Probabilistic Analysis of the (1+1)-Evolutionary Algorithm.

We give a detailed analysis of the optimization time of the [Formula: see text]-Evolutionary Algorithm under two simple fitness functions (OneMax and LeadingOnes). The problem has been approached in the evolutionary algorithm literature in various ways and with different degrees of rigor. Our asymptotic approximations for the mean and the variance represent the strongest of their kind. The approach we develop is based on an asymptotic resolution of the underlying recurrences and can also be extended to characterize the corresponding limiting distributions. While most of our approximations can be derived by simple heuristic calculations based on the idea of matched asymptotics, the rigorous justifications are challenging and require a delicate error analysis.

Assessing TGF-ß Prognostic Model Predictions for Chemotherapy Response and Oncogenic Role of FKBP1A in Liver Cancer.

BACKGROUND: The Transforming Growth Factor-Beta (TGF-ß) signaling pathway plays a crucial role in the pathogenesis of diseases. This study aimed to identify differentially expressed TGF-ß-related genes in liver cancer patients and to correlate these findings with clinical features and immune signatures. METHODS: The TCGA-STAD and LIRI-JP cohorts were utilized for a comprehensive analysis of TGF-ß- related genes. Differential gene expression, functional enrichment, survival analysis, and machine learning techniques were employed to develop a prognostic model based on a TGF-ß-related gene signature (TGFBRS). RESULTS: We developed a prognostic model for liver cancer based on the expression levels of nine TGF-ß- related genes. The model indicates that higher TGFBRS values are associated with poorer prognosis, higher tumor grades, more advanced pathological stages, and resistance to chemotherapy. Additionally, the TGFBRS-High subtype was characterized by elevated levels of immune-suppressive cells and increased expression of immune checkpoint molecules. Using a Gradient Boosting Decision Tree (GBDT) machine learning approach, the FKBP1A gene was identified as playing a significant role in liver cancer. Notably, knocking down FKBP1A significantly inhibited the proliferation and metastatic capabilities of liver cancer cells both in vitro and in vivo. CONCLUSION: Our study highlights the potential of TGFBRS in predicting chemotherapy responses and in shaping the tumor immune microenvironment in liver cancer. The results identify FKBP1A as a promising molecular target for developing preventive and therapeutic strategies against liver cancer. Our findings could potentially guide personalized treatment strategies to improve the prognosis of liver cancer patients.

Can kynurenine pathway be considered as a next-generation therapeutic target for Parkinson's disease? An update information.

By far, no revolutionary breakthrough in the treatment of Parkinson's disease (PD) was found. It is indeed a knotty problem to select a satisfactory strategy for treating some patients with advanced stage PD. Development of novel therapeutic targets against PD has been an urgent task faced by global PD researchers. Targets in the tryptophan-kynurenine pathway (KP) were then considered. Metabolites in the KP are liposoluble. Some neurotoxic metabolites, including 3-hydroxykynurenine and its downstream 3-hydroxyanthranilic acid and quinolinic acid, are mainly produced peripherally. They can easily cross the blood-brain barrier (BBB) and exert their neurotoxic effects in the central neuron system (CNS), which is considered as a potential pathophysiological mechanism of neurodegenerative diseases. Hence, agents against the targets in the KP have two characteristics: (1) being independent from the dopaminergic system and (2) being seldom affected by the BBB. Inspiringly, one agent, namely, the inhibitor of indoleamine 2,3-dioxygenase 1, has been currently reported to present satisfactory efficacy comparable to levodopa, implying that the KP might be a potential novel target for PD. This review collected and summarized the updated information regarding the association of the KP with PD, which is helpful for understanding the clinical value of the KP in the PD scenario.

Dolutegravir Plus Lamivudine Dual-Drug Regimen in Treatment-Naive HIV-1-Infected Patients With High-Level Viral Load: Preliminary Data From the Real World.

