In situ formed depot of elastin-like polypeptide-hirudin fusion protein for long-acting antithrombotic therapy.

Thrombosis, induced by abnormal coagulation or fibrinolytic systems, is the most common pathology associated with many life-threatening cardio-cerebrovascular diseases. However, first-line anticoagulant drugs suffer from rapid drug elimination and risk of hemorrhagic complications. Here, we developed an in situ formed depot of elastin-like polypeptide (ELP)-hirudin fusion protein with a prodrug-like feature for long-term antithrombotic therapy. Highly secretory expression of the fusion protein was achieved with the assistance of the Ffu312 tag. Integration of hirudin, ELP, and responsive moiety can customize fusion proteins with properties of adjustable in vivo retention and controllable recovery of drug bioactivity. After subcutaneous injection, the fusion protein can form a reservoir through temperature-induced coacervation of ELP and slowly diffuse into the blood circulation. The biological activity of hirudin is shielded due to the N-terminal modification, while the activated key proteases upon thrombus occurrence trigger the cleavage of fusion protein together with the release of hirudin, which has antithrombotic activity to counteract thrombosis. We substantiated that the optimized fusion protein produced long-term antithrombotic effects without the risk of bleeding in multiple animal thrombosis models.

REGγ Mitigates Radiation-Induced Enteritis by Preserving Mucin Secretion and Sustaining Microbiome Homeostasis.

Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota remains unknown. The current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as compared to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation after irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice after irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, minigut organoid systems and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, although administration of broad-spectrum antibiotics did not alter the goblet cell numbers or mucin 2 (MUC2) secretion, it effectively attenuated inflammation levels in the ileum of irradiated REGγ absent mice, bringing them down to the wild-type levels. Collectively, these findings highlight the contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.

High-quality genome assembly enables prediction of allele-specific gene expression in hybrid poplar.

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid "84K" (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.

Encapsulating Bi Nanoparticles in Reduced Graphene Oxide with Strong Interfacial Bonding toward Advanced Potassium Storage.

Bismuth (Bi) is regarded as a promising anode material for potassium ion batteries (PIBs) due to its high theoretical capacity, but the huge volume expansion during potassiation and intrinsic low conductivity cause poor cycle stability and rate capability. Herein, a unique Bi nanoparticles/reduced graphene oxide (rGO) composite is fabricated by anchoring the Bi nanoparticles over the rGO substrate through a ball-milling and thermal reduction process. As depicted by the in-depth XPS analysis, strong interfacial Bi-C bonding can be formed between Bi and rGO, which is beneficial for alleviating the huge volume expansion of Bi during potassiation, restraining the aggregation of Bi nanoparticles and promoting the interfacial charge transfer. Theoretical calculation reveals the positive effect of rGO to enhance the potassium adsorption capability and interfacial electron transfer as well as reduce the diffusion energy barrier in the Bi/rGO composite. Thereby, the Bi/rGO composite exhibits excellent potassium storage performances in terms of high capacity (384.8 mAh g-1 at 50 mA g-1), excellent cycling stability (197.7 mAh g-1 after 1000 cycles at 500 mA g-1 with no capacity decay) and superior rate capability (55.6 mAh g-1 at 2 A g-1), demonstrating its great potential as an anode material for PIBs.

Association of obesity with cardiovascular disease in the absence of traditional risk factors.

