Unveiling Mechanistic Insight into Accelerating Oxygen Molecule Activation by Oxygen Defects in Co3O4-x/g-C3N4 p-n Heterojunction for Efficient Photo-Assisted Uranium Extraction from Seawater.

Photo-assisted uranium extraction from seawater (UES) is regarded as an efficient technique for uranium resource recovery, yet it currently faces many challenges, such as issues like biofouling resistance, low charge separation efficiency, slow carrier transfer, and a lack of active sites. Based on addressing the above challenges, a novel oxygen-deficient Co3O4-x/g-C3N4 p-n heterojunction is developed for efficient photo-assisted uranium extraction from seawater. Relying on the defect-coupling heterojunction synergistic effect, the redistribution of molecular charge density formed the built-in electric field as revealed by DFT calculations, significantly enhancing the separation efficiency of carriers and accelerating their migration rate. Notably, oxygen vacancies served as capture sites for oxygen, effectively promoting the generation of reactive oxygen species (ROS), thereby significantly improving the photo-assisted uranium extraction performance and antibacterial activity. Thus, under simulated sunlight irradiation with no sacrificial reagent added, Co3O4-x/g-C3N4 extracted a high uranium extraction amount of 1.08 mg g-1 from 25 L of natural seawater after 7 days, which is superior to most reported carbon nitride-based photocatalysts. This study elaborates on the important role of surface defects and inerface engineering strategies in enhancing photocatalytic performance, providing a new approach to the development and design of uranium extraction material from seawater.

Network toxicological and molecular docking to investigate the mechanisms of toxicity of agricultural chemical Thiabendazole.

Food safety is closely linked to human health. Thiabendazole is widely used as a fungicide and deodorant on agricultural products like vegetables and fruits to prevent fungal infections during transport and storage. This study aims to investigate the toxicity and potential mechanisms of Thiabendazole using novel network toxicology and molecular docking techniques. First, the ADMETlab2.0 and ADMETsar databases, along with literature, predicted Thiabendazole's potential to induce cancer and liver damage. Disease target libraries were constructed using GeneCards and TCMIP databases, while Thiabendazole target libraries were constructed using Swiss Target Prediction and TCMIP databases. The Venn database identified potential targets associated with Thiabendazole-induced cancer and liver injury. Protein-protein interaction (PPI) networks were derived from the STRING database, and gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways were obtained from the DAVID database. Molecular docking assessed the binding affinity between Thiabendazole and core targets. The study revealed 29 potential targets for Thiabendazole-induced cancer and 30 potential targets for liver injury. PPI identified 5 core targets for Thiabendazole-induced cancers and 4 core targets for induced liver injury. KEGG analysis indicated that Thiabendazole might induce gastric and prostate cancer via cyclin-dependent kinase 2 (CDK2) and epidermal growth factor receptor (EGFR) targets, and liver injury through the same targets, with the p53 signaling pathway being central. GO analysis indicated that Thiabendazole-induced cancers and liver injuries were related to mitotic cell cycle G2/M transition and DNA replication. Molecular docking showed stable binding of Thiabendazole with core targets including CDK1, CDK2, EGFR, and checkpoint kinase 1 (CHEK1). These findings suggest Thiabendazole may affect the G2/M transition of the mitotic cell cycle through the p53 signaling pathway, potentially inducing cancer and liver injury. This study provides a theoretical basis for understanding the potential molecular mechanisms underlying Thiabendazole toxicity, aiding in the prevention and treatment of related diseases. Additionally, the network toxicology approach accelerates the elucidation of toxic pathways for uncharacterized agricultural chemicals.

Rational Design of Highly Comprehensive Liquid-Like Coatings with Enhanced Transparency, Concerted Multi-Function, and Excellent Durability: A Ternary Cooperative Strategy.

Durable repellent surfaces of high transparency find key applications in daily life and industry. Nevertheless, developing anti-reflective coatings with omni-repellency, concerted multi-function, and desirable durability remains a daunting challenge. Here, a highly comprehensive coating is designed based on the combination of structural design and molecular design. The resulting silica hybrid coating not only manifests enhanced transparency and exceptional omniphobicity, but also achieves integration of multi-function (e.g., anti-smudge, anti-icing, and anti-corrosion). The unprecedented durability of the coating is evidenced by maintaining slipperiness after rigorous treatments, such as 2.5 × 105-cycle mechanical abrasion with a high loading pressure of 100 kPa, 1000-cycle adhesion/peeling and soaking in extreme pH solutions, etc. This work provides a design blueprint for manufacturing versatile and durable coatings for wide-ranging applications.

