Biocontrol of rusted root rot in Panax ginseng by a combination of extracts from Bacillus amyloliquefaciens YY8 crude protein and Enterobacteriaceae YY115 ethyl acetate.

BACKGROUND: Rusted root rot is one of the most common root diseases in Panax ginseng, and Cylindrocarpon destructans is one of the main pathogenic fungus. The objective of this study was to screen and explore the extracts of biocontrol bacteria isolated from ginseng rhizosphere soil against Cylindrocarpon destructans. RESULTS: Bacterial strains Bacillus amyloliquefaciens YY8 and Enterobacteriacea YY115 were isolated and found to exhibit in vitro antifungal activity against C. destructans. A combination of crude protein extract from B. amyloliquefaciens YY8 and ethyl acetate extract from Enterobacteriacea YY115 in a 6:4 ratio exhibited the strongest antifungal activity against C. destructans. Measurements of electrical conductivity, protein content, and nucleic acid content in suspension cultures of C. destructans treated with a mixture extracts indicated that the extracts disrupted the cell membranes of rusted root rot mycelia, resulting in the leakage of electrolytes, proteins, and nucleic acids from the cells, and ultimately inhibiting the growth of C. destructans. The combined extracts suppressed the infection of ginseng roots discs by C. destructans effectively. CONCLUSION: The extracts obtained from the two bacterial strains effectively inhibited C. destructans in P. ginseng. It can provide scientific basis for the development of new biological control pesticides, reduce the use of chemical pesticides, and promote the sustainable development of agriculture.

Regulation of macroporous cellulose microspheres via phase separation force induced by carbon nanotubes doping for enhanced protein adsorption.

The burgeoning requirement for purified biomacromolecules in biopharmaceutical industry has amplified the exigency for advanced chromatographic separation techniques. Herein, macroporous cellulose microspheres (CCMs) with micron-sized pores are produced by a facile regulation via carbon nanotubes (CNTs). In this strategy, the incorporation of CNTs breaks the homogeneous regeneration of the cellulose, thus providing anisotropic phase force to produce macropores. The CCMs have manifested a faster mass transfer rate and more available adsorption sites owing to well-defined macropores (2.69 ± 0.57 µm) and high specific surface area (147.47 m2 g-1). Further, CCMs are functionalized by quaternary ammonium salts (GTAc-CCMs) and utilized as anion adsorbents to adsorb pancreatic kininogenase (PK). The prepared GTAc-CCMs show rapid adsorption kinetics for PK at pH 6.0, reaching 90 % equilibrium within 60 min. Also, GTAc-CCMs for PK exhibit high adsorptive capacity (632.50 mg g-1), excellent recyclability (> 80 % removal amount after 10 cycles) and selectivity especially at pH 6.0. Notably, the GTAc-CCMs have been successfully applied in a fixed-bed chromatography process, indicating their potential as an effective chromatographic medium for rapid separation of biomacromolecules.

Carotid Artery Wall Echogenicity Measured by Gray Scale Median of the Intima-Media Complex From Childhood to Young Adulthood.

BACKGROUND: Echogenicity of the carotid arterial wall, measured by gray scale median of the intima-media complex (IM-GSM), is a novel subclinical atherosclerosis marker with lower values indicating greater lipid deposition. Our longitudinal study investigated IM-GSM from childhood to adulthood and its associated risk factors. METHODS AND RESULTS: A total of 240 participants from the Southern California CHS (Children's Health Study) underwent carotid artery ultrasounds in 2008 (mean age±SD): (11.2±0.6 years), and again around 2022 (24.2±1.6 years) to assess IM-GSM, carotid artery intima-media thickness, and carotid artery distensibility. Questionnaires and anthropometric and blood pressure measurements were completed by participants at both times. Mean and SD of IM-GSM were 108.2±24.6 in childhood and 75.6±15.8 in adulthood. Each 1-year increase in age was associated with -2.52 change in IM-GSM (95% CI, -2.76 to -2.27). Childhood and adulthood IM-GSMs were highly correlated (ß=0.13 [95% CI, 0.05-0.22]). In childhood, Hispanic ethnicity, lower parental education levels and prenatal father smoking were significantly associated with lower IM-GSM. In adulthood, higher systolic blood pressure, carotid artery intima-media thickness, hypertension, and lower distensibility were significantly associated with lower IM-GSM. Weight status exhibited a consistent association with both childhood and adulthood IM-GSM. During the transition from childhood to adulthood, individuals who shifted from normal weight to overweight/obese or normal blood pressure to hypertension or experienced an increase in carotid artery intima-media thickness displayed lower levels of IM-GSM in adulthood. CONCLUSIONS: IM-GSM decreases with age. Maintaining healthy weight and blood pressure levels in children could potentially aid in preventing subclinical atherosclerosis.

