Automated Windows domain penetration method based on reinforcement learning

Windows domain provides a unified system service for resource sharing and information interaction among users.However, this also introduces significant security risks while facilitating intranet management.In recent years, intranet attacks targeting domain controllers have become increasingly prevalent, necessitating automated penetration testing to detect vulnerabilities and ensure the ongoing maintenance of office network operations.Then efficient identification of attack paths within the domain environment is crucial.The penetration process was first modeled using reinforcement learning, and attack paths were then discovered and verified through the interaction of the model with the domain environment.Furthermore, unnecessary states in the reinforcement learning model were trimmed based on the contribution differences of hosts to the penetration process, aiming to optimize the path selection strategy and improve the actual attack efficiency.The Q-learning algorithms with solution space refinement and exploration policy optimization were utilized to filter the optimal attack path.By employing this method, all security threats in the domain can be automatically verified, providing a valuable protection basis for domain administrators.Experiments were conducted on typical Windows domain scenarios, and the results show that the optimal path is selected from the thirteen efficient paths generated by the proposed method, while also providing better performance optimization in terms of domain controller intrusion, domain host intrusion, attack steps, convergence, and time cost compared to other approaches

Nontargeted Metabolomic Analysis of Plasma Metabolite Changes in Patients with Adolescent Idiopathic Scoliosis

Objective. Adolescent idiopathic scoliosis (AIS) is a relatively common spinal rotation deformity, and the pathogenesis of AIS is accompanied by metabolic dysfunction and changes in biochemical factors. In this study, plasma metabolite changes in AIS patients were analyzed based on nontargeted metabolomics to provide new insights for clarifying functional metabolic abnormalities in AIS patients. Methods. Clinical indexes and blood samples were collected from 12 healthy subjects and 16 AIS patients. Metabolomics was used to analyze the changes in metabolites in plasma samples. The correlation between plasma metabolites and clinical indexes was analyzed by the Spearman rank correlation coefficient. Results. Analysis of clinical data showed that the body weight, body mass index (BMI), and bone mineral density (BMD) index of the AIS group significantly decreased, while the blood phosphorus and Cobb angles increased significantly. Metabolomic analysis showed significant changes in 72 differential metabolites in the plasma of the AIS group, mainly including organooxygen compounds, carboxylic acids and derivatives, fatty acyls, steroids and steroid derivatives, and keto acids and derivatives. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that arginine biosynthesis, D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and citrate cycle (TCA cycle) were significantly enriched in the AIS and healthy groups. Spearman rank correlation coefficient analysis showed that the plasma metabolites C00026 (oxoglutarate), C00062 (L-arginine, arginine), C01042 (N-acetylaspartate), and C00158 (citrate) were significantly correlated with clinical indexes in AIS patients. In the healthy group, the plasma metabolites C00122 (fumarate), C00025 (glutamate and L-glutamic acid) and C00149 (malate, L-malic acid) were significantly correlated with clinical indexes, while C00624 (N-acetylglutamate) was not significantly correlated with the clinical indexes. Conclusion. The occurrence of AIS led to changes in clinical indexes and plasma metabolites. Plasma biomarkers and functional metabolic pathways were correlated with clinical indexes, which might provide new insights for the diagnosis and treatment of AIS

Dysregulated Bone Metabolism Is Related to High Expression of miR-151a-3p in Severe Adolescent Idiopathic Scoliosis

Adolescent idiopathic scoliosis (AIS) is a common complex disease, and bone homeostasis plays an important role in its pathogenesis. Recent advances in epigenetic research show that dysregulated miRNAs may participate in the development of orthopedic diseases and AIS. The aim of this study was to detect differentially expressed miRNAs in severe AIS and elucidate the mechanism of miRNA deregulation in the pathogenesis of AIS. In the present study, miRNA expression profiles were detected in severe and mild AIS patients as well as healthy controls by miRNA sequencing. Candidate miRNAs were validated in a larger cohort. Primary osteoblasts from severe AIS patients were extracted and isolated to determine the effect of the candidate miRNAs on bone metabolism. Finally, we determined the methylation level in primary osteoblasts from severe AIS patients. The result showed that miR-151a-3p was overexpressed in severe AIS patients. Reduced GREM1 expression was observed in primary osteoblasts from severe AIS patients. miR-151a-3p directly inhibited GREM1 in primary osteoblasts. Relatively lower methylation levels were detected in primary osteoblasts from severe AIS patients. In conclusion, our study revealed that plasma miR-151a-3p levels may serve as a biomarker for severe AIS. Overexpression of miR-151a-3p may interrupt bone homeostasis via inhibiting GREM1 expression. Our result may provide a new biomarker for the early detection of AIS and increase our understanding of the pathogenesis of AIS

