Twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke.

OBJECTIVE: The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes. METHODS: A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190-170 mm Hg), trajectory category 4 (180-140 mm Hg), trajectory category 3 (170-160 mm Hg), trajectory category 2 (155-145 mm Hg) and trajectory category 1 (150-130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke. RESULTS: Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events. CONCLUSION: Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.

Performance characterization and biocompatibility assessment of silicone polyurethanes for polymer heart valve applications.

Silicone polyurethanes have gained widespread application in the biomedical field due to their excellent biocompatibility. This study comprehensively investigates four silicone polyurethane materials suitable for polymer heart valves, each exhibiting distinct chemical compositions and structural characteristics, leading to significant differences, particularly in mechanical performance and biocompatibility. Surface analysis reveals an elevated surface silicon element content in all materials compared to the bulk, indicating a migration of silicon elements towards the surface, providing a structural basis for enhancing biological stability and biocompatibility. However, higher silicon content leads to a decrease in mechanical performance, potentially resulting in mechanical failure and rupture in artificial heart valves. Concerning biocompatibility, an increase in silicone content diminishes the material's adsorption capability for cells and proteins, consequently improving its biocompatibility and biological stability. In summary, while high silicone content leads to a reduction in mechanical performance, the formation of a "silicon protective layer" on the material surface mitigates cell and protein adsorption, thereby enhancing biocompatibility and biological stability. Through comprehensive testing of the four silicone polyurethane materials, this study aims to provide insightful perspectives and methods for selecting materials suitable for polymer heart valves. Additionally, the thorough performance exploration of these materials serves as a crucial reference for the performance assessment and biocompatibility research of polymeric artificial heart valve materials.

Molybdenum Concentration and the Risk of Spontaneous Preterm Birth: A Nested Case-Control Study - Beijing Municipality, China, 2018-2020.

What is already known about this topic?: The level of molybdenum (Mo) in a mother's urine has been linked to the growth rate of the fetus and the blood pressure levels in children. What is added by this report?: We evaluated the variations in maternal plasma Mo concentrations throughout pregnancy and their potential association with the risk of spontaneous preterm birth (SPB). What are the implications for public health practice?: Future research must determine the Mo levels in pregnant women across various regions in China. Moreover, particular attention needs to be given to the potential increase in Mo concentration throughout pregnancy and its possible adverse impacts on the health of both the mother and the fetus.

The association between atherogenic index of plasma and metabolic dysfunction-associated fatty liver disease as detected by FibroScan / Asociación entre el índice aterogénico del plasma y la enfermedad hepática grasa asociadaa disfunción metabólica detectada por FibroScan

Objectives: this study aimed to explore the potential of the atherogenic index of plasma (AIP) as a predictor of metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: a cross-sectional study, including data from 4473 participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2018, was performed. A control attenuation parameter (CAP) ≥ 285 dB/m was used to confirm hepatic steatosis. Degrees of liver stiffness were confirmed according to liver stiffness measurement (LSM). Weighted multivariate logistic regression models were used to assess the association between AIP and the risk for MAFLD and liver fibrosis. Finally, receiver operating characteristic (ROC) curve analysis was used to test the accuracy of AIP in predicting MAFLD. Results: the association between AIP and the prevalence of MAFLD was positive in all three multivariate logistic regression models (model 1, odds ratio (OR), 18.2 (95 % confidence interval (CI), 14.4-23.1); model 2, OR, 17.0 (95 % CI, 13.3-21.8); model 3, OR, 5.2 (95 % CI, 3.9-7.0)). Moreover, this positive relationship was found to be significant in patients of different sexes and whether they had diabetes. However, no significant differences were observed between AIP and significant fibrosis or cirrhosis as assessed by different liver fibrosis indices. Finally, ROC curve analysis demonstrated that the AIP index also demonstrated positive diagnostic utility (area under the ROC curve, 0.733 (95 % CI, 0.718-0.747); p < 0.001). Conclusion: This study revealed a positive association between AIP and MAFLD among American adults. Furthermore, this association persisted in different sexes and whether they had diabetes.(AU)

