Gamma-aminobutyric acid-mediated neuro-immune interactions in glioblastoma: Implications for prognosis and immunotherapy response.

AIMS: This study aimed to investigate the role of gamma-aminobutyric acid (GABA) in the glioblastoma (GBM) tumor immune microenvironment (TIME) and its impact on prognosis and response to immunotherapy. MAIN METHODS: This study employed single-cell RNA sequencing (scRNA-seq) to delineate the TIME of GBM, utilized non-negative matrix factorization (NMF) for GABA-associated cell clustering, and performed pseudotime analysis for cellular trajectories. Additionally, we integrated immunohistochemistry (IHC), immunofluorescence (IF), and protein-protein interaction (PPI) analysis to explore the regulatory mechanisms within the tumor microenvironment. KEY FINDINGS: The study identified distinct GABA-associated immune cell subtypes, particularly macrophages and T-cells, with unique gene expression and developmental trajectories. The development of the GABA-associated scoring model (GABAAS), introduced novel prognostic indicators, enhancing our ability to predict patient outcomes. This study also suggests that GABA-related genes, including NDRG2 and TIMP1, play a crucial role in immune modulation, with potential implications for immunotherapy responsiveness. SIGNIFICANCE: The findings underscore the potential of targeting GABA-related genes (NDRG2 and TIMP1) and M2 macrophage to reshape the glioblastoma immune landscape, offering a new frontier in personalized neuro-immunotherapy. This approach holds promise to counter individual tumor immunosuppressive mechanisms, enhancing patient outcomes.

Evidence summary on the rehabilitative management of dysphagia during radiotherapy for head and neck cancer patients.

Objective: To retrieve, extract, integrate and evaluate evidence on the rehabilitation of dysphagia in patients undergoing radiotherapy for head and neck cancer (HNC), and to provide a basis for the development of a rehabilitation management protocol for dysphagia in patients undergoing radiotherapy for HNC. Methods: An evidence-based systematic search of the literature related to the rehabilitation of dysphagia in patients with HNC during radiotherapy was conducted from January 2013 to March 2023, and the corresponding evaluation tools were selected according to the different types of literature for quality evaluation. "The Joanna Briggs Institute (JBI) evidence pre-grading system was used to evaluate the quality of the evidence. Results: A total of 17 articles were included, including 3 guidelines, 5 expert articles, 1 clinical decision, 1 practice recommendation, 2 evidence summaries and 5 systematic evaluations. A final total of 28 pieces of evidence were summarised, including 6 areas of swallowing disorder screening and assessment, physiotherapy, preventive swallowing function training, feeding management, pain control, and oral care. Conclusion: This study forms a multidisciplinary collaborative evidence summary for the rehabilitation management of dysphagia in patients undergoing radiotherapy for HNC, but the application of some of the evidence needs to be carried out in the context of the clinical setting and patient-specific circumstances for the rehabilitation evidence selected for patients' dysphagia to improve their swallowing function and their swallowing-related quality of life and reduce the occurrence of related complications.

LncRNA H19 Promotes Gastric Cancer Metastasis via miR-148-3p/SOX-12 Axis.

Background: Gastric cancer (GC) is the most common malignant tumor and ranks third in the world. LncRNA H19 (H19), one of the members of lncRNA, is overexpressed in various tumors. However, many undetermined molecular mechanisms by which H19 promotes GC progression still need to be further investigated. Methodology. A series of experiments was used to confirm the undetermined molecular mechanism including wound healing and transwell assays. Key Results. In this study, a significant upregulation of H19 expression was detected in GC cells and tissues. The poor overall survival was observed in GC patient with high H19 expression. Overexpression of H19 promoted the migration of GC cells, while knockdown of H19 significantly inhibited cell migration. Moreover, miR-148a-3p had a certain negative correlation with H19. Luciferase reporter assay confirmed that H19 could directly bind to miR-148a-3p. As expected, miR-148a mimics inhibited cell migration and invasion induced by H19 overexpression. The above findings proved that H19 functions as a miRNA sponge and verified that miR-148a-3p is the H19-associated miRNA in GC. We also confirmed that SOX-12 expression was upregulated in GC patient's samples. SOX-12 expression was positively correlated with expression of H19 and was able to directly bind to miR-148a-3p. Importantly, in vitro wound healing assay showed that knockout of SOX-12 could reverse the promoting effect of H19 overexpression on cell migration. Conclusion: In conclusion, H19 has certain application value in the diagnosis and prognosis of GC. Specifically, H19 accelerates GCs to migration and metastasis by miR-138a-3p/SOX-12 axis.

