20(S)-Protopanaxadiol Exerts Antidepressive Effects in Chronic Corticosterone-Induced Rodent Animal Models as an Activator of Brain-Type Creatine Kinase.

20(S)-Protopanaxadiol (PPD) is one of the bioactive ingredients in ginseng and possesses neuroprotective properties. Brain-type creatine kinase (CK-BB) is an enzyme involved in brain energy homeostasis via the phosphocreatine-creatine kinase system. We previously identified PPD as directly bound to CK-BB and activated its activity in vitro. In this study, we explored the antidepressive effects of PPD that target CK-BB. First, we conducted time course studies on brain CK-BB, behaviors, and hippocampal structural plasticity responses to corticosterone (CORT) administration. Five weeks of CORT injection reduced CK-BB activity and protein levels and induced depression-like behaviors and hippocampal structural plasticity impairment. Next, a CK inhibitor and an adeno-associated virus-targeting CKB were used to diminish CK-BB activity or its expression in the brain. The loss of CK-BB in the brain led to depressive behaviors and morphological damage to spines in the hippocampus. Then, a polyclonal antibody against PPD was used to determine the distribution of PPD in the brain tissues. PPD was detected in the hippocampus and cortex and observed in astrocytes, neurons, and vascular endotheliocytes. Finally, different PPD doses were used in the chronic CORT-induced depression model. Treatment with a high dose of PPD significantly increased the activity and expression of CK-BB after long-term CORT injection. In addition, PPD alleviated the damage to depressive-like behaviors and structural plasticity induced by repeated CORT injection. Overall, our study revealed the critical role of CK-BB in mediating structural plasticity in CORT-induced depression and identified CK-BB as a therapeutic target for PPD, allowing us to treat stress-related mood disorders.

Long-term abacus training gains in children are predicted by medial temporal lobe anatomy and circuitry.

Abacus-based mental calculation (AMC) is a widely used educational tool for enhancing math learning, offering an accessible and cost-effective method for classroom implementation. Despite its universal appeal, the neurocognitive mechanisms that drive the efficacy of AMC training remain poorly understood. Notably, although abacus training relies heavily on the rapid recall of number positions and sequences, the role of memory systems in driving long-term AMC learning remains unknown. Here, we sought to address this gap by investigating the role of the medial temporal lobe (MTL) memory system in predicting long-term AMC training gains in second-grade children, who were longitudinally assessed up to fifth grade. Leveraging multimodal neuroimaging data, we tested the hypothesis that MTL systems, known for their involvement in associative memory, are instrumental in facilitating AMC-induced improvements in math skills. We found that gray matter volume in bilateral MTL, along with functional connectivity between the MTL and frontal and ventral temporal-occipital cortices, significantly predicted learning gains. Intriguingly, greater gray matter volume but weaker connectivity of the posterior parietal cortex predicted better learning outcomes, offering a more nuanced view of brain systems at play in AMC training. Our findings not only underscore the critical role of the MTL memory system in AMC training but also illuminate the neurobiological factors contributing to individual differences in cognitive skill acquisition. RESEARCH HIGHLIGHTS: We investigated the role of medial temporal lobe (MTL) memory system in driving children's math learning following abacus-based mental calculation (AMC) training. AMC training improved math skills in elementary school children across their second and fifth grade. MTL structural integrity and functional connectivity with prefrontal and ventral temporal-occipital cortices predicted long-term AMC training-related gains.

