Metabolic profiling of idiopathic pulmonary fibrosis in a mouse model: implications for pathogenesis and biomarker discovery.

Background: Alterations in metabolites and metabolic pathways are thought to be important triggers of idiopathic pulmonary fibrosis (IPF), but our lack of a comprehensive understanding of this process has hampered the development of IPF-targeted drugs. Methods: To fully understand the metabolic profile of IPF, C57BL/6 J male mice were injected intratracheally with bleomycin so that it could be used to construct a mouse model of IPF, and lung tissues from 28-day and control IPF mice were analyzed by pathology and immunohistochemistry. In addition, serum metabolites from IPF mice were examined using LC-ESI-MS/MS, and the differential metabolites were analyzed for KEGG metabolic pathways and screened for biomarkers using machine learning algorithms. Results: In total, the levels of 1465 metabolites were detected, of which 104 metabolites were significantly altered after IPF formation. In IPF mouse serum, 52% of metabolite expression was downregulated, with lipids (e.g., GP, FA) and organic acids and their derivatives together accounting for more than 70% of the downregulated differentially expressed metabolites. In contrast, FA and oxidised lipids together accounted for 60% of the up-regulated differentially expressed metabolites. KEGG pathway enrichment analyses of differential metabolites were mainly enriched in the biosynthesis of unsaturated fatty acids, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism. Seven metabolites were screened by machine learning LASSO models and evaluated as ideal diagnostic tools by receiver operating characteristic curves (ROCs). Discussion: In conclusion, the serum metabolic disorders found to be associated with pulmonary fibrosis formation will help to deepen our understanding of the pathogenesis of pulmonary fibrosis.

An Integrated Pipeline for Phenotypic Characterization, Clustering and Visualization of Patient Cohorts in a Rare Disease-Oriented Clinical Data Warehouse.

Rare diseases pose significant challenges due to their heterogeneity and lack of knowledge. This study develops a comprehensive pipeline interoperable with a document-oriented clinical data warehouse, integrating cohort characterization, patient clustering and interpretation. Leveraging NLP, semantic similarity, machine learning and visualization, the pipeline enables the identification of prevalent phenotype patterns and patient stratification. To enhance interpretability, discriminant phenotypes characterizing each cluster are provided. Users can visually test hypotheses by marking patients exhibiting specific keywords in the EHR like genes, drugs and procedures. Implemented through a web interface, the pipeline enables clinicians to navigate through different modules, discover intricate patterns and generate interpretable insights that may advance rare diseases understanding, guide decision-making, and ultimately improve patient outcomes.

Association between dietary diversity changes and frailty among Chinese older adults: findings from a nationwide cohort study.

BACKGROUND: Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. METHODS: A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. RESULTS: Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. CONCLUSIONS: Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.

Abundance, characteristics and ecological risk assessment of microplastics in ship ballast water in ports around Liaodong Peninsula, China.

The development of the shipping industry has led to a large volume of ballast water discharge annually. This accelerates pollutants' transfer and dispersion, such as microplastics. Currently, empirical data on microplastics in ballast water are rarely available. This study innovatively investigated the abundance, morphological characteristics (particle size, shape, and color), and polymer composition of microplastics in ballast water from ports surrounding the Liaodong Peninsula. The results revealed that the average abundance of microplastics in 13 ships' ballast water was 6071.30 ± 1313.85 items/m3. Notably, the small microplastics (0.06-2.50 mm) were most abundant, accounting for 94.52 % of the total microplastics. Transparent, fiber, and polyethylene glycol terephthalate were the most prevalent color, shape, and polymer composition of microplastics detected in the ballast water. The risk assessment indicated that these microplastics present ecological risks to organisms. These findings suggest that ship ballast water is the potential "hotspot" for marine microplastics transport.

Biogeography and dynamics of prokaryotic and microeukaryotic community assembly across 2600 km in the coastal and shelf ecosystems of the China Seas.

