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The problem of Reissner–Mindlin–Timoshenko plate systems with nonlinear damping terms is considered. The main result is the existence of global attractors. By showing the system is gradient and asymptotic smoothness via a stabilizability inequality, we establish the existence of global attractors with finite fractal dimension. The continuity of global attractors regarding the parameter in a residual dense set is also proved. The above results allow the damping terms with polynomial growth. [ABSTRACT FROM AUTHOR]

In order to improve the interfacial bonding between copper and graphite, copper was coated on the graphite by electroless plating. Copper/graphite composites with copper‐coated graphite were fabricated by spark plasma sintering. The effects of copper‐coated graphite on the density, electrical conductivity, mechanical properties, friction and wear properties of copper/graphite composites were studied. The results show that: copper plating on the graphite surface can improve the wettability of graphite and copper, and the interface between them is well bonded. Compared with pure copper, the microstructure of the composites was significantly refined after adding copper‐coated graphite. The mechanical properties of the composites were significantly improved, with yield compressive strength and elastic modulus increasing by 220 % and 240 %, respectively. With the increase of copper‐coated graphite contents, the density and the conductivity of the composites gradually decreased. The friction coefficient and wear rate of the composites were significantly reduced. The friction and wear mechanisms of the composites are mainly oxidation wear, fatigue wear and adhesive wear. [ABSTRACT FROM AUTHOR]

Purpose: Currently, there are little to no published studies outlining general dentists' knowledge in the management of patients on anticoagulant/antiplatelet therapies in Australia. The aim of this study was to investigate the current practices of Western Australian (WA) general dentists with regards to dental management of patients taking anticoagulants/antiplatelets. Materials and methods: WA dentists were invited to undertake a survey to investigate their knowledge on the management of patients taking anticoagulant/antiplatelet. The questionnaire provided to WA general dentists consisted of pre‐extraction advice on patients (direct oral anticoagulants [DOACs], antiplatelets, warfarin, dual antiplatelets and antiplatelet/anticoagulant). Results were analysed using descriptive statistics as well as chi‐square tests. Results: Of the 89 participants, 40.5% had <5 years of general dental experience. Most WA general dentists (64%–71%) responded with 'no change' when performing extractions on patients on DOACs, antiplatelet therapy, warfarin, dual antiplatelets and antiplatelets/anticoagulants (P = 0.00). Furthermore, dentists with 6–10 years of experience were more likely to cease antiplatelet for 24 h before extractions (P < 0.05). Dentists who extracted 10–30 teeth per month were likely to stop antiplatelets and DOACs for more than 48 h compared to other groups (P < 0.05). Conclusion: Most WA dentists would not cease anticoagulant/antiplatelet therapy when undergoing dental extractions. [ABSTRACT FROM AUTHOR]

In this paper we consider laminated beams modelled from the well established Timoshenko system, which is a structure given by two identical layers uniform on top of each other, taking into account that an adhesive of small thickness is bonding the two surfaces and produces an interfacial slip. By using semi‐group approach, we prove the global well‐posedness of the system when a viscoelastic dissipation acts on the three equations. In addition, we prove that the dissipation through memory terms is strong enough to get exponential decay of the system without the condition of equal wave speeds. [ABSTRACT FROM AUTHOR]

Background and purpose: A recently proposed pre‐dementia syndrome, motoric cognitive risk (MCR) syndrome, is characterized by cognitive complaints and slow gait, and increases the risk of dementia and mortality. The aim of the present study was to explore the prevalence of and factors associated with MCR syndrome in elderly community‐dwelling Chinese subjects. Methods: The Ningbo Community Study on Aging recruited 953 Chinese community‐dwelling participants aged ≥ 65 years from November 2016 to March 2017. Handgrip, Five‐Times‐Sit‐to‐Stand (FTSS) test time and body composition, as well as comprehensive geriatric evaluation, were measured as potentially independent factors associated with MCR syndrome. Results: The prevalence of MCR syndrome was 12.8% in men and 12.6% in women, and high prevalence of MCR syndrome was not associated with age or sex. Multiple logistic regression analysis by sex showed that a 1‐SD increase in FTSS test time in males and females was associated with 45% (95% confidence intervals, 19–76; P < 0.01) and 20% (95% confidence intervals, 9–33; P < 0.01) higher risk of having MCR syndrome, respectively, whereas handgrip strength was inversely correlated with MCR syndrome in males [odds ratio (OR), 0.91; P = 0.02] but not females (P = 0.06). Moreover, the relationship of arm fat mass and MCR syndrome was statistically significant in both sexes (OR, 1.69–1.77), but leg fat mass was only associated with MCR syndrome (OR, 1.56; P = 0.02) in men. Conclusions: Handgrip, FTSS test time and body composition were associated in a sex‐specific manner with MCR syndrome in elderly community‐dwelling Chinese subjects. Our results on MCR syndrome are novel and should be considered as important information in future studies. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 32- year- old Chinese man with haemophilia B. Topics discussed include results of various medical tests; complications of haemophilia B, blood supply and the haemophilic pseudotumour ; and the usage of physical examination, and plain radiography in the treatment.