The Impact of School Reopening on Chinese Adolescents' Mental Health During COVID-19: Considering the Role of Academic Stress and Academic Orientation.

PURPOSE: Existing studies found that school closure during the COVID-19 pandemic negatively influenced adolescents' mental health. Yet, it remains unclear how adolescent mental health changed during the transition of school reopening as well as the academic-related risk and protective factors. METHODS: Immediately before (April 2020) and three months (July 2020) after school reopening, 879 adolescents in Shanghai, China (mean age = 13.14 years, standard deviation = 1.31, 51% girls) completed online surveys and reported on their mental health (i.e., depressive symptoms, anxiety symptoms, and anger problems). Adolescents also reported perceived academic stress and academic orientations (i.e., performance orientation and mastery orientation) before school reopening. RESULTS: Adolescents reported decreased depressive symptoms, anxiety symptoms, and anger problems three months after school reopening. Adolescents who reported higher perceived academic stress and performance orientation showed elevated mental health symptoms after school reopening, whereas those reported higher mastery orientation showed decreased anger problems. Higher mastery orientation buffered the negative influence of academic stress on mental health. DISCUSSION: The findings not only demonstrate the positive influence of school reopening on Chinese adolescents' mental health but also highlight the role of perceived academic stress and academic orientations in contributing to individual differences during this transition.

Study of the Rolling Effect on MoS2-Carbon Fiber Density and Its Consequences for the Functionality of Li-Ion Batteries.

In this study, an electrode slurry composed of molybdenum disulfide (MoS2) and vapor-grown carbon fiber (VGCF) prepared through a solid-phase synthesis method was blade-coated onto copper foil to form a thick film as the anode for lithium-ion batteries. In previously reported work, MoS2-based lithium-ion batteries have experienced gradual deformation, fracture, and pulverization of electrode materials during the charge and discharge cycling process. This leads to an unstable electrode structure and rapid decline in battery capacity. Furthermore, MoS2 nanosheets tend to aggregate over charge and discharge cycles, which diminishes the surface activity of the material and results in poor electrochemical performance. In this study, we altered the density of the MoS2-carbon fiber/Cu foil anode electrode by rolling. Three different densities of electrode sheets were obtained through varying rolling repetitions. Our study shows the best electrochemical performance was achieved at a material density of 2.2 g/cm3, maintaining a capacity of 427 mAh/g even after 80 cycles.

CLEC7A regulates M2 macrophages to suppress the immune microenvironment and implies poorer prognosis of glioma.

Background: Gliomas constitute a category of malignant tumors originating from brain tissue, representing the majority of intracranial malignancies. Previous research has demonstrated the pivotal role of CLEC7A in the progression of various cancers, yet its specific implications within gliomas remain elusive. The primary objective of this study was to investigate the prognostic significance and immune therapeutic potential of CLEC7A in gliomas through the integration of bioinformatics and clinical pathological analyses. Methods: This investigation involved examining and validating the relationship between CLEC7A and glioma using samples from Hospital, along with data from TCGA, GEO, GTEx, and CGGA datasets. Subsequently, we explored its prognostic value, biological functions, expression location, and impact on immune cells within gliomas. Finally, we investigated its potential impact on the chemotaxis and polarization of macrophages. Results: The expression of CLEC7A is upregulated in gliomas, and its levels escalate with the malignancy of tumors, establishing it as an independent prognostic factor. Functional enrichment analysis revealed a significant correlation between CLEC7A and immune function. Subsequent examination of immune cell differential expression demonstrated a robust association between CLEC7A and M2 macrophages. This conclusion was further substantiated through single-cell analysis, immunofluorescence, and correlation studies. Finally, the knockout of CLEC7A in M2 macrophages resulted in a noteworthy reduction in macrophage chemotaxis and polarization factors. Conclusion: CLEC7A expression is intricately linked to the pathology and molecular characteristics of gliomas, establishing its role as an independent prognostic factor for gliomas and influencing macrophage function. It could be a promising target for immunotherapy in gliomas.

Identifying and validating potential therapeutic targets for septic heart failure and the cardioprotective effects of lycorine.

