Background: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL) on TCIP. Methods: Spontaneous pain, paw withdrawal threshold and latency were assessed using TCIP mouse model. Immunofluorescence was used to identify the reactions of glia. RT-PCR and western blot or ELISA were used to determine mRNA or protein expression of tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), CC chemokine ligand 2 (CCL2) and chemotactic cytokine receptor 2 (CCR2) in vivo and in vitro. Results: l-CDL significantly attenuated TCIP hypersensitivity, accompanying with downregulation of TNF-α and IL-1β expression levels and declined astrocytes and microglial activation. It also significantly decreased the expression of the mRNA and protein level for CCL2 and CCR2. Further, l-CDL could suppress TNF-α-induced astrocytes activation and IL-1β expression through downregulating the CCL2/CCR2. Besides, CCL2-induced BV-microglia activation and inflammatory factors secretion were suppressed by l-CDL via CCR2. Conclusions: Suppression of CCL2/CCR2 by l-CDL may contribute to alleviate TCIP, offering an alternative medication for TCIP. Full article

Traveling surges are commonly adopted in protection devices of high-voltage direct current (HVDC) transmission systems. Lightning strikes also can produce large-amplitude traveling surges which lead to the malfunction of relays. To ensure the reliable operation of protection devices, recognition of traveling surges must be considered. Wavelet entropy, which can reveal time-frequency distribution features, is a potential tool for traveling surge recognition. In this paper, the effectiveness of wavelet entropy in characterizing traveling surges is demonstrated by comparing its representations of different kinds of surges and discussing its stability with the effects of propagation distance and fault resistance. A wavelet entropy-based recognition method is proposed and tested by simulated traveling surges. The results show wavelet entropy can discriminate fault traveling surges with a good recognition rate. Full article

Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-κB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu—a natural compound derived from Morinda officinalis F. C. How—has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear. In the present study, we found that Bajijiasu dose-dependently inhibited RANKL-induced osteoclast formation and bone resorption from 0.1 mM, and reached half maximal inhibitory effects (IC₅₀) at 0.4 mM without toxicity. Expression of RANKL-induced osteoclast specific marker genes including cathepsin K (Ctsk), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP), vacuolar-type H⁺-ATPase V0 subunit D2 (V-ATPase d2), and (matrix metalloproteinase-2 (MMP2) was inhibited by Bajijiasu treatment. Luciferase reporter gene studies showed that Bajijiasu could significantly reduce the expression and transcriptional activity of NFAT as well as RANKL-induced NF-κB activation in a dose-dependent manner. Further, Bajijiasu was found to decrease the RANKL-induced phosphorylation of extracellular signal-regulated kinases (ERK), inhibitor of κB-α (IκB-α), NFAT, and V-ATPase d2. Taken together, this study revealed Bajijiasu could attenuate osteoclast formation and bone resorption by mediating RANKL signaling pathways, indicative of a potential effect of Bajijiasu on osteolytic bone diseases. Full article

Osteoporosis and Alzheimer’s disease (AD) are common chronic degenerative disorders which are strongly associated with advanced age. We have previously demonstrated that amyloid beta peptide (Aβ), one of the pathological hallmarks of AD, accumulated abnormally in osteoporotic bone specimens in addition to having an activation effect on osteoclast (Bone 2014,61:164-75). However, the underlying molecular mechanisms remain unclear. Activation of NF-κB, extracellular signal-regulated kinase (ERK) phosphorylates, and calcium oscillation signaling pathways by receptor activator NF-κB ligand (RANKL) plays a pivotal role in osteoclast activation. Targeting this signaling to modulate osteoclast function has been a promising strategy for osteoclast-related diseases. In this study, we investigated the effects of Aβ on RANKL-induced osteoclast signaling pathways in vitro. In mouse bone marrow monocytes (BMMs), Aβ exerted no effect on RANKL-induced osteoclastogenesis but promoted osteoclastic bone resorption. In molecular levels, Aβ enhanced NF-κB activity and IκB-α degradation, activated ERK phosphorylation and stimulated calcium oscillation, thus leading to upregulation of NFAT-c1 expression during osteoclast activation. Taken together, our data demonstrate that Aβ enhances RANKL-induced osteoclast activation through IκB-α degradation, ERK phosphorylation, and calcium oscillation signaling pathways and that Aβ may be a promising agent in the treatment of osteoclast-related disease such as osteoporosis. Full article