Global trends and research hotspots of PCSK9 and cardiovascular disease: a bibliometric and visual analysis.

Background: Cardiovascular disease (CVD) is a prevalent non-communicable disease globally and holds the position of being the primary cause of mortality worldwide. Consequently, considerable focus has been directed towards the prevention and management of CVD. PCSK9, a frequently targeted element in the treatment and prevention of CVD, can reduce cardiovascular risk by effectively lowering lipid levels even in the context of statin therapy. It also exhibits substantial potential in the diagnosis and treatment of familial hypercholesterolemia from genetic aspects. This bibliometric study aims to analyze and visualize the global trends and emerging hotspots of PCSK9 and CVD researches and provide researchers with new perspectives in further studies. Methods: The data was obtained from the Web of Science Core Collection database. A total of 2,474 publications related to PCSK9 and CVD published between January 2006 and July 2023 were included. The VOSviewer was used to analyze most-cited references, co-authorship, co-citation, co-occurrence and generate a collaborative network map of authors, countries, and institutions. CiteSpace was used to analyze author and institution centroids, keyword bursts, and timeline graphs. Result: A total of 2,474 articles related to CVD and PCSK9 were included. The number of articles and citations show an increasing trend from year to year. Publications were mainly from the United States. The most active institution was Amgen Inc. Watts, Gerald F. was the most prolific author. Atherosclerosis was the most published journal. Literature co-citation and keyword co-occurrence revealed that early studies focused on the lipid-lowering effects of PCSK9 inhibitors in the context of statins therapy, long-term efficacy, adverse effects, LDLR, diagnosis and treatment of familial hypercholesterolemia. In recent years, myocardial ischemic protection, CRISPR-based editing, and new therapeutic strategies for arteriosclerotic cardiovascular disease have gotten wide attention. The protein convertase, inflammation, beta-polyacetate, and inclisiran may be the important future research directions. Conclusion: This study analyses the current status and global trends in the CVD and PCSK9 studies comprehensively, which may provide researchers and policymakers with new and comprehensive perspectives on in this field of research.

Sirtuin 5 alleviates apoptosis and autophagy stimulated by ammonium chloride in bovine mammary epithelial cells.

Ammonia (NH3) is an irritating and harmful gas that affects cell apoptosis and autophagy. Sirtuin 5 (SIRT5) has multiple enzymatic activities and regulates NH3-induced autophagy in tumor cells. In order to determine whether SIRT5 regulates NH3-induced bovine mammary epithelial cell apoptosis and autophagy, cells with SIRT5 overexpression or knockdown were generated and in addition, bovine mammary epithelial cells were treated with SIRT5 inhibitors. The results showed that SIRT5 overexpression reduced the content of NH3 and glutamate in cells by inhibiting glutaminase activity in glutamine metabolism, and reduced the ratio of ADP/ATP. The results in the SIRT5 knockdown and inhibitor groups were comparable, including increased content of NH3 and glutamate in cells by activating glutaminase activity, and an elevated ratio of ADP/ATP. It was further confirmed that SIRT5 inhibited the apoptosis and autophagy of bovine mammary epithelial cells through reverse transcription-quantitative PCR, western blot, flow cytometry with Annexin V FITC/PI staining and transmission electron microscopy. In addition, it was also found that the addition of LY294002 or Rapamycin inhibited the PI3K/Akt or mTOR kinase signal, decreasing the apoptosis and autophagy activities of bovine mammary epithelial cells induced by SIRT5-inhibited NH3. In summary, the PI3K/Akt/mTOR signal involved in NH3-induced cell autophagy and apoptosis relies on the regulation of SIRT5. This study provides a new theory for the use of NH3 to regulate bovine mammary epithelial cell apoptosis and autophagy, and provides guidance for improving the health and production performance of dairy cows.

Rational design and easy fabrication of transparent photothermal/hygroscopic composite coatings with long-lasting antifogging performance under sunlight activation.

