Regeneration of Bone Defects in a Rabbit Femoral Osteonecrosis Model Using 3D-Printed Poly (Epsilon-Caprolactone)/Nanoparticulate Willemite Composite Scaffolds.

Steroid-associated osteonecrosis (SAON) is a chronic disease that leads to the destruction and collapse of bone near the joint that is subjected to weight bearing, ultimately resulting in a loss of hip and knee function. Zn2+ ions, as an essential trace element, have functional roles in improving the immunophysiological cellular environment, accelerating bone regeneration, and inhibiting biofilm formation. In this study, we reconstruct SAON lesions with a three-dimensional (3D)-a printed composite made of poly (epsilon-caprolactone) (PCL) and nanoparticulate Willemite (npW). Rabbit bone marrow stem cells were used to evaluate the cytocompatibility and osteogenic differentiation capability of the PCL/npW composite scaffolds. The 2-month bone regeneration was assessed by a Micro-computed tomography (micro-CT) scan and the expression of bone regeneration proteins by Western blot. Compared with the neat PCL group, PCL/npW scaffolds exhibited significantly increased cytocompatibility and osteogenic activity. This finding reveals a new concept for the design of a 3D-printed PCL/npW composite-based bone substitute for the early treatment of osteonecrosis defects.

Negative Pressure Waves Based High Resolution Leakage Localization Method Using Piezoceramic Transducers and Multiple Temporal Convolutions.

The negative pressure wave (NPW) signals generated by a pipeline leakage often have a long signal duration. When these signals are utilized to compute the leakage position, the long signal duration will result in a large area being considered as leakage area. The localization resolution is low. A novel high-resolution localization algorithm is developed for pipeline leakage detection using piezoceramic transducers in this paper. The proposed algorithm utilizes multiple temporal convolutions to decrease the localization functional values at the points close to the leakage, in order to reduce the range of the leakage area revealed by the proposed algorithm. As a result, the localization resolution is improved. A measured experiment was conducted to study the proposed algorithm. In the experiment, the proposed algorithm was used to monitor a 55.8 m pressurized pipeline with two controllable valves and two Lead Zirconate Titanate (PZT) sensors. With the aid of the piezoceramic sensor, the experimental results show that the proposed algorithm results in a resolution which is better than that of the traditional method.

Central neuropeptide W has anorexigenic effect in rats.

Neuropeptide W (NPW) is produced in neurons located in hypothalamus, brain stem and antral G cells and its receptors are present in the hypothalamus, in particular in the paraventricular nucleus (PVN). There are two forms of the peptide, designated as neuropeptide W-23 (NPW23) and neuropeptide W-30 (NPW30). Neuropeptide W is an endogenous ligand for G-protein-coupled receptor, GPR7 and GPR8 receptors (R), which in humans are expressed in the hypothalamus and probably involved in the control of energy homoeostasis and neuroendocrine axes. We conducted this study to investigate the effects of NPW on feeding intake and energy expenditure in Wistar rats. Systemic (icv) injection of both forms of neuropeptide W (NPW23 and NPW30) to ad libitum feeding Wistar rats decreased dark feeding and fasting-induced feeding. One week of systemic treatment with NPW23 decreased feeding intake and weight gain during the treatment period. On the other hand, systemic treatment with antineuropeptide W antibody increased feeding intake. Moreover, systemic treatment with neuropeptide W-23 raised body temperature and consequently thermogenesis. These results strongly suggest that neuropeptide W may play an important central role in the feeding intake and energy balance control in mammals.

Effective impact of nano-plastic-waste incorporated with nanotitina on the physical, mechanical and microstructural properties of white cement pastes composites for progressing towards sustainability.

Plastic waste (PW) has received a lot of attention as a possible additional material for industrial and environmental applications, particularly cement and/or concrete production for a more environmentally and economically sound use of raw materials and energy sources. PW has been investigated as an inert and/or active hydraulic filler for cement and/or concrete by numerous scientists. Plastic garbage is cheap, abundant, and takes long period of time to degrade in the eco-system (soil and water). The main goal of the ongoing research is to offer safety and efficacy by partially substituting nano-plastic waste (NPW), incorporated with nano-titania (NT), for the composition of white cement (WC). Blends are built up by substitution of WC with different ratios of NPW incorporated with fixed ratios of nano-titania (1.0 wt.%). Workability, physical, mechanical and microstructural properties have gone through laboratory and instrumental analysis. The results showed improvement in the compressive strength, density and microstructure due to the effective impact of fillers. Consequently, a decrease in total porosity, whiteness reflection (Ry) and early-rapid expansion. Eventually, the outcomes may reduce the pandemic strength, especially in the external environment, and other epidemics.