Objetivos: este estudio tuvo como objetivo explorar el potencial del índice aterogénico del plasma (AIP) como predictor de enfermedad hepática grasa asociada a disfunción metabólica (MAFLD). Métodos: se realizó un estudio transversal que incluyó datos de 4473 participantes de la encuesta nacional de exémenes de salud y nutrición (NHANES) 2017-2018. Se utilizó un parámetro de atenuación de control (CAP) ≥ 285 dB/m para confirmar la esteatosis hepática. Los grados de rigidez hepática se confirmaron de acuerdo con la medición de rigidez hepática (LSM). Se utilizaron modelos de regresión logística multiva-riponderponderados para evaluar la asociación entre AIP y el riesgo de MAFLD y fibrosis hepática. Por último, se utilizó el análisis de la curva ROC para probar la precisión de la AIP en la predicción de la MAFLD.Resultados: la asociación entre AIP y prevalencia de MAFLD fue positiva en los tres modelos de regresión logística multivariable (modelo 1, odds ratio (OR): 18,2 (intervalo de confianza (IC) del 95 %: 14,4-23,1); Modelo 2, OR: 17,0 (IC del 95 %: 13,3-21,8); Modelo 3, OR: 5,2 (IC del 95 %: 3,9-7,0)). Además, esta relación positiva se encontró significativa en pacientes de diferentes sexos ya tuvieran o no diabetes. Sin embargo, no se observaron diferencias significativas entre la AIP y la fibrosis o cirrosis significativa evaluada por diferentes índices de fibrosis hepática. Finalmente, el análisis de la curva ROC demostró que el índice AIP también demostró utilidad diagnóstica positiva (área bajo la curva ROC = 0,733 (IC del 95 %: 0,718-0,747); p < 0,001). Conclusión: este estudio reveló una asociación positiva entre AIP y MAFLD en los adultos estadounidenses. Además, esta asociación persistióen los diferentes sexos ya tuvieran o no diabetes.(AU)

A Vascular Feature Detection and Matching Method Based on Dual-Branch Fusion and Structure Enhancement.

How to obtain internal cavity features and perform image matching is a great challenge for laparoscopic 3D reconstruction. This paper proposes a method for detecting and associating vascular features based on dual-branch weighted fusion vascular structure enhancement. Our proposed method is divided into three stages, including analyzing various types of minimally invasive surgery (MIS) images and designing a universal preprocessing framework to make our method generalized. We propose a Gaussian weighted fusion vascular structure enhancement algorithm using the dual-branch Frangi measure and MFAT (multiscale fractional anisotropic tensor) to address the structural measurement differences and uneven responses between venous vessels and microvessels, providing effective structural information for vascular feature extraction. We extract vascular features through dual-circle detection based on branch point characteristics, and introduce NMS (non-maximum suppression) to reduce feature point redundancy. We also calculate the ZSSD (zero sum of squared differences) and perform feature matching on the neighboring blocks of feature points extracted from the front and back frames. The experimental results show that the proposed method has an average accuracy and repeatability score of 0.7149 and 0.5612 in the Vivo data set, respectively. By evaluating the quantity, repeatability, and accuracy of feature detection, our method has more advantages and robustness than the existing methods.

The physiological response of oriental river prawn Macrobrachium nipponense to starvation-induced stress.

