Navigating Exploitative Traps: Unveiling the Uncontrollable Reward Seeking of Internet Gaming Disordered Individuals.

BACKGROUND: Internet Gaming Disorder (IGD) involves an imbalance in the brain's dual-system, characterized by heightened reward-seeking and diminished cognitive control, which leads to decision-making challenges. The exploration-exploitation strategy is key to decision-making, but how IGD affects this process is unclear. METHODS: To investigate the impact of IGD on decision-making, a modified version of the two-armed bandit task was employed. Participants included 41 IGD individuals and 44 healthy control (HC) individuals. The study assessed the strategies used by participants in the task, particularly focusing on the exploitation-exploration strategy. Additionally, functional magnetic resonance imaging (fMRI) was used to examine brain activation patterns during decision-making and estimation phasess. RESULTS: The study found that individuals with IGD demonstrated a higher reliance on exploitative strategies in decision-making due to their elevated value-seeking tendencies and decreased cognitive control. IGD individuals also displayed heightened activation in the pre-supplementary motor area (preSMA) and the ventral striatum (VS) compared to the HC group in both decision-making and estimation phases. Meanwhile, the prefrontal cortex (PFC) showed more inhibition in IGD individuals than in the HC group during exploitative strategies. This inhibition was found to decrease as cognitive control diminished. CONCLUSION: The study concludes that the imbalance in the development of the dual-system in individuals with IGD may lead to an over-reliance on exploitative strategies. This imbalance, marked by increased reward-seeking and reduced cognitive control, contributes to difficulties in decision-making and value-related behavioral processes in IGD individuals.

Therapeutic effects of orexin-A in sepsis-associated encephalopathy in mice.

BACKGROUND: Sepsis-associated encephalopathy (SAE) causes acute and long-term cognitive deficits. However, information on the prevention and treatment of cognitive dysfunction after sepsis is limited. The neuropeptide orexin-A (OXA) has been shown to play a protective role against neurological diseases by modulating the inflammatory response through the activation of OXR1 and OXR2 receptors. However, the role of OXA in mediating the neuroprotective effects of SAE has not yet been reported. METHODS: A mouse model of SAE was induced using cecal ligation perforation (CLP) and treated via intranasal administration of exogenous OXA after surgery. Mouse survival, in addition to cognitive and anxiety behaviors, were assessed. Changes in neurons, cerebral edema, blood-brain barrier (BBB) permeability, and brain ultrastructure were monitored. Levels of pro-inflammatory factors (IL-1ß, TNF-α) and microglial activation were also measured. The underlying molecular mechanisms were investigated by proteomics analysis and western blotting. RESULTS: Intranasal OXA treatment reduced mortality, ameliorated cognitive and emotional deficits, and attenuated cerebral edema, BBB disruption, and ultrastructural brain damage in mice. In addition, OXA significantly reduced the expression of the pro-inflammatory factors IL-1ß and TNF-α, and inhibited microglial activation. In addition, OXA downregulated the expression of the Rras and RAS proteins, and reduced the phosphorylation of P-38 and JNK, thus inhibiting activation of the MAPK pathway. JNJ-10,397,049 (an OXR2 blocker) reversed the effect of OXA, whereas SB-334,867 (an OXR1 blocker) did not. CONCLUSION: This study demonstrated that the intranasal administration of moderate amounts of OXA protects the BBB and inhibits the activation of the OXR2/RAS/MAPK pathway to attenuate the outcome of SAE, suggesting that OXA may be a promising therapeutic approach for the management of SAE.

Machine learning unveils immune-related signature in multicenter glioma studies.

In glioma molecular subtyping, existing biomarkers are limited, prompting the development of new ones. We present a multicenter study-derived consensus immune-related and prognostic gene signature (CIPS) using an optimal risk score model and 101 algorithms. CIPS, an independent risk factor, showed stable and powerful predictive performance for overall and progression-free survival, surpassing traditional clinical variables. The risk score correlated significantly with the immune microenvironment, indicating potential sensitivity to immunotherapy. High-risk groups exhibited distinct chemotherapy drug sensitivity. Seven signature genes, including IGFBP2 and TNFRSF12A, were validated by qRT-PCR, with higher expression in tumors and prognostic relevance. TNFRSF12A, upregulated in GBM, demonstrated inhibitory effects on glioma cell proliferation, migration, and invasion. CIPS emerges as a robust tool for enhancing individual glioma patient outcomes, while IGFBP2 and TNFRSF12A pose as promising tumor markers and therapeutic targets.