BACKGROUND: Septic heart failure has been recognized as a puzzle since antiquity and poses a major challenge to modern medicine. Our previous work has demonstrated the potential effects of lycorine (LYC) on sepsis and septic myocardial injury. Nonetheless, further exploration is needed to elucidate the underlying cellular and molecular mechanisms. METHODS: In this study, we conducted transcriptome analysis and weighted gene co-expression network analysis (WGCNA) to identify the key genes and reveal the mechanism of LYC against septic heart failure. PURPOSE: This study aims to apply bioinformatic analysis and experimental validations to explore the protective effects and underlying mechanism of LYC on the cecal ligation and puncture (CLP)-induced sepsis model mice. RESULTS: Transcriptome analysis revealed the differentially expressed genes (DEGs) following LYC treatment. WGCNA analysis identified gene modules associated with LYC-mediated protection, with BCL3 emerging as a core gene within these modules. Notably, BCL3 was an overlapping gene of DEGs and WGCNA core genes induced by LYC treatment, and is highly negatively correlated with cardiac function indicator. In vivo and in vitro study further prove that LYC exerted a protective effect against septic myocardial injury through inhibiting BCL3. BCL3 siRNA ameliorated LPS-induced cardiac injury and inflammation, while BCL3 overexpression reversed the protective effect of LYC against LPS injury. CONCLUSION: In summary, our findings demonstrate the significant attenuation of septic myocardial disorder by LYC, with the identification of BCL3 as a pivotal target gene. This study is the first to report the role of BCL3 in sepsis and septic myocardial injury. Furthermore, the strategy for hub genes screening used in our study facilitates a comprehensive exploration of septic targets and reveals the potential targets for LYC effect. These findings may offer a new therapeutic strategy for the management of septic heart failure, highlighting the cardioprotective effect of LYC as adjunctive therapy for sepsis management.

Pterostilbene protects against H2 O2 -induced oxidative stress by regulating GAS6/Axl signaling in HL-1 cells.

Pterostilbene (PTE, trans-3,5-dimethoxy-4'-hydroxystilbene), a natural plant polyphenol, possesses numerous pharmacological effects, including antioxidant, antidiabetic, antiatherosclerotic, and neuroprotective aspects. This study aims to investigate whether PTE plays a protective role against oxidative stress injury by GAS6/Axl signaling pathway in cardiomyocytes. Hydrogen peroxide (H2 O2 )-induced oxidative stress HL-1 cells were used as models. The mechanism by which PTE protected oxidative stress is investigated by combining cell viability, cell ROS levels, apoptosis assay, molecular docking, quantitative real-time PCR, and western blot analysis. GAS6 shRNA was performed to investigate the involvement of GAS6/Axl pathways in PTE's protective role. The results showed that PTE treatment improved the cell morphology and viability, and inhibited the apoptosis rate and ROS levels in H2 O2 -injured HL-1 cells. Particularly, PTE treatment upregulated the levels of GAS6, Axl, and markers related to oxidative stress, apoptosis, and mitochondrial function related. Molecular docking showed that PTE and GAS6 have good binding ability. Taken together, PTE plays a protective role against oxidative stress injury through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Particularly, GAS6/Axl axis is the surprisingly prominent in the PTE-mediated pleiotropic effects.

Isopropyl 3-(3,4-dihydroxyphenyl) 2-hydroxypropanoate protects septic myocardial injury via regulating GAS6/Axl-AMPK signaling pathway.

In a previous study, we used metabolomic techniques to identify a new metabolite of Danshen Dripping Pills called isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP), which has potential as a drug candidate for cardiovascular diseases. This study aimed to explore the protective effects of IDHP against septic myocardial injury, as well as its molecular mechanism. Wild type or GAS6 knockout mice injured by cecal ligation and puncture (CLP) were used to observe the effect of IDHP. Here, we found that a specific concentration of IDHP (60 mg/kg) significantly increased the survival rate of septic mice to about 75 % at 72 h post CLP, and showed improvements in sepsis score, blood biochemistry parameters, cardiac function, and myocardial tissue damage. Furthermore, IDHP inhibited myocardial oxidative stress, inflammatory response, apoptosis, and mitochondrial dysfunction. Molecularly, we discovered that IDHP treatment reversed the CLP-induced downregulation of GAS6, Axl, and p-AMPK/AMPK expression. In addition, GAS6 knockout reversed the positive effect of IDHP in septic mice, indicated by more severe myocardial tissue damage, oxidative stress, inflammatory response, and mitochondrial dysfunction. GAS6 knockout also resulted in decreased levels of GAS6, Axl, and p-AMPK/AMPK. Taken together, our study provides evidence that IDHP has significant cardioprotective effects against sepsis by regulating the GAS6/Axl-AMPK signaling pathway. This finding has important therapeutic potential for treating sepsis.

