Role of inflammatory mediators in intracranial aneurysms: A review.

The formation, growth, and rupture of intracranial aneurysms (IAs) involve hemodynamics, blood pressure, external stimuli, and a series of hormonal changes. In addition, inflammatory response causes the release of a series of inflammatory mediators, such as IL, TNF-α, MCP-1, and MMPs, which directly or indirectly promote the development process of IA. However, the specific role of these inflammatory mediators in the pathophysiological process of IA remains unclear. Recently, several anti-inflammatory, lipid-lowering, hormone-regulating drugs have been found to have a potentially protective effect on reducing IA formation and rupture in the population. These therapeutic mechanisms have not been fully elucidated, but we can look for potential therapeutic targets that may interfere with the formation and breakdown of IA by studying the relevant inflammatory response and the mechanism of IA formation and rupture involved in inflammatory mediators.

Are digital technologies an effective inhibitor of depression among middle-aged and older adults? Micro-level evidence from a panel study.

The increased number of middle-aged and older adults leads to depression in this stratum of the population as a topical social and public health issue. However, the new generation of information technologies has exerted a profound impact on the lives of middle-aged and older adults, and offers potential solutions for alleviating their depression. This study utilizes data from the China Health and Retirement Longitudinal Study (CHARLS) collected between 2011 and 2018 and combines them with city-level traits. The results demonstrate that digital technology can reduce depression levels effectively in this group. Mechanism analysis reveals that digital technology could improve life satisfaction and subjective health status levels, which, in turn, reduces depression levels. Heterogeneity analysis shows that the positive effects of digital technology on depression were more pronounced among middle-aged and older adults with urban household registration compared to the rural population. Finally, recommendations are provided for reducing depression levels among middle-aged and older adults.

Identification of diagnostic markers for moyamoya disease by combining bulk RNA-sequencing analysis and machine learning.

Moyamoya disease (MMD) remains a chronic progressive cerebrovascular disease with unknown etiology. A growing number of reports describe the development of MMD relevant to infection or autoimmune diseases. Identifying biomarkers of MMD is to understand the pathogenesis and development of novel targeted therapy and may be the key to improving the patient's outcome. Here, we analyzed gene expression from two GEO databases. To identify the MMD biomarkers, the weighted gene co-expression network analysis (WGCNA) and the differential expression analyses were conducted to identify 266 key genes. The KEGG and GO analyses were then performed to construct the protein interaction (PPI) network. The three machine-learning algorithms of support vector machine-recursive feature elimination (SVM-RFE), random forest and least absolute shrinkage and selection operator (LASSO) were used to analyze the key genes and take intersection to construct MMD diagnosis based on the four core genes found (ACAN, FREM1, TOP2A and UCHL1), with highly accurate AUCs of 0.805, 0.903, 0.815, 0.826. Gene enrichment analysis illustrated that the MMD samples revealed quite a few differences in pathways like one carbon pool by folate, aminoacyl-tRNA biosynthesis, fat digestion and absorption and fructose and mannose metabolism. In addition, the immune infiltration profile demonstrated that ACAN expression was associated with mast cells resting, FREM1 expression was associated with T cells CD4 naive, TOP2A expression was associated with B cells memory, UCHL1 expression was associated with mast cells activated. Ultimately, the four key genes were verified by qPCR. Taken together, our study analyzed the diagnostic biomarkers and immune infiltration characteristics of MMD, which may shed light on the potential intervention targets of moyamoya disease patients.

Clipping and coiling of intracranial aneurysms in the elderly patients: clinical features and treatment outcomes.