MTSC-Net: A Semi-Supervised Counting Network for Estimating the Number of Slash pine New Shoots.

The new shoot density of slash pine serves as a vital indicator for assessing its growth and photosynthetic capacity, while the number of new shoots offers an intuitive reflection of this density. With deep learning methods becoming increasingly popular, automated counting of new shoots has greatly improved in recent years but is still limited by tedious and expensive data collection and labeling. To resolve these issues, this paper proposes a semi-supervised counting network (MTSC-Net) for estimating the number of slash pine new shoots. First, based on the mean-teacher framework, we introduce the improved VGG19 to extract multiscale new shoot features. Second, to connect local new shoot feature information with global channel features, attention feature fusion module is introduced to achieve effective feature fusion. Finally, the new shoot density map and density probability distribution are processed in a fine-grained manner through multiscale dilated convolution of the regression head and classification head. In addition, a masked image modeling strategy is introduced to encourage the contextual understanding of global new shoot features and improve the counting performance. The experimental results show that MTSC-Net outperforms other semi-supervised counting models with labeled percentages ranging from 5% to 50%. When the labeled percentage is 5%, the mean absolute error and root mean square error are 17.71 and 25.49, respectively. These findings demonstrate that our work can be used as an efficient semi-supervised counting method to provide automated support for tree breeding and genetic utilization.

Bioproduction Platform to Generate Functionalized Disulfide-Constrained Peptide Analogues.

Disulfide-constrained peptides (DCPs) have gained increased attention as a drug modality due to their exceptional stability and combined advantages of large biologics and small molecules. Chemical synthesis, although widely used to produce DCPs, is associated with high cost, both economically and environmentally. To reduce the dependence on solid phase peptide synthesis and the negative environmental footprint associated with it, we present a highly versatile, low-cost, and environmentally friendly bioproduction platform to generate DCPs and their conjugates as well as chemically modified or isotope-labeled DCPs. Using the DCP against the E3 ubiquitin ligase Zinc and Ring Finger 3, MK1-3.6.10, as a model peptide, we have demonstrated the use of bacterial expression, combined with Ser ligation or transglutaminase-mediated XTEN ligation, to produce multivalent MK1-3.6.10 and MK1-3.6.10 with N-terminal functional groups. We have also developed a bioproduction method for the site-specific incorporation of unnatural amino acids into recombinant DCPs by the amber codon suppression system. Lastly, we produced 15N/13C-labeled MK1-3.6.10 with high yield and assessed the performance of a semiautomated resonance assignment workflow that could be used to accelerate binding studies and structural characterization of DCPs. This study provides a proof of concept to generate functionalized DCPs using bioproduction, providing a potential solution to alleviate the reliance on hazardous chemicals, reduce the cost, and expedite the timeline for DCP discovery.

Comparing qSMI and qCEUS for assessing vascularization in uterine cervical cancer: operable versus non-operable group.