BACKGROUND: Some inpatients with HIV-RNA ≥500,000 copies/mL in China need to use 2-drug regimen for some reasons, although limited data are available for dolutegravir plus lamivudine (3TC) in those patients with ultra-high viral loads. METHODS: We conducted a single-center retrospective-prospective study in China and enrolled 42 ART-naive HIV-infected inpatients who use a once-daily 2-drug regimen because of various reasons (drug interaction, renal impairment, age, and other related comorbidities).They were divided into 2 groups, low viral load group (baseline viral load <500,000 copies/mL, n = 20) and high viral load group (baseline viral load ≥500,000 copies/mL, n = 22). All patients were followed up for 48 weeks. RESULTS: The median of baseline viral load was 5.74 log10 copies/mL and CD4+ T-cell count was 59 cells/µL. At week 48, there was no significant difference (P = 0.598) in proportions of participants with HIV-1 RNA <50 copies/mL [90%, 95% confidence interval (CI) (75.6% to 104.4%) in low viral load groups vs 95.5%, 95% CI (86.0% to 104.9%) in high viral load groups]. No differences were found in mean increase of CD4+ T-cell count from baseline between 2 groups (218 ± 122 vs 265 ± 127 cells/µL, P = 0.245). There is no grade 3 or higher treatment-related adverse events and none discontinued treatment because of adverse events. CONCLUSIONS: The results of our study in real world support dolutegravir + 3TC dual regimen as a promising therapy option for treatment-naive HIV-infected patient with baseline viral load ≥500,000 copies/mL.

CD4+ T Cell Count, Sleep, Depression, and Anxiety in People Living With HIV: A Growth Curve Mixture Modeling.

We investigated changes in CD T cell counts related to sleep quality, depression, anxiety, and sociodemographic variables in heterogeneous groups of people living with HIV in a 6-month prospective study. Our longitudinal study involved 247 ambulatory patients living with HIV and using antiretroviral therapy. Sleep quality, anxiety, depression, and CD T cell counts were assessed three times at 3-month intervals. Growth curve mixture modeling was conducted to explore changes over time. A two-class mixture model with logarithmic change pattern fit the data best. For the majority of the sample (89.1%), anxiety, depression, and sleep quality did not change when CD T cells increased. For a small proportion of the sample (11.9%), sleep quality, anxiety, and depression deteriorated when CD T cells decreased. Marital status and alcohol use affected the classification significantly. Health care professionals should provide relevant services to people living with HIV with decreasing CD T cell counts.

Angelica polysaccharide mitigates lipopolysaccharide-evoked inflammatory injury by regulating microRNA-10a in neuronal cell line HT22.

Background: Angelica polysaccharide (AP) is disengaged from the roots of Angelica sinensis. The extensive pathological activities of AP have been discovered in disparate diseases. Nevertheless, the impression of AP in epilepsy (EP) remains unaware. The research attempted to probe the impact of AP on lipopolysaccharide (LPS)-evoked inflammatory injury in HT22 cells. Methods: AP were exploited to stimulate HT22 cells, cell cytotoxicity was monitored by CCK-8 assay. LPS was utilized to administrate HT22 cells to evoke inflammatory injury, meanwhile the involvements of AP in cell proliferation, apoptosis and inflammatory cytokines productions were examined. MicroRNA-10a (miR-10a) inhibitor and its negative control were one by one transfected into HT22 cells, the effect of miR-10a inhibition on LPS- and AP-treated cells was determined. NF-κB and JAK2/STAT3 pathways were ultimately detected. Results: AP promoted cell proliferation, inhibited apoptosis and suppressed IL-1ß, TNF-α and IL-6 productions in LPS-stimulated HT22 cells. Additionally, AP raised miR-10a expression in HT22 cells administration with LPS. These functions of AP in LPS-disposed cells were conversed by miR-10a suppression. Further, AP interdicted NF-κB and JAK2/STAT3 pathways via enhancing miR-10a. Conclusions: Data corroboarted that AP mitigated LPS-evoked inflammatory injury through repression of NF-κB and JAK2/STAT3 pathways by regulating miR-10a in HT22 cells.

