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Abstract Background Multi-rooted teeth with extensive dental defects often face challenges in stability and biomechanical failure. High-performance polymer PEEK materials, with properties closer to dentin, show promise in reducing stress concentration and preserving tooth structure. This report aimed to explore the use of a highly retentive polyetheretherketone (PEEK) for manufacturing custom-made split post and core for the restoration of grossly destroyed endodontically treated molars. Clinical considerations A 40-year-old female patient presented with complaints of loss of tooth substance in the posterior mandibular tooth. This case involved the digital design and fabrication of PEEK split post and core to restore multirooted molar with insufficient dental tissue remnants. The restorations were evaluated over a 3-year follow-up using the World Federation criteria (FDI). The restoration was clinically evaluated through intraoral examination, radiographic assessment, and subjective patient satisfaction, and was deemed clinically good according to FDI criteria. Conclusion The outstanding mechanical properties of PEEK, coupled with the structure of the split post, provide an effective treatment option for weakened multirooted teeth. Simultaneously, the restoration configuration effectively addressed the challenge of varying postinsertion directions, and the interlocking mechanism between the primary and auxiliary posts enhanced the stability of the post and core.

Abstract Objective High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. Methods Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. Results Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004–1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002–1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995–0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994–0.999 and 0.986, 0.975–0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993–0.996). Conclusions The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.

Abstract Accurate segmentation of oral surgery-related tissues from cone beam computed tomography (CBCT) images can significantly accelerate treatment planning and improve surgical accuracy. In this paper, we propose a fully automated tissue segmentation system for dental implant surgery. Specifically, we propose an image preprocessing method based on data distribution histograms, which can adaptively process CBCT images with different parameters. Based on this, we use the bone segmentation network to obtain the segmentation results of alveolar bone, teeth, and maxillary sinus. We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks. The tooth segmentation results can obtain the order information of the dentition. The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods. Its average Dice scores on the tooth, alveolar bone, maxillary sinus, and mandibular canal segmentation tasks were 96.5%, 95.4%, 93.6%, and 94.8%, respectively. These results demonstrate that it can accelerate the development of digital dentistry.

Abstract The use of robots to augment human capabilities and assist in work has long been an aspiration. Robotics has been developing since the 1960s when the first industrial robot was introduced. As technology has advanced, robotic-assisted surgery has shown numerous advantages, including more precision, efficiency, minimal invasiveness, and safety than is possible with conventional techniques, which are research hotspots and cutting-edge trends. This article reviewed the history of medical robot development and seminal research papers about current research progress. Taking the autonomous dental implant robotic system as an example, the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.

Abstract The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

Abstract The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase–AMP complex and the ligase–AMP–DNA complex can have four conformations. This finding suggests the parallel occurrence of four ligation reaction pathways, each characterized by specific conformations of the ligase–AMP complex that persist in the ligase–AMP–DNA complex. Notably, these complexes have DNA bending angles of ≈0°, 20°, 60°, or 100°. The mechanism of parallel reactions challenges the conventional notion of simple sequential reaction steps occurring among multiple conformations. The results provide insights into the dynamic conformational changes and the versatile attributes of T4 DNA ligase and suggest that the parallel multiple reaction pathways may correspond to diverse T4 DNA ligase functions. This mechanism may potentially have evolved as an adaptive strategy across evolutionary history to navigate complex environments.

Abstract Background Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life of BMP2 at protein level cannot meet the clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel to achieve sustained release for more efficient and safe bone regeneration. Results Bmp2 mRNA was enriched into exosomes by selective inhibition of translation in donor cells, in which NoBody (non-annotated P-body dissociating polypeptide, a protein that inhibits mRNA translation) and modified engineered BMP2 plasmids were co-transfected. The derived exosomes were named ExoBMP2+NoBody. In vitro experiments confirmed that ExoBMP2+NoBody had higher abundance of Bmp2 mRNA and thus stronger osteogenic induction capacity. When loaded into GelMA hydrogel via ally-L-glycine modified CP05 linker, the exosomes could be slowly released and thus ensure prolonged effect of BMP2 when endocytosed by the recipient cells. In the in vivo calvarial defect model, ExoBMP2+NoBody-loaded GelMA displayed great capacity in promoting bone regeneration. Conclusions Together, the proposed ExoBMP2+NoBody-loaded GelMA can provide an efficient and innovative strategy for bone regeneration.