Marine prokaryotes and microeukaryotes are essential components of microbial food webs, and drive the biogeochemical cycling. However, the underlying ecological mechanisms driving prokaryotic and microeukaryotic community assembly in large-scale coastal ecosystems remain unclear. In this study, we studied biogeographic patterns of prokaryotic and microeukaryotic communities in the coastal and shelf ecosystem of the China Seas. Results showed that prokaryotic richness was the highest in the Yangtze River Plume, whereas microeukaryotic richness decreased from south to north. Prokaryotic-microeukaryotic co-occurrence networks display greater complexity in the Yangtze River Plume compared to other regions, potentially indicating higher environmental heterogeneity. Furthermore, the cross-domain networks revealed that prokaryotes were more interconnected with each other than with microeukaryotes or between microeukaryotes, and all hub nodes were bacterial taxa, suggesting that prokaryotes may be more important for sustaining the stability and multifunctionality of coastal ecosystem than microeukaryotes. Variation Partitioning Analysis revealed that approximately equal proportions of environmental, biotic and spatial factors contribute to variations in microbial community composition. Temperature was the primary environmental driver of both prokaryotic and microeukaryotic communities across the China Seas. Additionally, stochastic processes (dispersal limitation) and deterministic processes (homogeneous selection) were two major ecological factors in shaping microeukaryotic and prokaryotic assemblages, respectively, suggesting their different environmental plasticity and evolutionary mechanisms. Overall, these results demonstrate both prokaryotic and microeukaryotic communities displayed a latitude-driven distribution pattern and different assembly mechanisms, improving our understanding of microbial biogeography patterns under global change and anthropogenic activity driven habitat diversification in the coastal and shelf ecosystem.

Does Higher Temperature During Moderate Hypothermic Circulatory Arrest Increase the Risk of Paraplegia in Acute DeBakey I Aortic Dissection Patients?

BACKGROUND: In this study, we sought to assess the safety of high-moderate (24.1-28.0°C) and low-moderate (20.1-24.0°C) systemic hypothermia during circulatory arrest (MHCA) in patients with acute DeBakey I aortic dissection (DeBakey I AAD), particularly concerning spinal cord protection. METHODS: From 2009 to 2020, 1759 patients with DeBakey I AAD who underwent frozen elephant trunk and total arch replacement surgery at a tertiary centre were divided into preoperative malperfusion (viscera, spinal cord, or lower extremities) and nonmalperfusion subgroups. The baseline differences were balanced with the use of propensity score matching. Prognoses were compared between those who were subjected to high-MHCA (nasopharyngeal temperature 24.1-28.0°C) and low-MHCA (nasopharyngeal temperature 20.1-24.0°C). RESULTS: In the nonmalperfusion subgroup (n = 1389), 469 pairs of matched patients showed lower in-hospital mortality and incidence of acute kidney injury in the high-MHCA group than in the low-MHCA group: in-hospital mortality 7.0% vs 10.2% (P = 0.01); acute kidney injury, 57.1% vs 64.6% (P < 0.01). The duration of mechanical ventilation was shorter in the high-MHCA group than that in the low-MHCA group (P = 0.03). No significant difference in the incidence of paraplegia was observed between the 2 groups. In the malperfusion subgroup (n = 370), 112 pairs of matched patients showed a higher incidence of paraplegia in the high-MHCA group than in the low-MHCA group (15.9% vs 6.5%; P = 0.04). CONCLUSIONS: The safety of high-MHCA, a commonly used temperature management strategy during aortic arch surgery, was recognised in most patients with DeBakey I AAD. However, among patients with preoperative distal organ malperfusion, low-MHCA may be more appropriate owing to an increased risk of postoperative paraplegia associated with high-MHCA.

Acute kidney injury and cardiogenic shock severity for mortality risk stratification in patients supported with VA ECMO.