Hygroscopic polymers are good candidates for antifogging coatings, but their long-term effectiveness is limited by the equilibrium between water absorption and expansion. As an efficient and environmentally friendly solution, photothermal materials are being introduced into the field of antifogging. However, there is a need for enhancement in the spectral characteristics of most photothermal materials within the visible light region. In addition, photothermal antifogging coatings often exhibit a delay in heating response, which hinders their ability to promptly evaporate condensed water droplets in the absence of illumination or during initial illumination. Here, a bilayer structure design of photothermal nanomaterials/hygroscopic polymers is proposed to achieve long-term antifogging under sunlight activation. Ensuring the rapid absorption of condensed water droplets on the coating surface, while simultaneously achieving efficient photothermal conversion for a swift temperature increase over the entire coating, is key to this approach, which will not only suppress early fogging but also lead to an exponential decrease of the nucleation rate of droplets. During this process, a dynamic equilibrium is gradually established between the condensation and evaporation of fog droplets, leading to long-term antifogging properties. The light transmittance of the composite coatings reaches as high as ca. 75% in the visible light region, making them well suited for a diverse range of transparent substrate and device applications. A clear field of view can be maintained for at least 6 h under 1 sun illumination above 65 °C hot steam. The antifogging/defogging performance is effectively demonstrated even under challenging non-ideal natural conditions, such as low solar irradiation during dusk or when placed indoors behind windows.

Fabrication of Robust Carbon Dots Containing Coatings with UV-Shielding, Light Conversion, and Antifogging Multiple Functions.

Although a wide variety of single-function coatings have been successfully developed, the integration of multiple functions onto a single coating has remained an immense challenge in the field. Here, we report a simple room-temperature fabrication of robust coatings with UV-shielding, light conversion, and antifogging functionalities. The addition of glutaraldehyde (GA) molecular cross-linker and carbon dot (CD) nanocross-linker with light conversion function to poly(vinyl alcohol) (PVA) resulted in the formation of robust spatial structures of coatings. The fluorescence intensity tests demonstrated that the coatings had an excellent ability to absorb and convert ultraviolet light into blue-violet light. Both cold-warm and hot-vapor tests showed that the coatings had excellent antifogging performance. To our surprise, no creases were observed after coatings were immersed in water for 1 month, indicating that these are much stronger than those reported so far. The 8H pencil hardness and wear resistance attested to their excellent mechanical properties. The current preparation method can be operated at ambient temperature and is not restricted by the substrate type and shape. Therefore, it may also expand the possibilities for future applications of coatings for glass windows, optical microscopes, eyeglasses, agricultural greenhouses, and so on.

Cohort profile: the China surgery and anesthesia cohort (CSAC).

The China Surgery and Anaesthesia Cohort (CSAC) study was launched in July 2020 and is an ongoing prospective cohort study recruiting patients aged 40-65 years who underwent elective surgeries with general anaesthesia across four medical centres in China. The general objective of the CSAC study is to improve our understanding of the complex interaction between environmental and genetic components as well as to determine their effects on a wide range of interested surgery/anaesthesia-related outcomes. To achieve this goal, we collected enriched phenotypic data, e.g., sociodemographic characteristics, lifestyle factors, perioperative neuropsychological changes, anaesthesia- and surgery-related complications, and medical conditions, at recruitment, as well as through both active (at 1, 3, 7 days and 1, 3, 6, 12 months after surgery) and passive (for more than 1 year after surgery) follow-up assessments. We also obtained omics data from blood samples. In addition, COVID-19-related information was collected from all participants since January 2023, immediately after COVID-19 restrictions were eased in China. As of July 18, 2023, 12,766 participants (mean age = 52.40 years, 57.93% were female) completed baseline data collection (response rate = 94.68%), among which approximately 70% donated blood and hair samples. The follow-up rates within 12 months after surgery were > 92%. Our initial analyses have demonstrated the incidence of and risk factors for chronic postsurgical pain (CPSP) and postoperative cognitive dysfunction (POCD) among middle-aged Chinese individuals, which may prompt further mechanistic exploration and facilitate the development of effective interventions for preventing those conditions. Additional studies, such as genome-wide association analyses for identifying the genetic determinants of CPSP and POCD, are ongoing, and their findings will be released in the future.

Efficacy of antioxidant supplementation in improving endocrine, hormonal, inflammatory, and metabolic statuses of PCOS: a meta-analysis and systematic review.