Review of Artificial Downwelling for Mitigating Hypoxia in Coastal Waters

Hypoxia is becoming a serious problem in coastal waters in many parts of the world. Artificial downwelling, which is one of the geoengineering-based adaptation options, was suggested as an effective means of mitigating hypoxia in coastal waters. Artificial downwelling powered by green energy, such as solar, wind, wave, or tidal energy, can develop a compensatory downward flow on a kilometer scale, which favors below-pycnocline ventilation and thus mitigates hypoxia in bottom water. In this paper, we review and assess the technical, numerical, and experimental aspects of artificial downwelling all over the world, as well as its potential environmental effects. Some basic principles are presented, and assessment and advice are provided for each category. Some suggestions for further field-based research on artificial downwelling, especially for long-term field research, are also given

Improving the catalytic activity of a detergent‐compatible serine protease by rational design

Abstract Serine proteases are among the most important biological additives in various industries such as detergents, leather, animal feed and food. A serine protease gene, Fgapt4, from Fusarium graminearum 2697 was identified, cloned and expressed in Pichia pastoris. The optimal pH and temperature of FgAPT4 were 8.5 and 40°C, respectively. The relative activity was >30% even at 10°C. It had a wide range of pH stability (4.0–12.0) and detergent compatibility. To improve the catalytic activity, a strategy combining molecular docking and evolutionary analysis was adopted. Twelve amino acid residue sites and three loops (A, B and C) were selected as potential hot spots that might play critical roles in the enzyme's functional properties. Twenty‐eight mutants targeting changes in individual sites or loops were designed, and mutations with good performance were combined. The best mutant was FgAPT4‐M3 (Q70N/D142S/A143S/loop C). The specific activity and catalytic efficiency of FgAPT4‐M3 increased by 1.6 (1008.5 vs. 385.9 U/mg) and 2.2‐fold (3565.1 vs. 1106.3/s/mM), respectively. Computational analyses showed that the greater flexibility of the substrate pocket may be responsible for the increased catalytic activity. In addition, its application in detergents indicated that FgAPT4‐M3 has great potential in washing

Ghrelin Modulates Lateral Amygdala Neuronal Firing and Blocks Acquisition for Conditioned Taste Aversion

<div><p>Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents. An increasing number of studies have reported that ghrelin and its identified receptor, the growth hormone secretagogue receptor 1a (GHS-R1a), produces remarkably wide and complex functions and biological effects on specific populations of neurons in central nervous system. In this study, we sought to explore the in vivo effects of acute ghrelin exposure on lateral amygdala (LA) neurons at the physiological and behavioral levels. <i>In vivo</i> extracellular single-unit recordings showed that ghrelin with the concentration of several nanomolars (nM) stimulated spontaneous firing of the LA neurons, an effect that was dose-dependent and could be blocked by co-application of a GHS-R1a antagonist D-Lys3-GHRP-6. We also found that D-Lys3-GHRP-6 inhibited spontaneous firing of the LA neurons in a dose-dependent manner, revealing that tonic GHS-R1a activity contributes to orchestrate the basal activity of the LA neurons. Behaviorally, we found that microinfusion of ghrelin (12 ng) into LA before training interfered with the acquisition of conditioned taste aversion (CTA) as tested at 24 h after conditioning. Pre-treatment with either purified IgG against GHS-R1a or GHS-R1a antagonist blocked ghrelin’s effect on CTA memory acquisition. Ghrelin (12 ng) had no effect on CTA memory consolidation or the expression of acquired CTA memory; neither did it affect the total liquid consumption of tested rats. Altogether, our data indicated that ghrelin locally infused into LA blocks acquisition of CTA and its modulation effects on neuronal firing may be involved in this process.</p></div

Ghrelin increases spontaneous firing rate of the LA neurons.