AIMS: To assess the stage of acute kidney injury (AKI), as an index of organ perfusion, combined with shock severity, measured by the Society for Cardiovascular Angiography and Interventions (SCAI) shock stage classification, to stratify the risk of mortality in patients diagnosed with cardiogenic shock (CS) and supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). METHODS ANS RESULTS: From January 2018 to December 2020, consecutive adult patients diagnosed with CS and received VA ECMO were retrospectively evaluated. The highest AKI stage within 48 h after ECMO initiation was assessed using the Kidney Disease: Improving Global Outcomes criteria. We included 216 patients with a mean age of 58.8 years and 31.0% were females. 88.4% of patients received ECMO for postcardiotomy, while 11.6% for medical CS. The total in-hospital mortality was 53.2%. AKI occurred in 182 (84.3%) patients receiving ECMO for CS. AKI stage 0, 1, 2, and 3 were present in 15.7%, 17.6%, 18.1%, and 48.6% of patients with in-hospital mortality of 26.5%, 26.3%, 61.5%, and 68.6%, respectively (P < 0.001). The AKI stage (P < 0.001), SCAI shock stage before ECMO (P = 0.008), and NYHA ≥ Class III on admission (P = 0.044) were independent predictors of in-hospital mortality. The area under the receiver operating characteristic curve of 0.754 (95% confidence interval: 0.690 to 0.811) for AKI stage combined with SCAI shock stage was better than those for AKI stage (0.676), SCAI shock stage (0.657), serum lactate level (0.682), SOFA score (0.644), SVAE score (0.582), and VIS score (0.530) prior to ECMO. CONCLUSIONS: In this single-center CS population who received VA ECMO for circulatory support, predominantly postcardiotomy cases, AKI occurred in 84.3% of the patients. AKI stage, as an index of organ perfusion combined with shock severity measured by the SCAI shock classification, demonstrates a good correlation with in-hospital mortality.

Distribution characteristics and ecological risk analysis of microplastics in sediments and effluents related to offshore oil and gas activities in the Bohai Sea, China.

Oil and gas activities are sources of marine microplastics (MPs) but have received less attention globally. This study assessed the distribution characteristics and ecological risks of MPs in 31 sediment samples and effluent samples of 5 oil and gas platforms related to offshore oil and gas activities in the Bohai Sea. The results showed that the mean abundance of MPs in sediment, produced water, and domestic sewage was 205.7 ± 151.5 items/kg d.w., 18 ± 11 items/L, and 26 ± 39 items/L, respectively. The MPs in sediments and effluents were dominated by transparent, rayon, and fibers <1 mm. Oil and gas activities may influence the abundance of MPs in the sediments. The sediments in the area were at a low level of risk, but some samples exhibited indexes beyond low levels. The mass of MPs carried by the effluents from oil and gas platforms in the Bohai Sea was less than that of other sources.

Contributions of Lipid-Related Metabolites and Complement Proteins to Early and Intermediate Age-Related Macular Degeneration.