Background and aim: A large number of recent studies have reported on the use of antioxidants in patients with polycystic ovary syndrome (PCOS). This study aimed to evaluate the antioxidant effects on PCOS. Methods: We searched PubMed, Embase, Web of Science, and The Cochrane Library to identify randomized controlled trials investigating the use of antioxidants in treating PCOS. Statistical analysis was performed using Review Manager 5.4. Stata17.0 software was used to conduct sensitivity analyses. Results: This meta-analysis included 49 articles and 62 studies. The sample comprised 1657 patients with PCOS from the antioxidant group and 1619 with PCOS from the placebo group. The meta-analysis revealed that the fasting blood glucose levels [standardized mean difference (SMD): -0.31, 95% confidence interval (CI): -0.39 to -0.22, P < 0.00001], the homeostatic model assessment of insulin resistance (SMD: -0.68, 95% CI: -0.87 to -0.50], P < 0.00001), and insulin levels (SMD: -0.68, 95% CI: -0.79 to -0.58, P < 0.00001) were significantly lower in patients with PCOS taking antioxidants than those in the placebo group. Further, total cholesterol levels (SMD: -0.38, 95% CI: -0.56 to -0.20, P < 0.001), low-density lipoprotein cholesterol levels (SMD: -0.24, 95% CI: -0.37 to -0.10, P = 0.0008), and very low-density lipoprotein levels (SMD: -0.53, 95% CI: -0.65 to -0.41, P < 0.00001) were lower in patients with PCOS taking antioxidant supplements compared with the placebo group. Total testosterone (TT) level (SMD: -0.78, 95% CI: -1.15 to -0.42, P < 0.0001), dehydroepiandrosterone level (SMD: -0.42, 95% CI: -0.58 to -0.25, P < 0.00001), and mean standard deviation modified Ferriman-Gallway (MF-G scores) (SMD: -0.63, 95% CI: -0.98 to -0.28, P = 0.0004) were lower in patients taking antioxidant supplements. C-reactive protein (CRP) levels (SMD: -0.48, 95% CI: -0.63 to -0.34, P < 0.000001), body mass index [mean difference (MD): -0.27, 95% CI: -0.50 to -0.03, P = 0.03], weight (MD: -0.73, 95% CI: -1.35 to -0.11, P = 0.02), and diastolic blood pressure (MD: -3.78, 95% CI: -6.30 to -1.26, P = 0.003) were significantly lower. Moreover, the levels of sex hormone-binding protein (SMD: 0.23, 95% CI: 0.07-0.38, P = 0.004), high-density lipoprotein cholesterol (SMD: 0.11, 95% CI: 0.01-0.20, P = 0.03), total antioxidant capacity (SMD: 0.59, 95% CI: 0.31-0.87, P < 0.0001), and quantitative insulin sensitivity index (SMD: 0.01, 95% CI: 0.01-0.02, P < 0.00001) were higher in patients with PCOS who took antioxidant supplements compared with the placebo group. Antioxidant supplements did not affect other analyzed parameters in these patients, including follicle-stimulating hormone, free androgen index, nitric oxide, glutathione, malondialdehyde, and diastolic blood pressure. Conclusions: Antioxidants are beneficial in treating PCOS. Our study might provide a new treatment strategy for patients with clinical PCOS. We hope that more high-quality studies evaluating the effects of antioxidants on patients with PCOS will be conducted in the future. Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023448088.

Preoperative psychological symptoms and chronic postsurgical pain: analysis of the prospective China Surgery and Anaesthesia Cohort study.

BACKGROUND: Both preoperative psychological symptoms and chronic postsurgical pain (CPSP) are prevalent conditions and major concerns among surgery patients, with inconclusive associations. METHODS: Based on the China Surgery and Anaesthesia Cohort (CSAC), we recruited 8350 surgery patients (40-65 yr old) from two medical centres between July 2020 and March 2023. Patients with preoperative psychological symptoms (i.e. anxiety, depression, stress reaction, and poor sleep quality) were identified using corresponding well-established scales. We then examined the associations of individual preoperative psychological symptoms and major patterns of preoperative psychological symptoms (identified by k-means clustering analysis) with CPSP, and different pain trajectories within 3 months. Lastly, mediation analyses were conducted to elucidate the mediating role of surgery/anaesthesia-related factors and the presence of 1-month postoperative psychological symptoms on the studied associations. RESULTS: We included 1302 (1302/8350, 15.6%) CPSP patients. When analysed separately, all studied preoperative psychological symptoms were associated with increased CPSP risk, with the most pronounced odds ratio noted for anxiety (1.52, 95% confidence interval [CI] 1.23-1.86). Compared with patients clustered in the minor symptom group, excess risk of CPSP and experiencing an increasing pain trajectory was increased among patients with preoperative psychological symptoms featured by sleep disturbances (odds ratio=1.46, 95% CI 1.25-1.70 for CPSP and 1.58, 95% CI 1.20-2.08 for increasing pain trajectory) and multiple psychological symptoms (1.84 [95% CI 1.48-2.28] and 4.34 [95% CI 3.20-5.88]). Mediation analyses revealed acute/subacute postsurgical pain and psychological symptoms existing 1 month after surgery as notable mediators of the observed associations. CONCLUSIONS: The presence of preoperative psychological symptoms might individually or jointly increase the risk of chronic postsurgical pain or experiencing deterioration in pain trajectory. Interventions for managing acute/subacute postsurgical pain and psychological symptoms at 1 month after surgery might help reduce such risk. CLINICAL TRIAL REGISTRATION: ChiCTR2000034039.