BACKGROUND: The association between obesity and cardiovascular disease (CVD) in people without traditional CVD risk factors is unclear. This study aimed to investigate the association of obesity with CVD and its subtypes in people without traditional CVD risk factors. METHODS: Based on the Kailuan cohort study, the included participants were divided into different groups according to levels of body mass index (BMI) and waist height ratio (WHtR), respectively. Multivariate Cox proportional hazard models were used to evaluate the associations. RESULTS: This study included 31,955 participants [men 63.99%; mean age (48.14 ± 3.33) years]. During a median follow-up period of 12.97 (interquartile range: 12.68-13.17) years, 1298 cases of CVD were observed. Compared with the normal BMI group, the hazard ratios (HRs) for CVD, stroke, and myocardial infarction (MI) in the BMI obese group were 1.31 (95% confidence interval [CI] 1.11-1.55), 1.21 (95%CI 1.01-1.46), 1.62 (95%CI 1.13-2.33), respectively. Compared with the WHtR non-obese group, the HRs for CVD, stroke, and MI in the obese group were 1.25(95%CI 1.11-1.41), 1.18 (95%CI 1.03-1.34), 1.57 (95%CI 1.18-2.09), respectively. There was an interaction between age and WHtR (P for interaction was 0.043). The association between WHtR and CVD was stronger in people under 60 years old, with a HR of 1.44 (95%CI 1.24-1.67). CONCLUSION: We found that obesity increased the risk of CVD in people without traditional CVD risk factors. The association of WHtR with CVD was stronger in people under 60 years old.

Association of Stroke With Metabolic Dysfunction-Associated Fatty Liver Disease With and Without CKD.

RATIONALE & OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD), a risk factor for stroke and all-cause mortality, is highly prevalent among patients with chronic kidney disease (CKD), but it is unclear whether the association of MAFLD with stroke and all-cause mortality differs within and outside of the setting of CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We enrolled 95,353 participants from the Kailuan Cohort Study, among whom 35,749 had CKD at baseline or developed CKD during the follow-up period, and 59,604 individuals who had no CKD at baseline or during the follow-up period. EXPOSURE: MAFLD. OUTCOME: Stroke (ischemic stroke, hemorrhagic stroke), all-cause mortality. ANALYTICAL APPROACH: Adjusted Cox regression models were used to estimate the influence of MAFLD on stroke outcomes within the subgroups defined by the presence of CKD. RESULTS: After a median follow-up of 12.8 years, 6,140 strokes (6.4%) and 11,975 deaths from any cause (12.6%) occurred. After adjusting for potential confounders, MAFLD was associated with an increased incidence of stroke among the participants with CKD (HR, 1.34 [95% CI, 1.23-1.45]) but not among those without CKD (HR, 1.05 [95% CI, 0.97-1.15]; Pinteraction<0.001). This association was principally related to ischemic stroke (HR, 1.38 [95% CI, 1.26-1.51]) and not hemorrhagic stroke (HR, 1.04 [95% CI, 0.85-1.26]). No association was found between MAFLD and all-cause mortality in the participants with CKD (HR,1.04 [95% CI, 0.98-1.10]) or those without CKD (HR,1.03 [95% CI, 0.97-1.09]). Among the participants with CKD, compared with non-MAFLD, MAFLD with diabetes (HR,1.36 [95% CI, 1.23-1.50]) or overweight/obesity (HR,1.30 [95% CI, 1.14-1.50]) was associated with a higher risk of stroke whereas MAFLD without overweight/obesity or diabetes was not associated with a higher risk (HR,1.08 [95% CI, 0.81-1.43]). LIMITATIONS: This was an observational study and included individuals with CKD who had a relatively high estimated glomerular filtration rate. CONCLUSIONS: MAFLD was associated with an increased risk of stroke in individuals with CKD but not in those without CKD. PLAIN-LANGUAGE SUMMARY: Metabolic dysfunction-associated fatty liver disease (MAFLD), which is recognized as a risk factor for stroke in the general population, is highly prevalent among individuals with chronic kidney disease (CKD). However, the impact of MAFLD on the risk of stroke in patients with CKD remains uncertain. We investigated the association of MAFLD with stroke in individuals with and without CKD. Our analysis revealed that MAFLD was associated with a significantly increased risk of stroke in individuals with CKD, and the magnitude of this increased risk was greater in the setting of CKD. These findings highlight the need for increased attention to MAFLD in patients with CKD and emphasize that addressing and preventing MAFLD in this population may contribute to reduced morbidity from stroke.