Background Chronic hepatitis C virus ( HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma ( HCC) in the United States ( US) and an emerging cause in China. Aim To compare the clinical characteristics of hepatitis C patients in the US and China, and factors influencing disease stage. Methods Prospective study of 2 cohorts of HCV patients recruited at 1 site in the US and 3 sites in China. Standardised questionnaire on risk factors and medical history were used and diagnosis of cirrhosis and HCC was based on pre-defined criteria. Results One thousand nine hundred and fifty seven patients (1000 US and 957 China) were enrolled. US patients were more likely to be men (61.4% vs 48.5%), older (median age 57 vs 53 years), obese (38.4% vs 16.8%) and diabetic (21.8% vs 10.8%). A significantly higher per cent of US patients had cirrhosis (38.2% vs 16.0%) and HCC (14.1% vs 2.7%). Investigator estimated time at infection in US was 10 years earlier than in Chinese patients but US patients were more likely to have advanced disease even after stratifying for duration of infection. Study site in the US, older age, truncal obesity, diabetes and prior HCV treatment were significant predictors of advanced disease on multivariate analysis. Conclusions HCV patients in the US had more advanced liver disease than those in China. We speculate that underlying fatty liver disease may be a major contributor to this difference, and management of glycometabolic abnormalities should occur in parallel with anti-viral therapy to achieve optimal outcomes. [ABSTRACT FROM AUTHOR]

Cytochrome P450 (P450 or CYP) genes are involved in fundamental physiological functions, and might be also associated with the olfactory recognition of sex pheromones in beetles and moths. A P450 gene, Spodoptera litura CYP4L4 ( SlituCYP4L4), was cloned for the first time from the antennae of S. litura. SlituCYP4L4 was almost exclusively expressed in the adult stage and predominantly expressed in the adult antennae. In situ hybridization showed that SlituCYP4L4 localized mainly at the base of the long sensilla trichoidea, which responds to sex pheromone components. Pretreatment with an S. litura sex pheromone significantly reduced the expression levels of SlituCYP4L4, consistent with other genes involved in sex pheromone recognition. The expression level of SlituCYP4L4 was different in moths collected with different ratios of sex pheromone lures and collected in different geographical locations. After gene knockdown of SlituCYP4L4 in the antennae, the electroantennogram (EAG) responses of male and female moths to (9Z,11E)-tetradecadienyl acetate or (9Z,12E)-tetradecadienyl acetate were significantly decreased. In contrast, EAG responses to plant volatiles and sex pheromones of other moth species were not significantly influenced in these moths. SlituCYP4L4 was also expressed in the gustatory tissues and sensilla, which suggests that SlituCYP4L4 may have other functions in the chemosensory system. Our results have shown for the first time the function of a CYP gene with appendage-specific expression in insect sex pheromone recognition, especially in adult moths. [ABSTRACT FROM AUTHOR]

Aim Extralevator abdominoperineal excision (ELAPR) is challenging 'conventional' abdominoperineal excision (APR), yet the safety and efficacy of ELAPR is still under debate. We therefore developed a laparoscopic APR with trans-abdominal individualized levator transection (LAPR-TILT) approach and compared the outcome with a conventional laparoscopic APR (CLAPR). Method All eligible patients were entered a single-centre randomized controlled trial to compare CLAPR and LAPR-TILT. We assessed the first 185 patients, including operative findings, complications, histopathology and urogenital function. Results Ninety-three patients in the CLAPR group and 92 patients in the APR-TILT group were included for analysis. The APR-TILT procedure took less time [137 (101-175) min vs 146 (102-187) min; P = 0.03], mainly owing to faster perineal dissection. APR-TILT resulted in a reduced rate of bowel perforation (1.1% vs 8.6%; P = 0.04), circumferential resection margin positivity (1.1% vs 10.8%; P = 0.01) and postoperative wound complications (5.4% vs 16.2%; P = 0.02) compared with the CLAPR procedure. At a median follow-up of 19 months after surgery, three patients (3.2%) in the CLAPR group had tumour recurrence while no tumour recurrence occurred in the LAPR-TILT group. Patients who underwent LAPR-TILT reported fewer urinary or sexual problems (LAPR-TILT vs CLAPR, 10.9% vs 24.7% and 17.4% vs 38.7%, respectively). Conclusion Compared with CLAPR, LAPR-TILT achieved better pathological results for factors that are surrogate parameters for local recurrence. LAPR-TILT could also reduce the risk of urogenital dysfunction. [ABSTRACT FROM AUTHOR]

The article offers information on the utility of the Extended Clearance Classification System (ECCS) informed approach for evaluating investigational drugs as substrates of drug transporters. It mentions the recognition given to drug transporters for their role in clinical pharmacokinetics and drug–drug interactions (DDIs). The article adds about the ability of ECCS in guiding transporter victim DDI assessments.