Background: Reproductive risk factors and air pollution for developing chronic obstructive pulmonary disease (COPD) have been documented separately. However, the combined effects of overall reproductive risk status on COPD and the extent to which this can be impacted by air pollution are unknown. The aim of this study was to construct a reproductive risk score (RRS) and an air pollution score (APS) and assess independent and joint associations between the two with incident COPD risk. Methods: 78,027 female participants aged 40–69 years without baseline COPD from UK Biobank recruited between 2006 to 2010 were included in this study. RRS was constructed by 17 women’s reproductive health-related items, and APS incorporating PM2.5, PM2.5–10, PM10, NO2, and NOx was calculated to assess the joint exposure level. The outcome of the incident COPD was identified through the in-patient hospital register. The associations of RRS and APS with COPD were examined by Cox proportional hazards regression. Results: The risk of COPD reached its highest in the fourth quartile of the RRS (adjusted HR: 2.23, 95% CI: 1.76–2.82, P for trend < 0.001). A dose-response manner can also be observed between higher tertile APS with increased COPD risk and the highest risk was found in the third tertile of the APS (adjusted HR: 1.37, 95% CI: 1.19–1.58, P for trend < 0.001). The relative excess risk due to interaction (RERI) of 0.030 (95% CI: 0.012–0.048) showed additive interaction between RRS and APS on COPD was significant. In the joint analysis, the combinations of both higher RRS and APS signified higher incident COPD risk. Conclusion: High RRS and high APS were jointly associated with increased COPD risks in a dose-response pattern. Using comprehensive indicators to identify women’s reproductive risk factors, together with the control of air pollution, is effective for COPD prevention.

Abstract Background The fat‐to‐muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk independent of overall obesity. However, little is known about the association between FMR and dementia risk. We aimed to prospectively investigate the sex‐specific associations between total and regional FMR and incident dementia. Methods A total of 491 420 participants (223 581 men and 267 839 women; mean age 56.7 ± 8.2 and 56.3 ± 8.0 years old, respectively) free of dementia at baseline from the UK Biobank were included. Fat mass and muscle mass were measured using a bioelectrical impedance assessment device. Cox regression analyses were used to examine the associations of total and regional FMR with incident all‐cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). The shape of the associations of the continuous scale of FMR and incident dementia were examined using restricted cubic spline analysis. Results During a median 8.65 years of follow‐up, we documented 2 225 incident all‐cause dementia cases, including 836 AD and 468 VD cases. There was an L‐shaped association between whole body FMR and all‐cause dementia risk in both sexes after adjusting body mass index (BMI) and other covariates (P for non‐linear

Abstract Background Iron and vitamin D (VD) is essential to health. Previous studies have shown that iron homeostasis has a potential effect on VD metabolism, but the mechanism is not fully understood. Objectives To explore the relationship between VD metabolism and iron metabolism, as well as the regulatory mechanism of iron on VD metabolism. Methods 40 male rats were fed adaptively for 7 days and randomly divided into control (C, n = 6 normal diet) group and model (M, n = 24 iron deficient diet) by simple randomization, the latter was used to establish iron deficiency anemia (IDA) model. After 6 weeks of feeding, the M group was randomly divided into: iron deficiency group (DFe), low iron group (LFe), medium iron group (MFe) and high iron group (HFe) by block randomization. Different doses of iron dextran (based on iron content (100 g·bw·d)): 0, 1.1, 3.3 and 9.9 mg) were given respectively. After 4 weeks, the rats were anesthetized with 8% chloral hydrate, Blood (collected from the abdominal aorta), liver and kidney tissues were collected. The serum and tissues were separately packed and frozen at -80℃ for testing. Results The results showed that the levels of hemoglobin (Hb), red blood cell (RBC), serum iron (SI), liver iron, and kidney iron in DFe group were lower than those in the other four groups, while the levels of total iron-binding capacity (TIBC), transferrin (TF) and transferrin receptor (Tfr) in DFe group were higher than those in other groups; The serum levels of 25-(OH)D3 and 1,25-(OH)2D3 in DFe group were significantly lower than those in C group (P