Association of triglyceride-glucose index and its related parameters with atherosclerotic cardiovascular disease: evidence from a 15-year follow-up of Kailuan cohort.

BACKGROUND: Triglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared. METHOD: A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD. RESULTS: During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged < 60 years (Pfor interaction<0.05). Using the updated mean or time-varying measurements instead of baseline indicators did not significantly alter the primary findings. Additionally, TyG-WC and TyG-WHtR showed better performance in predicting risk of ASCVD than TyG, with the IDI (95% CI) of 0.004 (0.001, 0.004) and 0.004 (0.001, 0.004) and the category-free NRI (95% CI) of 0.120 (0.025, 0.138) and 0.143 (0.032, 0.166), respectively. Similar findings were observed for MI and IS. CONCLUSIONS: Both the TyG index and its related parameters were significantly and positively associated with ASCVD. TyG-WC and TyG-WHtR had better performance in predicting incident ASCVD than TyG, which might be more suitable indices for risk stratification and enhance the primary prevention of ASCVD.

Ame-miR-1-3p of bee venom reduced cell viability through the AZIN1/OAZ1-ODC1-polyamines pathway and enhanced the defense ability of honeybee (Apis mellifera L.).

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.

Longitudinal cardiovascular health measured by life's essential 8 metrics with incident diabetes: A 13-year prospective cohort study.

AIMS: To investigate the associations of baseline and longitudinal cardiovascular health (CVH) measured by 'Life's Essential 8' (LE8) metrics with the risk of diabetes in Chinese people with normoglycaemia or prediabetes. MATERIALS AND METHODS: A total 86,149 participants without diabetes were enroled from the Kailuan study and were stratified by baseline glycaemic status (normoglycaemia or prediabetes). Cardiovascular health score ranged from 0 to 100 points was categorised into low (0-49), middle (50-79), and high (80-100) CVH status. Cox regressions were used to assess the associations of baseline and time-updated CVH status with incident diabetes in the overall cohort and across baseline glycaemic statuses. RESULTS: During a median follow-up of 12.94 (interquartile rage: 12.48-13.16) years, we identified 13,097 (15.20%) cases of incident diabetes. Baseline and time-updated high CVH status was associated with a lower risk of diabetes, the corresponding hazard ratio (HR) versus low CVH status was 0.27 (95% confidence interval [CI], 0.23-0.31) and 0.26 (95% CI, 0.23-0.30) in the overall cohort, respectively. Additionally, the effect of high CVH on diabetes was more prominent in participants with normoglycaemia than those with prediabetes (P < 0.0001), with an HR of 0.26 (95% CI, 0.22-0.31) versus 0.50 (95% CI, 0.41-0.62) for baseline CVH, and 0.25 (95% CI, 0.21-0.30) versus 0.39 (95% CI, 0.32-0.48) for time-updated CVH. CONCLUSIONS: Elevated baseline and longitudinal CVH score assessed by LE8 metrics is associated with a lower risk of subsequent diabetes, especially in normoglycaemic adults.

Rosmarinic acid alleviates fungal keratitis caused by Aspergillus fumigatus by inducing macrophage autophagy.

Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1ß, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.

Oxymatrine mitigates Aspergillus fumigatus keratitis by suppressing fungal activity and restricting pyroptosis.