Objective: Our objective was to determine the effects of lipids and complement proteins on early and intermediate age-related macular degeneration (AMD) stages using machine learning models by integrating metabolomics and proteomic data. Design: Nested case-control study. Subjects and Controls: The analyses were performed in a subset of the Singapore Indian Chinese Cohort (SICC) Eye Study. Among the 6753 participants, we randomly selected 155 Indian and 155 Chinese cases of AMD and matched them with 310 controls on age, sex, and ethnicity. Methods: We measured 35 complement proteins and 56 lipids using mass spectrometry and nuclear magnetic resonance, respectively. We first selected the most contributing lipids and complement proteins to early and intermediate AMD using random forest models. Then, we estimated their effects using a multinomial model adjusted for potential confounders. Main Outcome Measures: Age-related macular degeneration was classified using the Beckman classification system. Results: Among the 310 individuals with AMD, 166 (53.5%) had early AMD, and 144 (46.5%) had intermediate AMD. First, high-density lipoprotein (HDL) particle diameter was positively associated with both early and intermediate AMD (odds ratio [OR]early = 1.69; 95% confidence interval [CI],1.11-2.55 and ORintermediate = 1.72; 95% CI, 1.11-2.66 per 1-standard deviation increase in HDL diameter). Second, complement protein 2 (C2), complement C1 inhibitor (IC1), complement protein 6 (C6), complement protein 1QC (C1QC) and complement factor H-related protein 1 (FHR1), were associated with AMD. C2 was positively associated with both early and intermediate AMD (ORearly = 1.58; 95% CI, 1.08-2.30 and ORintermediate = 1.56; 95% CI, 1.04-2.34). C6 was positively (ORearly = 1.41; 95% CI, 1.03-1.93) associated with early AMD. However, IC1 was negatively associated with early AMD (ORearly = 0.62; 95% CI, 0.38-0.99), whereas C1QC (ORintermediate = 0.63; 95% CI, 0.42-0.93) and FHR1 (ORintermediate = 0.73; 95% CI, 0.54-0.98) were both negatively associated with intermediate AMD. Conclusions: Although both HDL diameter and C2 levels show associations with both early and intermediate AMD, dysregulations of IC1, C6, C1QC, and FHR1 are only observed at specific stages of AMD. These findings underscore the complexity of complement system dysregulation in AMD, which appears to vary depending on the disease severity. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Pushing Trap-Controlled Persistent Luminescence Materials toward Multi-Responsive Smart Platforms: Recent Advances, Mechanism, and Frontier Applications.

Smart stimuli-responsive persistent luminescence materials, combining the various advantages and frontier applications prospects, have gained booming progress in recent years. The trap-controlled property and energy storage capability to respond to external multi-stimulations through diverse luminescence pathways make them attractive in emerging multi-responsive smart platforms. This review aims at the recent advances in trap-controlled luminescence materials for advanced multi-stimuli-responsive smart platforms. The design principles, luminescence mechanisms, and representative stimulations, i.e., thermo-, photo-, mechano-, and X-rays responsiveness, are comprehensively summarized. Various emerging multi-responsive hybrid systems containing trap-controlled luminescence materials are highlighted. Specifically, temperature dependent trapping and de-trapping performance is discussed, from extreme-low temperature to ultra-high temperature conditions. Emerging applications and future perspectives are briefly presented. It is hoped that this review would provide new insights and guidelines for the rational design and performance manipulation of multi-responsive materials for advanced smart platforms.

Central (Aortic) Cannulation versus Peripheral (Axillary or Femoral) Cannulation in Acute Type A Aortic Dissections: A Meta-Analysis of Comparative Studies.

Background: There has been an increased interest in using antegrade cannulation techniques during surgery for type A aortic dissection. While the utilization of central artery cannulation has been on the rise in recent times, its effectiveness and safety still require thorough examination. This study aimed to explore both the efficiency and safety of central arterial cannulation. Methods: A meta-analysis was conducted on studies that evaluated surgical outcomes when using central artery cannulation (CAC) in comparison to axillary artery cannulation (AXC) or femoral artery cannulation (FAC). Results: 10 retrospective observational studies were included, enrolling 3022 patients (CAC = 1208 vs. FAC = 606; CAC = 1051 vs. AXC = 1119). Among these, 4 articles involved axillary artery cannulation, femoral artery cannulation, and central artery cannulation. Central cannulation was linked to decreased short-term mortality [odds ratio, 0.66, 95% confidence interval (CI) (0.48, 0.89), χ 2 = 3.27, p = 0.007; I 2 = 0; p = 0.86] compared to femoral cannulation. Additionally, central cannulation was associated with a lower occurrence of temporary neurological dysfunction (TND) [odds ratio, 0.57, 95% CI (0.38, 0.85), χ 2 = 0.88, p = 0.006; I 2 = 0%, p = 0.83] when compared with femoral cannulation. However, there was no statistical significance in mortality and TND between the central cannulation and axillary cannulation groups. Conclusions: This meta-analysis reveals that central cannulation surpasses femoral cannulation in lowering short-term mortality and the occurrence of TND among patients undergoing surgery for type A acute aortic dissection. However, central cannulation does not exhibit a higher mortality and TND compared to axillary cannulation.