Objective: In recent years, more and more cases of intracranial aneurysms (IAs) have been found in elderly patients, and neurosurgical interventions have increased, but there is still no consensus on the best treatment strategy for elderly patients. In elderly patients, endovascular coiling (EC) is more popular than surgical clipping (SC) due to its advantages of less trauma and faster recovery. However, SC has made great progress in recent years, significantly improving the prognosis of elderly patients. Therefore, it is necessary to further explore the effects of different treatment modalities on clinical prognosis, hospital stay, and hospital cost of elderly IA patients, and select the most appropriate treatment modalities. Methods: The authors retrospectively analyzed 767 patients with intracranial aneurysms admitted to the facility between August 2017 and December 2022. Prognostic risk factors and multivariate logistic regression were analyzed for elderly patients treated with EC or SC. The area under the receiver operating characteristic (ROC) curve was used to calculate the predictive power of each independent predictor between the treatment groups. Results: Our study included 767 patients with aneurysms, of whom 348 (45.4%) were elderly, 176 (22.9%) underwent endovascular coiling, and 172 (22.4%) underwent microsurgical clipping. A comparison of elderly patients treated with EC and SC showed a higher prevalence of hypertension in the EC group (P = 0.011) and a higher Hunt-Hess score on admission in the SC group (P = 0.010). Patients in the EC group had shorter hospital stays but higher costs (P = 0.000 and P = 0.000, respectively). Patients treated with SC had a higher incidence of postoperative cerebral infarction and poor prognosis (P = 0.002 and P = 0.008, respectively). Through multi-factor logistic analysis, it was found that age (OR 1.209, 95% CI 1.047-1.397, P = 0.010), length of stay (LOS) (OR 1.160, 95 CI% 1.041-1.289, P = 0.007), and complications (OR 31.873, 95 CI% 11.677-320.701, P = 0.000) was an independent risk factor for poor prognosis in elderly patients with EC. In elderly patients treated with SC, age (OR 1.105, 95% CI 1.010-1.209, P = 0.029) was an independent risk factor for poor prognosis. Conclusion: EC and SC interventions in elderly adults carry higher risks compared to non-older adults, and people should consider these risks and costs when making a decision between intervention and conservative treatment. In elderly patients who received EC or SC treatments, EC showed an advantage in improving outcomes in elderly patients although it increased the economic cost of the patient's hospitalization.

Development and initial validation of the Career Self-Management scale for Chinese coaches.

Objective: The purpose of the study was to develop and initially validate a context-specific scale assessing Career Self-Management for Chinese coaches (Career Self-Management Scale-CC; CSMS-CC). Methods: Firstly, qualitative data obtained from in-depth interview with coaches were contently analyzed to generate potential CSMS-CC items. The content validity of the items was evaluated by a panel of experts. Secondly, the factor structure and item performance of the CSMS-CC were examined using exploratory factor analysis (EFA) and internal consistency reliability of its subscales were evaluated in sample 1 (n = 229, 24.01% females). Thirdly, factor structure of the CSMS-CC was further examined using confirmatory factor analysis (CFA) in sample 2 (n = 295, 32.54% females). Internal consistency reliability was evaluated using Cronbach' alpha coefficient and composite reliability. Nomological validity was examined using Pearson correlation and structural equation modeling (SEM) by investigating the correlations between CSMS-CC subscales with career success. Finally, measurement invariance and latent mean difference of the CSMS-CC was examined across gender, professional title and coaching class using multiple-group CFA (MGCFA). Results: Based on the results of the content analysis and content validity evaluation, 18 CSMS-CC items were retained for further analysis. Results of EFA in sample 1 revealed that eight items were problematic and removed. The second round of EFA revealed that three components were retained and labelled as Networking Behavior (4 items), Training Exploration (3 items), and Guanxi Development (3 items). Results of CFA in sample 2 suggested that the 10-item three-correlated-factors model of CSMS-CC demonstrated acceptable model fit to the data, χ2 = 135.01, df = 32, p < 0.01, CFI = 0.91, TLI = 0.90, SRMR = 0.05, RMSEA = 0.092 (90% CI = 0.076-0.108). Composite reliability (ranging from 0.84 to 0.88) and Cronbach's alpha coefficients (ranging from 0.78 to 0.81) of three subscales were found satisfactory. Nomological validity was supported by the results that total score and subscale scores of the CSMS-CC were significantly associated with internal marketability and external marketability. It was found that the CSMS-CC measurement model was strict invariant across gender, professional title and coaching class. Significant differences on all three subscales across professional title and on Guanxi development across coaching class were revealed. Conclusion: Results of this study provided initial support for the psychometric properties of the 10-item CSMS-CC, which suggested that the CSMS-CC could be used for measuring the career self-management of Chinese coaches.