Contents This experiment was conducted to investigate the effects of inulin supplementation in low- or high-fat diets on both the reproductive performance of sow and the antioxidant defence capacity in sows and offspring. Sixty Landrace × Yorkshire sows were randomly allocated to four treatments with low-fat diet (L), low-fat diet containing 1.5% inulin ( LI), high-fat diet (H) and high-fat diet containing 1.5% inulin ( HI). Inulin-rich diets lowered the within-litter birth weight coefficient of variation ( CV, p = 0.05) of piglets, increased the proportion of piglets weighing 1.0-1.5 kg at farrowing (p < 0.01), reduced the loss of body weight ( BW) and backfat thickness ( BF) during lactation (p < 0.05) and decreased the duration of farrowing as well as improved sow constipation (p < 0.05). Sows fed fat-rich diets gained more BW during gestation (p < 0.01), farrowed a greater number of total (+1.65 pigs, p < 0.05) and alive (+1.52 pigs p < 0.05) piglets and had a heavier (+2.06 kg, p < 0.05) litter weight at birth as well as a decreased weaning-to-oestrous interval ( WEI, p < 0.01) compared with sows fed low-fat diets. However, it is worth noting that the H diet significantly decreased the serum activities of superoxide dismutase (T- SOD) and glutathione peroxidase ( GSH-Px) and increased the serum malondialdehyde ( MDA) levels in sows and piglets (p < 0.05). In contrast, HI diet enhanced the activities of T- SOD and GSH-Px and decreased the serum MDA concentrations (p < 0.05) in sows and piglets. In summary, the fat-rich diets fed to sows during gestation had beneficial effects on reproductive performance, but aggravated the oxidative stress in sow and piglets. Inulin-rich diets fed to sow during gestation had beneficial effects on within-litter uniformity of piglet birthweight and enhanced the antioxidant defence capacity of sows and piglets. [ABSTRACT FROM AUTHOR]

Contents The effects of dietary β-hydroxy- β-methylbutyrate ( HMB) supplementation during gestation on reproductive performance of sows and the mRNA expression of myogenic markers in skeletal muscle of neonatal pigs were determined. At day 35 of gestation, a total of 20 sows (Landrace × Yorkshire, at third parity) were randomly assigned to two groups, with each group receiving either a basal diet or the same diet supplemented with 4 g/day β-hydroxy- β-methylbutyrate calcium ( HMB-Ca) until parturition. At parturition, the total and live litter size were not markedly different between treatments, however, the sows fed HMB diet had a decreased rate of stillborn piglets compared with the sows fed the control ( CON) diets (p < 0.05). In addition, piglets from the sows fed HMB diet tended to have an increased birth weight (p = 0.08), and a reduced rate of low birth weight piglets (p = 0.05) compared with piglets from the CON sows. Nevertheless, lower feed intake during lactation was observed in the sows fed the HMB diet compared with those on the CON diet (p < 0.01). The relative weights of the longissimus dorsi ( LD) and semitendinosus ( ST) muscle were higher (p < 0.05) in neonatal pigs from the HMB than the CON sows. Furthermore, maternal HMB treatment increased the mRNA levels of the myogenic genes, including muscle regulatory factor-4 ( MRF4, p < 0.05), myogenic differentiation factor (MyoD) and insulin-like growth factor-1 ( IGF-1, p < 0.01). In conclusion, dietary HMB supplementation to sows at 4 g/day from day 35 of gestation to term significantly improves pregnancy outcomes and increases the expression of myogenic genes in skeletal muscle of neonatal piglets, but reduces feed intake of sows during lactation. [ABSTRACT FROM AUTHOR]

Background and Objective To investigate the feasibility of acellular bovine pericardium ( BP) for guided bone regeneration ( GBR) in vitro and in vivo. The success of GBR relies on the fact that various cellular components possess different migration rates into the defect site and that a barrier membrane plays a significant role in these processes. Material and Methods BP membrane was isolated and decellularized using an enzymatic method. The microarchitecture, mechanical properties, cytotoxicity and cell chemotaxis properties of the acellular BP were evaluated in vitro, and the in-vivo efficacy of the acellular BP was also investigated in a rabbit mandibular model. Results The acellular BP membrane possessed an interconnected fibrous structure. Glutaraldehyde ( GA) treatment was efficient for enhancement of the mechanical properties of the acellular BP bur and resulted in negligible cytotoxicity. After 16 wk, standardized osseous defects created in the rabbit mandible, and covered with acellular BP, were associated with an enhanced deposition of mineralized tissue when compared with defects left to spontaneous healing. Conclusion GA-treated acellular BP is promising as a barrier membrane for GBR for further in-vivo and clinical studies. [ABSTRACT FROM AUTHOR]

Heat stress has become an increasingly important factor in limiting wheat yields. In northern China, high temperature (>30 °C) during the grain filling is one of the major constraints in increasing wheat productivity. We used two winter wheat ( Triticum aestivum L.) cultivars with different sensitivities to heat stress (Jimai 22 ' JM22', low sensitivity and Xinmai 26 ' XM26', high sensitivity) to study the various aspects of photosynthetic characteristics during the grain filling stage under heat stress. The results showed that photosynthesis rates ( P n) in flag leaves of XM26 decreased faster than in JM22 under heat stress during the grain-filling stage. P n decreased more rapidly under heat stress than without stress, by up to 69.9% and 59.3%, respectively, at 10 days following heat stress (10 DAS). This decline of P n was not caused by heat-induced stomatal limitation, but rather by a decline in Rubisco activity and a functional drop in photosystem II ( PSII). After heat stress, the grain yield of JM22 decreased by 6.41%, but XM26 decreased by 11.43%, when compared with their respective controls. Heat stress also caused an alteration of mesophyll cell ultrastructure. Injury caused by heat stress to organelles in XM26 was more severe than JM22. Moreover, the JM22 cultivar showed some self-repair capacity following heat stress injury. These results indicate that declines in photosynthetic performance caused by heat stress were cultivar-dependent. Compared with XM26, the JM22 cultivar had superior heat stability in terms of PSII function and carboxylation activity, both of which are susceptible to heat stress. [ABSTRACT FROM AUTHOR]