Association between atherogenic index of plasma and all-cause mortality and specific-mortality: a nationwide population­based cohort study.

BACKGROUND: Atherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD). However, few studies have investigated association between AIP and all-cause mortality and specific-mortality in the general population. METHODS: This study included data from 14,063 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included all-cause mortality and specific-mortality. Survey-weighted cox regressions were performed to evaluate the relation between AIP and all-cause mortality and specific-mortality. Weighted restricted cubic spline was conducted to examin the non-linear relationship. RESULTS: During 10 years of follow-up, we documented 2,077, 262, 854, and 476 cases of all-cause mortality, diabetes mortality, CVD mortality and cancer mortality, respectively. After adjustment for potential confounders, we found that atherogenic index of plasma (AIP) was significantly associated with an increased risk of diabetes mortality when comparing the highest to the lowest quantile of AIP in female (p for trend = 0.001) or participants older than 65 years (p for trend = 0.002). AIP was not significantly associated with all-cause mortality, CVD mortality and cancer mortality (p > 0.05). Moreover, a non-linear association was observed between AIP and all-cause mortality in a U-shape (p for non-linear = 0.0011), while a linear relationship was observed with diabetes mortality and non-diabetes mortality (p for linear < 0.0001). CONCLUSIONS: In this study, there is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. Besides, a higher AIP was significantly associated with an increased risk of diabetes mortality, which only found in women older than 65 years. AIP was associated with all-cause mortality in a U-shape. This association could be explained by the finding that higher AIP predicted a higher risk of death from diabetes, and that lower AIP predicted a higher risk of death from non-diabetes causes.

We used a large national database and a prospective cohort study with a long follow-up period. Higher AIP was significantly associated with an increased risk of diabetes mortality, only in women older than 65 years. There is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. AIP was associated with all-cause mortality in a U-shape. This finding suggest that controlling AIP levels may have a positive effect on reducing diabetes mortality.

Surveillance of fluoroquinolones resistance in rifampicin-susceptible tuberculosis in eastern China with whole-genome sequencing-based approach.

Background: Leveraging well-established DNA-level drug resistance mechanisms, whole-genome sequencing (WGS) has emerged as a valuable methodology for predicting drug resistance. As the most effective second-line anti-tuberculosis (anti-TB) drugs, fluoroquinoloness (FQs) are generally used to treat multidrug-resistant tuberculosis (MDR-TB, defined as being resistant to resistant to rifampicin and isoniazid) or rifampicin-resistant tuberculosis (RR-TB). However, FQs are also commonly used in the management of other bacterial infections. There are few published data on the rates of FQs resistance among rifampicin-susceptible TB. The prevalence of FQs resistance among TB patients who are rifampicin-susceptible has not been studied in Zhejiang Province, China. The goal of this study was to provide a baseline characterization of the prevalence of FQs resistance, particularly among rifampicin-susceptible TB in Zhejiang Province, China. Methods: Based on WGS, we have investigated the prevalence of FQs resistance among rifampicin-susceptible TB in Zhejiang Province. All pulmonary TB patients with positive cultures who were identified in Zhejiang area during TB drug resistance surveillance from 2018 to 2019 have enrolled in this population-based retrospective study. Results: The rate of FQs resistance was 4.6% (32/698) among TB, 4.0% (27/676) among rifampicin-susceptible TB, and 22.7% (5/22) among RR-TB. According to WGS, strains that differ within 12 single-nucleotide polymorphisms (SNPs) were considered to be transmission of FQ-resistant strains. Specifically, 3.7% (1/27) of FQs resistance was caused by the transmission of FQs-resistant strains among the rifampicin-susceptible TB and 40.7% (11/27) of FQs resistance was identified as hetero-resistance. Conclusion: The prevalence of FQs resistance among TB patients who were rifampicin-susceptible was severe in Zhejiang. The emergence of FQs resistance in TB isolates that are rifampicin-susceptible was mainly caused by the selection of drug-resistant strains. In order to prevent the emergence of FQs resistance, the WGS-based surveillance system for TB should be urgently established, and clinical awareness of the responsible use of FQs for respiratory infections should be enhanced.