GnRH antagonist protocol versus progestin-primed ovarian stimulation in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

PURPOSE: The aim of this meta-analysis was comparing the efficacy of GnRH antagonist (GnRH-ant) protocol and progestin-primed ovarian stimulation (PPOS) in polycystic ovarian syndrome (PCOS) women. METHODS: A search was conducted from PubMed, Embase, The Cochrane library, Web of Science, and Scopus databases to collect clinical papers regarding GnRH-ant protocol and PPOS protocol from inception to September 2023. Subsequently, the retrieved documents were screened, and the content of the documents that conformed to the requirements was extracted. Moreover, statistical meta-analyses were conducted using the RevMan 5.4 software. Furthermore, with the use of a star-based system and the Cochrane handbook, the methodological quality of the covered papers was evaluated on the Ottawa-Newcastle scale. RESULTS: A total of eight papers were covered in the meta-analysis, with 2156 PCOS women enrolled (i.e., 1085 patients in the GnRH-ant protocol group and 1071 patients in the PPOS group). As indicated by the meta-analysis results, the PPOS group was correlated with a lower risk of ovarian hyperstimulation syndrome (OHSS) (SMD = 9.24, [95% CI: (2.50, 34.21)], P = 0.0009), more gonadotropin (Gn) dose (SMD = - 0.34, [95% CI: (- 0.56, - 0.13)], P = 0.002) compared with GnRH-ant group. No statistical difference was identified on the oocytes condition and pregnancy outcomes. CONCLUSIONS: As revealed by the data of this study, the progesterone protocol is comparable with the GnRH-ant protocol in oocytes condition and clinical outcomes. The progestin-primed ovarian stimulation could serve as an alternative for polycystic ovarian syndrome women who have failed in GnRH antagonist protocol. The above-described conclusions should be verified by more high-quality papers due to the limitation of the number and quality of included papers. TRIAL REGISTRATION: PROSPERO registration: CRD42023411284.

Active Fraction of Polyrhachis Vicina Roger (AFPR) Ameliorate Depression Induced Inflammation Response by FTO/miR-221-3p/SOCS1 Axis.

Purpose: Neuroinflammation is a significant etiological factor in the development of depression. Traditional Chinese medicine (TCM) has demonstrated notable efficacy in the treatment of inflammation. Our previous study surfaces that the active fraction of Polyrhachis vicina Roger (AFPR) has antidepressant and anti-neuroinflammatory effects, but the specific mechanisms remain to be elucidated. The objective of this study was to examine the impact of AFPR on inflammation in depression via the FTO/miR-221-3p/SOCS1 axis. Methods: Chronic unpredictable stress (CUMS)-induced rats and LPS-induced BV2 cells were employed to simulate depression models in vivo and in vitro. The levels of inflammatory factors were detected using the ELISA assay. The expression of genes and proteins was detected using qRT-PCR and Western blot. Gene interactions were detected using the dual luciferase reporter gene. Protein-RNA interactions were investigated using RNA methylation immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP). Neuroinflammation in the brain was examined through H&E staining, while neuronal apoptosis was assessed using TUNEL staining. Results: The results showed that AFPR ameliorated depression induced inflammation by increasing SOCS1 expression. However, SOCS1 was identified as a target of miR-221-3p. Overexpression of miR-221-3p decreased the expression of SOCS1 and increased the levels of NF-κB, IL-7, and IL-6. In addition, we found that miR-221-3p was regulated by FTO-mediated m6A modification through MeRIP and RIP experiments. Interference with miR-221-3p and overexpression of FTO resulted in increased SOCS1 gene expression and decreased levels of NF-κB, IL-7, and IL-6, which were reversed by AFPR. Conclusion: AFPR inhibits the maturation of pri-miR-221-3p through FTO-mediated m6A modification, reduces the production of miR-221-3p, increases the expression of SOCS1, and reduces the level of inflammation, thereby improving depressive symptoms.

Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice.

