT1-SM22α acts in a loop to reinforce the expression of SM22α, which limits the inflammatory response in VSMCs in vivo and in vitro. The anti-inflammatory effect of SIRT1 may be dependent on SM22α to some extent. Our data point to targeted activation of SIRT1 in VSMCs as a promising therapeutic avenue in preventing cardiovascular diseases.

Formulating an analytical theory, we study phase separation of a polyelectrolyte solution under poor solvent condition confined in three types of finite geometric spaces: slab, cylinder, and sphere. Divided by a Lifshitz line, bulk polyelectrolyte solution undergoes either micro- or macro-phase separation. Confinement effects for both scenarios are studied. Composition fluctuations inducing phase separation are classified in terms of eigenmodes of the inverse structure factor operator in the corresponding geometric spaces. Tracking each eigenmode, the instability lines under confinement effects are derived in closed forms. For the confined microphase separation, we find a decaying oscillatory dependence of the spinodal point on the confinement size, which represents the commensurability between the finite period of the soft mode and the confining boundary size. For the confined macrophase separation, a typical mean-field finite size scaling of the Ising universality class is observed under the strong screening condition.

Diffusion dynamics of charged nanoparticles on the lipid membrane is of essential importance to cellular functioning. Yet a fundamental insight into electrostatics-mediated diffusion dynamics of charged nanoparticles on the membrane is lacking and remains to be an urgent issue. Here we present the computational investigation to uncover the pivotal role of electrostatics in the diffusion dynamics of charged nanoparticles on the lipid membrane. Our results demonstrate diffusive behaviors and directional transport of a charged nanoparticle, significantly depending on the sign and spatial distribution of charges on its surface. In contrast to the Fickian diffusion of neutral nanoparticles, randomly charged nanoparticles undergo superdiffusive transport with directionality. However, the dynamics of uniformly charged nanoparticles favors Fickian diffusion that is significantly enhanced. Such observations can be explained in term of electrostatics-induced surface reconstruction and fluctuation of lipid membrane. We finally present an analytical model connecting surface reconstruction and local deformation of the membrane. Our findings bear wide implications for the understanding and control of the transport of charged nanoparticles on the cell membrane.

Purpose In an integrated circuit (IC) substrate, more fillers, including talcum powder and aluminium hydroxide, are added, which leads to much higher rigidity and hardness compared with a traditional printed circuit board. However, the micro drilling of IC substrates is harder. This paper aims to test the drilling process of IC substrates to improve the drilling process and the micro hole quality. Design/methodology/approach Substrate drilling by a micro drill with 0.11-mm diameter was used under several drilling conditions. The influence of drilling conditions on the drilling process was observed. Drilling forces, drill wear and micro hole quality were also studied. Findings The deformation circle around holes, hole location accuracy, bugle hole and burrs were the major defects of micro holes that were observed during the drilling of the substrate. Reducing the drilling force and drill wear was the effective way to improve hole quality. Originality/value The technology and manufacturing of IC substrates has been little investigated. Research data on drilling IC substrates is lacking. The micro hole quality directly affects the reliability of IC substrates. Thus, improving the drilling technology of IC substrates is very important.

The ability to understand and exploit entropic contributions to ordering transition is of essential importance in the design of self-assembling systems with well-controlled structures. However, much less is known about the role of assembly kinetics in entropy-driven phase behaviors. Here, by combining computer simulations and theoretical analysis, we report that the implementation of entropy in driving phase transition significantly depends on the kinetic process in the reaction-induced self-assembly of newly designed nanoparticle systems. In particular, such systems comprise binary Janus nanoparticles at the fluid-fluid interface and undergo phase transition driven by entropy and controlled by the polymerization reaction initiated from the surfaces of just one component of nanoparticles. Our simulations demonstrate that the competition between the reaction rate and the diffusive dynamics of nanoparticles governs the implementation of entropy in driving the phase transition from randomly mixed phase to intercalated phase in these interfacial nanoparticle mixtures, which thereby results in diverse kinetic pathways. At low reaction rates, the transition exhibits abrupt jump in the mixing parameter, in a similar way to first-order, equilibrium phase transition. Increasing the reaction rate diminishes the jumps until the transitions become continuous, behaving as a second-order-like phase transition, where a critical exponent, characterizing the transition, can be identified. We finally develop an analytical model of the blob theory of polymer chains to complement the simulation results and reveal essential scaling laws of the entropy-driven phase behaviors. In effect, our results allow for further opportunities to amplify the entropic contributions to the materials design via kinetic control.