Discovery and validation of COX2 as a target of flavonoids in Apocyni Veneti Folium: Implications for the treatment of liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Apocyni Veneti Folium (AVF), a popular traditional Chinese medicine (TCM), is known for its effects in soothing the liver and nerves and eliminating heat and water. It is relevant from an ethnopharmacological perspective. Pharmacological research has confirmed its benefits on antihypertension, antihyperlipidemia, antidepression, liver protection, immune system boosting, antiaging, and diabetic vascular lesions. Previous studies have shown that flavonoids, the active ingredients, have a hepatoprotective effect. However, the exact mechanism has not been clarified. AIM OF THE STUDY: This study aimed to identify the active flavonoids in AVF and their corresponding targets for liver injury. Multiple methods were introduced to confirm the targets. MATERIAL AND METHODS: AVF compounds were analyzed using liquid chromatography-mass spectrometry (LC-MS). Then, network pharmacology was utilized to screen potential hepatoprotection targets of the compounds. An enzyme activity assay was performed to determine the effect of the compounds on the targets. Biolayer interferometry (BLI) was applied to confirm the direct interaction between the compounds and the targets. RESULTS: A total of 71 compounds were identified by LC-MS and 19 compounds and 112 shared targets were screened using network pharmacology. These common targets were primarily involved in the TNF signaling pathway, cancer pathways, hepatitis B, drug responses, and negative regulation of the apoptotic process. Flavonoids were the primary pharmacological substance basis of AVF. The cyclooxygenase 2 (COX2) protein was one of the direct targets of flavonoids in AVF. The enzyme activity assay and BLI-based intermolecular interactions demonstrated that the compounds astragalin, isoquercitrin, and hyperoside exhibited stronger inhibition of enzyme activity and a higher affinity with COX2 compared to epigallocatechin, quercetin, and catechin. CONCLUSIONS: COX2 was preliminarily identified as a target of flavonoids, and the mechanism of the hepatoprotective effect of AVF might be linked to flavonoids inhibiting the activity of COX2. The findings can establish the foundation for future research on the traditional hepatoprotective effect of AVF on the liver and for clinical studies on liver disorders.

Finger motor representation supports the autonomy in arithmetic: neuroimaging evidence from abacus training.

Researches have reported the close association between fingers and arithmetic. However, it remains unclear whether and how finger training can benefit arithmetic. To address this issue, we used the abacus-based mental calculation (AMC), which combines finger training and mental arithmetic learning, to explore the neural correlates underlying finger-related arithmetic training. A total of 147 Chinese children (75 M/72 F, mean age, 6.89 ± 0.46) were recruited and randomly assigned into AMC and control groups at primary school entry. The AMC group received 5 years of AMC training, and arithmetic abilities and resting-state functional magnetic resonance images data were collected from both groups at year 1/3/5. The connectome-based predictive modeling was used to find the arithmetic-related networks of each group. Compared to controls, the AMC's positively arithmetic-related network was less located in the control module, and the inter-module connections between somatomotor-default and somatomotor-control modules shifted to somatomotor-visual and somatomotor-dorsal attention modules. Furthermore, the positive network of the AMC group exhibited a segregated connectivity pattern, with more intra-module connections than the control group. Overall, our results suggested that finger motor representation with motor module involvement facilitated arithmetic-related network segregation, reflecting increased autonomy of AMC, thus reducing the dependency of arithmetic on higher-order cognitive functions.

Reshaping the Cortical Connectivity Gradient by Long-Term Cognitive Training During Development.

The organization of the brain follows a topological hierarchy that changes dynamically during development. However, it remains unknown whether and how cognitive training administered over multiple years during development can modify this hierarchical topology. By measuring the brain and behavior of school children who had carried out abacus-based mental calculation (AMC) training for five years (starting from 7 years to 12 years old) in pre-training and post-training, we revealed the reshaping effect of long-term AMC intervention during development on the brain hierarchical topology. We observed the development-induced emergence of the default network, AMC training-promoted shifting, and regional changes in cortical gradients. Moreover, the training-induced gradient changes were located in visual and somatomotor areas in association with the visuospatial/motor-imagery strategy. We found that gradient-based features can predict the math ability within groups. Our findings provide novel insights into the dynamic nature of network recruitment impacted by long-term cognitive training during development.

Discovery and validation of PURA as a transcription target of 20(S)-protopanaxadiol: Implications for the treatment of cognitive dysfunction.

Background: 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, has prominent benefits for the central nervous system, especially in improving learning and memory. However, its transcriptional targets in brain tissue remain unknown. Methods: In this study, we first used mass spectrometry-based drug affinity responsive target stability (DARTS) to identify the potential proteins of ginsenosides and intersected them with the transcription factor library. Second, the transcription factor PURA was confirmed as a target of PPD by biolayer interferometry (BLI) and molecular docking. Next, the effect of PPD on the transcriptional levels of target genes of PURA in brain tissues was determined by qRT-PCR. Finally, bioinformatics analysis was used to analyze the potential biological features of these target proteins. Results: The results showed three overlapping transcription factors between the proteomics of DARTS and transcription factor library. BLI analysis further showed that PPD had a higher direct interaction with PURA than parent ginsenosides. Subsequently, BLI kinetic analysis, molecular docking, and mutations in key amino acids of PURA indicated that PPD specifically bound to PURA. The results of qRT-PCR showed that PPD could increase the transcription levels of PURA target genes in brain. Finally, bioinformatics analysis showed that these target proteins were involved in learning and memory function. Conclusion: The above-mentioned findings indicate that PURA is a transcription target of PPD in brain, and PPD upregulate the transcription levels of target genes related to cognitive dysfunction by binding PURA, which could provide a chemical and biological basis for the study of treating cognitive impairment by targeting PURA.

