Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology, cognition, and behavior in APP/PS1 mice.

JOURNAL/nrgr/04.03/01300535-202502000-00030/figure1/v/2024-05-28T214302Z/r/image-tiff In patients with Alzheimer's disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer's disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer's disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer's disease (Aß1-42-treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-ß in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of ß-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer's disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer's disease.

CBX2 enhances the progression and TMZ chemoresistance of glioma via EZH2-mediated epigenetic silencing of PTEN expression.

Chromobox (CBX) 2, a member of the CBX protein family and a crucial component of the polycomb repressive complex (PRC), exerts significant influence on the epigenetic regulation of tumorigenesis, including glioma. However, the precise role of CBX2 in glioma has remained elusive. In our study, we observed a substantial upregulation of CBX2 expression in glioma, which displayed a strong correlation with pathological grade, chemoresistance, and unfavorable prognosis. Through a series of in vivo and in vitro experiments, we established that heightened CBX2 expression facilitated glioma cell proliferation and bolstered resistance to chemotherapy. Conversely, CBX2 knockdown led to a significant inhibition of glioma cell growth and a reduction in chemoresistance. Notably, our investigation uncovered the underlying mechanism by which CBX2 operates, primarily by inhibiting PTEN transcription and activating the AKT/mTOR signalling pathway. Conversely, silencing CBX2 curtailed cell proliferation and attenuated chemoresistance by impeding the activation of the PTEN/AKT/mTOR signalling pathway. Delving deeper into the molecular intricacies, we discovered that CBX2 can recruit EZH2 and modulate the trimethylation of histone H3 lysine 27 (H3K27me3) levels on the PTEN promoter, effectively suppressing PTEN transcription. Our research unveils a comprehensive understanding of how CBX2 impacts the tumorigenesis, progression, chemoresistance, and prognosis of glioma. Furthermore, it presents CBX2 as a promising therapeutic target for drug development and clinical management of glioma.

PDCL3 as a prognostic factor and associated with the VEGF signaling pathway in glioma.

BACKGROUND: New targeted drugs about angiogenesis could develop the treatment of glioma. We aimed to explore the role of phosducin like 3 (PDCL3) in angiogenesis of glioma. MATERIALS AND METHODS: RNA sequencing data and matched clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. To screen for the reliable genes with the filtering analyses, survival, multivariate Cox, receiver operating characteristic (ROC) curve filtration, and clinical correlation analyses were performed. The PDCL3 gene was validated by immunohistochemistry as a reliable gene for further analysis. Then we used the combined data of TCGA and Genotype-Tissue Expression from UCSC to detect the differential gene expression of PDCL3. Related signal pathways in glioma were explored by the gene set enrichment analysis and co-expression analysis. Lastly, we performed in vitro experiments to verify the gene functions and related mechanisms. RESULTS: The three filtering analyses and immunostaining indicated that the expression of PDCL3 in glioma tissues was higher than the normal tissues. Gene function analysis showed that PDCL3 activated the vascular endothelial growth factor (VEGF) signal pathway, and its mechanism was related to pathways in cancer, like NOD like receptor signaling pathway, the RIG-I like receptor signaling pathway and the P53 signaling pathway by MAPK/AKT in gliomas. This suggested that the proliferation, migration and invasion of glioma cells might be inhibited by the downregulation of PDCL3 in vitro, which may be related to the activation of VEGF signaling pathway. CONCLUSION: We demonstrated that PDCL3 could function as an independent adverse prognostic marker in glioma. Its pro-oncogenic mechanism may be related to the VEGF signaling pathway.

A multi-mode stretching apparatus for in situ synchrotron x-ray scattering of polymer materials.

A compact and versatile tensile apparatus for polymer materials is designed and fabricated. Three distinct stretching modes are developed: constant speed, cyclic, and sinusoidal, with adjustable speeds ranging from 0.001 to 120 mm/s. To capture the true strain of the central region, a high-speed camera has been integrated into the apparatus. The temperature of the sample chamber is controlled by flowing air, enabling a homogeneous temperature in the range of RT ∼200 °C. The apparatus is particularly suitable for a synchrotron beamline. The structural evolution of natural rubber during sinusoidal stretching is investigated by in situ wide-angle x-ray scattering. Scattering patterns, force, clamp position, and sample images are saved simultaneously during stretching. Notably, the results reveal a sinusoidal variation in the crystallinity of crosslinked natural rubber when a sinusoidal strain was applied to the sample. The integration of advanced measurement techniques and controlled experimental conditions ensures the acquisition of reliable and accurate data, providing valuable insights into the structural evolution of materials under dynamic deformation conditions.