Prognostic Risk Factors of One-stage Surgical Clipping in aSAH Elderly Patients with MIAs.

OBJECTIVE: To discuss the prognostic factors affecting the prognosis of 1-stage surgical clipping in aneurysmal subarachnoid hemorrhage (aSAH) elderly patients with multiple intracranial aneurysms (MIAs). MATERIALS AND METHODS: A total of 84 elderly patients with aSAH who had MIAs and underwent 1-stage surgical clipping were retrospectively analyzed. Follow-up was conducted with patients 30 days after discharge using the Glasgow Outcome Scale (GOS). A GOS score of 1 to 3 was defined as a poor outcome, and a GOS score of 4 to 5 was defined as a good outcome. General information (gender, age, size of aneurysm, location of rupture of the responsible aneurysm, H-H grade, CT characteristics of aSAH, number of subarachnoid hemorrhages, operation opportunity, postoperative complications, and intraoperative rupture) and complications（cerebral infarction, hydrocephalus, electrolyte disturbance, and encephaledema）were recorded. Univariate analysis and multivariate regression analysis were used to analyze factors that may affect outcomes. RESULTS: Univariate analysis showed that the number of SAH events ( P =0.005), intraoperative rupture ( P =0.048) and postoperative complications ( P =0.002) were associated with the prognosis of aSAH elderly patients with MIAs undergoing 1-stage surgery. Multivariate analysis showed that the number of SAH events (odds ratio [OR] 4.740, 95% confidence interval [CI] 1.056 to 21.282, P =0.042) and postoperative complications (OR 4.531, 95% CI 1.266 to 16.220, P =0.020) were independently associated with the prognosis of aSAH elderly patients with MIAs undergoing 1-stage surgery. CONCLUSIONS: The number of SAH events and postoperative complications are independent risk factors for the prognosis of aSAH elderly patients with MIAs undergoing 1-stage surgery. These factors contribute to the timely treatment of potentially related patients.

Controlled Decompression Alleviates Motor Dysfunction by Regulating Microglial Polarization via the HIF-1α Signaling Pathway in Intracranial Hypertension.

Decompressive craniectomy (DC) is a major form of surgery that is used to reduce intracranial hypertension (IH), the most frequent cause of death and disability following severe traumatic brain injury (sTBI) and stroke. Our previous research showed that controlled decompression (CDC) was more effective than rapid decompression (RDC) with regard to reducing the incidence of complications and improving outcomes after sTBI; however, the specific mechanisms involved have yet to be elucidated. In the present study, we investigated the effects of CDC in regulating inflammation after IH and attempted to identify the mechanisms involved. Analysis showed that CDC was more effective than RDC in alleviating motor dysfunction and neuronal death in a rat model of traumatic intracranial hypertension (TIH) created by epidural balloon pressurization. Moreover, RDC induced M1 microglia polarization and the release of pro-inflammatory cytokines. However, CDC treatment resulted in microglia primarily polarizing into the M2 phenotype and induced the significant release of anti-inflammatory cytokines. Mechanistically, the establishment of the TIH model led to the increased expression of hypoxia-inducible factor-1α (HIF-1α); CDC ameliorated cerebral hypoxia and reduced the expression of HIF-1α. In addition, 2-methoxyestradiol (2-ME2), a specific inhibitor of HIF-1α, significantly attenuated RDC-induced inflammation and improved motor function by promoting M1 to M2 phenotype transformation in microglial and enhancing the release of anti-inflammatory cytokines. However, dimethyloxaloylglycine (DMOG), an agonist of HIF-1α, abrogated the protective effects of CDC treatment by suppressing M2 microglia polarization and the release of anti-inflammatory cytokines. Collectively, our results indicated that CDC effectively alleviated IH-induced inflammation, neuronal death, and motor dysfunction by regulating HIF-1α-mediated microglial phenotype polarization. Our findings provide a better understanding of the mechanisms that underlie the protective effects of CDC and promote clinical translational research for HIF-1α in IH.