Tough and Self-Healing Waterborne Polyurethane Elastomers via Dynamic Hydrogen Bonds Design for Flexible Conductive Substrate Applications.

Balancing the mechanical strength and self-healing performance of polyurethane (PU) remains a significant challenge in achieving excellent self-repairing PU materials. In this study, a self-healing waterborne PU elastomer was designed from a bionic concept by incorporating 2'-deoxythymidine (2'-dT) and isophorone diamine (IPDA) into the polymer chain. The loose stacking of IPDA's irregular cycloaliphatic structure resulted in the irregular arrangement of urethane bonds in the hard domain. The formation of sextuple hydrogen bonds between 2'-dT and urethane bonds, as well as quadruple hydrogen bonds between urethane bonds themselves, enhanced the mechanical properties of the material. The multiple hydrogen bonds can dissociate, recombine, and dissipate energy, thereby improving the material's repair capability. The hierarchical self-assembly of hydrogen bonds enabled the PU to achieve a tensile strength of 15.3 MPa and toughness of 100.75 MJ/m3. The prepared PU film is highly transparent and has a transmittance of more than 90%. Additionally, it can undergo rapid repair under high temperatures or under trace solvent conditions. When used as a flexible conductive substrate, it quickly restored the conductivity and enhanced the material's lifespan after surface damage. This environmentally friendly and self-healing waterborne PU elastomer will hold broad application prospects in the field of flexible electronic devices.

Non-targeted Profiling of Sea Buckthorn Fruit Oil Fingerprints from 3 Regions and Study on Its Antioxidant Activity.

This study investigated the chemical and volatile characteristics of sea buckthorn fruits from three different regions in China. The chemical composition of the volatile oil was determined by using a non-targeted gas chromatography and mass spectrometry (GC/MS) method and the differences in chemical composition among the three producing areas were compared by heatmap providing a visual basis for researchers. A total of 93 compounds were identified, including 52 compounds from the Northeast China, 51 from the Xinjiang region, and 37 from Inner Mongolia region. Then, the in vitro antioxidant activity of sea buckthorn fruit oil was measured using DPPH, ABTS, and SOD inhibition tests, and the results showed that sea buckthorn fruit oil in northeast China was the strongest antioxidant, followed by Inner Mongolia and Xinjiang. The results of the CCK-8 experiment indicated that within the tested concentration, there is no cell cytotoxicity of the essential oil in human umbilical vein endothelial cells (HUVECs) cells. The results could supply reference to distinguish sea buckthorn fruit from different production areas and, meanwhile, clarify the activity and safety of sea buckthorn oil.

Exploring the experience of meaning-centered group psychotherapy among Chinese cancer patients during active treatment: a descriptive qualitative study.

Objective: Meaninglessness poses a significant psychological challenge for cancer patients, negatively affecting their quality of life and increasing the risk of suicide. Meaning-Centered Group Therapy (MCGP) is an intervention designed specifically to enhance the meaning of life of cancer patients. Extensive research has documented its effectiveness across various cultures and populations. However, limited research has been conducted on the subjective experiences and perspectives of participants engaged in MCGP. Thus, the purpose of this study was to employ a qualitative design to explore the experiences and viewpoints of Chinese cancer patients who have undergone MCGP. Methods: Within a two-week timeframe following the conclusion of MCGP, semi-structured interviews were administered to twenty-one participants who had engaged in the therapy. The interview data were transcribed and subjected to thematic analysis. Results: Four main themes were identified: (a) Self-perceived personal change, (b) Overall experience of group therapy, (c) Barriers to participation of MCGP, and (d) Suggestions for future interventions. Conclusion: Despite the barriers to participation in the MCGP process, the overall experience for Chinese cancer patients undergoing active treatment is valuable and positive, providing multiple benefits. Future studies could explore the adaptation of MCGP to a broader range of cancer populations and diverse study populations.

Efficacy of meaning-centered group psychotherapy in Chinese patients with cancer: A randomized controlled trial.