Objective: The present study aimed to compare the effectiveness and reliability of quantified superb microvascular imaging (qSMI) and quantified contrast-enhanced ultrasonography (qCEUS) in assessing vascularization in both operable and non-operable uterine cervical cancer. Methods: A case-control study included 64 patients with pathology-proven and untreated cervical cancer, who underwent transvaginal ultrasonography combined with qSMI and qCEUS between January 2022 and June 2023. SMI results were quantified as the vascular index (VI), which were compared to 12 quantitative parameters of CEUS calculated with time-intensity curves (TIC). Results: According to FIGO staging and different treatment regimens, 64 patients with cervical cancer were divided into operable group (IA ~ IIA, n = 19) and non-operable group (IIB ~ IV, n = 45). In comparison to the operable group, the non-operable group showed significantly higher values in VI, peak intensity (PI), area under the curve (AUC), wash-in area (iAUC), wash-out area (oAUC), wash-in rate (WiR), mean intensity (Mean Int), and standard deviation (STD) (all P < 0.05). VI demonstrated strong correlations with CEUS parameters, notably PI (r = 0.854, P < 0.001) and AUC (r = 0.635, P < 0.001). Furthermore, VI showed a better predictive performance for treatment-group assignment than qCEUS parameters, with an 80.7% accuracy, 64.4% sensitivity and 89.5% specificity. Conclusion: Both qSMI and qCEUS exhibit significant and comparable utility in detecting microvascular hyperplasia and predicting treatment-group assignments in cervical cancer. Furthermore, qSMI may offer added convenience in implementation.

Protective effects of forsythoside A against severe acute pancreatitis- induced brain injury in mice.

OBJECTIVES: This study aimed to evaluate the therapeutic effects of forsythoside A (FA) on brain injury induced by severe acute pancreatitis (SAP) using a murine model. METHODS: Mice were induced with 3.5 % sodium taurocholate to model SAP-induced brain injury (SAP-IBI) and were randomly assigned to four distinct treatment regimens: the SAP-IBI model group (SAP-IBI), low-dose FA treatment group (FA L+SI), middle-dose FA treatment group (FA M+SI), and high-dose FA treatment group (FA H+SI). A sham-operation group (SO) served as a negative control. Serum levels of interleukin-1ß (IL-1ß) and IL-18 were quantified via ELISA, and serum amylase levels were assessed using optical turbidimetry. mRNA expression levels of AIM2, ASC, Caspase-1, and GAPDH in hippocampal brain tissue were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Protein levels of NLRP3, GSDMD, IL-1ß, and IL-18 in hippocampal brain tissue were evaluated using Western blotting. Neurological function in surviving mice was assessed through modified neurological severity scores (mNSS). Transmission electron microscopy (TEM) provided ultrastructural analysis of the hippocampus. Additionally, water content and pathological changes in hippocampal brain tissue were examined 24 hours post-operation, along with other relevant indicators. RESULTS: At 24 hours post-operation, the FA H+SI group exhibited significantly reduced levels of serum amylase, IL-1ß, and IL-18, along with decreased expression of AIM2, ASC, and Caspase-1 mRNA. Furthermore, NLRP3 protein levels, water content, pancreas and hippocampal brain pathological scores, and mNSS were significantly lower compared to the SAP-IBI group (P<0.01). CONCLUSIONS: FA demonstrates protective effects against SAP-IBI in mice, suggesting potential therapeutic benefits.

Association Between Cardiovascular Health and Subclinical Atherosclerosis Among Young Adults Using the American Heart Association's "Life's Essential 8" Metrics.

