This comprehensive review examines the synergistic effects of physical exercise and polyphenolic compounds, such as flavonoids, curcumin, and resveratrol, on spatial learning and memory. The interplay between these interventions highlights their potential to enhance cognitive function by promoting neurogenesis, synaptic plasticity, and resilience against oxidative stress and inflammation. Mechanistic insights reveal that exercise and polyphenols activate complementary neuroprotective pathways, including the upregulation of BDNF and CREB, as well as the modulation of antioxidant defenses via Nrf2. Evidence from both animal and human studies demonstrates significant improvements in spatial memory and hippocampal function when these strategies are combined. Despite promising findings, challenges related to bioavailability, dosing, and long-term efficacy remain, underscoring the need for further investigation. This review emphasizes the potential clinical applications of these combined approaches for preventing cognitive decline and promoting brain health during aging and in neurodegenerative conditions.

Glioma progression is heavily driven by heterogeneity and a highly immunosuppressive tumor microenvironment (TME). This study aimed to identify a robust long non-coding RNA (lncRNA) prognostic signature and elucidate its role in TME remodeling. An unbiased transcriptome-wide screening of the TCGA and CGGA databases was performed. A prognostic risk signature was constructed using univariate and multivariate Cox regression. Based on multivariate coefficients, the core protective gene SNAI3-AS1 was selected for in vitro validation in U87 and U251 cells. Additionally, a U87-derived conditioned medium (CM) co-culture system was established to investigate the cooperative reinforcement of SNAI3-AS1 overexpression and the ferroptosis inducer erastin on macrophage polarization (THP-1 cell line), assessed via RT-qPCR and ELISA. A 23-lncRNA prognostic signature was established, demonstrating high accuracy in predicting overall survival and correlating positively with immunosuppressive M2 macrophage infiltration. RT-qPCR results revealed that SNAI3-AS1 was significantly downregulated in glioma tissues. While SNAI3-AS1 overexpression did not alter cell proliferation, it profoundly suppressed three-dimensional matrix migration and invasion. Moreover, SNAI3-AS1 overexpression cooperates with erastin to elevate cellular levels of malondialdehyde and Fe2+, thereby promoting ferroptosis. Crucially, the CM co-culture model revealed that SNAI3-AS1 overexpression cooperated with erastin to trigger robust microenvironmental remodeling, repolarizing macrophages toward an antitumor M1 phenotype. This was evidenced by significantly upregulated M1 markers (iNOS, IL-6, TNF-α) and suppressed M2 markers expression (CD206, IL-10). Administration of ferrostatin-1 completely abrogated these polarization shifts, confirming a ferroptosis-dependent mechanism. We established a robust transcriptome-wide prognostic tool and identified SNAI3-AS1 as a specific suppressor of glioma invasion. Furthermore, SNAI3-AS1 cooperates with ferroptosis induction to drive M1 macrophage polarization, offering a promising TME-remodeling therapeutic strategy.

Wound healing in diabetes is a substantial clinical challenge due to the hyperglycemic microenvironment, high pH, bacterial infection, persistent inflammation, and impaired cellular functions, attributed to mitochondrial dysfunction. Here, we have developed an injectable photo-crosslinking nanocomposite hydrogel (BA/GOx@ZIF-8@GelMA, BGZ@GelMA) with baicalein (BA) and glucose oxidase (GOx) loaded Zinc metal-organic framework (ZIF-8) based on methacrylated gelatin (GelMA) to accelerate diabetic infected wound healing by regulating subcellular and cellular functions. The combination of ZIF-8 and BA gives the hydrogel excellent antibacterial properties. A high blood sugar environment triggers the release of GOx in BGZ@GelMA, reducing local glucose and pH, producing hydrogen peroxide (H2O2), and releasing BA and Zinc ions (Zn2+). This process provides a suitable microenvironment for wound healing. Zn2+ can significantly inhibit the proliferation of Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli). The released BA can clear ROS in cells and mitochondria, restore mitochondrial function and stability, and make the hydrogel fundamentally improve the cell function damage induced by hyperglycemia, and ultimately promote cell proliferation, migration and angiogenesis. In general, our multifunctional nanocomposite hydrogel provides a new strategy for diabetes wound healing at the subcellular and cellular functional levels.

Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models. The tirzepatide effectively reduced body weight, improved insulin resistance, decreased serum and hepatic lipid levels, and mitigated liver injury. Compared to semaglutide, tirzepatide exhibited superior efficacy in reducing hepatic lipid accumulation. 16S rRNA gene sequencing and targeted metabolomics of BAs revealed that tirzepatide ameliorated gut microbiota dysbiosis and BAs metabolism in diabetic mice. Notably, tirzepatide observably increased the abundance of beneficial genera such as Akkermansia, elevated the ratio of farnesoid X receptor (FXR) antagonists (glycoursodeoxycholic acid: GUDCA, β-muricholic acid: β-MCA, hyodeoxycholic acid: HDCA, ursodeoxycholic acid: UDCA) to natural agonists (cholic acid: CA, lithocholic acid: LCA, chenodeoxycholic acid: CDCA, glycocholic acid: GCA, taurodeoxycholic acid: TDCA), and reduced FXR expression in intestinal tissues. In conclusion, tirzepatide attenuated hepatic steatosis in diabetic mice and regulated the gut microbiota and BAs metabolism, which may help to provide a novel therapeutic approach and therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD).

Increasing evidence suggests that C1q/tumor necrosis factor-related proteins (CTRPs), as the adipokine superfamily, are secreted by adipose tissues. They play an important role in diabetic cardiovascular pathology. Diabetic vascular complications pose a significant threat to human health and are the primary cause of disability and mortality in diabetes. Adipose tissue dysfunction, including secretion and dysfunction of adipokines, is closely associated with diabetic vasculopathy. However, the expression levels of CTRPs show heterogeneity in different pathophysiological states, and their potential mechanisms of action have not been elucidated. Therefore, this review aims to summarize and discuss the differences in circulating expression of CTRPs in diabetic patients, as well as their roles and mechanisms in diabetic vasculopathy, to offer new insights and targets for the prevention and treatment of diabetic vasculopathy.

Brain and central nervous system (CNS) cancers are a major cause of cancer-related mortality and morbidity among adolescents and young adults (AYAs) aged 15-39, presenting significant global health challenges despite advances in treatment. This study assesses the global burden and future trends of CNS cancers in AYAs using data from the Global Burden of Disease (GBD) 2021 database. Data on incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021 were analyzed for 204 countries and territories. Age-standardized rates for incidence (ASIR), mortality (ASMR), and DALYs (ASDR) were calculated, with temporal trends assessed using Joinpoint regression and future projections estimated using the Bayesian Age-Period-Cohort (BAPC) model. Disparities were evaluated using the Socio-Demographic Index (SDI), a composite measure of income, education, and fertility rates. In 2021, global CNS cancer incidence among AYAs was 57,645 cases, with a prevalence of 271,770. The ASIR was 1.92 per 100,000, the ASMR 0.95 per 100,000, and DALYs totaled 1,744,650. High-SDI regions reported higher ASIR but lower ASMR and ASDR. By 2040, case numbers are projected to rise, while age-standardized rates may stabilize or decline. This study highlights significant global disparities in CNS cancer burden, calling for investments in cancer registries, equitable healthcare access, and tailored prevention and treatment strategies.

Background:Intracerebral hemorrhage (ICH) poses a significant health challenge, notably affecting adolescents and young adults (AYAs) aged 15-39 years. Despite advancements in medical technology, the global burden of ICH remains substantial, influenced by lifestyle factors, socioeconomic conditions, and disparities in healthcare access. This study leverages data from the 2021 Global Burden of Disease (GBD) to conduct a comprehensive analysis of ICH trends and burdens at global, regional, and national levels, emphasizing the role of the Social Development Index (SDI). Methods:We utilized data from the GBD 2021 to assess the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) associated with ICH from 1990 to 2021, covering 204 countries and regions. Age-standardized rates were calculated to ensure comparability. Temporal trends were evaluated using Joinpoint regression analysis, and future projections were made using a Bayesian Age-Period-Cohort model. Results:In 2021, ~246,938 new cases of ICH were reported among the global AYAs population, reflecting a decline in age-standardized incidence rates from 11.85 per 100,000 in 1990 to 8.14 in 2021. Prevalence rates also decreased from 124.44 to 94.58 per 100,000. Mortality rates and DALYs exhibited similar downward trends. Significant regional disparities were observed, with high SDI regions experiencing lower ICH burdens than low SDI regions, highlighting the influence of socioeconomic factors and healthcare access. Conclusion:While the global burden of ICH among AYAs has declined, significant disparities persist, particularly in regions with lower SDI. To further mitigate the impact of ICH, public health initiatives should focus on enhancing healthcare infrastructure, promoting health education, and addressing socioeconomic inequalities.