Environmental stresses play critical roles in the physiology of crustaceans. Food deprivation is an important environmental factor and a regular occurrence in both natural aquatic habitats and artificial ponds. However, the underlying physiological response mechanisms to starvation-caused stress in crustaceans are yet to be established. In the present study, the hepatopancreas tissue of Macrobrachium nipponense was transcriptome analyzed and examined for starvation effects on oxidative stress, DNA damage, autophagy, and apoptosis across four fasting stages (0 (control group), 7, 14, and 21 days). These results indicated that a ROS-mediated regulatory mechanism is critical to the entire fasting process. At the initial stage of starvation (fasting 0 d ~ 7 d), ROS concentration increased gradually, activating antioxidant enzymes to protect the cellular machinery from the detrimental effects of oxidative stress triggered by starvation-induced stress. ROS content production (hydrogen peroxide and superoxide anion) then rose continuously with prolonged starvation (fasting 7 d ~ 14 d), reaching peak levels and resulting in autophagy in hepatopancreas cells. During the final stages of starvation (fasting 14 d ~ 21 d), excessive ROS induced DNA damage and cell apoptosis. Furthermore, autophagolysosomes and apoptosis body were further identified with transmission electron microscopy. These findings lay a foundation for further scrutiny of the molecular mechanisms combating starvation-generated stress in M. nipponense and provide fishermen with the theoretical guidance for adopting fasting strategies in M. nipponense aquaculture.

The association between atherogenic index of plasma and metabolic dysfunction-associated fatty liver disease as detected by FibroScan.

Introduction: Objectives: this study aimed to explore the potential of the atherogenic index of plasma (AIP) as a predictor of metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: a cross-sectional study, including data from 4473 participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2018, was performed. A control attenuation parameter (CAP) ≥ 285 dB/m was used to confirm hepatic steatosis. Degrees of liver stiffness were confirmed according to liver stiffness measurement (LSM). Weighted multivariate logistic regression models were used to assess the association between AIP and the risk for MAFLD and liver fibrosis. Finally, receiver operating characteristic (ROC) curve analysis was used to test the accuracy of AIP in predicting MAFLD. Results: the association between AIP and the prevalence of MAFLD was positive in all three multivariate logistic regression models (model 1, odds ratio (OR), 18.2 (95 % confidence interval (CI), 14.4-23.1); model 2, OR, 17.0 (95 % CI, 13.3-21.8); model 3, OR, 5.2 (95 % CI, 3.9-7.0)). Moreover, this positive relationship was found to be significant in patients of different sexes and whether they had diabetes. However, no significant differences were observed between AIP and significant fibrosis or cirrhosis as assessed by different liver fibrosis indices. Finally, ROC curve analysis demonstrated that the AIP index also demonstrated positive diagnostic utility (area under the ROC curve, 0.733 (95 % CI, 0.718-0.747); p < 0.001). Conclusion: This study revealed a positive association between AIP and MAFLD among American adults. Furthermore, this association persisted in different sexes and whether they had diabetes.

Introducción: Objetivos: este estudio tuvo como objetivo explorar el potencial del índice aterogénico del plasma (AIP) como predictor de enfermedad hepática grasa asociada a disfunción metabólica (MAFLD). Métodos: se realizó un estudio transversal que incluyó datos de 4473 participantes de la encuesta nacional de exémenes de salud y nutrición (NHANES) 2017-2018. Se utilizó un parámetro de atenuación de control (CAP) ≥ 285 dB/m para confirmar la esteatosis hepática. Los grados de rigidez hepática se confirmaron de acuerdo con la medición de rigidez hepática (LSM). Se utilizaron modelos de regresión logística multivariponderponderados para evaluar la asociación entre AIP y el riesgo de MAFLD y fibrosis hepática. Por último, se utilizó el análisis de la curva ROC para probar la precisión de la AIP en la predicción de la MAFLD. Resultados: la asociación entre AIP y prevalencia de MAFLD fue positiva en los tres modelos de regresión logística multivariable (modelo 1, odds ratio (OR): 18,2 (intervalo de confianza (IC) del 95 %: 14,4-23,1); Modelo 2, OR: 17,0 (IC del 95 %: 13,3-21,8); Modelo 3, OR: 5,2 (IC del 95 %: 3,9-7,0)). Además, esta relación positiva se encontró significativa en pacientes de diferentes sexos ya tuvieran o no diabetes. Sin embargo, no se observaron diferencias significativas entre la AIP y la fibrosis o cirrosis significativa evaluada por diferentes índices de fibrosis hepática. Finalmente, el análisis de la curva ROC demostró que el índice AIP también demostró utilidad diagnóstica positiva (área bajo la curva ROC = 0,733 (IC del 95 %: 0,718-0,747); p < 0,001). Conclusión: este estudio reveló una asociación positiva entre AIP y MAFLD en los adultos estadounidenses. Además, esta asociación persistió en los diferentes sexos ya tuvieran o no diabetes.

Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke.

BACKGROUND: Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance. METHODS AND RESULTS: This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores. CONCLUSIONS: An increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Efficient and Selective Extraction of Rhamnogalacturonan-I-Enriched Pectic Polysaccharides from Tartary Buckwheat Leaves Using Deep-Eutectic-Solvent-Based Techniques.

Tartary buckwheat green leaves are considered to be among the most important by-products in the buckwheat industry. Although Tartary buckwheat green leaves are abundant in pectic polysaccharides, their potential applications in the food industry are quite scarce. Therefore, to promote their potential applications as functional or fortified food ingredients, both deep-eutectic-solvent-assisted extraction (DESE) and high-pressure-assisted deep eutectic solvent extraction (HPDEE) were used to efficiently and selectively extract pectic polysaccharides from Tartary buckwheat green leaves (TBP). The results revealed that both the DESE and HPDEE techniques not only improved the extraction efficiency of TBP but also regulated its structural properties and beneficial effects. The primary chemical structures of TBP extracted using different methods were stable overall, mainly consisting of homogalacturonan and rhamnogalacturonan-I (RG-I) pectic regions. However, both the DESE and HPDEE methods could selectively extract RG-I-enriched TBP, and the proportion of the RG-I pectic region in TBP obviously improved. Additionally, both the DESE and HPDEE methods could improve the antioxidant and anti-glycosylation effects of TBP by increasing its proportion of free uronic acids and content of bound polyphenolics and reducing its molecular weight. Moreover, both the DESE and HPDEE methods could partially intensify the immunostimulatory effect of TBP by increasing its proportion of the RG-I pectic region. These findings suggest that DES-based extraction techniques, especially the HPDEE method, can be promising techniques for the efficient and selective extraction of RG-I-enriched TBP.

Maternal cobalt concentration and risk of spontaneous preterm birth: the role of fasting blood glucose and lipid profiles.

Introduction: Spontaneous preterm birth (SPB) is a significant cause of neonatal mortality, yet its etiology remains unclear. Cobalt, an essential trace element, might be a risk factor for SPB. This study aims to investigate the relationship between maternal serum cobalt concentration and SPB, and to clarify the role of blood lipids and fasting blood glucose (FBG) in this relationship. Methods: We conducted a nested case-control study within the Beijing Birth Cohort Study. Serum samples were obtained from 222 pregnant women with SPB and 224 controls during the first (7-13 weeks of pregnancy) and third trimesters (32-42 weeks of pregnancy). Serum cobalt concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Fasting blood glucose and lipids levels were detected using a fully automated biochemical immunoassay instrument. Logistic regression models and linear regression models were established to explore the association between serum cobalt concentration and the risk of SPB in pregnant women, and to test the mediating effect of fasting blood glucose (FBG) and lipids. Results: We found that the serum cobalt concentration in mothers with SPB and controls was similar in the first trimester, with values of 0.79 (0.58-1.10) ng/mL and 0.75 (0.51-1.07) ng/mL, respectively. However, in the third trimester, the cobalt concentration increased to 0.88 (0.59-1.14) ng/mL and 0.84 (0.52-1.19) ng/mL, respectively. In the logistic regression model, when considering the third trimester of pregnancy, after adjusting for ethnicity, pre-pregnancy body mass index (BMI), maternal age, education, income, and parity, it was observed that the medium level of cobalt concentration (0.63-1.07 ng/ml) had a negative correlation with the risk of SPB. The odds ratio (OR) was 0.56, with a 95% confidence interval of 0.34-0.90 ng/mL and a p-value of 0.02. This suggests that cobalt in this concentration range played a protective role against SPB. Additionally, it was found that FBG in the third trimester of pregnancy had a partial intermediary role, accounting for 9.12% of the association. However, no relationship between cobalt and SPB risk was found in the first trimester. Conclusion: During the third trimester, intermediate levels of maternal cobalt appear to offer protection against SPB, with FBG playing a partial mediating role. To further clarify the optimal cobalt concentrations during pregnancy for different populations, a multi-center study with a larger sample size is necessary. Additionally, exploring the specific mechanism of FBG's mediating role could provide valuable insights for improving the prevention of SPB.

Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore.

Pathological opening of the mitochondrial permeability transition pore (mPTP) is implicated in the pathogenesis of many disease processes such as myocardial ischemia, traumatic brain injury, Alzheimer's disease, and diabetes. While we have gained insight into mPTP biology over the last several decades, the lack of translation of this knowledge into successful clinical therapies underscores the need for continued investigation and use of different approaches to identify novel regulators of the mPTP with the hope of elucidating new therapeutic targets. Although the mPTP is known to be a voltage-gated channel, the identity of its voltage sensor remains unknown. Here we found decreased gating potential of the mPTP and increased expression and activity of sulfide quinone oxidoreductase (SQOR) in newborn Fragile X syndrome (FXS) mouse heart mitochondria, a model system of coenzyme Q excess and relatively decreased mPTP open probability. We further found that pharmacological inhibition and genetic silencing of SQOR increased mPTP open probability in vitro in adult murine cardiac mitochondria and in the isolated-perfused heart, likely by interfering with voltage sensing. Thus, SQOR is proposed to contribute to voltage sensing by the mPTP and may be a component of the voltage sensing apparatus that modulates the gating potential of the mPTP.

Blocking the E2F transcription factor 1/high-mobility group box 2 pathway enhances the intervention effects of α-santalol on the malignant behaviors of liver cancer cells.

In view of the tumor-inhibiting effect of α-santalol in various cancers and the role of E2F transcription factor 1 (E2F1) as an important target for anticancer research, this study investigates the relation between α-santalol and E2F1, as well as the effect of α-santalol on liver cancer progression and the corresponding mechanism. Concretely, liver cancer cells were treated with different concentrations of α-santalol. The IC50 value of α-santalol was determined using Probit regression analysis. Then, transcription factors that are targeted by α-santalol and differentially expressed in liver cancer were screened out. The clinicopathological impact of E2F1 and its targets were evaluated and predicted. The expressions of E2F1 and high-mobility group box 2 (HMGB2) and their correlation in the liver cancer tissues were analyzed by bioinformatics. The effects of E2F1 and HMGB2 on the biological characteristics of liver cancer cells were examined through loss/gain-of-function and molecular assays. With the extension of treatment time, the inhibitory effects of 10 µmol/L and 20 µmol/L α-santalol on cancer cell survival rate were enhanced (P < 0.001). E2F1 and HMGB2 were highly expressed and positively correlated in liver cancer tissues (P < 0.05). High E2F1 expression was correlated with large tumors and high TNM stages (P < 0.05). E2F1 knockdown promoted the effects of α-santalol on dose-dependently inhibiting viability, colony formation, invasion and migration (P < 0.05). Moreover, E2F1 knockdown reduced the IC50 value and HMGB2 level, while HMGB2 overexpression produced opposite effects. HMGB2 overexpression and E2F1 knockdown mutually counteracted their effects on the IC50 value and on the viability and apoptosis of α-santalol-treated liver cancer cells (P < 0.01). Collectively, blocking the E2F1/HMGB2 pathway enhances the intervention effects of α-santalol on the proliferation, migration and invasion of liver cancer cells.

Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer.

Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the GSE164191 and the Cancer Genome Atlas-colorectal adenocarcinoma (TCGA-COAD) datasets, we identified LTB4R as a hub gene influencing CRC prognosis. Subsequently, we examined the relationship between LTB4R expression, apoptosis, and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway through cellular and mice experiments. Our findings revealed that LTB4R is highly expressed in CRC samples and is pivotal for determining prognosis. In vitro experiments demonstrated that silencing LTB4R significantly impeded CRC cell viability, migration, invasion, and colony formation. Correspondingly, in vivo tests indicated that LTB4R knockdown led to markedly slower tumor growth in mice models. Further in-depth investigation revealed that LTB4R knockdown significantly amplified the apoptosis in CRC cells and upregulated the expression of apoptosis-related proteins, such as caspase-3 and caspase-9, while diminishing p53 expression. Interestingly, silencing LTB4R also resulted in a significant downregulation of the PI3K/AKT/mTOR signaling pathway. Moreover, pretreatment with the PI3K activator 740Y-P only partially attenuated the effects of LTB4R knockdown on CRC cell behavior, emphasizing LTB4R's dominant influence in CRC cell dynamics and signaling pathways. LTB4R stands out as a critical factor in CRC progression, profoundly affecting cellular behavior, apoptotic responses, and the PI3K/AKT/mTOR signaling pathway. These findings not only shed light on LTB4R's role in CRC but also establish it as a potential diagnostic biomarker and a promising target for therapeutic intervention.

Transferrin Is Up-Regulated by Microbes and Acts as a Negative Regulator of Immunity to Induce Intestinal Immunotolerance.

Cross-talks (e.g., host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes) regulate immunotolerance and intestinal homeostasis. However, underlying mechanisms that regulate the cross-talks remain poorly understood. Here, we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14 (CD14) to inhibit pattern recognition receptor (PRR) signaling and induce host immunotolerance. Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis, which are characterized by impaired intestinal immunotolerance. Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism, suggesting an association between microbial commensalism, transferrin, and host immunotolerance. Mouse colitis models show that transferrin shortage impairs host's tolerogenic responses, while its supplementation promotes immunotolerance. Designed peptide blocking transferrin-CD14 interaction inhibits immunosuppressive effects of transferrin. In monkeys with idiopathic chronic diarrhea, transferrin shows comparable or even better therapeutic effects than hydrocortisone. Our findings reveal that by up-regulating host transferrin to silence PRR signaling, commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.

High-Serum Brain-Derived Neurotrophic Factor Levels Are Associated With Decreased Risk of Poststroke Cognitive Impairment.

BACKGROUND: BDNF (brain-derived neurotrophic factor) is widely implicated in the pathophysiological process of stroke, but the effect of BDNF on poststroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between baseline serum BDNF and the risk of PSCI at 3 months in a multicenter study based on a preplanned ancillary study of the CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke). METHODS: We examined serum BDNF levels at baseline and used the Mini-Mental State Examination and Montreal Cognitive Assessment to evaluate cognitive function at 3-month follow-up after ischemic stroke. PSCI was defined as Mini-Mental State Examination score <27 or Montreal Cognitive Assessment score <25. Logistic regression analyses were performed to evaluate the association between serum BDNF and the risk of 3-month PSCI. RESULTS: In this ancillary study, a total of 660 patients with ischemic stroke with hypertension were included, and 593 patients (mean age, 59.90±10.44 years; 410 males and 183 females) were finally included in this analysis. According to mini-mental state examination score, after adjustment for age, sex, education, baseline National Institutes of Health Stroke Scale score, APOE ɛ4 carriers, and other potential confounders, the odds ratio of PSCI for the highest tertile of BDNF was 0.60 ([95% CI, 0.39-0.94]; P=0.024) compared with the lowest tertile. Multiple-adjusted spline regression model showed a linear association of serum BDNF levels with PSCI at 3 months (P value for linearity=0.010). Adding serum BDNF to conventional prognostic factors slightly improved the risk reclassification of PSCI (net reclassification improvement: 27.46%, P=0.001; integrated discrimination index: 1.02%, P=0.015). Similar significant findings were observed when PSCI was defined by the Montreal Cognitive Assessment score. CONCLUSIONS: Elevated serum BDNF levels were associated with a decreased risk of PSCI at 3 months, suggesting that serum BDNF might be a potential predictive biomarker for PSCI among patients with ischemic stroke with hypertension.