BACKGROUND: This study investigated the association of American Heart Association's cardiovascular health guidelines Life's Essential 8 (LE8) and Life's Simple 7 (LS7) with carotid artery outcomes among young adults. METHODS AND RESULTS: This cross-sectional study included 240 young adults (age 24.2±1.6 years) who underwent a carotid ultrasound between 2018 and 2022. LE8 score was calculated from 4 health factors (body mass index, non-high-density lipoprotein cholesterol, fasting glucose, and blood pressure), and 4 health behaviors (dietary intake, physical activity, tobacco use, and sleep). LS7 was calculated from 7 metrics (all LE8 metrics, except for sleep) with a simpler algorithm. Higher LE8 and LS7 scores both indicate better health and better adherence to American Heart Association guidelines. Carotid artery outcomes included carotid artery intima-media thickness, arterial stiffness (eg, distensibility), and echogenicity determined by grayscale median of the intima media complex. Results of linear regression analyses, adjusting for age, sex, ethnicity, and parents' highest degree, indicated that a 1-SD increase in LE8 score was associated with 12.14 µm lower carotid artery intima-media thickness (95% CI, -20.93 to 3.35), 1.17 (10-6×m2/N) greater distensibility (95% CI, 0.09-2.24), suggesting less arterial stiffness, and 2.66 µm greater grayscale median of the intima media complex (95% CI, 0.58-4.75), suggesting less lipid deposition. Analyses using LS7 score demonstrated comparable findings. Health factor metrics demonstrated stronger association with carotid artery outcomes, as compared with behavior metrics. CONCLUSIONS: Greater adherence to the American Heart Association's cardiovascular health guidelines is associated with lower risk for subclinical atherosclerosis in young adults. LE8 and LS7 demonstrated comparable associations with carotid artery outcomes.

High-speed train drivers' human error under fatigue and stress: the role of situation awareness and individual differences.

Fatigue and stress are critical variables that impair railway train drivers' safety performance, and individual differences may influence these effects. This study investigates how fatigue and stress affect high-speed train drivers' human error and the role of individual differences. We hypothesised that situation awareness (SA) mediates the effects of fatigue and stress on human error, and individual differences (age and work experience) moderate these effects. We surveyed 1,391 male drivers from eight Chinese railway bureaus and used PROCESS Macro for data analysis. The results revealed that fatigue and stress increased human error, directly and indirectly through SA. Age and work experience moderated the effect of fatigue and stress on SA, respectively. Older drivers had better SA under high fatigue, while more experienced drivers had better SA under high stress. These findings can inform more tailored safety management strategies to lower human error and enhance the safety of high-speed train operations.

A cross-sectional survey of 1,391 high-speed train drivers in China indicated that fatigue and stress amplify human error by impairing situation awareness (SA). Age and work experience were observed to moderate the impact of fatigue and stress on SA, respectively. These insights guide the advancement of safety management strategies.

Purchase intention for second-hand luxury goods: An empirical study of Chinese consumers.

Second-hand luxury goods feature both characteristics of luxury products like perceived value including social, emotional, and quality value, and second-hand goods like price-performance ratio. Enlarging the second-hand luxury market is of significance to protect the environment and save rare and valuable natural resources, and thus investigating the determinants of purchase intention is meaningful. From the perspective of the psychology of consumers, the influence of factors related to consumers (recycling awareness, subjective norms, attitudes, perceived behavioral control) and products (perceived value, price-performance ratio) on the intention to buy second-hand luxury goods is explored in this study through an online survey with Chinese consumers as a sample. The results are analyzed using the structural equation model (SEM) and show that consumers' attitudes, perceived behavioral control, and recycling awareness will promote the intention of purchasing second-hand luxury goods, and the perceived value and price-performance ratio of second-hand luxury goods also have a positive impact on the purchase intention. However, there is no significant relationship between subjective norms and purchase intention. In addition, this study also explores the interrelationship between constructs and draws corresponding conclusions, providing references for the subsequent development of the second-hand luxury market.

Reconstruction of High Entropy Alloys on a Metal-Organic Framework Approaching Active Oxygen Reduction Electrocatalysts.

High-entropy alloys (HEAs) have garnered considerable attention as promising nanocatalysts for effectively utilizing Pt in catalysis toward oxygen reduction reactions due to their unique properties. Nonetheless, there is a relative dearth of attention regarding the structural evolution of HEAs in response to electrochemical conditions. In this work, we propose a thermal reduction method to synthesize high entropy nanoparticles by leveraging the confinement effect and abundant nitrogen-anchored sites provided by pyrolyzed metal-organic frameworks (MOFs). Notably, the prepared catalysts exhibit enhanced activity accompanied by structural reconstruction during electrochemical activation, approaching 1 order of magnitude higher mass activity compared to Pt/C in oxygen reduction. Atomic-scale structural characterization reveals that abundant defects and single atoms are formed during the activation process, contributing to a significant boost in the catalytic performance for oxygen reduction reactions. This study provides deep insights into surface reconstruction engineering during electrochemical operations, with practical implications for fuel cell applications.