Electrocatalytic oxidation of hexafluoropropylene oxide homologues in water using a boron-doped diamond electrode.

Hexafluoropropylene oxide (GenX) is a kind of substitute to PFOA, which has been listed in the Stockholm Convention. In this study, GenX was attempted to be degraded using a boron-doped diamond anode in the electrochemical oxidation system. The effects of operating parameters, including current density (0.5-10 mA/cm2), initial pH (3.0-11.49), initial concentration of GenX (20-150 mg/L), electrode distances (0.5-2 cm), electrolyte types (Na2SO4, NaCl, NaNO3 and NaHCO3) and Na2SO4 electrolyte concentration (40-80 mm), on GenX were studied. GenX can almost completely be degraded under the optimal operating parameters after 180 min of electrolysis. Free radical quenching experiments were carried out to investigate the effects of hydroxyl radicals and sulphate radicals on the degradation of GenX. The degradation intermediates were identified based on the ultra-high performance liquid chromatography equipped with a tandem mass spectrometer, and the degradation mechanisms were also proposed. Finally, the toxicities of GenX and its degradation products were evaluated using the QSAR models. The novelty is that the degradation mechanisms of the high concentration GenX (100 mg/L) were elucidated based on the free radical quenching experiments and the intermediates detected, when the degradation ratio reached 100%.

Variation in plant functional traits explains the substitution distribution and allocation strategy of Stipa species across natural grasslands of Ningxia, Northern China.

Functional traits reflect plants' adaptability to their environment, and environmental gradients influence their distribution. But few studies have investigated the link between these traits and species substitution patterns or the relevant ecological factors. We measured the aboveground (leaf) and belowground (root) functional traits of Stipa species in 17 plots across natural grasslands in Ningxia in Northern China. Redundancy analysis was used to explore the relationships between Stipa's functional traits and its species substitution distribution. Then, on the species substitution gradient, principal component analysis (PCA) was used to verify and quantify the leaf economic spectrum (LES), root economic spectrum (RES), and whole-plant economic spectrum (WPES), with the relation between these spectra investigated by fitting standardized major axis regressions. The effects of aboveground, belowground, and whole-plant ecological factors were quantified and ranked by variance decomposition and hierarchical partitioning. Our results showed that functional traits drive the substitution distribution of Stipa species, in being variously coupled with its desert, typical, and meadow steppe habitat types. The leaf, root, and whole-plant economic spectra of Stipa species in desert steppe exhibit a "quick investment-acquisition" strategy. In typical steppe, the leaf and whole-plant economic spectra of Stipa species correspond to a "fast investment-acquisition" strategy, whereas the root economic spectrum adopts a "slow investment-acquisition" strategy. On meadow steppe, the leaf, root, and whole-plant economic spectra of Stipa species similarly adopt a "slow investment-acquisition" strategy. Finally, when considering the environmental factors involved, we find that the substitution distribution of Stipa spp. is chiefly a response to shifting soil patterns, these mainly driven by soil total nitrogen and nitrogen/phosphorus ratio. Collectively, these findings provide an important reference for the ecological restoration and reconstruction of grassland ecosystems, to better understand the relationship between plant functional traits and ecological niche attributes, and thus guide the reasonable restoration of grassland vegetation.

Aortic Annular Enlargement versus Isolated Aortic Valve Replacement in Patients with Matched Annulus.