We investigate several structural properties of low-molecular weight AB diblock copolymer melts, focusing on a number of features that substantially deviate from those of high-molecular weight copolymer melts. The study is based on the wormlike chain formalism aided by random phase approximation and self-consistent field theory. We examine the effects that stemmed from both the finite molecular weight and the finite interaction range between unlike AB monomers. The latter yields profound effects on systems consisting of short wormlike block copolymers. The noticeable shift of the order-disorder transition point is discussed. Attention is also paid to the strong-segregation regime, where low molecular weight polymers are subject to finite stretchability.

OBJECTIVE To determine whether anxiety and depression are associated with greater respiratory discomfort in asthma. METHODS Adults with asthma (n = 230) underwent methacholine (Mch) challenge. Anxiety and depression, asthma control, and quality of life were evaluated at study entry by using the Hospital Anxiety and Depression Scale, Asthma Control Test, and Asthma Quality of Life Questionnaire, respectively. Qualitative descriptors of breathlessness, dyspnea intensity (modified Borg scale and visual analog scale [VAS]), and other respiratory symptoms were evaluated before and after Mch challenge. RESULTS Patients were classified as neither anxiety nor depression (NAD), anxiety only, depression only (D), or both anxiety and depression (AD) according to the Hospital Anxiety and Depression Scale score. Asthma Control Test and Asthma Control Test, and Asthma Quality of Life Questionnaire scores were lowest in the AD group (both p < 0.001). VAS scores for dyspnea and wheezing before Mch challenge were highest in the AD group (both p < 0.05). The increase in the modified Borg scale score after Mch challenge was higher in the AD group (mean [standard deviation] 2.5 ± 2.0) than in the NAD (1.5 ± 1.5) and D (0.8 ± 0.9) groups (p = 0.006 and p = 0.003, respectively). Most descriptors of breathlessness were more prevalent in the anxiety only, D, and AD groups than in the NAD group. Multivariable logistic regression models indicated that anxiety increased the risk of dyspnea (odds ratio 1.10, p < 0.001 for the Borg score; odds ratio 3.84, p = 0.032 for the VAS score) but not for other respiratory symptoms. CONCLUSIONS Anxiety but not depression was associated with greater perceived dyspnea intensity but not other measures of respiratory discomfort in individuals with asthma. Anxiety may shape the quality and intensity of dyspnea at a given respiratory load.

Polymers are found near surfaces and interfaces in a wide range of chemical and biological systems, and the structure and dynamics of adsorbed polymer chains have been the subject of intense interest for decades. While polymer structure is often inferred from dynamic measurements in bulk solution, this approach has proven difficult to implement at interfaces, and the understanding of interfacial polymer conformation remains elusive. Here we used single-molecule tracking to study the interfacial diffusion of isolated poly(ethylene glycol) molecules at oil-water interfaces. Compared to diffusion in dilute aqueous solution, which exhibited the expected dependence of the diffusion coefficient (D) upon molecular weight (M) of D ∼ M(-1/2) for a Gaussian chain, the behavior at the interface was approximately D ∼ M(-2/3), suggesting a significantly more expanded polymer conformation, despite the fact that the oil was a poor solvent for the polymer. Interestingly, this scaling remained virtually unchanged over a wide range of oil viscosity, despite the fact that at low viscosities the magnitude of the diffusion coefficient was consistent with expectations based on viscous drag (i.e., Stokes-Einstein diffusion), and for high viscosity oil, the interfacial mobility was much faster than expected and consistent with the type of intermittent hopping transport observed at the solid-liquid interface. The dependence on molecular weight, in both regimes, was consistent with results from both self-consistent field theory and previous Monte Carlo simulations, suggesting that an adsorbed polymer chain adopted a partially swollen (loop-train-tail) interfacial conformation.