A Combined Weighting Based Large Scale Group Decision Making Framework for MOOC Group Recommendation.

Massive open online courses (MOOC) are free learning courses based on online platforms for higher education, which not only promote the open sharing of learning resources, but also lead to serious information overload. However, there are many courses on MOOCs, and it can be difficult for users to choose courses that match their individual or group preferences. Therefore, a combined weighting based large-scale group decision-making approach is proposed to implement MOOC group recommendations. First, based on the MOOC operation mode, we decompose the course content into three stages, namely pre-class, in-class, and post-class, and then the curriculum-arrangement-movement- performance evaluation framework is constructed. Second, the probabilistic linguistic criteria importance through intercriteria correlation method is employed to obtain the objective weighting of the criterion. Meanwhile, the word embedding model is utilized to vectorize online reviews, and the subjective weighting of the criteria are acquired by calculating the text similarity. The combined weighting then can be obtained by fusing the subjective and objective weighting. Based on this, the PL-MULTIMIIRA approach and Borda rule is employed to rank the alternatives for group recommendation, and an easy-to-use formula for group satisfaction is proposed to evaluate the effect of the proposed method. Furthermore, a case study is conducted to group recommendations for statistical MOOCs. Finally, the robustness and effectiveness of the proposed approach were verified through sensitivity analysis as well as comparative analysis.

Controlled Decompression Alleviates Brain Injury via Attenuating Oxidative Damage and Neuroinflammation in Acute Intracranial Hypertension.

BACKGROUND: The benefits of controlled decompression (CDC) for patients with acute intracranial hypertension especially in terms of alleviating the complications caused by rapid decompression (RDC) have been confirmed by clinical studies. This study is aimed at evaluating the therapeutic potency of CDC with ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) by investigating the potential molecular mechanism in the acute intracranial hypertension (AICH) rabbit model. METHODS: Male New Zealand white rabbits were randomly subdivided into the sham-operated (SH) group, CDC group, and RDC group. Blood plasma samples and brain tissue were collected 2 days before operation (baseline) and at 3, 6, 24, and 72 hours after operation to measure the levels of UCH-L1, GFAP, oxidative stress indicators, and inflammatory cytokines by performing ELISA or Western blot. The neurological score of the rabbits and brain water content was graded 24 h after surgery. qPCR, immunofluorescence, and FJ-C staining were conducted. RESULTS: CDC improved neurological function, lowered brain water content, ameliorated neuronal degeneration, attenuated oxidative damage, and inflammatory responses to a greater extent than RDC. Plasma UCH-L1 level was significantly lower in the CDC group at 3 h postoperatively than in the RDC group. CDC reduced plasma GFAP levels to various degrees at 3 h, 6 h, and 24 h postoperatively compared with RDC. Immunofluorescence confirmed that the expression of UCH-L1 and GFAP in the cortex of the CDC group was lower than that of the RDC group. CONCLUSIONS: Our data collectively demonstrate that CDC could attenuate oxidative damage and inflammatory responses, downregulate UCH-L1 and GFAP levels, and contribute to an improved neuroprotective effect compared with RDC.

Controlled decompression attenuates brain damage in a rat model of epidural extreme intracranial hypertension: Partially via inhibiting necroptosis and inflammatory response.