High-resolution community-level sodium variation on the Tibetan Plateau: Content, density, and storage.

Sodium (Na), a beneficial mineral element, stimulates plant growth through osmotic adjustment. Previous studies focused on Na content at the individual or species level, however, it is hard to link to ecosystem functions without exploring the characteristics (content, density, and storage) of Na at the community level. We conducted grid-plot sampling of different plant organs in 2040 natural plant communities on the Tibetan Plateau (TP) to comprehensively characterize community-level Na on a regional scale. The Na content was 0.57, 0.09, 0.07, and 0.71 mg g-1 in leaves, branches, trunks, and roots, respectively. Across biomes Na content was higher in deserts under drought stress. Oxygen partial pressure, radiation, precipitation, soil Na supply, and temperature significantly affected the spatial variation in Na content. Furthermore, we accurately simulated the spatial variation in Na density and produced a highly precise 1 km × 1 km spatial map of plant Na density on the TP using random forest algorithm, which demonstrated higher Na density in the southeast of TP. The total plant Na storage on the TP was estimated as 111.80 × 104 t. These findings provide great insights and references for understanding the plant community-level adaptation strategies and evaluating the mineral element status on a large scale, and provide valuable data for ecological model optimization in the future.

Metabolic obesity phenotypes and all-cause mortality among the Chinese oldest-old population: a prospective cohort study.

BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

Piracetam reduces oxidative stress and mitochondrial function impairment in an in vitro model of vascular dementia.

Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD.

Clinical outcomes of the type II hybrid procedure for the repair of extensive aortic arch pathology.

Background: Type II hybrid arch repair (HAR) has been used for the repair of extensive aortic arch pathology. The aim of this study was to retrospectively analyze single-stage hybrid treatment involving replacement of the ascending aorta, arch debranching, and zone 0 stent graft deployment. Methods: We retrospectively analyzed clinical data from 41 patients with acute and chronic aortic disease who underwent a type II hybrid arch procedure at Beijing Anzhen Hospital and Beijing Chaoyang Hospital from January 2020 to August 2022. The femoral arteries and right axillary arteries were used as cannulation sites to decrease the risk of malperfusion. During surgery, the nasopharyngeal temperature was lowered to 30 ℃. Demographic, perioperative, and late results data were retrieved and analyzed. Results: The mean age of the patients was 54.9±11.1 years, and 31 patients (75.6%) were men. In all cases, zone 0 stent graft deployment was successful, with no in-hospital mortality. The median follow-up time was 10.5 [interquartile range (IQR), 4.8-17.6] months, and the survival rate was 94.9% during follow-up. Complications included cerebral infarction (3 patients, 7.3%) and renal failure requiring dialysis (3 patients, 7.3%). There were no occurrences of paraplegia, and no stent-related complications occurred during the follow-up period. Conclusions: The single-stage hybrid arch procedure achieved satisfactory early results and represents a less invasive approach for treating complex diffuse aortic disease that affects the arch. This strategy is an important technical advance in the treatment of high-risk patients with extensive aortic arch pathology.

Plexin D1 negatively regulates macrophage-derived foam cell migration via the focal adhesion kinase/Paxillin pathway.