Abstract 2D materials are promising nanomaterials for future applications due to their predominant quantum effects and unique properties in optics, electrics, magnetics, and mechanics. However, explorations in unique properties and potential applications of novel 2D materials have been hampered by synthesis and their stability under ambient conditions. Recently, in the graphene, 2D β‐CuI is observed experimentally under ambient conditions. Here, it is shown that this 2D β‐CuI@graphene possesses unexpected piezoresistive effect and room‐temperature ferromagnetism. Moreover, this 2D β‐CuI crystal is likely to be stable in a wide range of temperature, that is, below 900 K. Theoretical studies reveal that the unexpected piezoresistive effect is mainly attributable to the convergence of the electrons on Cu and I atoms to the Fermi level with increasing strain. There is a magnetic moment that is ≈0.97 μB on the edge of β‐CuI nanocrystal created by an iodine vacancy, which is considered the origin of such strong room‐temperature ferromagnetism. Clearly, the 2D β‐CuI@graphene provides a promising nanomaterial in the nano‐sensors with low power consumption pressure and magnetic nano‐devices with a size down to atomic scale. The discovery in the present work will evoke various new 2D nanomaterials with novel properties in nanotechnology, biotechnology, sensor materials, and technologies.

Background The evidence is equivocal on the association between meat consumption and ischemic heart disease (IHD) risk. To what extent the variation of individuals' metabolic responses to the same diet may account for this association is not fully understood. We aim to identify metabolomic signatures characterizing consumption of unprocessed red meat and processed meat and whether such signatures are associated with IHD risk. Methods and Results We conducted a cohort study of 92 246 individuals (mean age, 56.1 years; 55.1% women) using the UK Biobank. During the median follow‐up of 8.74 years, 3059 incident IHD events were documented. Unprocessed red meat and processed meat consumption was assessed using a touchscreen dietary questionnaire. Plasma metabolome was profiled by high‐throughput nuclear magnetic resonance spectroscopy. Cox proportional hazards regression model was used to test the association of meat consumption with IHD. Genome‐wide association analysis and 1‐sample Mendelian randomization were performed for metabolomic signatures and causal association of signatures with IHD. Using elastic net regularized regressions, we constructed metabolomic signatures consisting of 157 and 142 metabolites for unprocessed red meat (Spearman correlation coefficient [r]=0.223) and processed meat (r=0.329), respectively. These signatures showed positive associations with incident IHD (red meat related signature: hazard ratio [HR] per SD increment=1.11 [95% CI, 1.06–1.16], P

Background The Healthy Aging Index (HAI) has been regarded as useful in capturing the health status of multiple organ systems. However, to what extent the HAI is associated with major cardiovascular events remains largely unknown. The authors constructed a modified HAI (mHAI) to quantify the association of physiological aging with major vascular events and explored how the effects of a healthy lifestyle can modify this association. Methods and Results The participants with either missing values of any individual mHAI component or major illnesses such as heart attack, angina and stroke, and self‐reported cancer at baseline were excluded. The mHAI components include systolic blood pressure, reaction time, forced vital capacity, serum cystatin c, and serum glucose. The authors used Cox proportional hazard models to quantify the association of mHAI with major adverse cardiac events, major coronary events, and ischemic heart disease. Cumulative incidence at 5 and 10 years was estimated, and joint analyses were stratified by age group and 4 mHAI categories. The mHAI was significantly correlated with major cardiovascular events, which is a better reflection of the aging level of the body than chronological age. An mHAI was calculated in 338 044 participants aged 38 to 73 years in the UK Biobank. Each point increase in the mHAI was associated with a 44% higher risk of major adverse cardiac events (adjusted hazard ratio [aHR], 1.44 [95% CI, 1.40–1.49]), 44% higher risk of major coronary events (aHR, 1.44 [95% CI, 1.40–1.48]), and 36% higher risk of ischemic heart disease (aHR, 1.36 [95% CI, 1.33–1.39]). The percentage of population‐attribution risk was 51% (95% CI, 47–55) for major adverse cardiac events, 49% (95% CI, 45–53) for major coronary events, and 47% (95% CI, 44–50) for ischemic heart disease, which means that a substantial portion of these events could be prevented. Systolic blood pressure was the factor most significantly associated with major adverse cardiac events (aHR, 1.94 [95% CI, 1.82–2.08]; percentage of population‐attribution risk, 36%), major coronary events (aHR, 2.01 [95% CI, 1.85–2.17]; percentage of population‐attribution risk, 38%), and ischemic heart disease (aHR, 1.80 [95% CI, 1.71–1.89]; percentage of population‐attribution risk, 32%). A healthy lifestyle significantly attenuated mHAI associations with incidence of vascular events. Conclusions Our findings indicate that higher mHAI is associated with increased major vascular events. A healthy lifestyle may attenuate these associations.