Four new coordination polymers [Co(btmtmb)2(SCN)2] (1), [Co(bttmb)2(SCN)2] (2), [Co(btmtmb)2(SeCN)2] (3) and [Co(bttmb)2(SeCN)2] (4), where btmtmb = 1,3-bis-(1,2,4-triazol-1-ylmethyl)-5-methoxy-2,4,6-trimethylbenzene and bttmb = 1,3-bis-(1,2,4-triazol-1-ylmethyl)-2,4,6-trimethylbenzene, have been synthesized and structurally characterized. The X-ray crystal structures reveal that 1 and 3 are constructed of an infinite 1D chain, 2 and 4 contain a 2D (4,4)-network layer. Magnetic properties of the four complexes are investigated, which show that for all these four complexes the antiferromagnetic interactions occur and strong spin–orbit coupling of Co(II) ions exits as well.

Background Inhibition of nuclear factor κB (NF-κB) activation is a well-know strategy to ameliorate ventilation-induced lung injury (VILI). Inhibitory κB kinase (IKK) plays a key role in the regulation of NF-κB activation. In this study, we determined whether inhibition of IKK by an IKK inhibitor exerts lung protection in a rat model of VILI. Methods Anesthetized and mechanically ventilated Sprague-Dawley rats were randomly assigned to a standard (tidal volume, 8 mL/kg) or high-tidal volume (tidal volume, 25 mL/kg) ventilation group. An IKK inhibitor (IKK 16) or vehicle was administrated 1 hour before the induction of VILI. All groups were ventilated and observed for 5 hours. Results High-pressure ventilation caused activation of NF-κB, increased pulmonary inflammatory mediator levels, lung edema, and impairment of gas exchange. The IKK inhibitor treatment significantly reduced these changes and increased interleukin 10 levels, heme oxygenase 1 activity, protein kinase B (Akt) phosphorylation levels, and nuclear amounts of nuclear factor E2-related factor 2 protein. Conclusion IKK may be a therapeutic target for VILI. An IKK inhibitor, IKK 16, can dampen VILI in rats. The beneficial effect of the IKK 16 may be mediated through the inhibition of NF-κB pathway and up-regulation of nuclear factor E2-related factor 2-regulated heme oxygenase 1 through the activation of the phosphatidylinositol 3 kinase/Akt.

Galangin, an active ingredient of Alpinia galangal, has been shown to possess anti-inflammatory and antioxidant activities. Inflammation and oxidative stress are known to play vital effect in the pathogenesis of acute lung injury (ALI). In this study, we determined whether galangin exerts lung protection in lipopolysaccharide (LPS)-induced ALI. Male BALB/c mice were randomized to receive galangin or vehicle intraperitoneal injection 3 h after LPS challenge. Samples were harvested 24 h post LPS administration. Galangin administration decreased biochemical parameters of oxidative stress and inflammation, and improved oxygenation and lung edema in a dose-dependent manner. These protective effects of galangin were associated with inhibition of nuclear factor (NF)-κB and upregulation of heme oxygenase (HO)-1. Galangin reduces LPS-induced ALI by inhibition of inflammation and oxidative stress.

A moving model of close target in a certain velocity is established aiming at the characteristic of low maneuverability. The Extended kalman filter (EKF) is used to reduce the error in location tracking. From the simulation result, it can be concluded that the moving model can describe the moving characteristic of close ballistic target perfectly. The Extended kalman filter can reduce the error in tracking location clearly.