Abnormal lipid metabolism and chronic low-grade inflammation are the main traits of obesity. Especially, the molecular mechanism of concomitant deficiency in steroidogenesis-associated enzymes related to testosterone (T) synthesis of obesity dominated a decline in male fertility is still poorly understood. Here, we found that in vivo, supplementation of pyrroloquinoline quinone (PQQ) efficaciously ameliorated the abnormal lipid metabolism and testicular spermatogenic function from high-fat-diet (HFD)-induced obese mice. Moreover, the transcriptome analysis of the liver and testicular showed that PQQ supplementation not only inhibited the high expression of proprotein convertase subtilisin/Kexin type 9 (PCSK9) but also weakened the NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis, which both played a negative role in T synthesis of Leydig Cells (LCs). Eventually, the function and the pyroptosis of LCs cultured with palmitic acid in vitro were simultaneously benefited by suppressing the expression of NLRP3 or PCSK9 respectively, as well the parallel effects of PQQ were affirmed. Collectively, our data revealed that PQQ supplementation is a feasible approach to protect T synthesis from PCSK9-NLRP3 crosstalk-induced LCs' pyroptosis in obese men.

Early heart rate fluctuation and outcomes in critically ill patients with sepsis: A retrospective cohort study of the MIMIC-IV database.

Background: Heart rate (HR) abnormalities are common in critically ill patients, but the significance of HR fluctuation in sepsis remains unclear. We aimed to assess the association of HR fluctuation with intensive care unit (ICU) mortality, hospital mortality, and 28-day mortality in patients with sepsis and identify the cutoff value of HR fluctuation associated with the lowest risk of death. Methods: We conducted a retrospective cohort study using the medical information mart for the intensive care IV database. HR fluctuation, defined as the difference between maximum and minimum HR within the first 24 h of ICU admission, was analyzed for its association with outcomes using restricted cubic spline and multivariable Cox regression models. Results: Among 24,419 eligible patients with sepsis, HR fluctuation showed a J-shaped association with ICU mortality, hospital mortality, and 28-day mortality. The high HR fluctuation group (≥ 35 bpm) had a significantly increased risk of ICU mortality ([hazard ratio, 95% confidence interval] 1.12,1.02-1.22, P = 0.013), hospital mortality (1.10,1.02-1.19, P = 0.013), and 28-day mortality (1.11,1.03-1.20, P = 0.007) compared to the control group (HR fluctuation 25-34 bpm). The low HR fluctuation group (< 25 bpm) showed no significant difference in the risk of mortality compared to the control group. Conclusions: Our large-sample study suggests that early high HR fluctuation is indicative of poor prognosis in critically ill patients with sepsis. Early HR fluctuation may serve as a readily available "high-risk alert system" influencing therapeutic decision-making.

Active fraction of Polyrhachis vicina (Roger) alleviated cerebral ischemia/reperfusion injury by targeting SIRT3-mediated mitophagy and angiogenesis.

BACKGROUND: Damaged mitophagy and impaired angiogenesis involve in the pathogenic development of ischemic stroke. Active fraction of Polyrhachis vicina (Roger) (AFPR) showed great potential on neurological disease with it's remarkable anti-inflammatory and anti-oxidative effects. PURPOSE: This study designed to clarify the correlation between Pink1/Parkin-mediated mitophagy and angiogenesis after stroke, and to elucidate the role of SIRT3 in regulating mitophagy and angiogenesis, and to address the mechanism of AFPR on promoting mitophagy and angiogenesis in microvessels endothelium of ischemic brain. STUDY DESIGN: A cerebral ischemia/reperfusion (CIR) rat model was developed by middle cerebral artery occlusion procedure. bEnd.3 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic CIR process. Neurological function, mitophagy and angiogenesis related indicators were measured. SIRT3 siRNA and 3-MA were used to verify the interaction between SIRT3-mediated mitophagy and angiogenesis. METHODS: CIR rats were orally treated with AFPR (8 and 4 g raw drug /kg) and Nimodipine (10.8 mg/kg) for 12 days to mimic the recovery phase post-stroke. The neurological function assessment, TTC staining, HE staining, TUNEL staining and Nissl staining were performed to assess neuroprotective effects of AFPR against CIR. Then CD31-labeled microvessel density in brain was visualized and quantified by immunofluorescence staining. Mitochondrial ultrastructure was assessed by transmission electron microscope scanning. Expressions of relative proteins,e.g. SIRT3, Pink1, Parkin, LC3-II, p62, VEGFA, involving in mitophagy and angiogenesis, were detected by Western blotting analysis. In vitro, bEnd.3 cells were cultured with AFPR or in combination of autophagy inhibitor 3-MA during the reoxygenation. Then cell viability, and LDH releasing were measured. Angiogenic indicators,such as migration and tube formation activity, VEGFA level were determined. To assess effects of AFPR on mitophagy, mitophagy-related proteins were detected, as well as the autophagosome engulfment and lysosome degradation of mitochondria. To address the role of SIRT3, deacetylation activity of SIRT3 was validated by detecting acetylated FOXO3A level with co-immunoprecipitation (Co-IP) assay. Pre-treatment of siRNA or combination use of 3-MA were used to verify the detailed mechanism. RESULTS: AFPR remarkably reduced neurological scores and infarct size, alleviated neuron apoptosis in cortex, and increased Nissl density in hippocampus of CIR rats. In addition, AFPR significantly promoted angiogenesis by increasing microvessels density and VEGFA expressions, increased SIRT3 expression, and activated Pink1/Parkin mediated mitophagy. In bEnd.3 cells, the combination use of 3-MA and AFPR further demonstrated that AFPR might promote angiogenesis after OGD/R injury through activating Pink1/Parkin mediated mitophagy. Co-IP assay suggested AFPR reduced acetylated FOXO3A level. This might be correlated with an elevation of SIRT3 expression and it's deacetylation activity. SIRT3 siRNA pretreatment significantly abolished the activation of mitophagy through Pink1/Parkin axis, eventually inhibited angiogenesis. CONCLUSION: AFPR promoted angiogenesis through activating mitophagy after cerebral ischemia reperfusion, which might partially involved in the amelioration of SIRT3-mediated regulation on Pink1/Parkin axis. Our study will shed new light on the role of SIRT3 in ischemic brain, especially in regulating mitophagy and angiogenesis after stroke.