Abstract Understanding the configuration and properties of the simplest lithium‐ion crystal, the Li‐Cl crystal, is essential for developing Li‐based electrochemical energy storage and conversion devices. Under ambient conditions, LiCl in a 1:1 stoichiometry is the only known stable form of the Li‐Cl crystal, and the corresponding crystals are insulating. Here, using cryo‐electron microscopy (cryo‐EM) and X‐ray photoelectron spectroscopy (XPS), this work reports a novel abnormal 2D Li2Cl crystal in ultra‐thin reduced graphene oxide (rGO) membranes by simply soaking the rGO membrane in unsaturated LiCl solution under ambient conditions and showed its high‐resolution image. Unexpectedly, such Li2Cl crystal presents metallic properties rather than insulating properties. Using vacuum filtration of the unsaturated LiCl solution through rGO membranes, this work prepares the rGO membranes with high content Li2Cl, displaying a high areal capacitance of 220 mF cm−2. Remarkably, the Li2Cl‐rGO membranes also exhibit heterostructure property and piezoelectricity. For the excess Li and unique electrical characteristics, these Li2Cl‐rGO membranes can be used as a humidity sensor. These findings point to possibilities for creating new Li‐based materials and fabricating novel high‐performance electronic devices, transistors, and sensors.

Continuous global warming and frequent extreme high temperatures keep the urban climate health risk increasing, seriously threatening residents’ emotional health. Therefore, analysis on spatial distribution of the health risk that the urban heat island (UHI) effect imposes on emotional health as well as basic research on the characteristics of vulnerable populations need to be conducted. This study, with Tianjin city as the case, analyzed data from Landsat remote-sensing images, meteorological stations, and digital maps, explored the influence of summer UHI effect on distress (a typical negative emotion factor) and its spatiotemporal evolution, and conducted difference analysis on the age groups, genders, family state, and distress levels of vulnerable populations. The results show: (1) During the period of 1992–2020, the level and area of UHI influence on residents’ distress drastically increased–influence level elevated from level 2–4 to level 4–7, and highlevel influence areas were concentrated in six districts of central Tianjin. (2) Influence of the UHI effect on distress varied in different age groups–generally dropping with fluctuations as residents got older, especially residents aged 50–59. (3) Men experienced a W-shaped pattern in distress and were more irritable and unsteady emotionally; while women were more sensitive to distress in the beginning, but they became more placid as temperature got higher. (4) Studies on family status show that couples living together showed sound heat resistance in the face of heat stress, while middle-aged and elderly people living alone or with children were relatively weak in adjusting to high ambient temperature.

Summary: The preparation technology of unconventional low-dimensional Cu2O monocrystals, which exhibit specific crystal planes and present significantly unique interfacial and physicochemical properties, is attracting increasing attention and interest. Herein, by integrating a high-temperature oxidation process under vacuum and a pure-water incubation process under ambient conditions, we propose the self-assembled growth and synthesis of quasi-two-dimensional Cu2O monocrystals on reduced graphene oxide (rGO) membranes. The prepared Cu2O crystals have a single (110) crystal plane, regular rectangular morphology, and potentially well conductivity. Experimental and theoretical results suggest that this assembly is attributed to the pre-nucleation clusters aggregation and directional attachment of Cu and O on the rGO membranes in aqueous environment and cation-π interactions between the (110) crystal plane of Cu2O and rGO surface. Our findings offer a potential avenue for the discovery and design of advanced low-dimensional single-crystal materials with specific interfacial properties in a pure aqueous environment.