With the increasing interest in online shopping, the Last Mile delivery is regarded as one of the most expensive and pollutive—and yet the least efficient—stages of the e-commerce supply chain. To address this challenge, a novel location-routing problem with simultaneous home delivery and customer’s pickup is proposed. This problem aims to build a more effective Last Mile distribution system by providing two kinds of service options when delivering packages to customers. To solve this specific problem, a hybrid evolution search algorithm by combining genetic algorithm (GA) and local search (LS) is presented. In this approach, a diverse population generation algorithm along with a two-phase solution initialization heuristic is first proposed to give high quality initial population. Then, advantaged solution representation, individual evaluation, crossover and mutation operations are designed to enhance the evolution and search efficiency. Computational experiments based on a large family of instances are conducted, and the results obtained indicate the validity of the proposed model and method. Full article

Interleukin enhancer binding factor 2 (ILF2), a transcription factor, regulates cell growth by inhibiting the stabilization of mRNA. Currently, its role has gained recognition as a factor in the tumorigenic process. However, until now, little has been known about the detailed role ILF2 plays in hepatocellular carcinoma (HCC). In this study, we investigated the expression levels of ILF2 in HCC tissue with Western blot and immunohistochemical assays. To examine the effect of ILF2 on liver cancer cell growth and apoptosis, small interfering RNAs (siRNAs) targeting ILF2 were recombined to create lentiviral overexpression vectors. Our results showed higher expression levels of ILF2 mRNA and ILF2 protein in HCC tissue compared with matched peritumoral tissue. Expression of ILF2 may regulate cell growth and apoptosis in liver cancer cells via regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2 related ovarian killer (Bok), Bcl-2-associated X protein (BAX), and cellular inhibitor of apoptosis 1 (cIAP1). Moreover, we inoculated nude mice with liver cancer cells to investigate the effect of ILF2 on tumorigenesis in vivo. As expected, a rapid growth was observed in cancer cells inoculated with a lentiviral vector coding Flag-ILF2 (Lenti-ILF2) compared with the control cells. Hence, these results promote a better understanding of ILF2’s potential role as a therapeutic target in HCC. Full article

Quality improvement practice (QIP), as a competitive strategy, is increasingly vital for auto factories to improve the product quality and brand reputation. Quality activity on selected automotive parts among a variety of competing candidates is featured by prioritization calculation. It arouses our interest how to select the appropriate auto part to perform quality improvement action based on the collected data from the after-sale source. Managers usually select the QIP part by the rule of thumb that is based on the quantitative criterion or the subjective preference of individuals. The total quality management (TQM) philosophy requires multiple stakeholders’ involvement, regarded as a multi-criteria decision making (MCDM) issue. This paper proposes a novel hybrid MCDM framework to select the best quality improvement solution combining the subjective and objective information. The rough set-based attribute reduction (RSAR) technique was employed to establish the hierarchy structure of influential criteria, and the decision information was collected with triangular fuzzy numbers (TFNs) for its vagueness and ambiguity. In addition, the novel hybrid MCDM framework integrating fuzzy DEMATEL (decision making trial and evaluation laboratory) method, the anti-entropy weighting (AEW) technique and fuzzy VlseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR) was developed to rank the alternatives with the combined weight of criteria. The results argue that the optimal solution keeps a high conformance with Shemshadi’s and Chaghooshi’s methods, which is better than the existing determination. Besides, the result analysis shows the robustness and flexibility of the proposed hybrid MCDM framework. Full article

With the rapid depletion of natural resources and undesired environmental changes globally, more interest has been shown in the research of green supply chain practices, including end-of-life vehicle (ELV) recycling. The ELV recycling is mandatory for auto-manufacturers by legislation for the purpose of minimizing potential environmental damages. The purpose of the present research is to determine the best choice of ELV recycling service provider by employing an integrating hybrid multi-criteria decision making (MCDM) method. In this research, economic, environmental and social factors are taken into consideration. The linguistic variables and trapezoidal fuzzy numbers (TFNs) are applied into this evaluation to deal with the vague and qualitative information. With the combined weight calculation of criteria based on fuzzy aggregation and Shannon Entropy techniques, the normative multi-criteria optimization technique (FVIKOR method) is applied to explore the best solution. An application was performed based on the proposed hybrid MCDM method, and sensitivity analysis was conducted on different decision making scenarios. The present study provides a decision-making approach on ELV recycling business selection under sustainability and green philosophy with high robustness and easy implementation. Full article

Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP), a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX) mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT). Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk), TRACP (Acp5), and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis. Full article

Osteoporosis, a metabolic bone disease, is characterized by an excessive formation and activation of osteoclasts. Anti-catabolic treatment using natural compounds has been proposed as a potential therapeutic strategy against the osteoclast related osteolytic diseases. In this study, the activity of berberine sulfate (an orally available form of berberine) on osteoclast differentiation and its underlying molecular mechanisms of action were investigated. Using bone marrow macrophages (BMMs) derived osteoclast culture system, we showed that berberine sulfate at the dose of 0.25, 0.5 and 1 μM significantly inhibited the formation of osteoclasts. Notably, berberine sulfate at these doses did not affect the BMM viability. In addition, we observed that berberine sulfate inhibited the expression of osteoclast marker genes, including cathepsin K (Ctsk), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP, Acp5) and Vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2). Luciferase reporter gene assay and Western blot analysis further revealed that berberine sulfate inhibits receptor for activation of nuclear factor ligand (RANKL)-induced NF-κB and NFAT activity. Taken together, our results suggest that berberine sulfate is a natural compound potentially useful for the treatment of osteoporosis. Full article

Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A > compound C > compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-κB and IκBα degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis. Full article

Mango (Mangifera indica L.), also called “the king of fruits”, is one of the most popular fruits in tropical regions. Pulp and peel samples of mango cultivars were analyzed to estimate total phenolic, total flavonoid and total anthocyanin contents. Phenolic acids, hydrophilic peroxyl radical scavenging capacity (hydro-PSC) and oxygen radical scavenging capacity (ORAC) in vitro were also determined. Total phenolics and flavonoid contents were found maximum in the peel of Xiao Tainang and Da Tainang cultivars, respectively, whereas Xiao Tainang also exhibited significant antioxidant capacity. Noteworthy, concentrations of gallic acid, protocatechuic acid, ferulic acid, chlorogenic acid and caffeic acids at 79.15, 64.33, 33.75, 27.19 and 13.62 mg/100 g fresh weight (FW) were quantified for Da Tainang, Xiao Tainang and of Jidan cultivars, respectively. Comparatively, a higher level of phenolics and significant antioxidant capacity in mango peel indicated that it might be useful as a functional food and value-added ingredient to promote human health. Full article

Since 2009, great public attention has been paid in Lhasa City (Tibet, China) to mosquito bites and accompanying inflammatory complications. However, the potential contribution of knowledge levels, experiences, disease control and preventive practices (KEP) towards mosquitoes has not received much attention. To investigate community KEP concerning mosquitoes in Lhasa, a cross-sectional survey was undertaken in four sub-districts of urban Lhasa in 2012. Questionnaires were designed to collect information regarding socio-demographics and KEP concerning the harmful effects of mosquitoes on participants. The scoring for KEP was developed after consultation of literature. A total of 591 eligible questionnaires were examined. The majority of respondents were female (61.8%) with a mean age of 46 years. Nearly all of the respondents were of Tibetan nationality (97.4%) and living in registered native households (92.7%), who have less than primary school education. The averages of overall score, knowledge score, experience score, and practice score were 9.23, 4.53, 1.80, 2.90, respectively. The registered household with the highest overall score, knowledge score and practice score was non-native. Female subjects with monthly incomes between 1000 and 3000 RMB had higher experience scores. The correlation analysis revealed that significant positive linear correlations existed between knowledge and experience, knowledge and practices, and experience and practices towards mosquitoes. Past experiences with mosquitoes can result in a better knowledge of effective mosquito control practices in the present and the future. Though the average of overall scores related to mosquitoes is high among the participants in Lhasa, however, the knowledge about the ecological habits of mosquitoes should be strengthened. The findings in this study may help to develop strategies and measures of mosquito and mosquito-borne diseases in the future, not only in Lhasa, but also in similar altitude, latitude and longitude regions worldwide. Full article