Sustainable development goals for industry, innovation, and infrastructure: demolition waste incorporated with nanoplastic waste enhanced the physicomechanical properties of white cement paste composites.

The COVID-19 pandemic significantly impacts the increase in plastic waste from food packaging, masks, gloves, and personal protective equipment (PPE), resulting in an environmental disaster, if collected, processed, transported, or disposed inappropriately. Plastic waste has a very long deterioration time in the environment (soil and water), cheap, and plentiful. Additionally, construction waste disposal is a process that transfers debris to a state that does lead to any sustainable or environmental problems. The core objective of this current research work is to provide safety and efficacy by partial substitution of both ultrafine demolition waste (UDW), incorporated with nanoplastic waste (NPW), for eco-white cement (E-WC) composition. E-WC is designed by partially substituted WC with UDW (1.0, 5.0, 10.0, 15.0, and 20.0 wt.%); incorporated with NPW (1.0 and 3.0 wt.%); to adequately protect people and the environment over long periods. The context examines the high performance, physicomechanical properties and high durability of blends as presences of silica in UDW proposed a hydraulic filler material, plus; high surface area of NPW. The microstructure and workability are characterized by X-Ray Fluorescence (XRF), Scanning Electron Microscope (SEM), and Transmission Electron Microscope (TEM) measurements. The record results show greatly enhanced in the mechanical strength due to the combination of NPW and UDW (active silica). With the presence of NPW and UDW in WC matrix, the highest level of crystallization formed consequently a decrease in whiteness reflection (Ry) and total porosity. In summary, WC blend with NPW and UDW reflects better workability and energy saving qualities, which are economical and environmentally beneficial and may result in decreased construction budget and improve a long-term raw material sustainability.

Evidence for Neuropeptide W Acting as a Physiological Corticotropin-releasing Inhibitory Factor in Male Chickens.

In vertebrates, adrenocorticotropin (ACTH), released by the pituitary gland, is a critical part of the stress axis and stress response. Generally, the biosynthesis and secretion of ACTH are controlled by both hypothalamic stimulatory factors and inhibitory factors [eg, ACTH-releasing inhibitory factor (CRIF)], but the identity of this CRIF remains unrevealed. We characterized the neuropeptide B (NPB)/neuropeptide W (NPW) system in chickens and found that NPW could directly target the pituitary to inhibit growth hormone (GH) and prolactin (PRL) secretion via neuropeptide B/W receptor 2 (NPBWR2), which is completely different from the mechanism in mammals. The present study first carried out a series of assays to investigate the possibility that NPW acts as a physiological CRIF in chickens. The results showed that (1) NPW could inhibit ACTH synthesis and secretion by inhibiting the 3',5'-cyclic adenosine 5'-monophosphate/protein kinase A signaling cascade in vitro and in vivo; (2) NPBWR2 was expressed abundantly in corticotrophs (ACTH-producing cells), which are located mainly in cephalic lobe of chicken pituitary, as demonstrated by single-cell RNA-sequencing, immunofluorescent staining, and fluorescence in situ hybridization; (3) dexamethasone could stimulate pituitary NPBWR2 and hypothalamic NPW expression in chicks, which was accompanied by the decease of POMC messenger RNA levels, as revealed by in vitro and subcutaneous injection assays; and (4) the temporal expression profiles of NPW-NPBWR2 pair in hypothalamus-pituitary axis and POMC in pituitary were almost unanimous in chicken. Collectively, these findings provide comprehensive evidence for the first time that NPW is a potent physiological CRIF in chickens that plays a core role in suppressing the activity of the stress axis.

Old and New Systemic Immune-Inflammation Indexes Are Associated with Overall Survival of Glioblastoma Patients Treated with Radio-Chemotherapy.