Drug interactions due to efflux transport inhibition at the blood-brain barrier (BBB) have been receiving increasing scrutiny because of the theoretical possibility of adverse central nervous system (CNS) effects identified in preclinical studies. In this review, evidence from pharmacokinetic, pharmacodynamic, imaging, pharmacogenetic, and pharmacovigilance studies, along with drug safety reports, is presented supporting a low probability of modulating transporters at the human BBB by currently marketed drugs. [ABSTRACT FROM AUTHOR]

The International Transporter Consortium (ITC) organized a second workshop in March 2012 to expand on the themes developed during the inaugural ITC workshop held in 2008. The final session of the workshop provided perspectives from regulatory and industry-based scientists, with input from academic scientists, and focused primarily on the decision trees published from the first workshop. These decision trees have become a central part of subsequent regulatory drug-drug interaction (DDI) guidances issued over the past few years. [ABSTRACT FROM AUTHOR]

Root activity plays a dominant role in grain filling in cereal crops. However, the importance of deep roots for regulating post-anthesis leaf senescence is not clearly understood in wheat ( Triticum aestivum L.). In this study, we used 32P tracing to estimate the difference in wheat root activity at soil depths of 30 and 70 cm and the root restriction method to investigate the effects of vertical distribution of deep roots on leaf senescence, with non-restricted plants as controls. Recovery of radioactive 32P indicated that deep roots had significantly higher activity than upper roots in wheat. Root restriction at a soil depth of 50 cm caused significant decreases in the activities of superoxide dismutase ( EC 1.15.1.1), peroxidase ( EC 1.11.1.7), catalase ( EC 1.11.1.6) and ascorbate peroxidase ( EC 1.11.1.11) at 16 days after anthesis and thereafter resulting in an increase in malondialdehyde. As a result, chlorophyll levels and net photosynthesis decreased. Ultimately, the root-restricted wheat produced a significantly lower grain yield than the non-restricted controls. These data suggest that deep roots are pivotal for regulating plant senescence, duration of grain filling, and yield formation. [ABSTRACT FROM AUTHOR]

Ginseng (Araliaceae) has multiple pharmacological actions because of its diverse phytochemical constituents. The aims of the present study are to evaluate the preventive effects of North American ginseng on diabetic retinopathy and cardiomyopathy and to delineate the underlying mechanisms of such effects. Models of both type 1 (C57BL/6 mice with streptozotocin-induced diabetes) and type 2 diabetes (db/db mice) and age-matched and sex-matched controls were examined. Alcoholic ginseng root (200 mg/kg body weight, daily oral gavage) extract was administered to groups of both type 1 and type 2 diabetic mice for 2 or 4 months. Dysmetabolic state in the diabetic mice was significantly improved by ginseng treatment. In both the heart and retina of diabetic animals, ginseng treatment significantly prevented oxidative stress and diabetes-induced upregulations of extracellular matrix proteins and vasoactive factors. Ginseng treatment in the diabetic animals resulted in enhancement of stroke volume, ejection fraction, cardiac output, and left ventricle pressure during systole and diastole and diminution of stroke work. In addition, mRNA expressions of atrial natriuretic factor and brain natriuretic factor (molecular markers for cardiac hypertrophy) were significantly diminished in ginseng-treated diabetic mice. These data indicate that North American ginseng prevents the diabetes-induced retinal and cardiac biochemical and functional changes probably through inhibition of oxidative stress. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and aims: Mechanisms in sustaining the allergic hypersensitivity status in the body are unclear. Galectin-9 (Gal-9) has strong immune regulatory capacity. The present study aims to elucidate the role of Gal-9 in sustaining allergic status in the intestine. Methods: Duodenal biopsies were obtained from 20 patients with peptic ulcer and food allergy (FA). The expression of Gal-9 in intestinal tissue was examined at both protein level and mRNA level. Two coculture systems with intestinal epithelial cells (IEC) and mast cells, or dendritic cells (DC) and T cells were established to investigate the source of Gal-9 in the intestine and the mechanism by which Gal-9 modulated DC's phenotyping and sustained the T helper 2 polarization. Results: Normal IEC showed mild expression of Gal-9 that was markedly enhanced in patients with FA. Mast cells had the capability to induce IEC to produce Gal-9 via releasing tryptase that activated the proteinase-activated receptor 2 on IEC. Gal-9 activated DC to produce TIM4 (T-cell immunoglobulin mucin domain) via ligating TIM3 on DC via activating the cyclic guanosine monophosphate (cGMP) pathway. In a mouse FA model, blocking Gal-9 inhibited the allergic hypersensitivity status and the antigen-specific Th2 response in the intestine. Conclusions: IEC-derived Gal-9 contributes to sustaining the allergic status in the intestine. [ABSTRACT FROM AUTHOR]