Discovery and functional investigation of BMP4 as a new causative gene for human congenital heart disease.

OBJECTIVE: Aggregating evidence highlights the strong genetic basis underpinning congenital heart disease (CHD). Here BMP4 was chosen as a prime candidate gene causative of human CHD predominantly because BMP4 was amply expressed in the embryonic hearts and knockout of Bmp4 in mice led to embryonic demise mainly from multiple cardiovascular developmental malformations. The aim of this retrospective investigation was to discover a novel BMP4 mutation underlying human CHD and explore its functional impact. METHODS: A sequencing examination of BMP4 was implemented in 212 index patients suffering from CHD and 236 unrelated non-CHD individuals as well as the family members available from the proband carrying a discovered BMP4 mutation. The impacts of the discovered CHD-causing mutation on the expression of NKX2-5 and TBX20 induced by BMP4 were measured by employing a dual-luciferase analysis system. RESULTS: A new heterozygous BMP4 mutation, NM_001202.6:c.318T>G;p.(Tyr106*), was found in a female proband affected with familial CHD. Genetic research of the mutation carrier's relatives unveiled that the truncating mutation was in co-segregation with CHD in the pedigree. The nonsense mutation was absent from 236 unrelated non-CHD control persons. Quantitative biologic measurement revealed that Tyr106*-mutant BMP4 failed to induce the expression of NKX2-5 and TBX20, two genes whose expression is lost in CHD. CONCLUSION: The current findings indicate BMP4 as a new gene predisposing to human CHD, allowing for improved prenatal genetic counseling along with personalized treatment of CHD patients.

Diurnal biological effects of correlated colour temperature and its exposure timing on alertness, cognition, and mood in an enclosed environment.

Artificial lighting, which profits from the non-visual effects of light, is a potentially promising solution to support residents' psychophysiological health and performance at specific times of the day in enclosed environments. However, few studies have investigated the non-visual effects of daytime correlated colour temperature (CCT) and its exposure timing on human alertness, cognition, and mood. However, the neural mechanisms underlying these effects are largely unknown. The current study evaluated the effects of daytime CCT and its exposure timing on markers of subjective experience, cognitive performance, and cerebral activity in a simulated enclosed environment. Forty-two participants participated a single-blind laboratory study with a 4 within (CCT: 4000 K vs. 6500 K vs. 8500 K vs. 12,000 K) × 2 between (exposure timing: morning vs. afternoon) mixed design. The results showed time of the day dependent benefits of the daytime CCT on subjective experience, vigilant attention, response inhibition, working memory, emotional perception, and risk decisions. The results of the electroencephalogram (EEG) revealed that lower-frequency EEG bands, including theta, alpha, and alpha-theta, were quite sensitive to daytime CCT intervention, which provides a valuable reference for trying to establish the underlying mechanisms that support the performance-enhancement effects of exposure to CCT in the daytime. However, the results revealed no consistent intervention pattern across these measurements. Therefore, future studies should consider personalised optimisation of daytime CCT for different cognitive demands.

Cystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region.

Cystine-knot peptides (CKPs) are naturally occurring peptides that exhibit exceptional chemical and proteolytic stability. We leveraged the CKP carboxypeptidase A1 inhibitor as a scaffold to construct phage-displayed CKP libraries and subsequently screened these collections against HTRA1, a trimeric serine protease implicated in age-related macular degeneration and osteoarthritis. The initial hits were optimized by using affinity maturation strategies to yield highly selective and potent picomolar inhibitors of HTRA1. Crystal structures, coupled with biochemical studies, reveal that the CKPs do not interact in a substrate-like manner but bind to a cryptic pocket at the S1' site region of HTRA1 and abolish catalysis by stabilizing a non-competent active site conformation. The opening and closing of this cryptic pocket is controlled by the gatekeeper residue V221, and its movement is facilitated by the absence of a constraining disulfide bond that is typically present in trypsin fold serine proteases, thereby explaining the remarkable selectivity of the CKPs. Our findings reveal an intriguing mechanism for modulating the activity of HTRA1, and highlight the utility of CKP-based phage display platforms in uncovering potent and selective inhibitors against challenging therapeutic targets.