Intracranial hypertension (IH) remains a common symptom of neurological diseases, and requires stepwise treatments to release intracranial pressure (ICP). In the present study, we built a rat model of epidural extreme intracranial hypertension (EEIH) and verified the effectiveness of a surgery method called controlled decompression on attenuating brain injury induced by EEIH. For the model part, we determined the level of EEIH of rats via recording ICP and cerebral perfusion pressure (CPP) and the variation tendency of survival rates, mean blood artery pressure and mean velocity (Vm) of left middle cerebral artery (LMCA) as ICP ascending. SD rats were assigned into 4 groups: Sham group, Controlled decompression group (Con group), Rapid decompression group (Rap group) and Rapid decompression + Necrostatin-1 (Nec-1) group (Rap+Nec-1 group). The results suggested that controlled decompression lowered cerebral water content, improved neurological function, and attenuated EEIH-induced inflammation response and ROS generation to a greater extent than rapid decompression. Meanwhile, controlled decompression functioned to preserve more Nissl bodies, indicating alleviated neuron injury after EEIH. Additionally, the permeability of blood brain barrier (BBB) was also safeguarded in the Con group. Western blotting (WB) and Real-time Polymerase Chain Reaction (rt-PCR) assays consistently determined lower protein and mRNA levels of necroptosis-related molecules receptor interacting protein kinase 1 (RIPK1), interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) (WB only) in the Con and Rap+Nec-1 group. Double immunofluorescent staining found weaker fluorescence intensity of RIPK3 in the compressed cortex of the Con and Rap+Nec-1 group.

An OWA Distance-Based, Single-Valued Neutrosophic Linguistic TOPSIS Approach for Green Supplier Evaluation and Selection in Low-Carbon Supply Chains.

This paper presents a technique based on the ordered weighted averaging (OWA) distance for the single-valued neutrosophic linguistic (SVNL) technique for order preference by similarity to an ideal solution (TOPSIS). First, the inadequacies of the existing SVNL TOPSIS are analyzed in detail. Second, a SVNL OWA distance (SVNLOWAD) measure is presented, and based on this, a modified TOPSIS, termed the SVNLOWAD-TOPSIS, is developed for multiple attribute decision-making problems with SVNL information. Third, a revised relative coefficient is proposed to rank potential alternatives. Finally, a numerical example concerning green supplier selection in low-carbon supply chains is introduced to demonstrate the effectiveness of the model.

Blocking constitutive activity of GHSR1a in the lateral amygdala facilitates acquisition of conditioned taste aversion.

Ghrelin is a circulating peptide hormone promoting feeding and regulating energy metabolism in human and rodents. Ghrelin functions by binding to its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), which are widely distributed throughout the brain including the amygdala, a brain region important for regulating valenced behavior, such as aversion. Interestingly, GHSR1a was once characterized by highly constitutive, ligand-independent activity. However, the physiological importance of such ligand-independent signaling on aversive memory processing has not been tested yet. Here, we applied [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-Substance P (D-SP), a full inverse agonist for GHSR1a, into the lateral amygdala (LA) and investigated the effect of blocking GHSR1a constitutive activity on conditioned taste aversion (CTA) in rats. We found that intra-LA infusion of a single low dose of D-SP (8ng/0.5µl/side) facilitates CTA acquisition. Moreover, pre-administration of a high dose of D-SP into the LA abolishes the suppressive effect of exogenous ghrelin on CTA acquisition. In contrast, pre-administration of the same dose of D-SP does not affect the suppression of substance P, a potent neurokinin-1 (NK1) receptor ligand, on CTA. Therefore, our data indicated that the spontaneous or basal activity of GHSR1a signaling in the LA might interfere with CTA memory formation. D-SP decreases the constitutive activity of GHSR1a and thus facilitates CTA. Altogether, our present findings along with previous results support the idea that ghrelin/GHSR1a signaling in the LA circuit blocks conditioned taste aversion.

[Characteristics of Raman Spectra of Polyethylene Terephthalate].

Raman spectrometry was employed to study the characteristics of Raman spectra of polyethylene terephthalate (PET), which were treated with sodium hydroxide, sulfuric acid and copper sulfate, respectively. Raman spectra under different conditions were obtained and the characteristics of the Raman spectra were analyzed. The morphology structures were observed under different conditions using Atomic Force Microscope. The results show that the spectral intensity of PET treated with sodium hydroxide is higher than that untreated between 200-1 750 cm(-1), while the intensity of PET treated with sodium hydroxide is lower than that untreated beyond 1 750 cm(-1) and the fluorescence background of Raman spectra is decreased. The spectral intensity of PET treated with sulfuric acid is remarkably reduced than that untreated, and the intensity of PET treated with copper sulphate is much higher than that untreated. The research results obtained by Atomic Force Microscopy show that the variations of the Raman spectra of PET fibers are closely related to. the chemical bonds and molecular structures of PET fibers. The surface of the PET treated with sodium hydroxide is rougher than that untreated, the surface roughness of the PET treated with sulfuric acid is reduced as compared to that untreated, while the surface roughness of the PET treated with copper sulphate is increased. The results obtained by Raman spectroscopy are consistent with those by Atomic Force Microscopy, indicating that the combination of Raman spectroscopy and Atomic Force Microscopy is expected to be a promising characterization technology for polymer characteristics.