PurposeThis prospective cohort study aims to evaluate the impact of digital health technology especially Personal Digital Assistants (PDA) in neurosurgical procedure management, focusing on surgical safety check accuracy, efficiency, and patient satisfaction.MethodsThe study included 211 neurosurgical cases from January to December 2022. The control group of 106 patients followed traditional verification methods, while the experimental group of 105 patients used PDA. The PDA system facilitated real-time data collection, verification, and transmission. The study compared both groups in terms of check times, accuracy rates, and patient satisfaction, and used multivariate regression to assess the impact of baseline parameters on these outcomes.ResultsThe study found that the experimental group using the PDA system reduced the average verification time by approximately 8 min, achieving 100.0% accuracy in preoperative and postoperative checks, significantly better than the control group (91.5% pre- and post-operation). Multivariate regression confirmed a 48.1% reduction in postoperative verification time due to the PDA system (p < 0.001), with the model showing high explanatory power (R2 = 0.911). Other examined factors, including patient age and nurse experience, had no significant effects. Similarly, the PDA’s introduction markedly improved verification accuracy, with no significant impact from other variables (p = 0.010).ConclusionThe application of the PDA system in neurosurgical operations significantly enhanced the accuracy and efficiency of surgical safety checks, reduced nursing errors, optimized nursing workflows, and improved patient satisfaction. These results provide valuable insights for the application of PDA technology in high-risk medical fields, demonstrating potential of digital health tools in enhancing surgical safety and efficiency.

BACKGROUND:Elevated glycemic variability (GV) often occurs in intensive care unit (ICU) patients and is associated with patient prognosis. However, the association between GV and prognosis in ICU patients with traumatic brain injury (TBI) remains unclear. METHOD:Clinical data of ICU patients with TBI were obtained from the Medical Information Mart for Intensive Care (MIMIC) -IV database. The coefficient of variation (CV) was utilized to quantify GV, while the Glasgow Coma Scale (GCS) was employed to evaluate the consciousness status of TBI patients. Pearson linear correlation analysis, linear regression, COX regression and restricted cubic spline (RCS) were used to investigate the relationship between CV and consciousness impairment, as well as the risk of in-hospital mortality. RESULT:A total of 1641 ICU patients with TBI were included in the study from the MIMIC-IV database. Pearson linear correlation and restricted cubic spline (RCS) analysis results showed a negative linear relationship between CV and the last GCS (P = 0.002) with no evidence of nonlinearity (P for nonlinear = 0.733). Multivariable linear regression suggested a higher CV was associated with a lower discharge GCS [β (95 %CI) = -1.86 (-3.08 ∼ -0.65), P = 0.003]. Furthermore, multivariable COX regression indicated that CV ≥ 0.3 was a risk factor for in-hospital death in TBI patients [HR (95 %CI) = 1.74 (1.15-2.62), P = 0.003], and this result was also consistent across sensitivity and subgroup analyses. CONCLUSION:Higher GV is related to poorer consciousness outcomes and increased risk of in-hospital death in ICU patients with TBI. Additional research is needed to understand the logical relationship between GV and TBI progression.

Abstract Background Differentiation of glioma and solitary brain metastasis (SBM), which requires biopsy or multi-disciplinary diagnosis, remains sophisticated clinically. Histogram analysis of MR diffusion or molecular imaging hasn’t been fully investigated for the differentiation and may have the potential to improve it. Methods A total of 65 patients with newly diagnosed glioma or metastases were enrolled. All patients underwent DWI, IVIM, and APTW, as well as the T1W, T2W, T2FLAIR, and contrast-enhanced T1W imaging. The histogram features of apparent diffusion coefficient (ADC) from DWI, slow diffusion coefficient (Dslow), perfusion fraction (frac), fast diffusion coefficient (Dfast) from IVIM, and MTRasym@3.5ppm from APTWI were extracted from the tumor parenchyma and compared between glioma and SBM. Parameters with significant differences were analyzed with the logistics regression and receiver operator curves to explore the optimal model and compare the differentiation performance. Results Higher ADCkurtosis (P = 0.022), frackurtosis (P<0.001),and fracskewness (P<0.001) were found for glioma, while higher (MTRasym@3.5ppm)10 (P = 0.045), frac10 (P<0.001),frac90 (P = 0.001), fracmean (P<0.001), and fracentropy (P<0.001) were observed for SBM. frackurtosis (OR = 0.431, 95%CI 0.256–0.723, P = 0.002) was independent factor for SBM differentiation. The model combining (MTRasym@3.5ppm)10, frac10, and frackurtosis showed an AUC of 0.857 (sensitivity: 0.857, specificity: 0.750), while the model combined with frac10 and frackurtosis had an AUC of 0.824 (sensitivity: 0.952, specificity: 0.591). There was no statistically significant difference between AUCs from the two models. (Z = -1.14, P = 0.25). Conclusions The frac10 and frackurtosis in enhanced tumor region could be used to differentiate glioma and SBM and (MTRasym@3.5ppm)10 helps improving the differentiation specificity.