Free-fatty acids (FFAs) are well-characterized factor for causing production of inflammatory factors and insulin resistance in adipocytes. Using cultured adipocytes, we demonstrate that FFAs can activate endoplasmic reticulum (ER) stress pathway by examination of ER stress sensor activation and marker gene expression. Chemical chaperone tauroursodeoxycholic acid (TUDCA) can reduce FFA-induced adipocyte inflammation and improve insulin signaling whereas overexpression of spliced X-box protein 1 (XBP-1s) only attenuates FFA-induced inflammation. PKR-like eukaryotic initiation factor 2α kinase (PERK) is one of the three major ER stress sensor proteins and deficiency of PERK alleviates FFA-induced inflammation and insulin resistance. The key downstream target of FFA-induced ER stress is IκB kinase β (IKKβ), a master kinase for regulating expression of inflammatory genes. Deficiency of PERK attenuates FFA-induced activation of IKKβ and deficiency of IKKβ alleviates FFA-induced inflammation and insulin resistance. Consistently, overexpression of IKKβ in 3T3-L1 CAR adipocytes causes inflammation and insulin resistance. In addition, IKKβ overexpression has profound effect on adipocyte lipid metabolism, including inhibition of lipogenesis and promotion of lipolysis. Furthermore, increased endogenous IKKβ expression and activation is also observed in isolated primary adipocytes from mice injected with lipids or fed on high-fat diet (HFD) acutely. These results indicate that ER stress pathway is a key mediator for FFA-induced inflammation and insulin resistance in adipocytes with PERK and IKKβ as the critical signaling components. [ABSTRACT FROM AUTHOR]

The article presents a study on the preparation of magnetic poly(methyl methacrylate) (PMMA) microspheres through double-miniemulsion polymerization. It states that Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray powder diffraction, and thermogravimetry were used to characterize magnetic polymer particles. Results show the encapsulation of oleic acid coated magnetite particles in PMMA.

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Varenicline is predominantly eliminated unchanged in urine, and active tubular secretion partially contributes to its renal elimination. Transporter inhibition assays using human embryonic kidney 293 cells transfected with human renal transporters demonstrated that high concentrations of varenicline inhibited substrate uptake by hOCT2 (IC50=890 μM), with very weak or no measurable interactions with the other transporters hOAT1, hOAT3, hOCTN1, and hOCTN2. Varenicline was characterized as a moderate-affinity substrate for hOCT2 (Km=370 μM) and its hOCT2-mediated uptake was partially inhibited by cimetidine. Co-administration of cimetidine (1,200 mg/day) reduced the renal clearance of varenicline in 12 smokers, resulting in a 29.0% (90% CI: 21.5%–36.9%) increase in systemic exposure. This increase is not considered clinically relevant, as it should not give rise to safety concerns. Consequently, it can be reasonably expected that other inhibitors of hOCT2 would not cause greater renal interactions with varenicline than that seen with the efficient hOCT2 inhibitor cimetidine.Clinical Pharmacology & Therapeutics (2008); 83, 4, 567–576.doi:10.1038/sj.clpt.6100405 [ABSTRACT FROM AUTHOR]

The expression of the structural genes nit-3 and nit-6, which encode the nitrate assimilatory enzymes nitrate reductase and nitrite reductase, respectively, is highly regulated by the global-acting NIT2 regulatory protein. These structural genes are also controlled by nitrogen catabolite repression and by specific induction via nitrate. A pathway-specific regulatory protein, NIT4, appears to mediate nitrate induction of nit-3 and of nit-6. The NIT4 protein, composed of 1090 amino acids, contains a putative GAL4-like Cys-6 zinc cluster DNA-binding motif, which is joined by a short segment to a stretch of amino acids that appear to constitute a coiled-coil dimerization domain. Chemical crosslinking studies demonstrated that a truncated form of NIT4 forms homodimers. Mobility-shift and DNA-footprinting experiments have identified two NIT4-binding sites of significantly different strengths in the promoter region of the nit-3 gene. The stronger binding site contains a symmetrical octameric sequence, TCCGCGGA, whereas the weaker site has a related sequence. Sequences related to this palindromic element can be found upstream of the nit-6 gene. [ABSTRACT FROM AUTHOR]

In this paper, we study the asymptotic behavior for a Bresse‐Timoshenko type system with time‐dependent delay terms. Our results follow a recent approach given by Almeida Júnior and Ramos (Zeitschrift für angewandte Mathematik und Physik. 68, 1‐31. 2017) where they showed that the viscous damping acting on angle rotation of the classical Bresse‐Timoshenko model eliminates the damage consequences of the so called second spectrum of frequency. Moreover, for Bresse‐Timoshenko type systems which are free of these consequences the assumption of equal wave speeds is not necessary anymore to get the exponential stability. Here, by introducing an appropriate Lyapunov functional we prove the exponential stability for time dependent delay cases regardless of any relationship between wave propagation velocities. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of noiiglutide as an adjunct to lifestyle intervention on the reduction in body weight and tolerability in obese Chinese adults without diabetes., Materials and Methods: In this 24-week, randomized, double-blind, placebo-controlled phase 2 trial, 254 obese adults with a body mass index of 28.0-40.0 kg/m 2 and without diabetes were enrolled. Participants were initially randomized in a 1:1:1 ratio to one of three dose levels: 0.12, 0.24, or 0.36 mg of the study treatment. Within each dose level, participants were further randomized in a 3:1 ratio to receive either subcutaneous injection of noiiglutide or a matching placebo. The primary endpoint was the change in body weight from baseline to week 24., Results: Across all noiiglutide dosage levels, least squares mean reductions in body weight from baseline to week 24 ranged from 8.03 to 8.50 kg, compared with 3.65 kg in the placebo group (all p-values <.0001). In the noiiglutide groups (0.12, 0.24, 0.36 mg/day), a significantly higher proportion of participants achieved a weight loss ≥5% (68.8%, 60.0%, 73.0%) and ≥10% (37.5%, 36.9%, 39.7%), compared with the pooled placebo group (≥5%: 29.0%; ≥10%: 8.1%). Gastrointestinal adverse events, such as nausea, diarrhoea and vomiting, were more common in all noiiglutide groups (15.4%-30.2%, 18.8%-22.2%, 15.6%-18.5%) than in the pooled placebo group (8.1%, 6.5%, 0%)., Conclusions: In obese Chinese adults without diabetes, once-daily subcutaneous noiiglutide significantly reduced body week at week 24 compared with placebo, and had a manageable safety profile, primarily involving gastrointestinal disorders., (© 2023 John Wiley & Sons Ltd.)