Driving Forces of Meteorology and Emission Changes on Surface Ozone in the Huaihe River Basin, China.

Surface ozone (O3) pollution in China has become a serious environmental problem in recent years. In the present study, we targeted the HRB, a large region located in China's north-south border zone, to assess the driving forces of meteorology and emission changes on surface ozone. A Kolmogorov-Zurbenko (KZ) filter method was performed on the maximum daily average 8-h (MDA8) concentrations of ozone in the HRB during 2015-2020 to decompose the original time series. The findings demonstrated that the short-term (O3ST), seasonal (O3SN), and long-term components (O3LT) of MDA8 O3 variations accounted for 34.2%, 56.1%, and 2.9% of the total variance, respectively. O3SN has the greatest influence on the daily variation in MDA8 O3, followed by O3ST. In coastal cities, the influence of O3ST was enhanced. The influence of O3SN was stronger in the northwestern HRB. Air temperature is the prevailing variable that influences the photochemical formation of ozone. A clear phase lag (7-34 days) of the baseline component between MDA8 O3 and the atmospheric temperature was found in the HRB. Using multiple linear regression, the effect of temperature on ozone was removed. We estimated that the increase in ozone concentration in the HRB was mainly caused by the emission changes (79.4%), and the meteorological conditions made a small contribution (20.6%). This study suggests that reductions in volatile organic compounds (VOCs) will play an important role in further ozone pollution reduction in the HRB. Supplementary Information: The online version contains supplementary material available at 10.1007/s11270-023-06345-1.

Enhanced intersubject similarity in functional connectivity by long-term abacus training.

The individual difference of intrinsic functional connectivity is increasingly acknowledged to be biologically informative and behaviorally relevant. However, such valuable information is still discounted as a stochastic variation in previous studies of cognitive training. Here, we explored the plasticity of intersubject similarity in functional connectivity (ISFC), induced by long-term abacus-based mental calculation (AMC) training. Using a longitudinal dataset (AMC: n = 40, 5-year training; Control: n = 43), we found robust training effect of enhanced ISFC, after accounting for the factor of development. Notably, the enhancement focused on selective subsets of FCs, or the "critical FCs," which predominantly impacted the default-mode and visual networks. Using a cross-sectional dataset with a larger sample (AMC: n = 93, 1/3/5-year training; Control: n = 110), we observed that the "critical FCs" and its intersubject similarity could predict mental calculation ability and its intersubject similarity, respectively, in the AMC group. However, such predictions cannot be generalized to the control group, suggesting that long-term training may be a prerequisite for establishing such brain-behavior relationships. Jointly, our findings implicated that the enhanced ISFC with profound impact on the default-mode network could be a plastic change that is associated with behavioral gains of training.

A rare case of penetrating thoracic aortic injury.

INTRODUCTION AND IMPORTANCE: Thoracic aortic injuries could be lethal events. Penetrating injuries to aortic are highly fatal, but these cases are rare in hospital. CASE PRESENTATION: A 54-year-old man presented with cough for half a month and cough up blood for half a day before he went into our hospital. No obvious positive sign was detected in physical examination. CLINICAL FINDINGS AND INVESTIGATIONS: Chest computed tomography (CT) showed positive foreign body in the mediastinum, which penetrated the left main bronchus from front to back and penetrated the thoracic aorta backwards. INTERVENTIONS AND OUTCOME: An endovascular stent graft was implanted to ensure that the penetrating aortic injury remains stable; then bronchoscopic evaluation was performed to remove the foreign body. The patient recovered uneventfully. No discomfort has been complained of during regular follow-up. RELEVANCE AND IMPACT: Endovascular stent repair is an effective lifesaving method for patients with penetrating aortic injury and with surgical contraindications.