Correlation Studies and Literature Review of Medullary Artery Occlusion After Intracranial Vertebral Artery Stenting.

BACKGROUND: Stenosis of the target intracranial vertebral artery is one of the major causes of posterior circulation ischemic stroke. The objective of this paper is to explore methods for reducing the occurrence of medullary artery occlusion after intracranial vertebral artery stenting. CASE DESCRIPTION: The current research presents a retrospective analysis of 48 patients who received Gateway-Wingspan stent angioplasty to treat severe stenosis of the intracranial vertebral artery, evaluates the results of stenosis remission and perfusion improvement after stent angioplasty, and explores the causes of postoperative medullary artery occlusion. A total of 49 Wingspan stents were implanted in the 48 patients, with a surgical success rate of 100%. After stent implantation, the patients' rates of intracranial vertebral artery stenosis dropped from 75.9% ± 6.3% to 28.4% ± 5.1%. Transcranial Doppler or cranial computed tomography angiography 3 months after surgery showed that none of the patients suffered from in-stent restenosis. Within 24 hours after surgery, medullary perforating artery occlusion occurred in 2 patients, probably because atherosclerotic plaque in the stenotic area became less stable and displaced under the mechanical action of postoperative saccule and stent. As a result, the medullary artery was blocked. After drug and rehabilitation therapies, the patients' symptoms were alleviated. CONCLUSIONS: Perforating artery occlusion after intracranial vertebral artery stenting can be prevented by strict assessment and preparation before surgery, correct choices of saccule and stent during operation, and other measures. However, large sample data are needed for verification.

Asiatic acid protects differentiated PC12 cells from Aß25-35-induced apoptosis and tau hyperphosphorylation via regulating PI3K/Akt/GSK-3ß signaling.

Amyloid ß (Aß) peptide can cause neurotoxicity in Alzheimer's disease (AD). The main purpose of the present study is to investigate the protective role of asiatic acid (AA) against Aß25-35-induced neurotoxicity in neuronally differentiated PC12 cells. Differentiated PC12 cells were pretreated with 5, 10 or 20 µM AA before treatment with 20 µM Aß25-35. The viability and apoptosis of differentiated PC12 cells were determined by MTT assay and Annexin V-FITC/PI double staining, respectively. The mitochondrial membrane potential (MMP) of differentiated PC12 cells was analyzed by JC-1 staining. The expression levels of proteins were detected by western blot analysis. We found that AA significantly increased the viability of differentiated PC12 cells but attenuated the mitochondria-mediated apoptosis dose-dependently when challenging with Aß25-35. Besides, the results of western blot analysis showed that AA prevented IκBα degradation and p65 nuclear translocation, and promoted the phosphorylation of Akt and GSK-3ß in Aß25-35-treated differentiated PC12 cells. Moreover, LY294002, a specific PI3K inhibitor, was found to abolish the beneficial effects of AA on Aß25-35-induced apoptosis and tau protein hyperphosphorylation. Our findings demonstrated that AA protects differentiated PC12 cells from Aß25-35-induced apoptosis and tau protein hyperphosphorylation, which might be partially mediated by the activation of the PI3K/Akt/GSK-3ß signaling pathway.

Neuroprotective role of fucoxanthin against cerebral ischemic/reperfusion injury through activation of Nrf2/HO-1 signaling.

In the present study, an attempt was made to determine whether administration of fucoxanthin could attenuate cerebral ischemic/reperfusion (I/R) injury and its possible mechanisms using an in vivo middle cerebral artery occlusion (MCAO) model and an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model. Fucoxanthin was intragastrically administrated in different doses (30 mg/kg, 60 mg/kg, and 90 mg/kg, respectively) to the rats 1 h before MCAO induction. The neurological function, infarct area and brain water content of rats were then evaluated. Rat cortical neuron were pretreated with different doses of fucoxanthin (5 µM, 10 µM, and 20 µM) and then subjected to OGD/R. Expression levels of proteins in the brain tissues and cultured cells were determined by western blotting. Our results demonstrated that fucoxanthin pretreatment improved the neurologic deficit score, lowered the infarct volume and reduced the expression of apoptosis-associated proteins in brain tissues. In addition, fucoxanthin also suppresses OGD/R-induced apoptosis and ROS accumulation in cultured neurons. Furthermore, we found that fucoxanthin could significantly activate the Nrf2/HO-1 signaling through inducing Nrf2 nuclear translocation with enhanced HO-1 expression, and Nrf2 knockdown obviously abrogated the beneficial role of fucoxanthin in OGD/R-treated neurons. These findings suggested that fucoxanthin could be exploited as a therapeutic target for protecting neurons from cerebral I/R injury.