Aims: To assess the prevalence of diabetic peripheral neuropathy (DPN) and its risk factors in the type 2 diabetes mellitus (T2DM) population., Methods: This cross-sectional study enroled patients with T2DM between July and December 2017 from 24 provinces in China. Diabetic peripheral neuropathy and its severity were assessed by the Toronto clinical scoring system, neuropathy symptoms score (NSS) and neuropathy disability score. The prevalence of DPN and its risk factors were analysed., Results: A total of 14,908 patients with T2DM were enroled. The prevalence of DPN was 67.6%. Among 10,084 patients with DPN, 4808 (47.7%), 3325 (33.0%), and 1951 (19.3%) had mild, moderate, and severe DPN, respectively. The prevalence of DPN in females was higher than in males (69.0% vs. 66.6%, P = 0.002). The prevalence of DPN increased with age and course of diabetes and decreased with body mass index (BMI) and education level (all P for trend <0.05). The comorbidities and complications in patients with DPN were higher than in those without DPN, including hypertension, myocardial infarction, diabetic retinopathy, and diabetic nephropathy (all P < 0.001). Age, hypertension, duration of diabetes, diabetic retinopathy, diabetic nephropathy, glycated haemoglobin, high-density lipoprotein cholesterol, and lower estimated glomerular filtration rate were positively associated with DPN, while BMI, education level, fasting C-peptide, and uric acid were negatively associated with DPN., Conclusions: Among patients with T2DM in China, the prevalence of DPN is high, especially in the elderly, low-income, and undereducated patients., (© 2023 John Wiley & Sons Ltd.)

The high rates of misdiagnosis and untreated mortality with regard to Budd-Chiari syndrome (BCS) indicated the need to screen effective biomarkers. The aim of this study was to explore the function of extracellular vesicles (EVs) in patients with BCS as well as associated mechanisms. First, differentially expressed long non-coding RNAs (lncRNAs) from EVs separated from serum between BCS and healthy controls were screened using microarray analysis. Second, the proliferation, migration and tube formation of human vascular endothelial cells (HUVECs) were detected after EVs treatment, along with vascular endothelial growth factor (VEGF) levels and inflammatory factors from the cell supernatant. Last, the overexpressed lncRNA was transfected into the cells to further explore the mechanisms involved. Extracellular vesicles of BCS patients have significantly higher levels of lncRNA MTUS2-5 than healthy controls. Apparently, treatment with EVs from BCS or the ones transfected with plasmids that overexpress lncRNA MTUS2-5 enhances proliferation, migration and angiogenesis capacity. The results were considerably better than those obtained from treatment with EVs from healthy controls or transfection with the normal control plasmid, which also elevated the level of VEGF and inflammatory factors. Furthermore, FOS and PTGS2 were potentially regulated by the lncRNA MTUS2-5 transmitted by EVs. The lncRNA MTUS2-5 in EVs plays an important role in angiogenesis in the Budd-Chiari syndrome., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: To evaluate the association between cumulative body mass index (BMI) and long-term BMI change with non-alcoholic fatty liver disease (NAFLD)., Methods: We included 19 477 adult participants (12 556 men and 6921 women) from the Kailuan study from January 2006 to December 2013. Cumulative BMI was assessed using a quadratic mixed-effects method by sex before the index year; then, the NAFLD outcome was followed till December 2019. The long-term BMI change was calculated as the percentage change in average cumulative BMI from the baseline BMI., Results: During a median follow-up of 5.63 years, 6229 individuals developed incident NAFLD. Independent of baseline BMI, the NAFLD risk escalated with the cumulative BMI with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 1.60 (1.48-1.73) and 2.28 (2.06-2.53) for the intermediate tertile and the highest tertile (P trend  <0.001). The association is amplified in women and the young. Compared to a stable weight (BMI change: -3% to 3%), NAFLD risk increased in the baseline BMI < 24 kg/m 2 group with weight gain (BMI change: >3%) and decreased in BMI ≥24 kg/m 2 group with weight loss (BMI change: <-3%) for men and women. However, we only observed a decreased NAFLD risk in men (HR: 0.82, 95% CI: 0.69-0.97) with BMI < 24 kg/m 2 and weight loss., Conclusions: Monitoring cumulative BMI may help to identify high-risk NAFLD populations. The association between weight gain or loss varies by sex and baseline BMI, suggesting the importance of individualized weight management for NAFLD prevention., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated., Objective: To interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS., Materials and Methods: According to different treatments, RWPE-1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS (lipopolysaccharide) group, or Li-ESWT group (LPS-induced RWPE-1 managed by Li-ESWT). Following the Li-ESWT treatment, the levels of oxidative stress were assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague-Dawley rats were randomly divided into the control group, EAP group, or Li-ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and Western blot analysis., Results: Histological analysis showed reduced inflammation and expression of cytokines (TNF-α, IL-1β, IL-6, COX-2, SP) in prostate tissues from the Li-ESWT group compared with those from the EAP group (all p < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li-ESWT group compared with the EAP group (all p < 0.05). Besides, Li-ESWT treatment could decrease oxidative stress in the prostate and in RWPE-1 cells, respectively (both p < 0.05). Moreover, the Li-ESWT upregulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway., Discussion and Conclusions: Li-ESWT may reduce inflammation, oxidative stress, and pain in rats with autoimmunity-induced prostatitis via the PI3 K/AKT/FOXO1 pathway. It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS., (© 2021 American Society of Andrology and European Academy of Andrology.)