This study was dedicated to investigating the effects of microRNA-128-3p (miR-128-3p) on neuronal apoptosis and neurobehavior in cerebral palsy (CP) rats via the Smurf2/YY1 axis. In vivo modeling of hypoxic-ischemic (HI) CP was established in neonatal rats. Neurobehavioral tests (geotaxis reflex, cliff avoidance reaction, and grip test) were measured after HI induction. The HI-induced neurological injury was evaluated by HE staining, Nissl staining, TUNEL staining, immunohistochemical staining, and RT-qPCR. The expression of miR-128-3p, Smurf2, and YY1 was determined by RT-qPCR and western blot techniques. Moreover, primary cortical neurons were used to establish the oxygen and glucose deprivation (OGD) model in vitro, cell viability was detected by CCK-8 assay, neuronal apoptosis was assessed by flow cytometry and western blot, and the underlying mechanism between miR-128-3p, Smurf2 and YY1 was verified by bioinformatics analysis, dual luciferase reporter assay, RIP, Co-IP, ubiquitination assay, western blot, and RT-qPCR. In vivo, miR-128-3p and YY1 expression was elevated, and Smurf2 expression was decreased in brain tissues of hypoxic-ischemic CP rats. Downregulation of miR-128-3p or overexpression of Smurf2 improved neurobehavioral performance, reduced neuronal apoptosis, and elevated Nestin and NGF expression in hypoxic-ischemic CP rats, and downregulation of Smurf2 reversed the effects of downregulation of miR-128-3p on neurobehavioral performance, neuronal apoptosis, and Nestin and NGF expression in hypoxic-ischemic CP rats, while overexpression of YY1 reversed the effects of Smurf2 on neurobehavioral performance, neuronal apoptosis, and Nestin and NGF expression in hypoxic-ischemic CP rats. In vitro, downregulation of miR-128-3p effectively promoted the neuronal survival, reduced the apoptosis rate, and decreased caspase3 protein expression after OGD, and overexpression of YY1 reversed the ameliorative effect of downregulation of miR-128-3p on OGD-induced neuronal injury. miR-128-3p targeted to suppress Smurf2 to lower YY1 ubiquitination degradation and decrease its expression. Inhibition of miR-128-3p improves neuronal apoptosis and neurobehavioral changes in hypoxic-ischemic CP rats by promoting Smurf2 to promote YY1 ubiquitination degradation and reduce YY1 expression.

Several studies have investigated the role of HIF-1α in predicting the prognosis of patients with glioblastoma, yielding contradictory results. Therefore, we performed a meta-analysis to document the correlation between HIF-1α and glioblastoma in individuals diagnosed with glioblastoma. We searched the PubMed, Cochrane Library, EMBASE, and Web of Science by January 25, 2024. Hazard Ratio (HR) was used to evaluate the relationship between HIF-1α and survival outcome, and Odds Ratio (OR) was adopted for tumor features.There was incorporation of nine observational studies with 607 individuals. The total prevalence of HIF-1α (higher than cut-off values) among individuals with glioblastoma was 0.72 (95