p38 mitogen-activated protein kinase gene silencing rescues rat hippocampal neurons from ketamine-induced apoptosis: An in vitro study.

Ketamine (KTM) is an anesthetic drug with several advantages, including the elevation of cardiac output and blood pressure. However, KTM may also induce the apoptosis of hippocampal neurons. Notably, p38 mitogen­activated protein kinase (p38MAPK) has previously been studied for its role in neuronal injury. Therefore, the present study evaluated the effect of lentivirus­mediated p38MAPK gene silencing on KTM­induced apoptosis of rat hippocampal neurons. Hippocampal neurons were extracted from neonatal Sprague­Dawley rats, and then treated with KTM, p38MAPK­short hairpin RNA or SB203580 (an inhibitor of p38MAPK). Next, the expression levels of p38MAPK and apoptosis­associated genes, including caspase­3, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax), were detected. In addition, cell viability and apoptosis were determined using an MTT assay and flow cytometry, respectively. Finally, telomerase activity of hippocampal neurons was detected by ELISA. The results revealed that silencing of p38MAPK in KTM­treated cells decreased the expression levels of p38MAPK, caspase­3 and Bax, and the extent of p38MAPK phosphorylation, while it increased the expression of Bcl­2. Furthermore, silencing p38MAPK promoted cell viability, cell cycle progression and the telomerase activity of hippocampal neurons, and inhibited the apoptosis of hippocampal neurons. Taken together, the results suggested an inhibitory role of lentivirus­mediated p38MAPK gene silencing on KTM­induced apoptosis of rat hippocampal neurons. Thus, p38MAPK gene silencing may serve as a potential target for preventing the KTM­induced apoptosis of hippocampal neurons.

A fast response & recovery H2S gas sensor based on α-Fe2O3 nanoparticles with ppb level detection limit.

H2S gas sensor based on α-Fe2O3 nanoparticles was fabricated by post-thermal annealing of Fe3O4 precursor which was synthesized using a facile hydrothermal route. The characteristic techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were adopted to characterize the chemical composition and microstructure of the obtained samples. Gas-sensing performance of the sensor was investigated at different operation temperatures from 100°C to 400°C. Results showed that the sensor exhibited the best sensitivity, reproducibility and long-term stability for detecting H2S gas at an operating temperature of 300°C. The detection limit towards H2S gas was 0.05 ppm, and the response time and recovery time was 30s and 5s, respectively. In addition, sensing mechanism of the sensor towards H2S was discussed.

Applied investigation on the interaction of hazardous elements binding on ultrafine and nanoparticles in Chinese anthracite-derived fly ash.

A multifaceted instrumental approach was employed to determine the chemistry and mineralogy of pulverized-coal-combustion fly ashes from two Chinese power plants. Techniques included traditional optical microscopy, X-ray diffraction, and chemical analysis along with a variety of electron beam methods. The aim is to demonstrate and bring together the wide variety of procedures dealing with F as the key element of concern, and determining its location in the mineral nanoparticles. The Hg content of the Anwen (Songzao coalfield) fly ashes is higher than that of the Diandong (East Yunnan) fly ashes, possibly owing to the greater C and Cl in the Anwen fly ashes. Both fly ash sources contain a variety of amorphous and nano-crystalline trace-element-bearing particles, both associated with multi-walled carbon nanotubes and as particles independent of carbons.