Fungal keratitis (FK) is a refractory keratitis caused by excessive inflammation and fungal damage. Excessive inflammation can lead to tissue damage and corneal opacity, resulting in a poor prognosis for FK. Oxymatrine (OMT) is a natural alkaloid, which has rich pharmacological effects, such as antioxidant and anti-inflammation. However, its antifungal activity and the mechanism of action in FK have not been elucidated. This study confirmed that OMT suppressed Aspergillus fumigatus growth, biofilm formation, the integrity of fungal cell and conidial adherence. OMT not only effectively reduced corneal fungal load but also inflammation responses. OMT lessened the recruitment of neutrophils and macrophages in FK. In addition, OMT up-regulated the expression of Nrf2 and down-regulated the expression of IL-18, IL-1ß, caspase-1, NLRP3 and GSDMD. Pre-treatment with Nrf2 inhibitor up-regulated the expression of IL-1ß, IL-18, caspase-1, NLRP3 and GSDMD supressed by OMT. In conclusion, OMT has efficient anti-inflammatory and antifungal effects by suppressing fungal activity and restricting pyroptosis via Nrf2 pathway. OMT is considered as a potential option for the treatment of FK.

miR-125a-3p regulates the expression of FSTL1, a pro-inflammatory factor, during adipogenic differentiation, and inhibits adipogenesis in mice.

Adipogenesis is tightly regulated by various factors, including genes and microRNAs. Excessive fat deposition is the key feature of obesity, which is a low-grade chronic inflammatory disease. Follistatin-like 1 (FSTL1) has been reported to be an important mediator involved in various inflammatory diseases. However, the underlying mechanism of FSTL1 in preadipocyte differentiation and inflammatory response is still unclear. The current study was designed to explore the biological function and potential mechanism of FSTL1 in mouse subcutaneous preadipocyte differentiation. We found that FSTL1 was highly expressed in the early stage of differentiation and subsequently decreased sharply, suggesting that FSTL1 played a possible role in adipogenesis. Meanwhile, the gain- and loss-of-function assays showed that FSTL1 was not only involved in the inflammatory response by inducing the expression of pro-inflammatory factors IL-1ß and CCL2 but also significantly attenuated preadipocyte differentiation, as evidenced by the reduction of lipid accumulation and the levels of adipogenic genes, including PPARγ and FABP4. In addition, the target gene prediction and luciferase reporter assay validated that miR-125a-3p targeted the 3' UTR region of FSTL1. These results demonstrated that miR-125a-3p negatively regulated the expression of FSTL1 at the mRNA and protein levels. Furthermore, overexpressing miR-125a-3p in preadipocytes dramatically accelerated adipogenic differentiation and downregulated the levels of IL-1ß and CCL2, which were in accordance with the knockdown of FSTL1. On the contrary, treatment with miR-125a-3p inhibitors attenuated adipogenesis but induced the expression of inflammatory genes. In summary, this study suggests a positive function of FSTL1 in adipocyte-induced inflammation and negatively regulates preadipocyte differentiation. Further studies demonstrated that miR-125a-3p could reverse the effect by targeting FSTL1, which might provide a better understanding of treating obesity-related inflammatory diseases.

Differential effect of ticagrelor versus clopidogrel by homocysteine levels on risk of recurrent stroke: a post hoc analysis of the CHANCE-2 trial.

BACKGROUND: Elevated homocysteine levels are associated with increased blood coagulation and platelet activity and may modulate the response to antiplatelet therapies. We aimed to investigate the effects of homocysteine levels on the efficacy and safety of ticagrelor-acetylsalicylic acid (ASA) versus clopidogrel-ASA among patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. METHODS: We conducted a post hoc analysis of the CHANCE-2 (The Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial. Participants were randomly assigned to treatment with ticagrelor-ASA or clopidogrel-ASA. We categorized participants into groups with elevated and non-elevated homocysteine levels, based on the median level. The primary efficacy outcome was recurrent stroke within 90-day follow-up. The primary safety outcome was severe or moderate bleeding within 90 days. RESULTS: A total of 2740 participants were randomly assigned to receive ticagrelor-ASA and 2700 to receive clopidogrel-ASA. Use of ticagrelor-ASA was associated with a reduced risk of recurrent stroke among participants with elevated homocysteine levels (74 [5.3%] v. 119 [8.5%]; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.45-0.81), but not among those with non-elevated levels (86 [6.4%] v. 87 [6.7%]; HR 0.97, 95% CI 0.71-1.32; p = 0.04 for interaction). When analyzed as a continuous variable, the benefits of ticagrelor-ASA with regard to recurrent stroke increased as homocysteine levels increased (p = 0.04 for interaction). No significant interaction between homocysteine levels and treatment with regard to severe or moderate bleeding was observed (p = 0.7 for interaction). We found a significant interaction between homocysteine levels and therapy with regard to recurrent stroke in females (p = 0.04 for interaction) but not males. INTERPRETATION: In comparison with clopidogrel-ASA, ticagrelor-ASA conferred more benefit to patients with elevated homocysteine levels, particularly to female patients, in this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04078737.