Postsurgery Subjective Cognitive and Short-Term Memory Impairment Among Middle-Aged Chinese Patients.

Importance: Perioperative neurocognitive disorder, particularly postoperative cognitive impairment, is common and associated with multiple medical and social adversities, although data from China are lacking. Objective: To examine the incidence, trajectory, and risk factors for subjective cognitive and short-term memory impairment after surgery in the Chinese population. Design, Setting, and Participants: This cohort study used data from the China Surgery and Anesthesia Cohort to assess surgical patients aged 40 to 65 years from 2 medical centers between July 15, 2020, and March 31, 2023, with active follow-up within 1 year after the surgery. Of 11 158 patients who were successfully recruited (response rate, 94.4%), 10 149 participants were eligible and available for analysis. From this population, separate cohorts were constructed for analyzing subjective cognitive impairment (8105 noncardiac and 678 cardiac surgery patients) and short-term memory impairment (5246 noncardiac and 454 cardiac surgery patients). Exposures: Twenty-four potential risk factors regarding comorbidities, preoperative psychological conditions, anesthesia- or surgery-related factors, and postsurgical events were included. Main Outcomes and Measures: Outcomes included subjective cognitive function measured by the 8-Item Informant Interview to Differentiate Aging and Dementia (AD8; scores range from 0 to 8, with higher scores indicating more severe cognitive impairment) and short-term memory measured by the 3-Word Recall Test (TRT; scores range from 0 to 3, with lower scores indicating more severe short-term memory impairment) at 1, 3, 6, and 12 months after noncardiac and cardiac surgery. Generalized linear mixed models were used to identify risk factors associated with the presence of AD8 (score ≥2) or TRT (score <3) abnormality as well as the aggressively deteriorative trajectories of those cognitive measurements. Results: For noncardiac surgery patients, the AD8 analysis included 8105 patients (mean [SD] age, 52.3 [7.1] years; 3378 [41.7%] male), and the TRT analysis included 5246 patients (mean [SD] age, 51.4 [7.0] years; 1969 [37.5%] male). The AD8 abnormality incidence rates after noncardiac surgery increased from 2.2% (175 of 8105) at 7 days to 17.1% (1059 of 6191) at 6 months after surgery, before appearing to decrease. In contrast, the TRT abnormality incidence rates followed a U-shaped pattern, with the most pronounced incidence rates seen at 7 days (38.9% [2040 of 5246]) and 12 months (49.0% [1394 of 2845]). Similar patterns were seen among cardiac surgery patients for the AD8 analysis (678 patients; mean [SD] age, 53.2 [6.3] years; 393 [58.0%] male) and TRT analysis (454 patients; mean [SD] age, 52.4 [6.4] years; 248 [54.6%] male). Among noncardiac surgery patients, the top risk factors for aggressively deteriorative AD8 trajectory and for AD8 abnormality, respectively, after surgery were preoperative sleep disturbances (Pittsburgh Sleep Quality Index ≥16 vs 0-5: odds ratios [ORs], 4.04 [95% CI, 2.20-7.40] and 4.54 [95% CI, 2.40-8.59]), intensive care unit stay of 2 days or longer (ORs, 2.43 [95% CI, 1.26-4.67] and 3.07 [95% CI, 1.67-5.65]), and preoperative depressive symptoms (ORs, 1.76 [95% CI, 1.38-2.24] and 2.23 [95% CI, 1.79-2.77]). Analyses for TRT abnormality and trajectory, as well as the analyses conducted among cardiac surgery patients, found fewer associated factors. Conclusions and Relevance: This cohort study of middle-aged Chinese surgery patients found subjective cognitive and short-term memory impairment within 12 months after both cardiac and noncardiac surgery, with multiple identified risk factors, underscoring the potential of preoperative psychological interventions and optimized perioperative management for postoperative cognitive impairment prevention.

