The essence of data plays a critical role in decision making in supply chain management (SCM). When data embedded in supply chains (SCs) are fuzzy, the associated equilibrium and performance measures ...also become fuzzy. This paper investigates the effects of fuzzy data on decision making in a two-echelon SC with a supplier and duopolistic retailers playing a Stackelberg strategic game in both intra- and inter-echelons. In contrast to existing approaches, this paper devises an analysis method to provide a likely interval of the fuzzy maximal profit with a known possibility level (degree of certainty) rather than a singleton (crisp value). The idea is based on the extension principle to reformulate the two-level optimization problem as a pair of parametric quadratic programs in order to calculate the lower and upper bounds of the leader’s fuzzy maximal profit at each possibility level of the obtained information. The analytic results indicate that the higher the degree of uncertainty, the smaller (larger) the lower (upper) bound of the maximum profit of each SC member. Moreover, the main results obtained from eight scenarios show that when the degree of demand diversity between the two retailers is significantly high, the Stackelberg leader is most likely to obtain lower profit and the marginal contribution of the primary demand to the total profit of the duopolistic retailers will exceed that of the powerful supplier’s maximum profit.
The aim of this study was to investigate the functional networks in subjects with reversible cerebral vasoconstriction syndrome (RCVS) using resting-state functional magnetic resonance imaging ...(rs-fMRI).
We prospectively recruited patients with RCVS and healthy controls (HCs) between February 2017 and April 2021. The rs-fMRI data were analyzed using graph theory methods. We compared node-based global and regional topological metrics (Bundle 1) and network-based intranetwork and internetwork connectivity (Bundle 2) between RCVS patients and HCs. We also explored the associations of clinical and vascular (ie, the Lindegaard index, LI) parameters with significant rs-fMRI metrics.
A total of 104 RCVS patients and 93 HCs were included in the final analysis. We identified significantly decreased local efficiency of the left dorsal anterior insula (dAI; p = 0.0005) in RCVS patients within 30 days after disease onset as compared to HCs, which improved 1 month later. RCVS patients also had increased global efficiency (p = 0.009) and decreased average degree centrality (p = 0.045), clustering coefficient (p = 0.033), and assortativity values (p = 0.003) in node-based analysis. In addition, patients with RCVS had increased internetwork connectivity of the default mode network (DMN) with the salience (p = 0.027) and dorsal attention (p = 0.016) networks. Significant correlations between LI and regional local efficiency in left dAI (r
= -0.418, p = 0.042) was demonstrated.
The significantly lower local efficiency of the left dAI, suggestive of impaired central autonomic modulation, was negatively correlated with vasoconstriction severity, which is highly plausible for the pathogenesis of RCVS. ANN NEUROL 2023.
Alzheimer's disease (AD) is a detrimental neurodegenerative disease, and early diagnosis appears to be the key to successful treatment. Acrolein, a byproduct of lipid peroxidation, has been shown to ...contribute to the pathological process of AD. This study recruited 118 elderly subjects consisting of 58 non-demented control subjects and 62 AD patients. We analyzed the acrolein-related metabolites in the plasma, cerebrospinal fluid (CSF), and urine of all subjects. We found that the levels of acrolein-conjugated protein (Acr-PC) in the plasma (p = 0.00012) and CSF (p = 0.00161) of AD patients were significantly higher than those of control subjects, whereas the levels of a urinary acrolein metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA), were markedly decreased (p = 0.00882) in AD patients. These data suggest that deregulated acrolein metabolism may be correlated with neuronal damage in AD patients, which might provide further insights into the disease progression and early diagnosis of AD.