Long non-coding RNA HOTAIR exerts regulatory functions in various biological processes in cancer cells, such as proliferation, apoptosis, mobility, and invasion. We previously found that HOX transcript antisense RNA (HOTAIR) is a negative prognostic factor and exhibits oncogenic activity in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the role and molecular mechanism of HOTAIR in promoting HCC cell migration and invasion. Firstly, we profiled its gene expression pattern by microarray analysis of HOTAIR loss in Bel-7402 HCC cell line. The results showed that 129 genes were significantly down-regulated, while 167 genes were significantly up-regulated (fold change >2, p < 0.05). Bioinformatics analysis indicated that RNA binding proteins were involved in this biological process. HOTAIR suppression using RNAi strategy with HepG2 and Bel-7402 cells increased the mRNA and protein expression levels of RNA binding motif protein 38 (RBM38). Moreover, the expression levels of RBM38 in HCC specimens were significantly lower than paired adjacent noncancerous tissues. In addition, knockdown of HOTAIR resulted in a decrease of cell migration and invasion, which could be specifically rescued by down-regulation of RBM38. Taken together, HOTAIR could promote migration and invasion of HCC cells by inhibiting RBM38, which indicated critical roles of HOTAIR and RBM38 in HCC progression. Full article

Summer extreme heat threatens the health of individuals, especially persons who are involved in outdoor activities. Ensuring the normal function of a city, bus drivers are among those who participate in outdoor physical activities and are exposed to excessive heat in hot summer weather. This qualitative study was performed to explore professional bus drivers’ in-depth views of extreme heat risks to their health, and ultimately develop targeted advice and policy interventions for city bus drivers. An interview-based study was performed among professional bus drivers in Jinan, China, including four focus groups with professional bus drivers (n = 37) and three interviews with their managers (n = 14). Five central themes or categories from the bus driver interviews were found: concerns about summer heat; health effects related to extreme heat; adaptive measures; barriers in implementing these adaptive measures; and suggested interventions. The beneficial role of cooling facilities (particularly air-conditioning) during extreme heat are addressed. The barriers not only impede the implementation of behavioral adaptive measures but also enhance the negative attitudes of bus drivers towards their effectiveness. The responsibilities of managers in promoting preventive actions are addressed. Full article

Quikclot has been used many years for treating external hemorrhage in the battle field. In this study, the hemostatic performance of NZG-JY (natural zeolite granules from Jinyun, China) was evaluated and compared with Quikclot in a lethal rabbit model of complex groin injury. Fifty-six anesthetized rabbits were randomized to three different groups: (1) NZG-JY (n = 19); (2) Quikclot (n = 19); and (3) medical gauze (n = 18). Survival was recorded three hours after the application of the hemostatic agents. The wound healing properties of the survived animals (n = 4 for each group) were observed a week later. The clotting efficiency is 100% for the animals in the NZG-JY and the Quikclot group, while only 5.6% in the gauze group. The mortality in the NZG-JY group (21.0%) is significantly less than that in the Quikclot group (52.6%) and the gauze group (66.7%). A good healing property was achieved in all animals that survived in the NZG-JY group, while three quarters of the animals in the Quikclot group had serious necrotic tissue. NZG-JY significantly decreases the mortality in a lethal rabbit model of complex groin injury and demonstrates good healing properties. Full article

Two new 9,19-cycloartane triterpene glycosides 1-2, together with four known compounds—26-deoxyactein (3), actein (4), 7,8-didehydro-26-deoxyactein (5) and cimiaceroside B (6)—were isolated from the rhizome of Cimicifuga foetida. The new triterpene glycosides were identified as 23-O-methyl-24-deoxy-2'-O-(3''-methylmalonyl)-cimiaceroside B (1) and 2'-O-(3''-methylmalonyl)actein (2) based on analysis of their spectral data and chemical reactions. Full article

Five new 9,19-cycloartane triterpene diglycosides, which have been named cimiaceroside C (1), and cimifosides A-D (2-5) together with the known compounds cimiracemoside D (6), cimidahurine (7) and α-D-glucopyranosyl-l-β-D-fructofuranoside (8) were isolated from the rhizome of Cimicifuga foetida. The new triterpene diglycosides 1-5 were identified as cimiacerol-3-O-β-D-xylopyranosyl-(1''→3')-β-D-xylopyranoside, 12β-hydroxycimigenol-3-O-β-D-xylopyranosyl-(1''→3')-β-D-xylopyranoside, 25-Oacetylcimig- enol-3-O-β-D-xylopyranosyl-(1''→3')-β-D-xylopyranoside, 24- acetylhydroshengmanol-3-O-β-D-xylopyranosyl-(1''→3')-β-D-xylopyranoside and 26- deoxyacetylacteol-3-O-β-D-xylo- pyranosyl-(1''→3')-β-D-xylopyranoside, respectively, based on analysis of their spectral data and chemical reactions. Full article