The deformation behaviors of three types of polyethylene (PE) with different molecular weights and short chain branch contents were studied by in-situ Fourier transformation infrared microspectroscopic imaging (FTIRI) with a Focal Plane Array (FPA) detector during uniaxial tensile test. The crystal orientation distributions within a 250 × 250 μm2 region during tensile test were obtained, especially in the front of necking profile. The results show that either increasing the molecular weight or adding the short chain branches could enhance the resistance of crystal to be orientated. With the aid of the Landau-de Gennes theory of nematic–isotropic transition, the spatial distribution of crystal orientation during the steady neck propagation is quantitatively analyzed, coupling with its corresponding mechanical behavior coherently. The theoretical analysis reveals that the constant Φ 0 and the coefficient of the Gaussian term A in the Landau-de Gennes model are valid parameters to evaluate the mechanical property of PE materials, which may be generalized as a new method to quantify the mechanical property of semi-crystalline polymers.

Structurally dynamic polymers are recognized as a key potential to revolutionize technologies ranging from design of self-healing materials to numerous biomedical applications. Despite intense research in this area, optimizing reactivity and thereby improving self-healing ability at the most fundamental level pose urgent issue for wider applications of such emerging materials. Here, the authors report the first mechanistic investigation of the fundamental principle for the dependence of reactivity and self-healing capabilities on the properties inherent to dynamic polymers by combining large-scale computer simulation, theoretical analysis, and experimental discussion. The results allow to reveal how chain stiffness and spatial organization regulate reactivity of dynamic polymers grafted on Janus nanoparticles and mechanically mediated reaction in their reverse chemistry, and, particularly, identify that semiflexible dynamic polymers possess the optimal reactivity and self-healing ability. The authors also develop an analytical model of blob theory of polymer chains to complement the simulation results and reveal essential scaling laws for optimal reactivity. The findings offer new insights into the physical mechanism in various systems involving reverse/dynamic chemistry. These studies highlight molecular engineering of polymer architecture and intrinsic property as a versatile strategy in control over the structural responses and functionalities of emerging materials with optimized self-healing capabilities.

Rationale: We have demonstrated that smooth muscle (SM) 22α inhibits cell proliferation via blocking Ras-ERK1/2 signaling in vascular smooth muscle cells (VSMCs) and in injured arteries. The recent study indicates that SM22α disruption can independently promote arterial inflammation through activation of reactive oxygen species (ROS)-mediated NF-κB pathways. However, the mechanisms by which SM22α controls ROS production have not been characterized. Objective: To investigate how SM22α disruption promotes ROS production and to characterize the underlying mechanisms. Methods and Results: ROS level was measured by dihydroethidium staining for superoxide and TBA assay for malondialdehyde, respectively. We showed that downregulation and phosphorylation of SM22α were associated with angiotensin (Ang) II–induced increase in ROS production in VSMCs of rats and human. Ang II induced the phosphorylation of SM22α at Serine 181 in an Ang II type 1 receptor–PKCδ pathway–dependent manner. Phosphorylated SM22α activated the protein kinase C (PKC)δ-p47 phox axis via 2 distinct pathways: (1) disassociation of PKCδ from SM22α, and in turn binding to p47 phox , in the early stage of Ang II stimulation; and (2) acceleration of SM22α degradation through ubiquitin-proteasome, enhancing PKCδ membrane translocation via induction of actin cytoskeletal dynamics in later oxidative stress. Inhibition of SM22α phosphorylation abolished the Ang II–activated PKCδ-p47 phox axis and inhibited the hypertrophy and hyperplasia of VSMCs in vitro and in vivo, accompanied with reduction of ROS generation. Conclusions: These findings indicate that the disruption of SM22α plays pivotal roles in vascular oxidative stress. PKCδ-mediated SM22α phosphorylation is a novel link between actin cytoskeletal remodeling and oxidative stress and may be a potential target for the development of new therapeutics for cardiovascular diseases.