Cyclizine, an over‐the‐counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, ...dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine‐induced cytotoxicity and apoptosis remain unclear. During the 24 h incubation duration, RAW264.7 macrophages were exposed to different concentrations of cyclizine. Cytotoxicity was assessed through the lactate dehydrogenase assay. Flow cytometry employing annexin V‐fluorescein isothiocyanate and propidium iodide was utilized to evaluate apoptosis and necrosis. Caspase activity and mitochondrial dysfunction were evaluated through a fluorogenic substrate assay and JC‐1 dye, respectively. Flow cytometry employing fluorogenic antibodies was utilized to evaluate the release of cytochrome c and expression of death receptor, including tumor necrosis factor‐α receptor and Fas receptor. Western blotting was utilized to evaluate the expression of the Bcl2 and Bad apoptotic regulatory proteins. The findings unveiled from the present study demonstrated that cyclizine exerted a concentration‐dependent effect on RAW264.7 macrophages, leading to the induction of cytotoxicity, apoptosis, and necrosis. This compound further activated the intrinsic apoptotic pathway by inducing mitochondrial dysfunction, Bcl2/Bad exchange expression, cytochrome c liberation, and activation of caspases contained caspase 3, 8, and 9. Moreover, the activation of the extrinsic apoptotic pathway was observed as cyclizine induced the upregulation of death receptors and increased caspase activities. Based on our investigations, it can be inferred that cyclizine prompts cytotoxicity and apoptosis in RAW264.7 macrophages in a concentration‐dependent manner by triggering both the intrinsic and extrinsic apoptotic pathways.
Silver nanowires (AgNWs) have been widely used for stretchable and foldable conductors due to their percolating network nanostructure. To enhance the mechanical strength of AgNW thin films under ...extreme stretching conditions, in this study, we utilize a simple chemical reaction to join AgNW network connections. Upon applying a reactive ink over AgNW thin films, silver nanoparticles are preferentially generated over the nanowire junctions and solder the nanomesh structures. The soldered nanostructure reinforces the conducting network and exhibits no obvious change in electrical conductivity in the stretching or rolling process with elongation strains up to 120%. Several examples are also demonstrated to show potential applications of this material in stretchable electronic devices.
Spreading depolarization is a wave of neuronal and glial depolarization. Within minutes after spreading depolarization, the neuronal hemichannel pannexin 1 (PANX1) opens and forms a pore complex with ...the ligand-gated cation channel P2X7, allowing the release of excitatory neurotransmitters to sustain spreading depolarization and activate neuroinflammation. Here, we explore the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility with important consequences for neuroinflammation and trigeminovascular activation. We found that genetic loss of function or ablation of the P2x7 gene inhibits spreading depolarization. Moreover, pharmacological suppression of the P2X7-PANX1 pore complex inhibits spreading depolarization in mice carrying the human familial hemiplegic migraine type 1 R192Q missense mutation as well as in wild-type mice and rats. Pore inhibitors elevate the electrical threshold for spreading depolarization, and reduce spreading depolarization frequency and amplitude. Pore inhibitors also suppress downstream consequences of spreading depolarization such as upregulation of interleukin-1 beta, inducible nitric oxide synthase and cyclooxygenase-2 in the cortex after spreading depolarization. In addition, they inhibit surrogates for trigeminovascular activation, including expression of calcitonin gene-related peptide in the trigeminal ganglion and c-Fos in the trigeminal nucleus caudalis. Our results are consistent with the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility and its downstream consequences, of potential relevance to its signature disorders such as migraine.
Novel transparent conductive electrodes (TCEs) with copper (Cu)/silver (Ag) core/shell nanofibers (NFs) containing random, aligned, and crossed structures were prepared using a combination of ...electrospinning (ES) and chemical reduction. The ES process was used to prepare continuous copper nanofibers (Cu-NFs), which were used as core materials and were then immersed in silver ink (Ag ink) to form a protective layer of Ag to protect the Cu-NFs from oxidation. The Ag shell layer protected the Cu-NFs against oxidation and enhanced their conductivity. Such Cu/Ag core/shell webs can be easily transferred on the flexible matrix and can be applied in TCEs. The metal NF webs of different structures exhibited various degrees of conductivity and followed the order random type > crossed type > aligned type; however, the order with respect to transmittance (T) was inverse. The aligned nanowire networks exhibited a high T of over 80%, and the random ones exhibited a low sheet resistance of less than 102 Ω/sq (the best value is 7.85 Ω/sq). The present study demonstrated that TCEs based on Cu/Ag core/shell NF webs have considerable flexibility, transparency, and conductivity and can be applied in novel flexible light-emitting diode devices and solar cells in the future.