BACKGROUND: We aimed to determine the effect of aortic annular enlargement on the mid-term outcomes of aortic valve replacement surgery by comparing patients with the same-sized (≤23 mm) native aortic annuli. METHODS: From January 2011 to June 2022, 1,328 patients underwent isolated aortic valve replacement-1,163 without aortic annular enlargement (AVR group) and 165 with aortic annular enlargement (AVR+AAE group). Propensity score matching identified 112 pairs, controlling for native aortic annulus diameter, age, sex, diabetes, chronic lung disease, dialysis, ejection fraction, prior cardiac surgery, indication, hypertension, dyslipidemia, valve type, prior stroke, prior myocardial infarction, and case status. RESULTS: Demographic and preoperative parameters were similar, except body surface area was larger in the AVR+AAE group (2.1 m2 vs 1.9 m2). Median native aortic annulus diameter was 23 mm in both groups. Median prosthesis size was 25 and 23 in the AVR+AAE and AVR groups, respectively. The AVR+AAE group had longer cardiopulmonary bypass (143 vs 111 mins) and cross-clamp (115 vs 82 mins) times. Incidences of perioperative complications including operative mortality (1.8% AVR+AAE vs 3.6% AVR) were similar between groups. 6-year survival was 98% in the AVR+AAE group and 74% in the AVR group (p=0.016). Aortic annular enlargement was an independent protective factor for mid-term mortality with a hazard ratio of 0.19 (p=0.006). The rate of moderate/severe patient-prosthesis mismatch was 19% in the AVR+AAE group and 31% in the AVR group (p=0.16). CONCLUSIONS: Patients with small native aortic annuli (≤23 mm) undergoing isolated aortic valve replacement may benefit from aortic annular enlargement.

DEAF-Net: Detail-Enhanced Attention Feature Fusion Network for Retinal Vessel Segmentation.

Retinal vessel segmentation is crucial for the diagnosis of ophthalmic and cardiovascular diseases. However, retinal vessels are densely and irregularly distributed, with many capillaries blending into the background, and exhibit low contrast. Moreover, the encoder-decoder-based network for retinal vessel segmentation suffers from irreversible loss of detailed features due to multiple encoding and decoding, leading to incorrect segmentation of the vessels. Meanwhile, the single-dimensional attention mechanisms possess limitations, neglecting the importance of multidimensional features. To solve these issues, in this paper, we propose a detail-enhanced attention feature fusion network (DEAF-Net) for retinal vessel segmentation. First, the detail-enhanced residual block (DERB) module is proposed to strengthen the capacity for detailed representation, ensuring that intricate features are efficiently maintained during the segmentation of delicate vessels. Second, the multidimensional collaborative attention encoder (MCAE) module is proposed to optimize the extraction of multidimensional information. Then, the dynamic decoder (DYD) module is introduced to preserve spatial information during the decoding process and reduce the information loss caused by upsampling operations. Finally, the proposed detail-enhanced feature fusion (DEFF) module composed of DERB, MCAE and DYD modules fuses feature maps from both encoding and decoding and achieves effective aggregation of multi-scale contextual information. The experiments conducted on the datasets of DRIVE, CHASEDB1, and STARE, achieving Sen of 0.8305, 0.8784, and 0.8654, and AUC of 0.9886, 0.9913, and 0.9911 on DRIVE, CHASEDB1, and STARE, respectively, demonstrate the performance of our proposed network, particularly in the segmentation of fine retinal vessels.

Saikosaponin-d mediates FOXG1 to reverse docetaxel resistance in prostate cancer through oxidative phosphorylation.

BACKGROUND: Prostate cancer (PCa), a prevalent malignancy worldwide, is frequently identified in advanced stages due to the absence of distinctive early symptoms, thereby culminating in the development of chemotherapy-induced drug resistance. Exploring novel resistance mechanisms and identifying new therapeutic agents can facilitate the advancement of more efficacious strategies for PCa treatment. METHODS: Bioinformatics analysis was employed to investigate the expression of FOXG1 in PCa tissues. Subsequently, qRT-PCR was utilized to validate FOXG1 mRNA expression levels in corresponding PCa cell lines. FOXG1 knockdown was performed, and cell proliferation was assessed using CCK-8 assays, while cell migration and invasion capabilities were evaluated through wound healing and Transwell assays. Western blot and Seahorse analyzer were used to measure oxidative phosphorylation (OXPHOS) levels. Additionally, to explore potential approaches to alleviate PCa drug resistance, this study assessed the impact of biologically active saikosaponin-d (SSd) on PCa malignant progression and resistance by regulating FOXG1 expression. RESULTS: FOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway. CONCLUSION: This work demonstrated that SSd mediated FOXG1 to reverse malignant progression and docetaxel resistance in PCa through OXPHOS.