We investigated the interaction between embedded nanotube and biomembrane using molecular dynamics (MD) simulations. The effects of embedded nanotube on biomembrane were characterized by investigating the influence on the conformational fluctuation of individual lipid molecules, the organization of membrane molecules, the diffusion behavior of lipid molecules, and the diffusion behavior of penetrants inside biomembrane. The steric interaction with the nanotube leads to an entropy reduction of interfacial membrane molecules, while the long-range electrostatic interaction with the N-DWCNT enhances the conformational fluctuation of lipid molecules. The curvature of embedded nanotube could also influence the flexibility of lipid molecules. When the interaction between nanotube and the membrane molecules is weak, the packing density of the membrane is almost unaffected. On the contrary, when the attraction between nanotube and the membrane molecules significantly increases, the attraction among the membrane molecules decreases effectively, which leads to a relaxation of the organization of membrane. With the increase of the strength of electrostatic interaction between nanotube and small polar molecules, interaction-modified friction increases, which leads to the decrease of the diffusion constant of penetrants inside the biomembrane.

The present study was designed to investigate the clinicopathological correlation between the expression of KLF5 and MMP-9, which are associated with extracellular matrix degradation and cartilage degeneration in human knee osteoarthritis (OA). Tibiofemoral joint samples from 20 patients with OA, treated with surgery alone, were divided into two groups: 0=no change (NC, n=17), and severe changes with a higher mean score (≥ 3) (SC, n=29). The latter group contains samples with severe damages in cartilages and subchondral bones at medial tibial plateaux. The expression of the proteins was detected by immunofluorescence and quantitative RT-PCR, respectively. Neurovascular invasion was evaluated by protein gene product (PGP) 9.5 and CD34-positive staining and scanning electron microscopy, respectively. Safranin O staining showed that the sections from the SC group had increased cartilage degeneration. The number of vascular invasions in the SC group (16/29, 55.2%) was higher than that in NC controls (2/17, 11.7%, P

Inula britanica Linn. (Compositae) is a traditional Chinese medicinal herb that has been used to treat bronchitis and inflammation. The total flavonoid extracts (TFEs) isolated from its flowers can inhibit neointimal formation induced by balloon injury in vivo.To investigate the mechanism by which TFE suppresses oxidative stress generation and the subsequent inflammation response in vitro.The cultured vascular smooth muscle cells (VSMCs) form rats were exposed to oxidative stress following pretreatment with or without TFE at different concentration. Then, fluorescence staining was used to detect superoxide anion (O₂(˙-)) production, and the lever of maleic dialdehyde (MDA) and superoxide dismutase (SOD) was measured at the same time. Furthermore, tumor necrosis factor-α (TNF-α) was measured by enzyme linked immunosorbent assay (ELISA), reverse transcription-PCR and western blot were performed to detect the expression activity of p47(phox) gene, and immunoprecipitation was used to test the level of p47(phox) phosphorylation.TFE inhibited the production of O₂(˙-) induced by H₂O₂ in VSMCs, with decrease in secretion of TNF-α; elevated the activity of SOD in the medium, similar to the effect of quercetin; reduced the level of MDA in culture medium of VSMCs. The pretreatment with TFE resulted in decrease the level of p47(phox) mRNA and protein, and even p47(phox) phosphorylation in VSMCs, compared with H₂O₂ control.These findings demonstrate that TFE is capable of attenuating the oxidative stress generation and the subsequent inflammation response via preventing the overexpression and activation of p47(phox) and the increased TNF-α secretion in VSMCs in vitro.

Background The purpose of this study was to determine whether LAPTM4B over-expression is associated with the prognosis and chemotherapy resistance in patients with stages III and IV epithelial ovarian carcinoma, i.e., patients with peritoneal metastasis or lymph node metastasis of epithelial ovarian carcinoma. Methods LAPTM4B expression was evaluated in 10 normal ovarian and 113 stages III–IV ovarian carcinomas specimens by Western blotting analyses and immunohistochemistry. Univariate and multivariate analyses were performed to determine the association between LAPTM4B expression and prognosis and the relationship between LAPTM4B over-expression and chemotherapy resistance. Results Western blotting analysis demonstrated that LAPTM4B was overexpressed in ovarian cancers, and immunohistochemistry results revealed that 80 patients were LAPTM4B over-expression. The five-year overall survival (OS) rates for patients with high LAPTM4B expression and low LAPTM4B expression were 27.36% and 90.7%, respectively (hazard ratio = 20.611, 95% CI: 5.916–71.808, P