Association of Pulse Pressure Fluctuation During Hospitalization With Adverse Outcomes Within 3 Months After Ischemic Stroke.

BACKGROUND: Pulse pressure (PP) depends on heart function and arterial wall elasticity, which is closely related to the incidence of ischemic stroke. However, the association of PP fluctuation during hospitalization with adverse outcomes after ischemic stroke remains unclear. METHODS: The present study included 3,971 patients with ischemic stroke. The primary outcome was the composite outcome of death or vascular events within 3 months after ischemic stroke. PP fluctuation was reflected by successive variation of PP (PP-SV). RESULTS: The cumulative incidence rates of the primary outcome were the highest in the patients in the highest quartiles of PP-SV (P < 0.05). The multivariable-adjusted hazard ratios (95% confidence intervals) of the primary outcome in the highest quartiles were 1.86 (1.03-3.38) for death or vascular events, and 2.15 (1.06-4.37) for vascular events (all Ptrend < 0.05). Multivariable-adjusted restricted cubic spline analyses showed linear associations of PP-SV during hospitalization with the primary outcome (P for linearity <0.05). CONCLUSIONS: Large PP fluctuation during hospitalization was associated with increased risks of adverse outcomes within 3 months after ischemic stroke, which provided valuable new insight for blood pressure management in the acute phase of ischemic stroke. Controlling PP fluctuation may be contributing to improving prognosis after ischemic stroke.

The Synergistic Effect of Phosphonic and Carboxyl Acid Groups for Efficient and Stable Perovskite Solar Cells.

Reducing the interfacial defects between the perovskite/electron transport layer (ETL) is the key point to improving the efficient and stable performance of perovskite solar cells (PSCs). In this study, two self-assembled molecules ((aminomethyl)phosphonic acid and glycine) with different functional groups (phosphonic acid (-H2PO3) and carboxylic acid (-COOH)) were mixed to form the buried bottom interface of PSCs. The synergistic effect of -H2PO3 with its higher anchoring ability and -COOH with its fast carrier transport improved the performance of PSCs. Additionally, the SnO2 modified by mixed self-assembly molecules (M-SAM) showed a more appropriate energy level alignment, favoring charge transport and minimizing energy loss. In addition, the amine group (-NH2) on the two small molecules effectively interacted with uncoordinated Pb2+ in perovskite and improved the quality of the perovskite films. Consequently, the (FAPbI3)0.992(MAPbBr3)0.008 PSCs with M-SAM reached a PCE of 24.69% (0.08 cm2) and the perovskite modules achieved a champion efficiency of 18.57% (12.25 cm2 aperture area). Meanwhile, it still maintained more than 91% of its initial PCE after being placed in nitrogen atmosphere at 25 °C for 1500 h, which is better than that of the single-SAM and control devices. Further reference is provided for the future commercialization of perovskite with efficient and stable characteristics.

Optimal treatment of tannic acid for the anti-calcification of bovine jugular veins and the underlying mechanism.