BACKGROUND: Macrophage-derived foam cell formation is a hallmark of atherosclerosis and is retained during plaque formation. Strategies to inhibit the accumulation of these cells hold promise as viable options for treating atherosclerosis. Plexin D1 (PLXND1), a member of the Plexin family, has elevated expression in atherosclerotic plaques and correlates with cell migration; however, its role in macrophages remains unclear. We hypothesize that the guidance receptor PLXND1 negatively regulating macrophage mobility to promote the progression of atherosclerosis. METHODS: We utilized a mouse model of atherosclerosis based on a high-fat diet and an ox-LDL- induced foam cell model to assess PLXND1 levels and their impact on cell migration. Through western blotting, Transwell assays, and immunofluorescence staining, we explored the potential mechanism by which PLXND1 mediates foam cell motility in atherosclerosis. RESULTS: Our study identifies a critical role for PLXND1 in atherosclerosis plaques and in a low-migration capacity foam cell model induced by ox-LDL. In the aortic sinus plaques of ApoE-/- mice, immunofluorescence staining revealed significant upregulation of PLXND1 and Sema3E, with colocalization in macrophages. In macrophages treated with ox-LDL, increased expression of PLXND1 led to reduced pseudopodia formation and decreased migratory capacity. PLXND1 is involved in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK. Additionally, FAK inhibitors counteract the ox-LDL-induced migration suppression by modulating the phosphorylation states of FAK, Paxillin and their downstream effectors CDC42 and PAK. CONCLUSION: Our findings indicate that PLXND1 plays a role in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK to promoting atherosclerosis.

Phase transformation of schwertmannite in paddy soil under different water management regimes and its impact on the migration of arsenic in soil.

Schwertmannite (Sch) holds a great promise as an iron material for remediating Arsenic (As)-contaminated paddy soils, due to its extremely high immobilization capacities for both arsenate [As(V)] and arsenite [As(III)]. However, there is still limited knowledge on the mineral phase transformation of this metastable iron-oxyhydroxysulfate mineral in paddy soils, particularly under different water management regimes including aerobic, intermittent flooding, and continuous flooding, and how its phase transformation impacts the migration of As in paddy soils. In this study, a membrane coated with schwertmannite was first developed to directly reflect the phase transformation of bulk schwertmannite applied to paddy soils. A soil incubation experiment was then conducted to investigate the mineral phase transformation of schwertmannite in paddy soils under different water management regimes and its impact on the migration of As in paddy soil. Our findings revealed that schwertmannite can persist in the paddy soil for 90 days in the aerobic group, whereas in the continuous flooding and intermittent flooding groups, schwertmannite transformed into goethite, with the degree or rate of mineral phase transformation being 5% Sch >1% Sch > control. These results indicated that water management practices and the amount of schwertmannite applied were the primary factors determining the occurrence and degree of mineral transformation of schwertmannite in paddy soil. Moreover, despite undergoing phase transformation, schwertmannite still significantly reduced the porewater As (As(III) and As(V)), and facilitated the transfer of non-specifically adsorbed As (F1) and specifically adsorbed As (F2) to amorphous iron oxide-bound As (F3), effectively reducing the bioavailability of soil As. These findings contribute to a better understanding of the mineralogical transformation of schwertmannite in paddy soils and the impact of mineral phase transformation on the retention of As in soil, which carry important implications for the application of schwertmannite in remediating As-contaminated paddy soils.

Psychological profiles among people with HIV: A latent profile analysis and examination of the relationship with interpersonal personality.

People living with HIV (PWH) often experience an increased vulnerability to psychiatric disorders as a result of social stigma and discrimination. This study utilized latent profile analysis on a sample of 3040 Chinese PWH to identify distinct psychological profiles. Furthermore, the study investigated the relationships between these profiles with interpersonal personalities, demographic characteristics, social variables and disease-related variables using a three-step regression (R3STEP). The findings from the latent profile analysis revealed that the psychological symptoms of PWH can be categorized into three distinct classes. Multinomial logistic regression analysis indicated that interpersonal personalities, region, sex, age, religious beliefs, marital status, occupation, monthly income, time of HIV infection diagnosis and transmission route were significant factors associated with the psychological profiles of PWH. These findings provide valuable insights for the development of individualized management strategies for PWH and contribute to a deeper understanding of the mechanisms underlying psychological symptoms of PWH.