The combined effect of global warming and the heat island effect keeps the temperature of cities rising in the summer, seriously threatening the physical and mental health of urban residents. Taking the area within the Sixth Ring Road of Beijing as an example, based on Landsat remote sensing images, meteorological stations, and questionnaires, this study established a relational model between temperature and hostility and then analyzed the changes in the emotional health risk (hostility) in the study area and the mechanism of how outdoor activity duration influences hostility. Results show that: (1) the area within the Sixth Ring Road of Beijing had a higher and higher temperature from 1991 to 2020. Low-temperature areas gradually shrank, and medium- and high-temperature areas extended outwards from the center. (2) The threat of high temperature to residents' hostility gradually intensified—the sphere of influence expanded, low-risk areas quickly turned into medium-high-risk areas, and the level of hostility risk increased. Level 1 risk areas of hostility had the most obvious reduction—a 74.33% reduction in area proportion; meanwhile, Level 3 risk areas had the most significant growth—a 50.41% increase in area proportion. (3) In the first 120 min of outdoor activities under high temperature, residents' hostility was negatively correlated with outdoor activity duration; after more than 120 min, hostility became positively correlated with duration. Therefore, figuring out how temperature changes influence human emotions is of great significance to improving the living environment and health level of residents. This study attempts to (1) explore the impact of temperature changes and outdoor activity duration on hostility, (2) evaluate residents' emotional health risk levels affected by high temperature, and (3) provide a theoretical basis for the early warning mechanism of emotional health risk and the planning of healthy cities.

Background and AimsPlatelets are linked to atherosclerotic development and pathological thrombosis. Single dose of water-soluble tomato extract (WTE) which is a natural extraction can exert anti-platelet effects after 3 or 7 h in British healthy people. However, the effects of WTE supplementation on platelet function in Chinese healthy middle-aged and older individuals have not been studied, and the effects or safety of 4-week WTE supplementation also remain unclear. The present study aims to determine the effects of WTE on platelet function, and explore the safety of 4-week WTE supplementation in Chinese healthy middle-aged and older individuals.MethodsA randomized, double-blinded, and crossover clinical trial was conducted. Firstly, 105 individuals were randomly divided into two groups that received WTE (150 mg/day) or placebo for 4 weeks. Then, after a washout period of 2 weeks, two groups exchanged groups and continued for another 4-week intervention. Platelet aggregation, P-selectin, activated GPIIbIIIa, plasma platelet factor 4 (PF4), β-thromboglobulin (β-TG), and thromboxane B2 (TXB2) were tested at baseline, 4, 6, and 10 weeks.ResultsCompared with the placebo group, 150 mg/day WTE supplement for 4 weeks significantly reduced ADP-induced or collagen-induced platelet aggregation (−10.8 ± 1.8 or −3.9 ± 1.5%, P < 0.05), ADP-induced or collagen-induced platelet P-selectin expression (−6.9 ± 1.5 or −6.6 ± 1.3%, P < 0.05), ADP-induced or collagen-induced activated GPIIbIIIa (−6.2 ± 2.0 or −3.8 ± 2.0%, P < 0.05). Besides, 4-week intervention of 150 mg WTE per day also resulted in significant reductions in plasma PF4 (−120.6 ± 33.2 ng/mL, P < 0.05) and β-TG (−129.7 ± 27.5 ng/mL, P < 0.05) and TXB2 (−42.0 ± 4.0 ng/mL, P < 0.05), while had no effects on coagulation function and liver or renal function. Interestingly, 2-week washout period is enough to reverse the inhibitory effect of 4-week WTE supplementation on platelet function.ConclusionWTE supplementation for 4 weeks could moderately reduce platelet activation, aggregation, and granule secretion in Chinese healthy middle-aged and older individuals, and these effects are safe. After 2-week washout period, the inhibitory effect of 4-week WTE on platelet function can be eliminated.Clinical Trial Registration[http://www.chictr.org.cn/], identifier [ChiCTR-POR-17012927].