OBJECTIVE:This study aims to analyze the global burden of subarachnoid hemorrhage (SAH) among adolescents and young adults (AYAs) aged 15-39 years from 1990 to 2021, highlighting spatial and temporal trends and providing insights for future public health strategies. METHODS:Data were collected from the Global Burden of Disease Study 2021 (GBD 2021), which includes comprehensive evaluations of health conditions and associated risk factors across 204 countries and territories. The focus was on SAH incidence, prevalence, mortality, and disability-adjusted life years (DALYs) among AYAs. The data were segmented by age groups (15-19, 20-24, 25-29, 30-34, 35-39 years) and socio-demographic index (SDI) quintiles. Statistical analyses, including Joinpoint regression and decomposition analysis, were employed to assess temporal trends and the impact of population growth, aging, and epidemiological changes. RESULTS:From 1990 to 2021, the global number of SAH incident cases among AYAs increased by 12.6%, from 109,120 cases in 1990 to 122,822 cases in 2021. Prevalent cases rose by 17.1%, from 1,212,170 cases in 1990 to 1,419,127 cases in 2021. Conversely, the number of deaths decreased by approximately 26.6%, from 30,348 cases in 1990 to 22,266 cases in 2021. Similarly, DALYs decreased by 23.7%, from 1,996,041 cases in 1990 to 1,523,328 cases in 2021. Notably, over these thirty years, the age-standardized rates (ASR) of incidence, prevalence, mortality, and DALYs for the AYA population showed an overall decreasing trend, despite fluctuations in specific periods. The age-standardized mortality rate (ASMR) and age-standardized DALYs (ASR for DALYs) decreased continuously with an average annual percentage change (AAPC) of -2.2% (95% CI: -2.36, -2.04) and -2.02% (95% CI: -2.17, -1.88), respectively. The age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) had an AAPC of -0.8% (95% CI: -0.85, -0.75) and -0.65% (95% CI: -0.66, -0.64), respectively. Particularly, the ASIR showed a continuous decline from 1990 to 2015, followed by a slight increase from 2014 to 2019 (APC: 0.14%, 95% CI: 0.03, 0.25), and accelerated growth from 2019 to 2021 (APC: 1.23%, 95% CI: 0.88, 1.57). The ASPR declined from 1990 to 2019, followed by an increase from 2019 to 2021 (APC: 0.15%, 95% CI: 0.05, 0.25). Regional analysis revealed substantial burdens in the Middle-SDI and Low-Middle-SDI regions, with the Middle-SDI region having the highest incidence, prevalence, mortality, and DALYs. Decomposition analysis indicated that population growth was the primary driver of increased SAH cases, while epidemiological changes contributed significantly to the decline in deaths and DALYs. CONCLUSION:The findings underscore the need for targeted public health interventions, particularly in low and low-middle-SDI regions, to reduce the burden of SAH among AYAs. Improved healthcare resources, enhanced health education, and preventive strategies are crucial. This study provides valuable data to inform future public health policies and resource allocation, emphasizing the importance of addressing the unique challenges faced by AYAs.

Background:Leukocyte transendothelial migration-related genes (LTEMGs) play a crucial role in the immune response and have been extensively studied in various pathological conditions, including inflammation, infection, and cancer. In recent years, increasing attention has been given to understanding the biological mechanisms of LTEMGs in the context of tumor progression and metastasis. The potential function of LTEMGs in cancer progression remains unclear. The aim of this study is to systematically delineate the relationship between LTEMGs and tumor prognosis and immune microenvironment at the pan-cancer level, providing new biomarkers for personalized immunotherapy. Methods:The gene alteration, messenger RNA (mRNA) expression, and prognostic value of LTEMGs in pan-cancer were evaluated using Bulk and single-cell RNA (scRNA) sequence data. The LTEMGs score was calculated by R package "GSVA". The association of LTEMGs score with tumor microenvironment and immunotherapy response were deeply explored. Results:We assessed the mRNA expression of 114 LTEMGs across various cancers, finding significant upregulation in acute myeloid leukemia (LAML) and pancreatic adenocarcinoma (PAAD). Prognostic analysis indicated most LTEMGs were risk factors in low-grade glioma (LGG), PAAD, uveal melanoma (UVM), and LAML. The LTEMGs score, highest in kidney renal clear cell carcinoma (KIRC) and lowest in UVM, was higher in tumor tissues compared to normal tissues in several cancers. The score was a risk factor for overall survival (OS) in LGG, UVM, and others, but protective in KIRC and some others. LTEMGs score correlated positively with Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling, apoptosis, and immune responses. It also correlated with immune and stromal scores, and immune-related pathways. Higher LTEMGs score was linked to greater immune cell infiltration and poorer immunotherapy outcomes. Single-cell analysis revealed higher LTEMGs score in endothelial and monocyte cells, consistent with reduced immunotherapy responsiveness. Conclusions:Our results reveal that LTEMGs are closely associated with tumor microenvironment. Patients with high LTEMGs score might be resistant to immunotherapy.