Antigen presentation for the generation of binding molecules.

In the last few decades, several new methods have been established to isolate full antibodies and fragments thereof, some even using alternative scaffolds from in vivo and in vitro sources. These methods encompass robust techniques including immunization and hybridoma technology or phage display and also more laborious and novel approaches including ribosome display or B-cell immortalization. All methodologies are dependent upon proper antigen presentation for isolation, screening, and further characterization of the selected binding molecules. Here, antigens are classes of molecules including soluble or membrane proteins, part or domains thereof (extracellular domains of GPCRs), peptides, carbohydrates, and small-molecular-weight moieties. Presentation of the antigen in a functional state or perhaps even mimicking the intended application is crucial for successful isolation of useful binding molecules. Moreover, it is also necessary to consider the expression host and any posttranslational modifications of target proteins. The increasing demand to target more complex antigens, for instance, receptors and ion channels, is leading to the development of alternative procedures to present these proteins appropriately, for example by the use of virus-like particles and DNA immunization. This chapter describes in general approaches for the preparation of different forms of immunogens including synthetic peptides, proteins, cell-based antigens for immunization and in vitro display systems and in detail the preparation of a soluble protein as antigen.

Hybridoma technology for the generation of monoclonal antibodies.

Hybridoma technology has long been a remarkable and indispensable platform for generating high-quality monoclonal antibodies (mAbs). Hybridoma-derived mAbs have not only served as powerful tool reagents but also have emerged as the most rapidly expanding class of therapeutic biologics. With the establishment of mAb humanization and with the development of transgenic-humanized mice, hybridoma technology has opened new avenues for effectively generating humanized or fully human mAbs as therapeutics. In this chapter, an overview of hybridoma technology and the laboratory procedures used routinely for hybridoma generation are discussed and detailed in the following sections: cell fusion for hybridoma generation, antibody screening and characterization, hybridoma subcloning and mAb isotyping, as well as production of mAbs from hybridoma cells.

Geometries and electronic properties of the neutral and charged rare earth Yb-doped Si(n) (n = 1-6) clusters: a relativistic density functional investigation.

The neutral and charged YbSi(n) (n = 1-6) clusters considering different spin configurations have been systematically investigated by using the relativistic density functional theory with generalized gradient approximation. The total bonding energies, equilibrium geometries, Mulliken populations (MP), Hirshfeld charges (HC), fragmentation energies, and highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gaps are calculated and discussed. The optimized geometries indicate that the most stable YbSi(n) (n = 1-6) clusters keep basically the analogous frameworks as the low-lying Si(n)(+1) clusters, while the charged species deviate from their neutral counterparts, and that the doped Yb tends to occupy the substitutional site of the neutral and charged YbSi(n) isomers. The relative stabilities are investigated in terms of the calculated fragmentation energies, exhibiting enhanced stabilities for the remarkably stable neutral and charged YbSi2 and YbSi5 clusters. Furthermore, the calculated MP and HC values show that the charges of the neutral and charged YbSi(n) clusters transfer from the Yb atom to Si(n) atoms and the Yb atom acts as an electron donor, and that the f orbitals of the Yb atom in the neutral and charged YbSi(n) clusters behave as core without involvement in chemical bonding. The calculated HOMO-LUMO gaps indicate that the YbSi2 and YbSi4+ clusters have stronger chemical stabilities. Comparisons of the Yb-doped Si(n) (n = 1-6) with available theoretical results of transition-metal-doped silicon clusters are made. The growth pattern is investigated also.