Background. Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods. We tested 12 different SI using blood tests from patients with isocitrate dehydrogenase 1 and 2 wild-type glioblastomas, treated with radio-chemotherapy. The primary endpoint was their overall survival. Results. A total of 77 patients, comprising 43 males and 34 females, with a median age of 64 years (age range 26-84), who were treated between October 2010 and July 2020, were included in the present analysis (approved by a local ethics committee). In the univariate Cox regression analysis, all the indexes except two showed a statistically significant impact on OS. In the multivariate Cox regression analysis, neutrophil × platelet × leukocyte/(lymphocyte × monocyte) (NPW/LM) and neutrophil × platelet × monocyte/lymphocyte (NPM/L) maintained their statistically significant impact value. Conclusions. This univariate analysis confirms the potential of systemic inflammation indexes in patients with glioblastoma, while the multivariate analysis verifies the prognostic value of NPW/LM and NPM/L.

FoxO3a suppresses neuropeptide W expression in neuronal cells and in rat hypothalamus and its implication in hypothalamic-pituitary-adrenal (HPA) axis.

FoxO3a, a forkhead family member of transcription factors, is involved in the regulation of cell metabolism, proliferation, differentiation and apoptosis. However, whether FoxO3a participates in the regulation of glucocorticoids induced-hypothalamic-pituitary-adrenal (HPA) dysfunction is still unknown. Our present results indicate that dexamethasone(DEX) increased FoxO3a expression in PC12 and hypothalamic neuronal cultures in correlation to reduced expression of NPW, a process that could be blocked by GR2 antagonist. DEX restrained the phosphorylation of Akt and FoxO3a, but not ERK1/2 phosphorylation, resulting with FoxO3a nuclear localization. Overexpression of FoxO3a inhibited NPW expression, while FoxO3a knockdown by siRNA had the opposite effect. The regulatory region of NPW promoter contains multiple FoxO3a binding sites, and FoxO3a bonding to these sites inhibited its transcriptional activity. In a rat model, chronic administration of corticosterone reduced animals' body weight and sucrose consumption and caused stress- depression like behavior. Corticosterone treatment induced a marked increase in FoxO3a levels, while decreased the expression of NPW protein in the hypothalamus. Immunofluorescent double labeling demonstrated that FoxO3a and NPW were collocated in the hypothalamus. Taken together, these data indicate that NPW is a new direct downstream target gene of FoxO3a. FoxO3a suppressed the transcription of NPW and modulated glucocorticoids-induced HPA dysfunction by directly regulating the expression of NPW. Thus, present findings suggest that FoxO3a and NPW may be potential therapeutic targets for endocrine and psychiatric disorders.

Distribution and Function of Neuropeptides W/B Signaling System.

Neuropeptide W (NPW) and neuropeptide B (NPB) are two structurally and functionally related regulatory peptides, which are highly expressed in several brain regions and, additionally, in some peripheral tissues. Nevertheless, their distributions in the tissues are not similar. They act on target tissues via two subtypes of G protein-coupled receptors which are designated as NPBWR1 (GPR7) and NPBWR2 (GPR8), respectively, and possess different binding affinities. NPB activates NPBWR1, whereas NPW stimulates both the receptors with similar potency. Both of these peptides takes a part in the central regulation of neuroendocrine axes, feeding behavior, energy homeostasis, cardiovascular functions, circadian rhythm, pain sensation, modulation of inflammatory pain, and emotions. Over the past few years, studies have shown that NPB is also involved in sleep regulation. On the contrary, NPW participates in regulation of vascular myogenic tone, inhibits gastric tension sensitive vagal afferents and insulin secretion. Also, expression of NPW in the stomach is regulated by feeding. Abovementioned findings clearly demonstrate the functional diversity among NPW versus NPB signaling systems. In this review, signal transduction pathways of NPW/NPB are critically evaluated and observed together with mapping of expression of their signaling systems.

Nordic pole walking improves walking capacity in patients with intermittent claudication: a randomized controlled trial.

PURPOSE: The aim of the study was to compare the efficacy of Nordic pole walking (NPW) training with traditional treadmill training (TT) on a claudication (CD) and maximum walking distance (MWD) in patients with peripheral arterial disease (PAD). METHOD: Patients with intermittent claudication (IC) (n = 70; age=68.27) in the Fontaine class II were randomized into a two three-month rehabilitation programs performed three times per week. TT were finished by 31 patients, NPW by 21. Walking capacity was measured by an exercise treadmill test (ETT) with the Gardner-Skinner protocol (before and after the program) and six minute walk test (6MWT) (before, during and after the program). RESULTS: In an ETT both groups reached significant increase in CD and MWD (p ≤ 0.005). In 6MWT NPW group reached significant increase in both CD (p = 0.001) and MWD (p = 0.001), whereas the TT group only in MWD (p = 0.001). CONCLUSIONS: NPW has been shown to be as effective as the standard TT and is much less expensive. It should be the preferred method of exercise for PAD patients with IC. IMPLICATIONS FOR REHABILITATION: Nordic walking training is a valuable form of rehabilitation for peripheral arterial disease (PAD) patients with intermittent claudication (IC). Nordic walking has been shown to be as efficient as traditional treadmill training. It is however more cost-effective method of rehabilitation in PAD patients.