<p><b>A</b>, Ghrelin increases spontaneous firing rate of the LA neurons in average, which is reversed by GHS-R1a antagonist D-Lys3-GHRP-6. <b>Left</b>, example firing rate histograms recorded in LA neurons that display increased, decreased or unchanged spontaneous firing after pressure microinjection of ghrelin at a concentration of 3 nM. <b>Right,</b> summarized data showing that ghrelin administration increases the spontaneous firing rate of LA neurons in a dose-dependent manner. Co-ejection of GHS-R1a antagonist D-Lys3-GHRP-6 (250 nM) with ghrelin (30 nM) not only reversed the effects of ghrelin, but further altered the firing rate beyond baseline levels. <i>n</i> = 8 neurons from 2 rats for saline control group, <i>n</i> = 16–20 neurons from 6 rats for ghrelin-treated groups. <b>B,</b> GHS-R1a antagonist D-Lys3-GHRP-6 reduces the basal firing rate of the LA neurons in a concentration-dependent manner. <b>Left</b>, example firing rate histograms recorded in two LA neurons with different basal firing rate, both displaying reduced firing after administration of 10 nM D-Lys3-GHRP-6. <b>Right</b>, summarized data showing that D-Lys3-GHRP-6 administration attenuated the frequency of spontaneous firing of LA neurons in a dose-dependent manner. <i>n</i> = 8 neurons from 2 rats for saline control group, <i>n</i> = 4–20 neurons from total 10 rats for D-Lys3-GHRP-6 treatment groups. Arrows indicate time of drug administration. *p<0.05, **p<0.01 or ***p<0.001 means significant, error bars indicate SEM. <b>C,</b> Illustration of reconstructed recording sites. Bilateral recording placements are indicated as closed circles in the basolateral amygdala complex, mainly in LA (n = 125 neurons). At brain structure diagrams the numbers refer to anterior-posterior distance from bregma in millimeter adapted from the stereotaxic atlas of Paxinos and Watson.</p

Characteristics of Electroencephalogram in the Prefrontal Cortex during Deep Brain Stimulation of Subthalamic Nucleus in Parkinson’s Disease under Propofol General Anesthesia

Background: Monitoring the depth of anesthesia by electroencephalogram (EEG) based on the prefrontal cortex is an important means to achieve accurate regulation of anesthesia for subthalamic nucleus (STN) deep brain stimulation (DBS) under general anesthesia in patients with Parkinson’s disease (PD). However, no previous study has conducted an in-depth investigation into this monitoring data. Here, we aimed to analyze the characteristics of prefrontal cortex EEG during DBS with propofol general anesthesia in patients with PD and determine the reference range of parameters derived from the depth of anesthesia monitoring. Additionally, we attempted to explore whether the use of benzodiazepines in the 3 days during hospitalization before surgery impacted the interpretation of the EEG parameters. Materials and Methods: We included the data of 43 patients with PD who received STN DBS treatment and SedLine monitoring during the entire course of general anesthesia with propofol in a single center. Eighteen patients (41.86%) took benzodiazepines during hospitalization. We divided the anesthesia process into three stages: awake state before anesthesia, propofol anesthesia state, and shallow anesthesia state during microelectrode recording (MER). We analyzed the power spectral density (PSD) and derived parameters of the patients’ prefrontal EEG, including the patient state index (PSI), spectral edge frequency (SEF) of the left and right sides, and the suppression ratio. The baseline characteristics, preoperative medication, preoperative frontal lobe image characteristics, preoperative motor and non-motor evaluation, intraoperative vital signs, internal environment and anesthetic information, and postoperative complications are listed. We also compared the groups according to whether they took benzodiazepines before surgery during hospitalization. Results: The average PSI of the awake state, propofol anesthesia state, and MER state were 89.86 ± 6.89, 48.68 ± 12.65, and 62.46 ± 13.08, respectively. The preoperative administration of benzodiazepines did not significantly affect the PSI or SEF, but did reduce the total time of suppression, maximum suppression ratio, and the PSD of beta and gamma during MER. Regarding the occurrence of postoperative delirium and mini-mental state examination (MMSE) scores, there was no significant difference between the two groups (chi-square test, p = 0.48; Mann–Whitney U test, p = 0.30). Conclusion: For the first time, we demonstrate the reference range of the derived parameters of the depth of anesthesia monitoring and the characteristics of the prefrontal EEG of patients with PD in the awake state, propofol anesthesia state, and shallow anesthesia during MER. Taking benzodiazepines in the 3 days during hospitalization before surgery reduces suppression and the PSD of beta and gamma during MER, but does not significantly affect the observation of anesthesiologists on the depth of anesthesia, nor affect the postoperative delirium and MMSE scores