This study investigated the use of bi-exponential diffusion-weighted imaging (DWI) combined with structural features to differentiate high-grade glioma (HGG) from solitary brain metastasis (SBM). A total of 57 patients (31 HGG, 26 SBM) who underwent pre-surgical multi-b DWI and structural MRI (T1W, T2W, T1W + C) were included. Volumes of interest (VOI) in the peritumoral edema area (PTEA) and enhanced tumor area (ETA) were selected for analysis. Histogram features of slow diffusion coefficient (Dslow), fast diffusion coefficient (Dfast), and perfusion fraction (frac) were extracted. Results showed that HGG patients had higher skewness of Dfast (P = 0.022) and frac (P = 0.077), higher kurtosis of Dslow (P = 0.019) and frac (P = 0.025), and lower entropy of Dslow (P = 0.005) and frac (P = 0.001) within the ETA. Additionally, HGG exhibited lower mean frac in both ETA (P = 0.007) and PTEA (P = 0.017). Combining skewness of frac in ETA with clear tumor margin enhanced diagnostic performance, achieving an optimal AUC of 0.79. These findings suggest that histogram analysis of diffusion and perfusion characteristics in ETA and structural features can effectively differentiate HGG from SBM.

Background Recent studies have reported associations between periodontitis and autoimmune disorders; however, it remains unclear whether the association between periodontitis and autoimmune thyroiditis (AIT) is causal. The purpose of this study was to investigate the causal association between periodontitis and AIT. Methods We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) statistics. The single-nucleotide polymorphisms (SNPs) for AIT were derived from 244 patients and 187,684 controls. The pooled periodontitis association data included up to 17,353 individuals. The inverse-variance weighted (IVW) method was used for the primary analysis. We applied two complementary methods, the weighted median and MR-Egger. Then, these causal estimates were expressed as dominance ratios [odds ratios (ORs)]. Results Genetically determined AIT did not have a causal effect on probing depth (PD) (IVW OR = 0.998, 95% confidence interval (CI) = 0.948 ~ 1.051, p = 0.952). Furthermore, we did not find a significant causal effect of PD on AIT in the reverse MR analysis (IVW OR = 1.044, 95% confidence interval (CI) = 0.789 ~ 1.382, p = 0.759). The MR-Egger regression and weighted median results were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates according to the sensitivity analysis. Conclusion Within the limits of MR studies, the outcomes neither supported periodontitis affecting autoimmune thyroiditis nor autoimmune thyroiditis affecting periodontitis.

Simultaneously modulating the inflammatory microenvironment and promoting local bone regeneration is one of the main challenges in treating bone defects. In recent years, osteoimmunology has revealed that the immune system plays an essential regulatory role in bone regeneration and that macrophages are critical components. In this work, a mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nano platform (Gold/hydroxyapatite nanocomposites functionalized with polydopamine - PDA@Au-HA) is developed to accelerate bone tissues regeneration by regulating the immune microenvironment. PDA coating endows nanomaterials with the ability to scavenge reactive oxygen species (ROS) and anti-inflammatory properties, and it also exhibits an immunomodulatory ability to inhibit M1 macrophage polarization and activate M2 macrophage secretion of osteogenesis-related cytokines. Most importantly, this nano platform promotes the polarization of M2 macrophages and regulates the crosstalk between macrophages and pre-osteoblast cells to achieve bone regeneration. Au-HA can synergistically promote vascularized bone regeneration through sustained release of Ca and P particles and gold nanoparticles (NPs). This nano platform has a synergistic effect of good compatibility, scavenging of ROS, and anti-inflammatory and immunomodulatory capability to accelerate the bone repair process. Thus, our research offers a possible therapeutic approach by exploring PDA@Au-HA nanocomposites as a bifunctional platform for tissue regeneration.