Cloning and distribution of neuropeptide W and its receptors in pigs.

Neuropeptide W (NPW), a novel hypothalamic peptide, is an endogenous ligand for the orphan G protein-coupled receptors GPR7 (NPBWR1) and GPR8 (NPBWR2). Although several studies have implicated NPW in the regulation of feeding and energy metabolism in many species, the precise physiological function of NPW in pigs remains unclear. In this study, we cloned and sequenced NPW, GPR7, and GPR8 cDNA from pigs. NPW, GPR7, and GPR8 mRNA expression was quantified in the pig brain and peripheral tissues by semiquantitative reverse transcriptase polymerase chain reaction. Immunohistochemistry showed that NPW protein expression was limited in the brain and abundant in peripheral tissues. These results suggest that NPW is involved in the regulation of various physiological functions in pigs. The molecular and morphological data from this study provide a basis for further research on the functions of NPW in pigs.

Molecular dynamics simulation of neuropeptide B and neuropeptide W in the dipalmitoylphosphatidylcholine membrane bilayer.

GPR7 and GPR8 are recently deorphanized G-protein-coupled receptors that are implicated in the regulation of neuroendocrine function, feeding behavior, and energy homeostasis. Neuropeptide B (NPB) and neuropeptide W (NPW) are two membrane-bound hypothalamic peptides, which specifically antagonize GPR7 and GPR8. Despite years of research, an accurate estimation of structure and molecular recognition of these neuropeptide systems still remains elusive. Herein, we investigated the structure, orientation, and interaction of NPB and NPW in a dipalmitoylphosphatidylcholine bilayer using long-range molecular dynamics (MD) simulation. During 30-ns simulation, membrane-embedded helical axes of NPB and NPW tilted 30 and 15°, respectively, from the membrane normal in order to overcome possible hydrophobic mismatch with the lipid bilayer. The calculation of various structural parameters indicated that NPW is more rigid and compact as compared to NPB. Qualitatively, the peptides exhibited flexible N-terminal (residues 1-12) and rigid C-terminal α-helical parts (residues 13-21), confirming previous NMR data. A strong electrostatic attraction between C-termini and headgroup atoms caused translocation of the peptides towards lower leaflet of the bilayer. The stabilizing hydrogen bonds (H-bonds) between phosphate groups and Trp1, Lys3, and Arg15 of the peptides played important roles for membrane anchoring. MD simulations of Alanine (Ala) mutants revealed that WYK->Ala variant of NPB/NPW lacked crucial H-bond interactions with phospholipid headgroups and also caused severe misfolding in NPB. Altogether, the knowledge of preferred structural fold and interaction of neuropeptides within the membrane bilayer will be useful to develop synthetic agonist or antagonist peptides for GPR7 and GPR8.

A chronic high fat diet alters the homologous and heterologous control of appetite regulating peptide receptor expression.

Leptin, ghrelin and neuropeptide W (NPW) modulate vagal afferent activity, which may underlie their appetite regulatory actions. High fat diet (HFD)-induced obesity induces changes in the plasma levels of these peptides and alters the expression of receptors on vagal afferents. We investigated homologous and heterologous receptor regulation by leptin, ghrelin and NPW. Mice were fed (12 weeks) a standard laboratory diet (SLD) or HFD. Nodose ganglia were cultured overnight in the presence or absence of each peptide. Leptin (LepR), ghrelin (GHS-R), NPW (GPR7) and cholecystokinin type-1 (CCK1R) receptor mRNA, and the plasma leptin, ghrelin and NPW levels were measured. SLD: leptin reduced LepR, GPR7, increased GHS-R and CCK1R mRNA; ghrelin increased LepR, GPR7, CCK1R, and decreased GHS-R. HFD: leptin decreased GHS-R and GPR7, ghrelin increased GHS-R and GPR7. NPW decreased all receptors except GPR7 which increased with HFD. Plasma leptin was higher and NPW lower in HFD. Thus, HFD-induced obesity disrupts inter-regulation of appetite regulatory receptors in vagal afferents.