Fucoxanthin is a natural pigment widely distributed in macroalgae and microalgae. An orange‐colored xanthophyll, it has several bioactive effects, including anticancer, anti‐obesity, oxidative stress ...reduction, and anti‐inflammation. Acute lung injury (ALI) caused by acute infections or injurious stimuli to the lung tissues is a severe pulmonary inflammatory disease. To date, no evidence has shown ALI to be reduced by fucoxanthin through activation of Ras homolog family member A (RhoA) and the nuclear factor (NF)‐κB pathway in lipopolysaccharide (LPS)‐treated mice. Pretreatment with fucoxanthin inhibited histopathological changes in lung tissues and neutrophil infiltration into bronchoalveolar lavage fluid induced by LPS in ALI mice. Moreover, LPS‐induced proinflammatory cytokine expression and neutrophil infiltration were inhibited by fucoxanthin in a concentration‐dependent manner. Pretreatment of mice with fucoxanthin inhibited NF‐κB phosphorylation and IκB degradation in the lungs of mice with LPS‐induced ALI. We further found that phosphorylation of Akt and p38 mitogen‐activated protein KINASE (MAPK) was inhibited by fucoxanthin. By contrast, the phosphorylation of extracellular signal‐regulated kinase and c‐Jun N‐terminal kinase was not inhibited by fucoxanthin. Furthermore, we found that the activation of RhoA was inhibited by fucoxanthin in LPS‐induced ALI. On the basis of these results, we propose that fucoxanthin disrupts the RhoA activation‐mediated phosphorylation of Akt and p38 MAPK, leading to NF‐κB activation in mice with LPS‐induced ALI.
Purpose of Review
Spreading depression (SD) is a wave of simultaneous and near-complete depolarization of virtually all cells in brain tissue associated with a transient “depression” of all ...spontaneous or evoked electrical activity in the brain. SD is widely accepted as the pathophysiological event underlying migraine aura and may play a role in headache pathogenesis in secondary headache disorders such as ischemic stroke, subarachnoid or intracerebral hemorrhage, traumatic brain injury, and epilepsy. Here, we provide an overview of the pathogenic mechanisms and propose plausible hypotheses on the involvement of SD in primary and secondary headache disorders.
Recent Findings
SD can activate downstream trigeminovascular nociceptive pathways to explain the cephalgia in migraine, and possibly in secondary headache disorders as well. In healthy, well-nourished tissue (such as migraine), the intense transmembrane ionic shifts, the cell swelling, and the metabolic and hemodynamic responses associated with SD do not cause tissue injury; however, when SD occurs in metabolically compromised tissue (e.g., in ischemic stroke, intracranial hemorrhage, or traumatic brain injury), it can lead to irreversible depolarization, injury, and neuronal death. Recent non-invasive technologies to detect SDs in human brain injury may aid in the investigation of SD in headache disorders in which invasive recordings are not possible.
Summary
SD explains migraine aura and progression of neurological deficits associated with other neurological disorders. Studying the nature of SD in headache disorders might provide pathophysiological insights for disease and lead to targeted therapies in the era of precision medicine.
The lack of available historical data resulting from increasing market turbulence and very short product life cycles means that the demand in an inventory system varies non-stochastically and must ...therefore be subjectively determined. This paper investigates the economic production lot size inventory problem, in which a positive lead time and shortages are allowed, with fuzzy demands and an unknown explicit membership function. An analysis method based on an <inline-formula><tex-math notation="LaTeX">\alpha </tex-math></inline-formula>-cut representation and fuzzy ranking is proposed to derive the optimal inventory policy. In addition, the necessary and sufficient conditions for the optimal inventory policy are determined. The merits of the proposed approach include the ability to obtain a numeric and precise optimal policy rather than a fuzzy policy and no requirement for explicit forms of the membership functions of the fuzzy demands, which increases the generality of the proposed model. Additionally, practical insights are provided.
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