Chitinase-3 like-protein-1, matrix metalloproteinase -9 and positive intracranial arterial remodelling.

Introduction: Positive intracranial arterial remodelling is a dilated lesion of the large intracranial vessels; however, its pathogenesis is currently unknown. Some studies have identified chitinase-3 like-protein-1 (YKL-40) and matrix metalloproteinase (MMP)-9 as circulating inflammatory factors involved in positive vascular remodelling. Herein, we aimed to investigate the relationship between changes in serum YKL-40 and MMP-9 levels and positive intracranial arterial remodelling in patients with cerebral small vessel disease (CSVD). Methods: A total of 110 patients with CSVD were selected. Patients with brain arterial remodelling (BAR) scores >1 times the standard deviation were defined as the positive intracranial artery remodelling group (n = 21 cases), and those with BAR scores ≤1 times the standard deviation were defined as the non-positive intracranial artery remodelling group (n = 89 cases). Serum YKL-40 and MMP-9 levels were measured using an enzyme-linked immunosorbent assay kit. Factors influencing positive intracranial artery remodelling using binary logistic regression analysis and predictive value of YKL-40 and MMP-9 for positive intracranial arterial remodelling in patients with CSVD were assessed by a subject receiver operating characteristic curve. Results: Statistically significant differences in serum YKL-40 and MMP-9 levels were observed between the positive and non-positive remodelling groups (p < 0.05). The integrated indicator (OR = 9.410, 95% CI: 3.156 ~ 28.054, P<0.01) of YKL-40 and MMP-9 levels were independent risk factors for positive intracranial arterial remodelling. The integrated indicator (OR = 3.763, 95% CI: 1.884 ~ 7.517, p < 0.01) of YKL-40 and MMP-9 were independent risk factors for positive arterial remodelling in posterior circulation, but were not significantly associated with positive arterial remodelling in anterior circulation (p > 0.05). The area under the curve for YKL-40 and MMP-9 diagnostic positive remodelling was 0.778 (95% CI: 0.692-0.865, p < 0.01) and 0.736 (95% CI: 0.636-0.837, p < 0.01), respectively. Discussion: Elevated serum YKL-40 and MMP-9 levels are independent risk factors for positive intracranial arterial remodelling in patients with CSVD and may predict the presence of positive intracranial arterial remodelling, providing new ideas for the mechanism of its occurrence and development and the direction of treatment.

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. AIM OF THE STUDY: The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. METHODS: To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. RESULTS: Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. CONCLUSION: According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

3D porous carbon-embedded nZVI@Fe2O3 nanoarchitectures enable prominent performance and recyclability in antibiotic removal.

Overcoming the instability and poor recyclability during the practical applications of contaminant scavengers is a challenging topic. Herein, a three-dimensional (3D) interconnected carbon aerogel (nZVI@Fe2O3/PC) embedding a core-shell nanostructure of nZVI@Fe2O3 was elaborately designed and fabricated via an in-situ self-assembly process. The porous carbon with 3D network architecture exhibits strong adsorption towards various antibiotic contaminants in water, where the stably embedded nZVI@Fe2O3 nanoparticles not only serve as magnetic seeds for recycling, but also avoid the shedding and oxidation of nZVI in the adsorption process. As a result, nZVI@Fe2O3/PC efficiently captures sulfamethoxazole (SMX), sulfamethazine (SMZ), ciprofloxacin (CIP), tetracycline (TC) and other antibiotics in water. In particular, an excellent adsorptive removal capacity of 329 mg g-1 and a rapid capture kinetics (99% of removal efficiency in 10 min) under a wide pH adaptability (2-8) are achieved using nZVI@Fe2O3/PC as an SMX scavenger. nZVI@Fe2O3/PC displays exceptional long-term stability given that it shows excellent magnetic property after it is stored in water solution for 60 d, making it an ideal stable scavenger for contaminants in an etching-resistant and efficient manner. This work would also provide a general strategy to develop other stable iron-based functional architectures for efficient catalytic degradation, energy conversion and biomedicine.