Prevalence and associated factors of obesity in patients with major depressive disorder at different ages of onset.

Major depressive disorder (MDD) and obesity are two serious public health problems. Although there have been some research on both, there have few studies on differences in obesity among MDD patients at different ages of onset. The study aims to evaluate the prevalence and factors associated with obesity in MDD patients at different ages of onset. This study totally recruited 1718 first-episode drug-naive MDD patients aged from 18 to 60 years. All subjects were divided into two subgroups: early adulthood onset (EAO, 18-45 years) and mid-adulthood onset (MAO, 45-60 years). Clinical symptoms of patients were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale. Baseline parameters including body mass index (BMI), blood pressure, and hematological biochemical parameters were assessed to investigate the association between these parameters and weight gain risk. The percentages of overweight and obesity patients with MDD in EAO group were 54.4% and 4.1%, respectively, and the percentages of overweight and obesity patients with MDD in MAO group were 60.4% and 2.8%, respectively. MDD patients in the MAO group had a longer duration of illness and higher scores in HAMD, HAMA, and PANSS positive subscale. They also had higher levels of thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), fasting blood glucose (FBG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic and diastolic blood pressures (SBP and DBP) levels. BMI did not differ significantly between the two groups. In the EAO group, statistically significant differences were found among normal weight, overweight and obese group in duration of illness, age of onset, TSH, TgAb, thyroid peroxidase antibody (TPOAb), free thyroxine (FT4), TC, triglycerides (TG), SBP and DBP. The TSH, TgTb and SBP were identified as risk factors for weight gain. In the MAO group, statistically significant differences were found among normal weight, overweight and obese group in TSH and FBG. The two indicators were identified as risk factors for weight gain. There were no significant differences in the weight of MDD patients at different ages of onset, while the factors that could potentially lead to obesity did show some differences.

Characterization of insulin-like growth factor 3 and its potential role in the spotted steed Hemibarbus maculatus ovary development.

As a new member of the insulin-like growth factors (Igfs), Igf3 was reported to play a vital role in fish reproduction. However, in spotted steed, the function of Igf3 remains largely unknown. In the present study, we identified and characterized Igf3 gene in spotted steed. Structural analysis showed that Igf3 contained five domains (B, C, A, D, E) and six conserved cysteine residues. The expression of Igf3 mRNA and protein were increased during ovary development and peaked in the maturation stage. The subcellular localization of IGF3 was highly expressed in granulosa cells and theca cells. Furthermore, recombinant IGF3 protein was produced and in vitro treatment with ovarian follicles significantly promoted the germinal vesicle breakdown (GVBD) rates of spotted steed follicles. The mRNA expression of cdc2 and cyclinB genes were significantly increased after IGF3 treatment, which were main components of maturation promoting factor (MPF). In addition, transcription levels of 3ß-hsd, 20ß-hsd, Cyp17a and Cyp19a1a were also changed. Taken together, these findings suggest that Igf3 is essential for ovary steroidogenesis and maturation in spotted steed.

Image fusion-based low-dose CBCT enhancement method for visualizing miniscrew insertion in the infrazygomatic crest.