Preserving mitochondrial homeostasis protects against drug-induced liver injury via inducing OPTN (optineurin)-dependent Mitophagy.

Disruption of mitochondrial function is observed in multiple drug-induced liver injuries (DILIs), a significant global health threat. However, how the mitochondrial dysfunction occurs and whether maintain mitochondrial homeostasis is beneficial for DILIs remains unclear. Here, we show that defective mitophagy by OPTN (optineurin) ablation causes disrupted mitochondrial homeostasis and aggravates hepatocytes necrosis in DILIs, while OPTN overexpression protects against DILI depending on its mitophagic function. Notably, mass spectrometry analysis identifies a new mitochondrial substrate, GCDH (glutaryl-CoA dehydrogenase), which can be selectively recruited by OPTN for mitophagic degradation, and a new cofactor, VCP (valosin containing protein) that interacts with OPTN to stabilize BECN1 during phagophore assembly, thus boosting OPTN-mediated mitophagy initiation to clear damaged mitochondria and preserve mitochondrial homeostasis in DILIs. Then, the accumulation of OPTN in different DILIs is further validated with a protective effect, and pyridoxine is screened and established to alleviate DILIs by inducing OPTN-mediated mitophagy. Collectively, our findings uncover a dual role of OPTN in mitophagy initiation and implicate the preservation of mitochondrial homeostasis via inducing OPTN-mediated mitophagy as a potential therapeutic approach for DILIs.Abbreviation: AILI: acetaminophen-induced liver injury; ALS: amyotrophic lateral sclerosis; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DILI: drug-induced liver injury; FL: full length; GCDH: glutaryl-CoA dehydrogenase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GO: gene ontology; GSEA: gene set enrichment analysis; GPT/ALT: glutamic - pyruvic transaminase; INH: isoniazid; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MMP: mitochondrial membrane potential; MST: microscale thermophoresis; MT-CO2/COX-II: mitochondrially encoded cytochrome c oxidase II; OPTN: optineurin; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; TSN: toosendanin; VCP: valosin containing protein, WIPI2: WD repeat domain, phosphoinositide interacting 2.

Homocysteine levels are associated with diabetes mellitus in Chinese with H-type hypertension.

BACKGROUND/OBJECTIVES: The study examined the association between homocysteine and diabetes mellitus in patients with H-type hypertension and assessed the possible effect modifiers. SUBJECTS/METHODS: This cross-sectional study included 1,255 eligible participants in the 'H-type Hypertension Management and Stroke Prevention Strategic International Science and Technology Innovation Cooperation Project' among rural Chinese people with H-type hypertension. A multivariate logistic regression model was used to evaluate the relationship between homocysteine and diabetes mellitus. RESULTS: The mean level of total homocysteine (tHcy) in the diabetes mellitus population was 19.37 µmol/L, which was significantly higher than the non-diabetic patients (18.18 µmol/L). When tHcy was analyzed as a continuous variable, the odds ratio (OR) of diabetes was 1.17 (95% confidence interval [CI], 1.01-1.35; per interquartile range). When tHcy was stratified according to the quintile, the ORs for diabetes were 2.86 (95% CI, 1.22-6.69) in the highest quintile (tHcy ≥ 20.60 µmol/L) compared to the reference group (tHcy < 12.04 µmol/L). When tHcy was grouped by 15 µmol/L and 20 µmol/L, patients with tHcy ≥ 20 µmol/L had a significantly (P = 0.037) higher risk of diabetes (OR, 2.03; 95% CI, 1.04-3.96) than in those with tHcy < 15 µmol/L. Subgroup analysis showed that the tHcy-diabetes association was unaffected by other variables. CONCLUSION: In this study of rural Chinese people with H-type hypertension, the tHcy levels showed a positive association with diabetes mellitus. This independent association is unaffected by other potential risk factors.

Inhibition of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptors Ameliorates Atrial Inflammation and Vulnerability to Atrial Fibrillation in Rats with Anxiety Disorders.