OBJECTIVES: Meaninglessness is one of the most common psychological problems in cancer patients, which can lead to anxiety, depression and psychological distress, and diminished quality of life. Recent evidence indicates that meaning-centered group psychotherapy (MCGP) effectively enhances the meaning in life among cancer patients. This study aimed to evaluate the impact of MCGP on the meaning in life, post-traumatic growth, psychological distress, and fear of recurrence among Chinese cancer patients with a favorable prognosis. METHODS: Sixty-six cancer patients were randomly assigned to either the MCGP group (n = 33) or the control group (n = 33). Participants in the MCGP group underwent a 4-week, 8-session MCGP, while those in the control group received usual care. Meaning in life, post-traumatic growth, psychological distress, and fear of recurrence were assessed at both baseline and postintervention to evaluate the impact of the intervention. The intervention outcomes were analyzed using paired t-tests or analysis of covariance, as appropriate. RESULTS: Patients in the MCGP group demonstrated significant improvements in meaning in life, post-traumatic growth, and fear of recurrence from baseline to postintervention. In comparison to the control group, the MCGP group displayed positive effects on meaning in life and post-traumatic growth following the intervention. However, no significant effects were observed in terms of psychological distress and fear of recurrence. SIGNIFICANCE OF RESULTS: Our research offers evidence supporting the effectiveness of MCGP in enhancing meaning in life and post-traumatic growth among Chinese cancer patients with a favorable prognosis.

Comparative transcriptome analysis of unfractionated peripheral blood leukocytes after exercise in human.

Exercise has profound but variable effects on the immune system. However, only limited information exists about the changes of exercise-induced gene expression in whole immune cells. The aim of this study is to unravel the potential molecular changes of genes which are related to immunity after exercise. The raw expression data and corresponding clinical of GSE18966 were downloaded from Gene Expression Omnibus database. The differentially expressed genes between control group and treat groups were performed by in-house developed perl scripts. A total of 83 differentially expressed genes (DEGs) (|log2 FC|> 1, FDR < 0.05) were identified between control and treat group 1 (0 h after exercise), 128 DEGs (|log2 FC|> 1, FDR < 0.05) between control and treat group 2 (4 h after exercise), and there was no significant difference between control and treat group 3 (20 h after exercise). Next, we identified 51 overlapping genes between treat group 1 (0 h after exercise) and treat group 2 (4 h after exercise) using Venn analysis. Protein-protein interaction (PPI) network was constructed by Cytoscape 3.7.2, and nine hub genes (S100A12, FCGR3B, FPR1, VNN2, AQP9, MMP9, OSM, NCF4, HP) were identified. Finally, 9 hub genes were identified as the potential biomarkers of exercise using validation set (GSE83578) verification analysis. These hub genes might serve as potential molecular targets of monitoring exercise and training processes in the further.

Parents' Self-Development Socialization Goals and Chinese Adolescents' Academic Motivation: The Mediating Role of Parents' Autonomy Support.

The socialization goals parents hold for their adolescents, which reflect the qualities, skills, or behaviors they want their adolescents to acquire, play an important role in shaping adolescents' adjustment via parenting practices. Nevertheless, there is a lack of studies that examine the longitudinal implications of parents' socialization goals for adolescents' academic motivation, especially in non-Western cultures. Moreover, evidence is still scarce regarding the full process from parents' socialization goals to parenting practices and further to adolescents' academic adjustment. To address these gaps, the current two-wave longitudinal study spanning one year examined whether two critical socialization goals endorsed by parents in Chinese culture, namely self-development (i.e., parents wanting adolescents to be unique, autonomous, and self-assertive) and academic achievement socialization goals (i.e., parents wanting adolescents to achieve academic success), predicted Chinese adolescents' academic motivation over time via parents' autonomy support. Two hundred and eighty-five Chinese adolescents (Mean age = 12.29 years, SD = 0.64, range = 11-14, 51% girls) reported on perceived parental socialization goals and autonomy support, as well as different aspects of their own academic motivation (i.e., academic interest, mastery orientation, and persistent responses to academic failure). Results showed that perceived parents' self-development socialization goals positively predicted adolescents' academic motivation one year later, which was mediated by parents' increased autonomy support. The findings highlight the positive role of parents' self-development socialization goals in Chinese adolescents' academic adjustment in the changing society, and identify the underlying socialization processes via parenting practices.

Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas.