Causal effects of gut microbiota on sepsis and sepsis-related death: insights from genome-wide Mendelian randomization, single-cell RNA, bulk RNA sequencing, and network pharmacology.

BACKGROUND: Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear. METHODS: We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets. RESULTS: Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential. CONCLUSION: Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.

Analysis of the Imaging Features and Prognosis of Pulmonary Tuberculosis Complicated with Pulmonary Embolism

OBJECTIVE: This study aimed to explore the imaging characteristics of patients with pulmonary tuberculosis complicated with pulmonary embolism and analyze the prognosis of the condition, thereby reducing the mortality and misdiagnosis rate of complications in this type of pulmonary tuberculosis. METHODS: In this retrospective study, a total of 70 patients diagnosed with pulmonary embolism by computed tomography pulmonary angiography (CTPA) from January 2016 to May 2021 in Anhui Chest Hospital were included. Among them, 35 patients with pulmonary embolism combined with pulmonary tuberculosis were set as the study group, and the other 35 patients with pulmonary embolism only were set as the control group. The imaging findings of chest CT examination, the incidence of pulmonary hypertension, the level of N-terminal proto-B-type brain natriuretic peptide (NT-proBNP), and the prognosis of patients were compared between the two groups. The incidence of deep venous embolism was evaluated by ultrasonography of the lower extremity. RESULTS: In the study group, the median age of patients was 71 years, and the ratio of males to females was 2.5 to 1. In the control group, the median age was 66 years old, and the male-to-female ratio was 2.2 to 1. There were 16 cases (16/35, 45.71%) in the study group and 10 cases (10/35, 28.57%) in the control group with an increased level of NT-proBNP. Pulmonary hypertension occurred in 10 patients (10/35, 28.57%) in the study group and 7 patients (7/35, 20.00%) in the control group. Patients who lost follow-up included 5 in the study group (5/35, 14.29%) and 3 in the control group (3/35, 8.57%). There were 17 cases (17/35, 48.57%) in the study group and 3 cases (3/35, 8.57%) in the control group with pulmonary artery widening, and the difference was significant (P < 0.001). There were 13 deaths in the study group (13/35, 37.14%) and 1 death in the control group (1/35, 2.86%), and the difference was significant (P <0.001). CONCLUSION: Special signs of pulmonary artery widening, pulmonary hypertension of varying degrees, and increased levels of NT-proBNP of varying degrees can be found in patients with pulmonary tuberculosis complicated with pulmonary embolism, and the three signs are positively correlated. The mortality of patients with pulmonary tuberculosis complicated with pulmonary embolism is significantly higher than that of patients with pulmonary embolism alone. Pulmonary tuberculosis and pulmonary embolism both occur in the ipsilateral lung, causing clinical symptoms to cover each other, thereby making diagnosis difficult.

Estimating the occurrence of labial bone perforation and implantation into the maxillary sinus maxillary premolars based on the morphology of maxillary premolars: A clinical study.