ABSTRACT: Previous studies have found that anxiety disorders may increase the incidence of atrial fibrillation (AF). More and more studies have shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are involved in the occurrence and development of cardiovascular diseases. However, the role of AMPARs in AF associated with anxiety disorder remains unclear. The aim of this study was to investigate the effect of AMPARs on AF susceptibility in rats with anxiety disorder and its possible mechanism. The anxiety disorder rat model was established by unpredictable empty bottle stimulation and was treated with AMPARs agonist and antagonist. Our results showed that AMPARs antagonist treatment significantly reduced sympathetic activity, improved heart rate variability, shortened action potential duration, prolonged effective refractory period, reduced AF induction rate, and improved cardiac electrical remodeling and the expression of inflammatory factors. In addition, inhibition of AMPARs reduced the phosphorylation of IκBα and p65. Our experimental results suggest that inhibition of AMPARs can reduce autonomic remodeling, improve atrial electrical remodeling, and suppress myocardial inflammation, which provides a potential therapeutic strategy for the treatment of AF associated with anxiety disorder.

Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK.

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

[Prenatal diagnosis of a fetus with Rubinstein-Taybi syndrome].

OBJECTIVE: To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). METHODS: A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c.4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+PS2_Moderate+PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy of the fetus. CONCLUSION: The c.4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

HSDF: Hybrid Sign and Distance Field for Neural Representation of Surfaces with Arbitrary Topologies.

Neural implicit function based on signed distance field (SDF) has achieved impressive progress in reconstructing 3D models with high fidelity. However, such approaches can only represent closed surfaces. Recent works based on unsigned distance function (UDF) are proposed to handle both watertight and single-layered open surfaces. Nonetheless, as UDF is signless, its direct output is limited to the point cloud, which imposes an additional challenge on extracting high-quality meshes from discrete points. To address this challenge, we present a novel neural implicit representation coded HSDF, which is a hybrid of signed and unsigned distance fields. In particular, HSDF is able to represent arbitrary topologies containing both closed and open surfaces while being compatible with existing iso-surface extraction techniques for easy field-to-mesh conversion. In addition to predicting a UDF, we propose to learn an additional sign field. Unlike traditional SDF, HSDF is able to locate the surface of interest before level surface extraction by generating surface points following NDF [1]. We are then able to obtain open surfaces via an adaptive meshing approach that only instantiates regions containing surfaces into a polygon mesh. HSDF benefits downstream tasks like neural rendering, as it enables the rendering of back-faces of open surfaces. We also propose HSDF-Net, a dedicated learning framework that factorizes the learning of HSDF into two easier sub-problems. Experiments and evaluations show that HSDF outperforms the state-of-the-art techniques both qualitatively and quantitatively on some of the used datasets.

Boosting Weak-to-Strong Agents in Multiagent Reinforcement Learning via Balanced PPO.

Multiagent policy gradients (MAPGs), an essential branch of reinforcement learning (RL), have made great progress in both industry and academia. However, existing models do not pay attention to the inadequate training of individual policies, thus limiting the overall performance. We verify the existence of imbalanced training in multiagent tasks and formally define it as an imbalance between policies (IBPs). To address the IBP issue, we propose a dynamic policy balance (DPB) model to balance the learning of each policy by dynamically reweighting the training samples. In addition, current methods for better performance strengthen the exploration of all policies, which leads to disregarding the training differences in the team and reducing learning efficiency. To overcome this drawback, we derive a technique named weighted entropy regularization (WER), a team-level exploration with additional incentives for individuals who exceed the team. DPB and WER are evaluated in homogeneous and heterogeneous tasks, effectively alleviating the imbalanced training problem and improving exploration efficiency. Furthermore, the experimental results show that our models can outperform the state-of-the-art MAPG methods and boast over 12.1 % performance gain on average.

Correlations between non-suicidal self-injury and problematic internet use among Chinese adolescents: a systematic review and meta-analysis.