Digital dental technology covers oral cone-beam computed tomography (CBCT) image processing and low-dose CBCT dental applications. A low-dose CBCT image enhancement method based on image fusion is proposed to address the need for subzygomatic small screw insertion. Specifically, firstly, a sharpening correction module is proposed, where the CBCT image is sharpened to compensate for the loss of details in the underexposed/over-exposed region. Secondly, a visibility restoration module based on type II fuzzy sets is designed, and a contrast enhancement module using curve transformation is designed. In addition to this, we propose a perceptual fusion module that fuses visibility and contrast of oral CBCT images. As a result, the problems of overexposure/underexposure, low visibility, and low contrast that occur in oral CBCT images can be effectively addressed with consistent interpretability. The proposed algorithm was analyzed in comparison experiments with a variety of algorithms, as well as ablation experiments. After analysis, compared with advanced enhancement algorithms, this algorithm achieved excellent results in low-dose CBCT enhancement and effective observation of subzygomatic small screw implantation. Compared with the best performing method, the evaluation metric is 0.07-2 higher on both datasets. The project can be found at: https://github.com/sunpeipei2024/low-dose-CBCT .

Systemic Immune-Inflammation Response is Associated with Futile Recanalization After Endovascular Treatment.

BACKGROUND: Frequent incidence of futile recanalization decreases the benefit of endovascular treatment (EVT) in acute ischemic stroke. We hypothesized that the inflammation and immune response after ischemic are associated with futile recanalization. We aimed to investigate the correlation of admission systemic immune-inflammation index (SII) with futile recanalization post EVT. METHODS: Patients with successful recanalization (modified Thrombolysis in Cerebral Ischemia angiographic score 2b-3) and maintained artery recanalized after 24 h of EVT were chosen from a prospective nationwide registry study. Futile recanalization was defined as a poor functional outcome (modified Rankin Scale score 3-6) at 90 days, irrespective of a successful recanalization. At admission, SII was calculated as (platelet count × neutrophil count)/lymphocyte count/100. Logistic regression analysis helped to test the relationship of SII with futile recanalization. RESULTS: Among the 1,002 patients included, futile recanalization occurred in 508 (50.70%). No matter whether tested as quartiles or continuous variables, SII was significantly associated with futile recanalization (P < 0.05), and for every one standard deviation increase of SII, the risk of futile recanalization elevated by 22.3% (odds ratio 1.223, 95% confidence interval 1.053-1.444, P = 0.0093). Moreover, no significant interactions could be observed between SII or SII quartiles and age, baseline National Institutes of Health Stroke Scale scores, onset-to-recanalization time, and modified Thrombolysis in Cerebral Ischemia angiographic scores (all P for interaction > 0.05). CONCLUSIONS: Early SII elevation was associated with an increased risk of futile recanalization among patients with EVT. Our results indicated that therapeutic drug targeting hyperreactive immune-inflammation response might be helpful for reducing the incidence of futile recanalization.

Ozone Improves Oxygenation and Offers Organ Protection after Autologous Blood Transfusion in a Simulated Carbon Dioxide Pneumoperitoneal Environment in a Rabbit Hemorrhagic Shock Model.

Objectives: Autologous blood transfusion techniques are well applied in surgery, but the red blood cells (RBCs) collected during laparoscopic surgery may forfeit their ability to oxygenate. O3 is a potent oxidation gas. This study investigates whether O3 could improve the oxygen-carrying capacity of RBCs, reduce inflammatory reactions, and offer organ protection. Methods: We established a hemorrhagic shock model in rabbits, and simulated CO2 pneumoperitoneum and O3 were applied before autologous blood transfusion. Perioperative mean arterial pressure and arterial blood gas were recorded, blood gas and RBC morphology of collected blood were analyzed, plasma IL-6, ALT, AST, CRE, and lung histopathology POD0 and POD3 were tested, as well as postoperative survival quality. Results: Autologous blood that underwent simulated CO2 pneumoperitoneum had a lower pH and SaO2 and a higher PaCO2 than the control group. After O3 treatment, PaO2 and SaO2 increased significantly, with unchanged pH values and PaCO2. RBCs in autologous blood were drastically deformed after CO2 conditioning and then reversed to normal by O3 treatment. Rabbits that received CO2-conditioned autologous blood had a compromised survival quality after surgery, higher plasma IL-6 levels, higher lung injury scores on POD0, higher ALT and AST levels on POD3, and O3 treatment alleviated these adverse outcomes. Conclusion: O3 can restore RBC function, significantly improve blood oxygenation under simulated CO2 pneumoperitoneum, offer organ protection, and improve the postoperative survival quality in the rabbit hemorrhage shock model.