Abstract Background: To investigate the value of diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and amide proton transfer-weighted (APTW) imaging in differentiating the primary glioma from solitary brain metastases (SBM) with the histogram and texture features. Methods: A total of 65 patients with newly diagnosed glioma or metastases were enrolled. All patients underwent DWI, IVIM, and APTW imaging, as well as the T1W, T2W, T2FLAIR, and enhanced T1W imaging. The first-order texture and histogram features of apparent diffusion coefficient (ADC) from DWI, diffusion coefficient (D), perfusion fraction (f), pseudo-diffusion coefficient (D*) from IVIM, and MTRasym (3.5 ppm) from APTW were extracted from the tumor parenchyma and compared between glioma and SBM. Parameters with significant differences were analyzed with the logistics regression and receiver operator curves to explore the optimal model and compare the differentiation performance. Results: Higher ADCkurtosis (p=0.02), f90 (p＜0.01), and fkurtosis (p=0.01) were found for glioma, while higher MTRasym (3.5ppm)10 (p= 0.05), fentropy (p＜0.01), and fmean (p＜0.01) were observed for SBM. fkurtosis (OR =0.66, 95%CI 0.48-0.92, p=0.02), and fmean (OR=1.44, 95%CI 1.16-1.18, p<0.01) were independent factors for SBM differentiation. The model combining age, fkurtosis, and fmean showed an AUC of 0.83, while the model combined with fkurtosis and fmean with improved sensitivity had an AUC of 0.81. Conclusion: The fmean and fkurtosis in enhanced tumor region could be used to differentiate glioma and SBM.

Background Although obstructive sleep apnea (OSA) and periodontitis are associated, whether this association is causative is uncertain. Methods We conducted a bidirectional Mendelian randomization (MR) analysis using data from publically accessible genome-wide association studies. The single-nucleotide polymorphisms (SNPs) for OSA were derived from 16,761 cases and 201,194 controls. The pooled data of periodontitis association involved up to 17,353 individuals. Disease-associated single-nucleotide polymorphisms were selected as an instrumental variable at the genome-wide significance level ( p < 5.0 × 10 − 6 ). Subsequently, the causal effects were estimated using three different methods: inverse variance weighting (IVW), MR-Egger, and weighted median. Then, these causal estimates were expressed as dominance ratios [odds ratio (OR)]. Results The MR analysis revealed that genetically determined OSA promotes the development of periodontitis [ IVW OR = 1.117, 95% confidence interval (CI) = 1.001–1.246, p = 0.048). Furthermore, no causal effect of genetically predicted periodontitis on OSA was noted in the reverse MR analysis (IVW OR = 1, 95% CI: 0.95–1.06, p = 0.87). The trend in results from the MR-Egger regression and weighted median (WM) was consistent with that in results from the IVW method. The robustness of the results was confirmed by the sensitivity analysis. Conclusions In summary, the results of our MR investigation suggest an association between OSA and periodontitis, proposing that early screening and treatment of OSA is beneficial for the prevention and prognosis of periodontitis.

Background and Objective: Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) represent a heterogeneous tumor type that lacks effective medical treatment. MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. In this study, we measured the expression levels and role of MDM2 in non-functioning PitNET patients' combined clinical features and investigated the effect of etoposide on the cell bioactivity of the GT1-1 cell line in vivo and in vitro. Methods: RT-PCR and immunochemistry measured the expression levels and role of MDM2 in 103 NF-PitNET patients' combined clinical features. Cell proliferation, migration, colony and apoptosis experiments measured the effect of etoposide on the GT1-1 cell line in vivo and in vitro. Results: There was more invasive behavior (p = 0.013) in patients with high MDM2, who were also younger (p = 0.007), were more frequently female (p = 0.049) and had larger tumor sizes (p = 0.018) compared with patients with low MDM2. Patients with high p53 were younger (p = 0.017) and had larger tumor sizes (p = 0.034) compared with patients with low p53. Univariate (p = 0.018) and multivariate (p = 0.023) Cox regression analysis showed that MDM2 was the independent factor for invasive behavior in NF-PitNET patients. Log-rank analysis showed that the average progression-free survival (PFS) time in the low MDM2 patients was longer than that in the high MDM2 patients (p = 0.044). Functional studies indicated that etoposide inhibited cell proliferation and cell migration and induced apoptosis in p53 independence in GT1-1 cells. Furthermore, etoposide significantly inhibited the growth of GT1-1-xenograft in BALB/c nude mice. The tumor growth inhibition rate of etoposide was 67.4 ± 4.6% after 14 d of treatment, which suggested the anti-tumor activity of etoposide. Conclusions: MDM2 played the role of tumorigenesis of NF-PitNET in a p53 independence manner, and an MDM2 inhibitor could be a potential choice for the treatment of NF-PitNET patients.