Selective Adsorption of Quercetin by the Sol-Gel Surface Molecularly Imprinted Polymer.

Quercetin, as one of the most biologically active natural flavonoids, is widely found in various vegetables, fruits and Chinese herbs. In this work, molecularly imprinted polymer (MIP) was synthesized through surface molecular imprinting technology with sol-gel polymerization mechanism on SiO2 at room temperature using quercetin as the template, SiO2 as the supporter, 3-aminopropyltriethoxysilane (APTES) as the functional monomer, and tetraethoxysilane (TEOS) as the cross-linker. The prepared MIP was characterized via scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR) and nitrogen adsorption measurements to validate its surface morphology, structure and functionality. SEM images revealed that the morphology of MIP was rough and spherical with the particle size of 260 nm larger than that of the support SiO2. In the FTIR spectra of MIP, the band around 1499 cm-1 and 2932 cm-1 were assigned to N-H and C-H groups, respectively. The results indicated that the imprinted polymer layers were grafted on the surface of SiO2 and the MIP had been successfully prepared. Since the specific surface area and pore volume of MIP were markedly higher than those of NIP and SiO2 and were 52.10 m2 g-1 and 0.150 cm3 g-1, respectively, it was evident that the imprinting process created corresponding imprinted cavities and porosity. The MIP for adsorbing quercetin was evaluated by static adsorption experiment. The results indicated that the adsorption equilibrium could be reached within 90 min and the maximum adsorption capacity was as high as 35.70 mg/g. The mechanism for adsorption kinetics and isotherm of MIP for quercetin was proved to conform the pseudo-second-order kinetics model (R2 = 0.9930) and the Freundlich isotherm model (R2 = 0.9999), respectively, revealing that chemical adsorption and heterogeneous surface with multilayer adsorption dominated. In contrast to non-imprinted polymer (NIP), the MIP demonstrated high selectivity and specific recognition towards quercetin whose selectivity coefficients for quercetin relative to biochanin A were 1.61. Furthermore, the adsorption capacity of MIP can be maintaining above 90% after five regeneration cycles, indicating brilliant reusability and potential application for selective adsorption of quercetin.

Protective Effect of 20(S)-Protopanaxadiol on D-Gal-Induced Cognitively Impaired Mice Based on Its Target Protein Brain-type Creatine Kinase.

Ginseng is an important medicinal herb consumed as dietary supplements. Ginsenosides and their metabolites have been reported to enhance cognitive performance, but their underlying mechanisms remain unclear. Brain-type creatine kinase (CK-BB) was previously screened out as one of the potential targets in brain tissues. In vitro, the strongest direct interaction between 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, and CK-BB was detected using biolayer interferometry (BLI). Drug affinity responsive target stability, cellular thermal shift assay, BLI, and isothermal titration calorimetry were subsequently used, and the binding of PPD to CK-BB was verified. The binding sites of the CK-BB/PPD complex were clarified by molecular docking and site-directed mutagenesis. Enzyme activity assay showed that the binding of PPD to CK-BB in vitro enhanced its activity. In vivo, PPD increased CK-BB activity in D-gal-induced mice. PPD also improved the D-gal-induced cognitive deficits and ameliorated alterations in oxidative stress and hippocampal synaptic plasticity. Therefore, the integration of PPD with its target protein CK-BB may promote CK-BB activity, thereby ameliorating hippocampal synaptic plasticity and cognitive deficits in D-gal-treated mice.

Different impacts of long-term abacus training on symbolic and non-symbolic numerical magnitude processing in children.