Efficient treatment of colon cancer with codelivery of TRAIL and imatinib by liposomes.

To solve the problem of resistance of tumor cells to TRAIL and the inevitable side effects of imatinib during treatment, we successfully prepared a kind of multifunctional liposome that encapsulated imatinib in its internal water phase and inserted TRAIL on its membrane in this study, which named ITLPs. The liposomes appeared uniform spherical and the particle size was approximately 150 nm. ITLPs showed high accumulation in TRAIL-resistance cells and HT-29 tumor-bearing mice model. In vitro cytotoxicity assay results showed that the killing activity of HT-29 cells treated with ITLPs increased by 50% and confirmed that this killing activity was mediated by the apoptosis pathway. Through mechanism studies, it was found that ITLPs arrested up to 32.3% of cells in phase M to exert anti-tumor effects. In vivo anti-tumor study showed that ITLPs achieved 61.8% tumor suppression and little toxicity in the HT-29 tumor-bearing mice model. Overall results demonstrated that codelivery of imatinib and TRAIL via liposomes may be a prospective method in the treatment of the TRAIL-resistance tumor.

[Association between exposure to PM_(2.5) and chronic kidney disease in a population with metabolic syndrome].

OBJECTIVE: To investigate the association between long-term fine particulate matter(PM_(2.5)) exposure and the risk of chronic kidney disease(CKD) in people with abnormal metabolism syndrome(MS) components. METHODS: Based on health checkup data from a hospital in Beijing, a retrospective cohort study was used to collect annual checkup data from 2013-2019. A questionnaire was used to obtain information on demographic characteristics and lifestyle habits. We measured blood pressure, height, weight, waist circumference, concentrations of triglycerides(TG), fasting glucose, and high-density lipoprotein cholesterol(HDL-C). Longitude and latitude were also extracted from the addresses of the study subjects for pollutant exposure data estimation. Logistic regression models were used to explore the estimated effect of long-term PM_(2.5) exposure on the risk of CKD prevalence in people with abnormal MS components. Two-pollutant and multi-pollutant models were developed to test the stability of these result. Subgroup analysis was conducted based on age, the presence of MS, individual MS component abnormalities, and dual-component MS abnormalities. RESULTS: The study included 1540 study subjects with abnormal MS components at baseline, 206 with CKD during the study period. The association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions was statistically significant, with a 2.26-fold increase in risk of CKD for every 10 µg/m~3 increase in PM_(2.5) exposure(OR=3.26, 95% CI 2.72-3.90). The result in the dual-pollutant models and multi-pollutant models suggested that the association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions remained stable after controlling for contemporaneous confounding by other air pollutants. The result of subgroup analysis revealed that individuals aged 45 or older, without MS, with TG<1.7 mmol/L, HDL-C≥1.04 mmol/L, without hypertension, and with central obesity and high blood sugar had a stronger association between PM_(2.5) exposure and CKD-related health effects. CONCLUSION: Long-term exposure to PM_(2.5) may increase the risk of CKD in people with abnormal MS components. More attention should be paid to middle-aged and elderly people aged ≥45 years, people with central obesity and hyperglycemia.