Microbial fermentation has been widely used to improve the quality and functional composition of food and edibles; however, the approach has rarely been applied to traditional Chinese medicines. In this study, to understand the effect of microbial fermentation on the active ingredients of traditional Chinese medicines, we used Bifidobacterium bifidum and Bacillus subtilis to ferment the traditional Chinese medicine, Cornus officinalis fruit (COF), and determined the levels of active ingredients using HPLC (high-performance liquid chromatography). According to the results, both B. subtilis and B. bifidum substantially increased the amount of gallic acid in the COF culture broth after fermentation; however, the two species of bacteria had no effect on the loganin content. Moreover, the B. subtilis fermentation reduced the contents of ursolic acid and oleanolic acid in the COF broth, whereas the B. bifidum fermentation did not. This study contributes to a better understanding of the mechanism by which microbial fermentation alters the active ingredient levels of traditional Chinese medicines, and suggests that fermentation may potentially improve their functional ingredients.

Fermentation is considered a promising way to increase the bioactive substance content as well as the curing efficacy of foods and herbal medicines. However, in the vast majority of cases, it remains unknown what bioactive ingredient and physiological activity are altered in traditional herbs after fermentation. Here, in order to find the effect of fermentation on the bioactive compound content and health efficacy of Cornus officinalis fruit, an important Chinese traditional medicine, its total phenolic content, total flavonoid content, antioxidant activity and anti-tyrosinase activity were estimated during Bifidobacterium bifidum fermentation process. The results showed that, during COF (Cornus officinalis fruit)’s fermentation, the total phenolic contents were significantly increased, however, the total flavonoid contents weren’t obviously changed, and that the antioxidant activity as well as the anti-tyrosinase activity was enhanced. In addition, the total phenolic content was positively related not only to the antioxidant activity but also to the anti-tyrosinase activity. This research can help us better understand the alterations of ingredients and physiological activities of fermented traditional medicines that influence curing efficacy.

Objective: The associations between intake of anthocyanins and anthocyanin-rich berries and cardiovascular risks remained to be established. We aimed to quantitatively summarize the effects of purified anthocyanins and anthocyanin-rich berries on major surrogate markers of cardiovascular diseases (CVDs) and the longitudinal associations between dietary anthocyanins and CVD events.Methods: Meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies.Results: We included 44 eligible RCTs and 15 prospective cohort studies in this study. Pooled analysis of RCTs showed that purified anthocyanin supplementation could significantly reduce blood LDL cholesterol (weighted mean difference (WMD): −5.43 mg/dL, 95% CI: −8.96, −1.90 mg/dL; p = 0.003) and triglyceride (WMD: −6.18 mg/dL, 95% CI: −11.67, −0.69 mg/dL; p = 0.027) while increase HDL cholesterol (WMD: 11.49 mg/dL, 95% CI: 7.43, 15.55 mg/dL; p < 0.001) concentrations. Purified anthocyanins also markedly decreased circulating tumor necrosis factor alpha (WMD: −1.62 pg/mL, 95% CI: −2.76, −0.48 pg/mL; p = 0.005) and C-reactive protein (WMD: −0.028 mg/dL, 95% CI: −0.050, −0.005 mg/dL; p = 0.014). Besides, administration of anthocyanin-rich berries could significantly lower blood total cholesterol (WMD: −4.48 mg/dL, 95% CI: −8.94, −0.02 mg/dL; p = 0.049) and C-reactive protein (WMD: −0.046 mg/dL, 95% CI: −0.070, −0.022 mg/dL; p < 0.001). Neither purified anthocyanins nor anthocyanin-rich berries could cause any substantial improvements in BMI, blood pressure, or flow-mediated dilation. In addition, meta-analysis of prospective cohort studies suggested that high dietary anthocyanins were related to lower risk of coronary heart disease (CHD) (relative risk (RR): 0.83, 95% CI: 0.72, 0.95; p = 0.009), total CVD incidence (RR: 0.73, 95% CI: 0.55, 0.97; p = 0.030), and total CVD deaths (RR: 0.91, 95% CI: 0.87, 0.96; p < 0.001).Conclusion: Habitual intake of anthocyanins and anthocyanin-rich berries could protect against CVDs possibly via improving blood lipid profiles and decreasing circulating proinflammatory cytokines.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020208782.