Background: Non-Suicidal Self-Injury (NSSI) has continued to be a major issue for public health worldwide, especially among teenagers. Studies have found a certain correlation between NSSI and Problematic Internet Use (PIU). However, this relationship is still unclear among Chinese adolescents, a specific population. Hence, a meta-analysis was carried out on observational studies to explore the connection between NSSI and PIU in Chinese teenagers, aiming to provide more clarity on the correlation. Methods: To identify the link between NSSI and PIU, we scoured seven digital repositories until November 16, 2023. Employing a random-effects meta-analysis framework, we delved into the association between NSSI and PIU. Additionally, we carried out subgroup evaluations to scrutinize variables including geographical location, age demographics, research methodology, diagnostic instruments, gender, and variables controlled for confounding, like symptoms of depression. For amalgamating data, STATA software (version 16) was deployed. Results: In this analysis, we included 15 research papers encompassing a collective sample of 137,166 individuals. Our findings revealed a significant positive association between NSSI and PIU within the adolescent population in China, with an Odds Ratio (OR) of 2.02 and a 95% Confidence Interval (CI) ranging from 1.73 to 2.37. Notably, this correlation was markedly stronger in specific subgroups: adolescents from China's Western regions exhibited an OR of 4.22 (95% CI: 3.44, 5.18); middle school attendees had an OR of 2.09 (95% CI: 1.92, 2.28); those diagnosed with concurrent depression disorders showed an OR of 2.32 (95% CI: 1.98, 2.73); and female adolescents demonstrated an OR of 2.49 (95% CI: 2.26, 2.75), highlighting the nuanced dynamics of this relationship. Conclusion: This meta-analysis indicates that PIU among adolescents is associated with an increased risk of NSSI. Our findings underscore the importance of targeting specific populations, including those in the western region of China, middle school students, adolescents with comorbid depression disorders, and female adolescents, who may be at higher risk of PIU and subsequently NSSI. These results emphasize the need for tailored interventions and preventive strategies to address these intertwined issues effectively. Systematic review registration: PROSPERO, identifier CRD42024496579.

Surgical technical experience of adult aortic coarctation concomitant with poststenotic aneurysm or dissection.

Background: Aortic coarctation (COA) in adults combined with poststenotic aneurysm (PA) or poststenotic dissection (PD) is rare and challenging to manage. The existence of multiple factors such as kinking, comorbidities, previous surgical history, and descending aortic lesions increases the difficulty of treatment, and there are currently few clinical reports. The purpose of this study was to present our surgical experience in dealing with such patients. Methods: A retrospective study was conducted on 20 consecutive patients with COA combined with PA or PD who were treated in our center from December 2015 to April 2019. The basic principles, methods, and short- and mid-term prognosis of surgery are present carefully. This paper introduces the individualized treatment scheme as well as its advantages and disadvantages in detail. Results: The condition of the included patients was complicated, including 12 cases of PA and 8 of PD. Although different surgical schemes were adopted, procedural success rate was 100%. There were no other surgical complications except 2 cases of anastomotic bleeding and 1 case of spinal cord injury. The results of computed tomography angiography (CTA) demonstrated that 9 cases achieved anatomical correction, 10 cases of PA or PD were eliminated or thrombosed to varying degrees, and only 1 case of PA had no obvious change. Up to the follow-up period, except for 1 patient who had a slight cerebrovascular accident and 1 who had no change in PA underwent cheatham platinum (CP) stent surgery, no other cardiovascular adverse events occurred and all patients recovered well. Conclusions: The optimal surgical strategy developed collaboratively by cardiac surgeons and endovascular specialists has achieved satisfactory short- and mid-term results for COA patients combined with PA or PD. Further research is still necessary, due to the limited number of cases.

Potential biomarkers of recurrent FSGS: a review.

Focal segmental glomerulosclerosis (FSGS), a clinicopathological condition characterized by nephrotic-range proteinuria, has a high risk of progression to end-stage renal disease (ESRD). Meanwhile, the recurrence of FSGS after renal transplantation is one of the main causes of graft loss. The diagnosis of recurrent FSGS is mainly based on renal puncture biopsy transplants, an approach not widely consented by patients with early mild disease. Therefore, there is an urgent need to find definitive diagnostic markers that can act as a target for early diagnosis and intervention in the treatment of patients. In this review, we summarize the domestic and international studies on the pathophysiology, pathogenesis and earliest screening methods of FSGS and describe the functions and roles of specific circulating factors in the progression of early FSGS, in order to provide a new theoretical basis for early diagnosis of FSGS recurrence, as well as aid the exploration of therapeutic targets.