Abacus-based mental calculation (AMC) has been shown to be effective in promoting math ability in children. Given that AMC relies on a visuospatial strategy to perform rapid and precise arithmetic, previous studies mostly focused on the promotion of AMC training on arithmetic ability and mathematical visual-spatial ability, as well as its transfer of advanced cognitive ability. However, little attention has been given to its impact on basic numerical comparison ability. Here, we aim to examine whether and how long-term AMC training impacts symbolic and non-symbolic numerical comparisons. The distance effect (DE) was utilized as a marker, indicating that the comparison between two numbers becomes faster as their numerical distance enlarges. In the current study, forty-one children matched for age and sex were recruited at primary school entry and randomly assigned to the AMC group and the control group. After three years of training, the event-related potential (ERP) recording technique was used to explore the temporal dynamics of number comparison, of which tasks were given in symbolic (Arabic number) or non-symbolic (dot array) format. In the symbolic task, the children in the AMC group showed a smaller DE than those in the control group. Two ERP components, N1 and P2p, located in parietal areas (PO7, PO8) were selected as neural markers of numerical processing. Both groups showed DE in the P2p component in both tasks, but only the children in the AMC group showed DE in the N1 component in the non-symbolic task. In addition, the DE size calculated from reaction times and ERP amplitudes was correlated with higher cognitive capacities, such as coding ability. Taken together, the present results provide evidence that long-term AMC training may be beneficial for numerical processing in children, which may be associated with neurocognitive indices of parietal brain regions.

Core decompression with ß-tri-calcium phosphate grafts in combination with platelet-rich plasma for the treatment of avascular necrosis of femoral head.

BACKGROUND: This study was aimed to investigate whether the application of platelet-rich plasma (PRP) combined with ß-tri-calcium phosphate (ß-TCP) grafts after core decompression (CD) could improve the clinical outcomes of early stage of avascular necrosis of femoral head. METHODS: Forty-five (54 hips) patients with Ficat-Arlet classification stage I-II treated by CD with ß-TCP grafts with or without the application of PRP from July 2015 to October 2020 were reviewed. Group A (CD + ß-TCP grafts) included 24 patients (29 hips), while group B (CD + ß-TCP grafts + PRP) included 21 patients (25 hips). Visual analogue scale (VAS) score, Harris hip score (HHS), change in modified Kerboul angle and the hip joint survival were evaluated and compared between the groups. Patients had a mean follow-up period of 62.1 ± 17.2 months and 59.3 ± 14.8 months in group A and group B, respectively. RESULTS: The mean VAS scores in group A was significantly higher than group B at the 6 months (2.9 ± 0.7 vs 1.9 ± 0.6, p < 0.01) and final follow up postoperative (2.8 ± 1.2 vs 2.2 ± 0.7, p = 0.04). The mean HHS in group A was significantly lower than group B at the 6 months (80.5 ± 13.8 vs 89.8 ± 12.8, p = 0.02). However, at the final follow up, there is no significant difference between the groups (77.0 ± 12.4 vs 83.1 ± 9.3, p = 0.07). The mean change in modified Kerboul angle was -7.4 ± 10.6 in group A and -19.9 ± 13.9 in group B which is statistically significant (p < 0.01). Survivorship from total hip arthroplasty were 86.2%/84% (p = 0.86) at the final follow up, which was not statistically significant. No serious complications were found in both groups. CONCLUSIONS: A single dose of PRP combined with CD and ß-TCP grafts provided significant pain relief, better functional outcomes, and delayed progression in the short term compared to CD combined with ß-TCP grafts. However, the prognosis of the femoral head did not improve significantly in the long term. In the future, designing new implants to achieve multiple PRP injections may improve the hip preservation rate.

ccTCM: A quantitative component and compound platform for promoting the research of traditional Chinese medicine.

Traditional Chinese medicine (TCM) databases play a vital role in bridging the gap between TCM and modern medicine, as well as in promoting the popularity of TCM. Elucidating the bioactive ingredients of Chinese medicinal materials is key to TCM modernization and new drug discovery. However, one drawback of current TCM databases is the lack of quantitative data on the constituents of Chinese medicinal materials. Herein, we present ccTCM, a web-based platform designed to provide a component and compound-content-based resource on TCM and analysis services for medical experts. In terms of design features, ccTCM combines resource distribution, similarity analysis, and molecular-mechanism analysis to accelerate the discovery of bioactive ingredients in TCM. ccTCM contains 273 Chinese medicinal materials commonly used in clinical settings, covering 29 functional classifications. By searching and comparing, we finally adopted 2043 studies, from which we collected the compounds contained in each TCM with content greater than 0.001 %, and a total of 1449 were extracted. Subsequently, we collected 40,767 compound-target pairs by integrating multiple databases. Taken together, ccTCM is a versatile platform that can be used by TCM scientists to perform scientific and clinical TCM studies based on quantified ingredients of Chinese medicinal materials. ccTCM is freely accessible at http://www.cctcm.org.cn.