OBJECTIVES: To evaluate the effects of combined treatment with tannic acid and ferric ions on the biomechanical and anti-calcification properties of glutaraldehyde-fixed bovine jugular veins after xenografting. METHODS: Two-point bending test and uniaxial tensile test were used to evaluate the flexural and biomechanical properties; Subcutaneous implantation in rat and right ventricular outflow tract reconstruction of sheep were used to evaluate the anti-calcification effects; The performance of the graft in sheep models was evaluated every month after the surgery with echocardiography examination. Markers of macrophages, T lymphocytes, smooth muscle cell osteogenic differentiation and matrix metalloproteinases in sheep explants were detected by immunohistochemistry. RESULTS: The flexibility of the bovine jugular veins cotreated with ferric ions-tannic acid was improved while maintaining biomechanical properties and excellent anti-calcification effects. Echocardiography results showed that the grafts functioned well in the animals without stenosis or reflux of the valve. Immunohistochemical studies showed that the osteogenic differentiation marker (Runx2) was detected in calcified regions and colocalised with the SMC marker (α-SMA). Compared to the glutaraldehyde-treated samples, T-cell marker (CD3), matrix metalloproteinase-2 and 9 expressions were reduced in the ferric ions-tannic acid treated group. CONCLUSION: Ferric ions-tannic acid treatment can give the conduits better flexibility with excellent biomechanical properties and anti-calcification effects, making it a promising bovine jugular veins processing method.

Functional Analyses of Three Targeted DNA Antimicrobial Peptides Derived from Goats.

With the increase in drug-resistant bacteria, new antibacterial drugs have emerged as a prominent area of research and development. Antimicrobial peptides (AMPs), as innate immune agents, have garnered significant attention due to their potent, rapid, and broad-spectrum antibacterial activity. This study focused on investigating the functionality of three AMPs (CATH 1, CATH 2, and MAP34-B) derived from goat submandibular glands. Among these AMPs, CATH 2 and MAP34-B exhibited direct antibacterial activity against both Gram-negative and Gram-positive bacteria, primarily targeting the bacterial membrane. Additionally, these two AMPs were found to have the potential to induce reactive oxygen species (ROS) production in bacterial cells and interact with bacterial genome DNA, which may play a crucial role in their mechanisms of action. Furthermore, both CATH 1 and CATH 2 demonstrated significant antioxidant activity, and all three AMPs exhibited potential anti-inflammatory activity. Importantly, the cytotoxic activity of these AMPs against mammalian cells was found to be weak, and their hemolytic activity was extremely low. Overall, the characteristics of these three AMPs found in goat submandibular glands offer new insights for the study of host protection from an immunological perspective. They hold promise as potential candidates for the development of novel antibacterial agents, particularly in the context of combating drug-resistant bacteria.

Association between light rare earth elements in maternal plasma and the risk of spontaneous preterm birth: a nested case-control study from the Beijing birth cohort study.

BACKGROUND: Parental exposure to rare earth elements (REEs) could increase the risk of premature rupture of membranes, a major cause of spontaneous preterm birth (SPB). In addition, different subtypes of SPB, such as spontaneous preterm labor (SPL) and preterm premature rupture of membranes (PPROM), may have different susceptibility to environmental exposure. Therefore, we investigated the potential associations between REE exposure in different trimesters and SPB and its subtypes. METHODS: A nested case-control study was performed. We included 244 women with SPB as cases and 244 women with full-term delivery as controls. The plasma concentrations of light REEs were measured in the first and third trimesters. Logistic regression was used to analyze the associations between single REE levels and SPB, and Bayesian kernel machine regression (BKMR) was used to analyze the mixed-exposure effect. RESULTS: Exposure to light REEs was associated with SPB and its subtypes only in the third trimester. Specifically, the intermediate- and highest-tertile concentration groups of La and the highest-tertile concentration group of Sm were associated with an increased risk of SPL, with adjusted odds ratios (AORs) of 2.00 (95% CIs: 1.07-3.75), 1.87 (95% CIs: 1.01-3.44), and 1.82 (95% CIs: 1.00-3.30), respectively. The highest-tertile concentration group of Pr was associated with an increased risk of PPROM, with an AOR of 1.69 (95% CIs: 1.00-2.85). Similar results were also found in BKMR models. CONCLUSIONS: La and Sm levels in plasma may be associated with the risk of SPL, and Pr levels in plasma may be associated with the risk of PPROM.