Prediction of cyanidin 3-rutinoside content in Michelia crassipes based on near-infrared spectroscopic techniques.

Currently the determination of cyanidin 3-rutinoside content in plant petals usually requires chemical assays or high performance liquid chromatography (HPLC), which are time-consuming and laborious. In this study, we aimed to develop a low-cost, high-throughput method to predict cyanidin 3-rutinoside content, and developed a cyanidin 3-rutinoside prediction model using near-infrared (NIR) spectroscopy combined with partial least squares regression (PLSR). We collected spectral data from Michelia crassipes (Magnoliaceae) tepals and used five different preprocessing methods and four variable selection algorithms to calibrate the PLSR model to determine the best prediction model. The results showed that (1) the PLSR model built by combining the blockScale (BS) preprocessing method and the Significance multivariate correlation (sMC) algorithm performed the best; (2) The model has a reliable prediction ability, with a coefficient of determination (R2) of 0.72, a root mean square error (RMSE) of 1.04%, and a residual prediction deviation (RPD) of 2.06. The model can be effectively used to predict the cyanidin 3-rutinoside content of the perianth slices of M. crassipes, providing an efficient method for the rapid determination of cyanidin 3-rutinoside content.

Temperature Dependence of the Dynamic Contact Angles of Water on a Smooth Stainless-Steel Surface under Elevated Pressures.

The temperature dependence of the dynamic contact angles (DCAs) of water on a metallic surface remains unclear, especially under elevated pressures. Here in this work, the advancing and receding contact angles (RCAs), as well as the contact angle hysteresis (CAH), of water on stainless-steel 316 (SS316) surfaces were studied using the dynamic sessile drop method for temperatures up to 300 °C and pressures up to 10 MPa. It was found that the temperature dependence of the DCAs exhibits a different pattern as compared to the piecewise linear decline of static contact angles. The advancing contact angle (ACA) remains nearly constant and does not decrease until the temperature becomes close to the saturated temperature. The decrease in ACA is attributed to evaporation, which reduces the advancement of energy barrier. The RCA linearly declines below 120 °C and remains stable above 120 °C. The increasing temperature enhances the pinning effect and changes the droplet receding mode. Under all pressures tested, the CAH demonstrates a "increase-constant-decrease" trilinear relationship with temperature. Furthermore, the mean solid surface entropy and solid-gas interfacial tension of SS316 were estimated to be 0.1152 mJ/(m2·°C) and 61.49 mJ/m2, respectively.

Distributional Policy Gradient With Distributional Value Function.

In this article, we propose a distributional policy-gradient method based on distributional reinforcement learning (RL) and policy gradient. Conventional RL algorithms typically estimate the expectation of return, given a state-action pair. Furthermore, distributional RL algorithms consider the return as a random variable and estimate the return distribution that can characterize the probability of different returns resulted by environmental uncertainties. Thus, the return distribution provides more valuable information than its expectation, leading to superior policies in general. Although distributional RL has been investigated widely in value-based RL methods, very few policy-gradient methods take advantage of distributional RL. To bridge this research gap, we propose a distributional policy-gradient method by introducing a distributional value function to the policy gradient (DVDPG). We estimate the distribution of policy gradient instead of the expectation estimated in conventional policy-gradient RL methods. Furthermore, we propose two policy-gradient value sampling mechanisms to do policy improvement. First, we propose a distribution-probability-sampling method that samples the policy-gradient value according to the quantile probability of return distribution. Second, a uniform sample mechanism is proposed. With our sample mechanisms, the proposed distributional policy-gradient method enhances the stochasticity of the policy gradient, improving the exploration efficiency and benefiting to avoid falling into local optimal solutions. In sparse-reward tasks, the distribution-probability-sampling method outperforms the uniform sample mechanism. In dense-reward tasks, the two sample mechanisms perform similarly. Moreover, we show that the conventional policy-gradient method is a special case of the proposed method. Experimental results on various sparse-reward and dense-reward OpenAI-gym tasks illustrate the efficiency of the proposed method, outperforming baselines in almost environments.