Colorectal cancer (CRC) is the leading cause of cancer-related mortality in the world. Accumulating evidence indicate that tumour infiltrating immune cells participated in cancer progression. Among them, tumour infiltrating neutrophils (TINs) are reported to play crucial role in various cancers. In this study, we used CIBERSORTx, a digital cytometry tool to evaluate the neutrophils infiltration in CRC based on gene expression data of CRC tissues from GSE39582 data set and The Cancer Genome Atlas data set (TCGA-COAD and TCGA-READ). Weighted gene co-expression network analysis (WGCNA) was conducted in GSE39582 data set to identify hub genes associated with neutrophil infiltration. The association of hub gene and neutrophils was then validated in TCGA cohorts and an independent RJ cohort. Functional analysis was performed to investigate the molecular mechanisms of the interested hub gene. We found that neutrophil infiltration is elevated in CRC tissues, and it is related to a poorer prognosis. A total of 18 gene modules are identified by WGCNA in GSE39582 data set, among which lightcyan module is significantly correlated with neutrophils infiltration. Furthermore, Superoxide Dismutase 2 (SOD2) in lightcyan module was proved to correlated with neutrophils infiltration in various cancer types. In addition, SOD2 expression is highly associated with several chemokines, including CXCL8, a neutrophils-related attractant, and functional analysis revealed that SOD2 is involved in neutrophils recruitment biological process. These results indicate that an 'SOD2-CXCL8-neutrophil recruitment' axis plays a potential role in colorectal cancer progression., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background & Aims: Non-invasive assessment criteria to rule out high-risk varices (HRV) in compensated hepatitis B virus (HBV) cirrhosis on antiviral therapy remains unclear., Methods: HBV-related compensated cirrhotic patients who underwent screening endoscopy during antiviral therapy were enrolled and randomly divided into the derivation and validation sets. HRV were defined as medium to large varices or small varices with red signs. Univariate and multivariate logistic analysis were used to determine the parameters associated with HRV., Results: A total of 436 HBV-related compensated cirrhotic patients screened for varices were enrolled, the median duration of antiviral therapy was 4 years (IQR: 2.5-5.5 years). In the derivation set (N = 290, 17.2% with HRV), only platelet (PLT) count (OR = 0.972, 95% CI 0.961-0.984, P < .05) was independently associated with HRV, whereas liver stiffness measurement was not associated with the presence of HRV. With a PLT count cut-off value of 105 × 10 9 /L, unnecessary endoscopies could be spared in 56.9% patients, with a 3.6%. risk of missing HRV. In the validation cohort (N = 146, 16.4% with HRV), the proportion of patients that could safely spare endoscopies (61.0%) identified by this PLT count cut-off value was higher than that obtained by using Baveno VI criteria (34.9%), with an acceptable risk of missing HRV (3.4%)., Conclusion: Compared with the 'Baveno VI criteria or beyond' criteria, PLT count higher than 105 × 10 9 /L could safely spare more screening endoscopies without increasing the risk of missing HRV in patients with HBV-related compensated cirrhosis on antiviral therapy., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Long non-coding RNAs (lncRNAs) have been well demonstrated to emerge as crucial regulators in cancer progression, and they can function as regulatory network based on their interactions. Although the biological functions of FAM83H-AS1 have been confirmed in various tumour progressions, the underlying molecular mechanisms of FAM83H-AS1 in oesophageal squamous cell carcinoma (ESCC) remained poorly understood. To address this, we treated human oesophageal cancer cell line Eca109 cells with TGF-β and found FAM83H-AS1 was notably overexpressed. In the present study, FAM83H-AS1 was observed to be significantly up-regulated in ESCC tissues and was associated with TNM stage, pathological differentiation and lymph node metastasis. FAM83H-AS1 reinforced oesophageal cancer cell proliferation, migration and invasion, and participated in epithelial-to-mesenchymal transition (EMT) process at mRNA and protein levels. In addition, a concordant regulation between FAM83H-AS1 and its sense strand FAM83H was detected at the transcriptional and translational levels. Furthermore, FAM83H-AS1 could act as competing endogenous RNA to affect the expression of Girdin by sponging miR-10a-5p verified by RIP and luciferase reporter assays. Consequently, the study provided a unique perspective of FAM83H-AS1 in ESCC progression, which may be considered as potential biomarker and therapeutic target for ESCC therapy., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background Posttranslational protein modification with O-linked N -acetylglucosamine (O-GlcNAc) is linked to high glucose levels in type 2 diabetes mellitus (T2DM) and may alter cellular function. We sought to elucidate the involvement of O-GlcNAc modification in endothelial dysfunction in patients with T2DM. Methods and Results Freshly isolated endothelial cells obtained by J-wire biopsy from a forearm vein of patients with T2DM (n=18) was compared with controls (n=10). Endothelial O-GlcNAc levels were 1.8-ford higher in T2DM patients than in nondiabetic controls ( P =0.003). Higher endothelial O-GlcNAc levels correlated with serum fasting blood glucose level ( r =0.433, P =0.024) and hemoglobin A 1c ( r =0.418, P =0.042). In endothelial cells from patients with T2DM, normal glucose conditions (24 hours at 5 mmol/L) lowered O-GlcNAc levels and restored insulin-mediated activation of endothelial nitric oxide synthase, whereas high glucose conditions (30 mmol/L) maintained both O-GlcNAc levels and impaired insulin action. Treatment of endothelial cells with Thiamet G, an O-GlcNAcase inhibitor, increased O-GlcNAc levels and blunted the improvement of insulin-mediated endothelial nitric oxide synthase phosphorylation by glucose normalization. Conclusions Taken together, our findings indicate a role for O-GlcNAc modification in the dynamic, glucose-induced impairment of endothelial nitric oxide synthase activation in endothelial cells from patients with T2DM. O-GlcNAc protein modification may be a treatment target for vascular dysfunction in T2DM.