Right Fusiform Gray Matter Volume in Children with Long-Term Abacus Training Positively Correlates with Arithmetic Ability.

Abacus-based mental calculation (AMC) training has a positive effect on number-related cognitive abilities. While visuospatial strategy may distinguish AMC from conventional calculation method, the underlying neural mechanism is still elusive. The current study aimed to address this question by examining the plasticity of fusiform induced by AMC training and whether this training affects the association between the volume of fusiform and behavioral performance in numerical cognitive tasks using voxel-based morphometry analysis. The results showed that gray matter volumes of bilateral fusiform were significantly smaller in the AMC group relative to the control group. In addition, the volume of right fusiform was positively correlated with digit memory span and negatively correlated with reaction time of an arithmetic operation task only within the AMC group. These results indicate that bilateral fusiform may be the essential neural substrate for AMC experts to recognize and reconstruct abacus-based representations for numbers. These results may advance our understanding of the neural mechanisms of AMC and shield some lights to potential interactions between brain development and cognitive training in children.

Target engagement of ginsenosides in mild cognitive impairment using mass spectrometry-based drug affinity responsive target stability.

Background: Mild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC-MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a protein-protein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

A possible mechanism to the antidepressant-like effects of 20 (S)-protopanaxadiol based on its target protein 14-3-3 ζ.

Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3ß activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3ß (p-Ser9 GSK 3ß), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3ß activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3ß polypeptide. PPD promoted the binding and subsequently decreased GSK 3ß activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3ß (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3ß kinase activity, thereby activating the plasticity-related CREB-BDNF signaling pathway.

Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis.

Platelets have emerged as key inflammatory cells implicated in the pathology of sepsis, but their contributions to rapid clinical deterioration and dysregulated inflammation have not been defined. Here, we show that the incidence of thrombocytopathy and inflammatory cytokine release was significantly increased in patients with severe sepsis. Platelet proteomic analysis revealed significant upregulation of gasdermin D (GSDMD). Using platelet-specific Gsdmd-deficient mice, we demonstrated a requirement for GSDMD in triggering platelet pyroptosis in cecal ligation and puncture (CLP)-induced sepsis. GSDMD-dependent platelet pyroptosis was induced by high levels of S100A8/A9 targeting toll-like receptor 4 (TLR4). Pyroptotic platelet-derived oxidized mitochondrial DNA (ox-mtDNA) potentially promoted neutrophil extracellular trap (NET) formation, which contributed to platelet pyroptosis by releasing S100A8/A9, forming a positive feedback loop that led to the excessive release of inflammatory cytokines. Both pharmacological inhibition using Paquinimod and genetic ablation of the S100A8/A9-TLR4 signaling axis improved survival in mice with CLP-induced sepsis by suppressing platelet pyroptosis.

ULMR: An Unsupervised Learning Framework for Mismatch Removal.

Due to radiometric and geometric distortions between images, mismatches are inevitable. Thus, a mismatch removal process is required for improving matching accuracy. Although deep learning methods have been proved to outperform handcraft methods in specific scenarios, including image identification and point cloud classification, most learning methods are supervised and are susceptible to incorrect labeling, and labeling data is a time-consuming task. This paper takes advantage of deep reinforcement leaning (DRL) and proposes a framework named unsupervised learning for mismatch removal (ULMR). Resorting to DRL, ULMR firstly scores each state-action pair guided by the output of classification network; then, it calculates the policy gradient of the expected reward; finally, through maximizing the expected reward of state-action pairings, the optimal network can be obtained. Compared to supervised learning methods (e.g., NM-Net and LFGC), unsupervised learning methods (e.g., ULCM), and handcraft methods (e.g., RANSAC, GMS), ULMR can obtain higher precision, more remaining correct matches, and fewer remaining false matches in testing experiments. Moreover, ULMR shows greater stability, better accuracy, and higher quality in application experiments, demonstrating reduced sampling times and higher compatibility with other classification networks in ablation experiments, indicating its great potential for further use.

Human adenovirus (HAdV) infection in children with acute respiratory tract infections in Guangzhou, China, 2010-2021: a molecular epidemiology study.

BACKGROUND: Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China. METHODS: We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children's Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis. RESULTS: Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community. CONCLUSION: Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.