Yunnan Baiyao Might Mitigate Periodontitis Bone Destruction by Inhibiting Autophagy and Promoting Osteoblast Differentiation in vivo, ex vivo and in vitro.

Background and Objective: Periodontitis is an inflammatory disease that eventually destroys tooth-supporting tissue. Yunnan Baiyao (YNBY), a traditional Chinese medicine compound with haemostatic and anti-inflammatory properties has shown therapeutic potential in several diseases. Our previous study revealed that YNBY suppressed osteoclast differentiation in periodontitis. The purpose of this study is to investigate the influences of YNBY on osteoblasts and explore its potential mechanisms. Materials and Methods: A rat periodontitis model was established by ligation of maxillary second molars. After the end of modelling, histopathological observation by hematoxylin-eosin (HE) staining and Masson trichrome staining, detection of bone resorption by Micro-CT scanning, detection of osteoclasts by tartrate-resistant acid phosphatase (TRAP) staining, expression of osteocalcin (OCN) and microtubule-associated protein 1 light chain 3 (LC3) by immunohistochemistry. Lipopolysaccharides was used to irritate MC3T3-E1 osteoblastic cells and ex vivo calvarial organ as an in vitro model of inflammation. CCK-8 assay was performed to examine the toxicity of YNBY to MC3T3-E1 osteoblastic cells. Osteogenesis was assessed with alizarin red staining, immunofluorescence staining, Western blot and immunohistochemical staining. Transmission electron microscopy, fluorescent double staining, Western blot and immunohistochemical staining were employed to detect autophagy. Results: Histological and micro-CT analyses revealed that YNBY gavage reduced bone loss caused by experimental periodontitis and upregulated osteogenic proteins in vivo. YNBY attenuated the production of autophagy-related proteins in periodontitis rats. Additionally, YNBY promoted osteogenesis by inhibiting inflammation-induced autophagy in vitro. Furthermore, YNBY suppressed LPS-mediated bone resorption and promoted the production of osteoblast-related proteins in inflamed calvarial tissues ex vivo. Conclusion: This study demonstrated, through in vivo, in vitro and ex vivo experiments, that YNBY promoted osteoblast differentiation by suppressing autophagy, which markedly alleviated bone destruction caused by periodontitis.

Combined effect of time in target range and variability of systolic blood pressure on cardiovascular outcomes and mortality in patients with hypertension: A prospective cohort study.

Time in target range (TTR) and blood pressure variability (BPV) of systolic blood pressure (SBP) are independent risk factors for major adverse cardiovascular events (MACE) and all-cause mortality in hypertensive patients. However, the association of the combination of low TTR and high BPV of SBP with the risk of MACE and all-cause mortality is unclear. This study sought to investigate the combined effect of the TTR and BPV on the risk of MACE and all-cause mortality in patients with hypertension. A total of 11 496 hypertensive patients from the Kailuan cohort study were included in our study. All participants were divided into four groups according to their TTR and BPV levels. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident MACE and all-cause mortality. During a median follow-up of 5.64 years, 839 MACEs (included 99 cases of myocardial infarction, 591 cases of stroke, and 191 cases of heart failure) and 621 deaths occurred. Compared with the high-TTR and low-BPV group, the HRs (95% CI) of MACE and all-cause mortality were 1.309 (1.025-1.671) and 1.842 (1.373-2.473) for the high-TTR and high-BPV group, 1.692 (1.347-2.125) and 1.731 (1.298-2.309) for the low-TTR & low-BPV group, 2.132 (1.728-2.629) and 2.247 (1.722-2.932) for the low-TTR & high-BPV group. Our study suggests that the combination of low TTR and high BPV of SBP was associated with a higher risk of MACE and all-cause mortality in patients with hypertension.