The CRISPR-Cas technologies derived from bacterial and archaeal adaptive immune systems have emerged as a series of groundbreaking nucleic acid-guided gene editing tools, ultimately standing out among several engineered nucleases because of their high efficiency, sequence-specific targeting, ease of programming and versatility. Facilitated by the advancement across multiple disciplines such as bioinformatics, structural biology and high-throughput sequencing, the discoveries and engineering of various innovative CRISPR-Cas systems are rapidly expanding the CRISPR toolbox. This is revolutionizing not only genome editing but also various other types of nucleic acid-guided manipulations such as transcriptional control and genomic imaging. Meanwhile, the adaptation of various CRISPR strategies in multiple settings has realized numerous previously non-existing applications, ranging from the introduction of sophisticated approaches in basic research to impactful agricultural and therapeutic applications. Here, we summarize the recent advances of CRISPR technologies and strategies, as well as their impactful applications., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Isoliquiritigenin (ISL) is a flavonoid substance with a chalcone structure, which exerts anti-tumour, anti-oxidation and anti-inflammatory activity. The large-conductance calcium-activated potassium channel (BK C a ) is an important potassium channel with negative feedback regulation on the vascular smooth muscle cells (VSMCs) membrane. The activation of BK C a channel causes the hyperpolarization of VSMCs. It plays an important role in relaxation of blood vessels. Previous studies have shown that ISL causes the relaxation of the aorta and the basilar artery of the rat. However, there have not been studies on regulation of ISL in mesenteric arteries. To examine whether ISL causes the relaxation of the mesenteric artery of mice, we recorded vasodilation of mouse mesenteric arterial rings with a myograph. After contraction of arterial rings with phenylephrine, we added ISL to the arterial rings and measured its relaxation effect. To further examine which channel was involved in this relaxation effect, we tested the effects of ISL on endothelium-dependent and endothelium-independent vasodilation. Then we used BK C a channel blockers tetraethylammonium and iberiotoxin, to detect whether the BK C a channel is involved in ISL-induced vasodilation. Mesenteric arterial smooth muscle cells were isolated by enzyme digestion. Bis-(1, 3-dibutylbarbituric acid) trimethine oxonol staining was used to measure membrane potential of mesenteric arterial smooth muscle cells. We identified a vasodilation effect caused by ISL on mouse mesenteric arterial rings pre-contracted by phenylephrine in a concentration-dependent manner, with an EC 50 of 13.71 ± 1.1 μmol/L. The vasodilation effect of ISL is endothelium-independent. K + channel inhibitors tetraethylammonium and iberiotoxin reduced the vasodilation induced by ISL which suggested the involvement of BK C a channel., (© 2019 John Wiley & Sons Australia, Ltd.)

Aims: Febrile seizures (FSs) are the most common types of seizures in young children. However, little is known whether the memory deficits induced by early-life FSs could transmit across generations or not., Methods: The memory functions of different generations of FS rats were behaviorally evaluated by morris water maze, inhibitory avoidance task, and contextual fear conditioning task. Meanwhile, molecular biology and pharmacological methods were used to investigate the role of DNA methylation in transgenerational transmission of memory defects., Results: Prolonged FSs in infant rats resulted in memory deficits in adult and transgenerationally transmitted to next generation, which was mainly through mothers. For these two generations, DNA methyltransferase (DNMT) 1 was upregulated, leading to transcriptional inhibition of the synaptic plasticity protein reelin but not the memory suppressor protein phosphatase 1. DNMT inhibitors prevented the high expression of DNMT1 and hypermethylation of reelin gene and reversed the transgenerationally memory deficits. In addition, enriched environment in juvenile rats rescued memory deficits induced by prolonged FSs., Conclusions: Our study demonstrated early experience of prolonged FSs led to memory deficits in adult rats and their unaffected offspring, which involved epigenetic mechanisms, suggesting early environmental experiences had a significant impact on the transgenerational transmission of neurological diseases., (© 2018 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)