STATEMENT OF PROBLEM: Previous studies have classified the sagittal root position of the maxillary anterior teeth and measured buccal plate thickness to aid treatment planning. A thin labial wall and buccal concavity may cause buccal perforation, dehiscence, or both in maxillary premolars. However, data on the restoration-driven principle to classify the maxillary premolar region are lacking. PURPOSE: The purpose of this clinical study was to investigate the occurrence of labial bone perforation and implantation into the maxillary sinus between various tooth-alveolar classifications with respect to the crown axis in maxillary premolars. MATERIAL AND METHODS: Cone beam computed tomography images of 399 participants (1596 teeth) were analyzed to determine the probability of labial bone perforation and implantation into the maxillary sinus when associated with variables that included tooth position and tooth-alveolar classification. RESULTS: The morphology in the maxillary premolars was classified as straight, oblique, or boot-shaped. The first premolars were 62.3% straight, 37.0% oblique, and 0.8% boot-shaped, and labial bone perforation occurred in 4.2% (21 of 497) of the straight, 54.2% (160 of 295) of the oblique, and 83.3% (5 of 6) of the boot-shaped first premolars when the virtual implant was 3.5×10 mm. When the virtual tapered implant was 4.3×10 mm, labial bone perforation occurred in 8.5% (42 of 497) of the straight, 68.5% (202 of 295) of the oblique, and 83.3% (5 of 6) of the boot-shaped first premolars. The second premolars were 92.4% straight, 7.5% oblique, and 0.1% boot-shaped, and labial bone perforation occurred in 0.5% (4 of 737) of the straight, 33.3% (20 of 60) of the oblique, and 0% (0 of 1) of the boot-shaped, respectively, when the virtual tapered implant was 3.5×10 mm; and labial bone perforation occurred in 1.3% (10/737) of the straight, 53.3% (32/60) of the oblique, and 100% (1/1) of the boot-shaped second premolars when the virtual tapered implant was 4.3×10 mm. CONCLUSIONS: When an implant is placed in the long axis of a maxillary premolar, the tooth position and tooth-alveolar classification should be considered when assessing the risk of labial bone perforation. Attention should be paid to the implant direction, diameter, and length in the oblique and boot-shaped maxillary premolars.

Influence of bone anatomical morphology of mandibular molars on dental implant based on CBCT.

BACKGROUND: To apply CBCT to investigate the anatomical relationship between the mandibular molar and alveolar bone, aimed to provide clinical guidelines for the design of implant restoration. METHODS: 201 CBCT data were reevaluated to measure height of the alveolar process (EF), width of the alveolar process (GH), width of the basal bone (IJ), the angle between the long axis of the first molar and the alveolar bone (∠a) and the angle between the long axis of the alveolar bone and basal bone (∠b). The angle and width were measured to determine the implant-prosthodontic classification of the morphology in the left lower first molar (36) and right lower first molar (46). All measurements were performed on the improved cross-sectional images. RESULTS: EF, GH and IJ were measured as (10.83 ± 1.31) mm, (13.93 ± 2.00) mm and (12.68 ± 1.96) mm for 36, respectively; and (10.87 ± 1.24) mm, (13.86 ± 1.93) mm and (12.60 ± 1.90) mm for 46, respectively. No statistical significance was observed in EF, GH, IJ, ∠a and ∠b between 36 and 46 (all P > 0.05). The morphology was divided into three categories including the straight (68.7-69.2%), oblique (19.9-20.4%) and concave types (11%). Each type was consisted of two subcategories. CONCLUSIONS: The proposed classification could provide evidence for appropriate selection and direction design of the mandibular molar implant in clinical. The concave type was the most difficult to implant with the highest risk of lingual perforation. The implant length, width, direction required more attention.

Cyclic tensile forces enhance the angiogenic properties of HUVECs by promoting the activities of human periodontal ligament cells.

BACKGROUND: This study aimed to investigate whether human periodontal ligament (PDL) cells secrete pro-angiogenic factors that induce the vascularization of surrounding bone tissue under tensile stress. METHODS: Quantitative real-time PCR and Western blotting were used to analyze the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), Angiopoietin-I (Ang-I), connective tissue growth factor （CTGF）, and macrophage colony-stimulating factor (M-CSF) in PDL cells after tensile force treatments of different durations. Enzyme-linked immunosorbent assay was used to measure the VEGF concentration in the supernatants of cell cultures. Cell viability assay, wound healing assay, and tube formation assay were performed to evaluate the angiogenic behaviors of human umbilical vein endothelial cells (HUVECs). RESULTS: The mRNA expression and protein expression of VEGF, bFGF, Ang-I, and M-CSF was increased in the cells that received 6 to 48 hours of tensile force treatment. And, the VEGF level in the supernatant significantly increased in the human PDL cell cultures stressed for 6 to 48 hours. The abilities of HUVECs to proliferate, migrate, and form tubes were enhanced in media conditioned with tensile-stressed human PDL cells. Hence, tensile force induced human PDL cells to express and release pro-angiogenic factors enhancing the proliferation, migration, and angiogenic capacity of HUVECs. CONCLUSION: Tensile stress induced human PDL cells to express and release pro-angiogenic factors, including VEGF, bFGF, Ang-I, and M-CSF, thereby enhancing the proliferation, migration, and angiogenic capacity of HUVECs.