Background: Siglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods. Methods: The bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed. Results: Bioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs. Conclusion: Siglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas.

Graphene Oxide/Styrene-Butadiene Latex Hybrid Aerogel with Improved Mechanical Properties by PEI Grafted GO and CNT.

Graphene oxide aerogel (GOA) has wide application prospects due to its low density and high porosity. However, the poor mechanical properties and unstable structure of GOA have limited its practical applications. In this study, polyethyleneimide (PEI) was used to graft onto the surface of GO and carbon nanotubes (CNTs) to improve compatibility with polymers. Composite GOA was prepared by adding styrene-butadiene latex (SBL) to the modified GO and CNTs. The synergistic effect of PEI and SBL, resulted in an aerogel with excellent mechanical properties, compressive resistance, and structural stability. When the ratio of SBL to GO and GO to CNTs was 2:1 and 7:3, respectively, the obtained aerogel performance was the best, and the maximum compressive stress was 784.35% higher than that of GOA. The graft of PEI on the surface of GO and CNT could improve the mechanical properties of the aerogel, with greater improvements observed with grafting onto the surface of GO. Compared with GO/CNT/SBL aerogel without PEI grafting, the maximum stress of GO/CNT-PEI/SBL aerogel increased by 5.57%, that of GO-PEI/CNT/SBL aerogel increased by 20.25%, and that of GO-PEI/CNT-PEI/SBL aerogel increased by 28.99%. This work not only provided a possibility for the practical application of aerogel, but also steered the research of GOA in a new direction.

The regulatory role of PI3K in ageing-related diseases.

Ageing is a physiological/pathological process accompanied by the progressive damage of cell function, triggering various ageing-related disorders. Phosphatidylinositol 3-kinase (PI3K), which serves as one of the central regulators of ageing, is closely associated with cellular characteristics or molecular features, such as genome instability, telomere erosion, epigenetic alterations, and mitochondrial dysfunction. In this review, the PI3K signalling pathway was firstly thoroughly explained. The link between ageing pathogenesis and the PI3K signalling pathway was then summarized. Finally, the key regulatory roles of PI3K in ageing-related illnesses were investigated and stressed. In summary, we revealed that drug development and clinical application targeting PI3K is one of the focal points for delaying ageing and treating ageing-related diseases in the future.

Identification of CCR2 as a hub in septic myocardial injury and cardioprotection of silibinin.

Myocardial injury is a serious complication of sepsis associated with high morbidity and mortality. Our previous work has confirmed that silibinin (SIL) alleviates septic myocardial injury, but the specific molecular mechanism has not been fully elucidated. This study aimed to identify its potential targets through network pharmacology combined with experimental verification. Firstly, a total of 29 overlapping genes between sepsis and SIL targets were obtained from RNA-seq analysis and the known databases. Subsequently, KEGG and GO analysis showed that these genes were enriched in immune response and cytokine-cytokine receptor interaction pathways. Notably, CCR2 was identified as an important candidate hub by protein-protein interaction analysis and molecular docking approach. In vivo experiments showed that SIL treatment significantly improved survival rate and cardiac function in septic mice, accompanied by decreased CCR2 expression. Moreover, in vitro experiments obtained the similar results. Especially, CCR2 siRNA attenuated inflammation response. In conclusion, this study systematically elucidated the key target of SIL in the treatment of septic myocardial injury. These findings provide valuable insights into the targets of sepsis and offer new avenues for exploring drug effect systematically.

Odd-even effect on the thermal conductivity of liquid crystalline epoxy resins.

Rapid developments in high-performance computing and high-power electronics are driving needs for highly thermal conductive polymers and their composites for encapsulants and interface materials. However, polymers typically have low thermal conductivities of ∼0.2 W/(m K). We studied the thermal conductivity of a series of epoxy resins cured by one diamine hardener and seven diepoxide monomers with different precise ethylene linker lengths (x = 2-8). We found pronounced odd-even effects of the ethylene linker length on the liquid crystalline order, mass density, and thermal conductivity. Epoxy resins with even x have liquid crystalline structure with the highest density of 1.44 g/cm3 and highest thermal conductivity of 1.0 W/(m K). Epoxy resins with odd x are amorphous with the lowest density of 1.10 g/cm3 and lowest thermal conductivity of 0.17 W/(m K). These findings indicate that controlling precise linker length in dense networks is a powerful route to molecular design of thermally conductive polymers.