Abnormal proliferation of vascular smooth muscle cells (VSMCs) occurs in hypertension, atherosclerosis and restenosis after angioplasty, leading to pathophysiological vascular remodeling. As an important growth arrest gene, p21 plays critical roles in vascular remodeling. Regulation of p21 expression by retinoic acid receptor (RAR) and its ligand has important implications for control of pathological vascular remodeling. Nevertheless, the mechanism of RAR-mediated p21 expression in VSMCs remains poorly understood. Here, we show that, under basal conditions, RARα forms a complex with histone deacetylase 2 (HDAC2) and Krüppel-like factor 5 (Klf5) at the p21 promoter to inhibit its expression. Upon RARα agonist stimulation, HDAC2 is phosphorylated by CK2α. Phosphorylation of HDAC2, on the one hand, promotes its dissociation from RARα, thus allowing the liganded-RARα to interact with co-activators; on the other hand, it increases its interaction with Klf5, thus leading to deacetylation of Klf5. Deacetylation of Klf5 facilitates its dissociation from the p21 promoter, relieving its repressive effect on the p21 promoter. Interference with HDAC2 phosphorylation by either CK2α knockdown or the use of phosphorylation-deficient mutant of HDAC2 prevents the dissociation of Klf5 from the p21 promoter and impairs RAR agonist-induced p21 activation. Our results reveal a novel mechanism involving a phosphorylation-deacetylation cascade that functions to remove the basal repression complex from the p21 promoter upon RAR agonist treatment, allowing for optimum agonist-induced p21 expression.

MicroRNAs are phenotypic regulators of vascular smooth muscle cells (VSMCs). In this paper, we demonstrate that miR-146a targets the Krüppel-like factor 4 (KLF4) 3'-untranslated region and has an important role in promoting VSMC proliferation in vitro and vascular neointimal hyperplasia in vivo. Silencing of miR-146a in VSMCs increases KLF4 expression, whereas overexpression of miR-146a decreases KLF4 levels. Furthermore, we demonstrate that KLF4 competes with Krüppel-like factor 5 (KLF5) to bind to and regulate the miR-146a promoter, and that KLF4 and KLF5 exert opposing effects on the miR-146a promoter. Overexpression of KLF4 in VSMCs decreases miR-146a transcription levels. By using both gain-of-function and loss-of-function approaches, we found that miR-146a promotes VSMC proliferation in vitro. Transfection of antisense miR-146a oligonucleotide into balloon-injured rat carotid arteries markedly decreased neointimal hyperplasia. These findings suggest that miR-146a and KLF4 form a feedback loop to regulate each other's expression and VSMC proliferation.

The increased proliferation and migration of vascular smooth muscle cells (VSMCs) are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC proliferation, accompanied with the reduction of proliferating cell nuclear antigen (PCNA) expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF receptor β (PDGFRβ)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFRβ-ERK1/2 signaling cascade.

We investigate the finite-extensibility effect on the equilibrium size of a single polymer chain by using a Flory-type calculation. The finite extensibility of the chain is effectively taken into account by modifying the Gaussian stretching energy to a non-Gaussian form which recovers the harmonic spring behavior in the limit of weak stretch and diverges when the chain extension approaches the total contour length. In general, the finite extensibility decreases the equilibrium size of the chain compared to that obtained from Flory's classic theory, due to a steeper free energy or effective potential of the chain generated by the finite-extensibility effect. It is illustrated clearly that, for a chain with a short contour length and/or with strong repulsions between monomers, the finite-extensibility correction is important and necessary to be taken into account. A typical system where the finite extensibility plays an important role is suggested to be the highly charged and highly crosslinked hydrogel.