Design, synthesis, and evaluation of 1, 4-benzodioxan-substituted chalcones as selective and reversible inhibitors of human monoamine oxidase B.

The inhibition of monoamine oxidase B (MAO-B) could be an effective approach for the treatment of various neurological disorders. In this study, a series of 1, 4-benzodioxan-substituted chalcone derivatives were designed, synthesised and evaluated for their inhibitory activity against human MAO-B (hMAO-B). The majority of these compounds showed inhibitory activity and high selectivity. The most potent compound, (E)-1-(3-bromo-4-fluorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)prop-2-en-1-one (22), exhibited an IC50 of 0.026 µM with a selectivity index greater than 1538. Kinetics and reversibility studies confirmed that the representative active compounds acted as competitive and reversible inhibitors of hMAO-B. The enzyme-inhibitor interactions were investigated by molecular docking studies and the rationale was provided. As these potent hMAO-B inhibitors exhibited low neurotoxicity and possessed promising drug-like properties, we believe that these active compounds could be further investigated as potential drug candidates for future in vivo studies.

[Synthesis and monoamine oxidase B inhibitory activities of isoquiritigenin derivatives].

Isoquiritigenin,one of the active constituents in the Chinese herb liquorice,is found to have moderate inhibitory activity against rat monoamine oxidase B(MAO-B,IC5047. 2 µmol·L-1). However,the structure-activity relationship(SAR) remains unclear until now. In an attempt to reveal the SAR of inhibition by isoquiritigenin,and to identify more potent and selective inhibitors of MAOB,a series of 13 derivatives based on the scaffold of isoquiritigenin were prepared,and their purities and structures were confirmed by UPLC,1 H-NMR,13 C-NMR and HRMS. These compounds were then evaluated for their ability to inhibit the enzymatic activity of human MAO-B. The SAR of inhibition was summarized and a potent compound C8 with high inhibitory activity(IC501. 4 µmol·L-1) and selectivity(>57 folds over MAO-A) was identified. Enzyme kinetics studies suggested that C8 acted as a competitive inhibitor. In addition,C8 showed little cytotoxicity to glial cells in vitro,which could be a promising lead compound for further study.

A Reversible Colorimetric and Fluorescence "Turn-Off" Chemosensor for Detection of Cu2+ and Its Application in Living Cell Imaging.

Dual-function chemosensors that combine the capability of colorimetric and fluorimetric detection of Cu2+ are still relatively rare. Herein, we report that a 3-hydroxyflavone derivative (E)-2-(4-(dimethylamino)styryl)-3-hydroxy-4H-chromen-4-one (4), which is a red-emitting fluorophore, could serve as a reversible colorimetric and fluorescence "turn-off" chemosensor for the detection of Cu2+. Upon addition of Cu2+ to 4 in neutral aqueous solution, a dramatic color change from yellow to purple-red was clearly observed, and its fluorescence was markedly quenched, which was attributed to the complexation between the chemosensor and Cu2+. Conditions of the sensing process had been optimized, and the sensing studies were performed in a solution of ethanol/phosphate buffer saline (v/v = 3:7, pH = 7.0). The sensing system exhibited high selectivity towards Cu2+. The limit of naked eye detection of Cu2+ was determined at 8 × 10-6 mol/L, whereas the fluorescence titration experiment showed a detection limit at 5.7 × 10-7 mol/L. The complexation between 4 and Cu2+ was reversible, and the binding constant was found to be 3.2 × 104 M-1. Moreover, bioimaging experiments showed that 4 could penetrate the cell membrane and respond to the intracellular changes of Cu2+ within living cells, which indicated its potential for biological applications.