Lower Paleozoic carbonate rocks are an important exploration area in craton area of the Tarim Basin, with the proven oil and gas reserves of more than 2.2×108 t, but no large-scale discovery has been made in the Gucheng area so far. The key issues restricting exploration are that the source rock, reservoir scale and law of oil and gas enrichment are unclear. By systematically examining the petroleum geological conditions of Lower Paleozoic carbonate rocks, the following findings are reached: (1) Source rocks of slope-basin facies developed in Cambrian-Lower Ordovician in the Gucheng area. (2) The dolomitized beach in the lower part of Ordovician Yingshan Formation has large-scale reservoirs, good reservoir-cap assemblage and developed gas source faults, and is an important field for increasing reserves and production in the near future; hydrocarbon enrichment is controlled by reservoir and gas source faults, and the central dolomitized beach zone is the main exploration area. (3) The Cambrian platform margin reef beach, large in scale, good in physical properties and close to source rocks, has the possibility to form monolithic gas field; the caprock and preservation conditions are the key factors for hydrocarbon enrichment; the northern part of the phases I and II platform margin reefs has better sealing conditions, and is the main direction of next exploration. (4) Limestone fault solution reservoirs in the upper part of Ordovician Yingshan Formation, controlled by faults and small in scale, but good in reservoir-cap combination, worth exploring. (5) The granular limestone beach of Ordovician Yijianfang Formation is well developed and gas-bearing, but short in exposure dissolution time, and the reservoirs are strongly heterogeneous, and are a potential exploration field. Key words: Tarim Basin, Gucheng Area, Lower Paleozoic, carbonate rock, petroleum geological conditions, exploration potential

Background: This study aimed to evaluate the prevalence of restless legs syndrome (RLS) in patients with migraine and explore its association with vitamin D deficiency, aiming to provide biological support for the comorbidity of migraine with RLS, and shed new lights into clinical diagnosis and treatment.Methods: A case-control study was performed on 175 migraine patients and 151 non-headache controls. The information of all subjects concerning headache severity [visual analog scale (VAS) score], RLS, RLS severity [International Restless Legs Scale (IRLS) score], sleep quality [Pittsburgh sleep quality index (PSQI)], anxiety and depression symptoms [hospital anxiety and depression scale (HADS)], and demographic data were collected. At the same time, serum 25-(OH) D levels were also measured (concentration

Background: Dyslipidemia induces platelet hyperactivation and hyper-aggregation, which are linked to thrombosis. Anthocyanins could inhibit platelet function in vitro and in mice fed high-fat diets with their effects on platelet function in subjects with dyslipidemia remained unknown. This study aimed to investigate the effects of different doses of anthocyanins on platelet function in individuals with dyslipidemia. Methods: A double-blind, randomized, controlled trial was conducted. Ninety-three individuals who were initially diagnosed with dyslipidemia were randomly assigned to placebo or 40, 80, 160 or 320 mg/day anthocyanin groups. The supplementations were anthocyanin capsules (Medox, Norway). Platelet aggregation by light aggregometry of platelet-rich plasma, P-selectin, activated GPⅡbⅢa, reactive oxygen species (ROS), and mitochondrial membrane potential were tested at baseline, 6 weeks and 12 weeks. Findings: Compared to placebo group, anthocyanins at 80 mg/day for 12 weeks reduced collagen-induced platelet aggregation (-3.39±2.36%) and activated GPⅡbⅢa (-8.25±2.45%) (P

Increased oxidative stress and platelet apoptotic in middle-aged and elderly adults are important risk factors for atherosclerotic cardiovascular disease (ASCVD). Therefore, it is of great significance to control the oxidative stress and platelet apoptosis in middle-aged and elderly adults. Previous acute clinical trials have shown that water-soluble tomato concentrate (WSTC) from fresh tomatoes could exert antiplatelet benefits after 3 h or 7 h, but its effects on platelet apoptosis and oxidative stress are still unknown, especially in healthy middle-aged and elderly adults. This current study aimed to examine the efficacies of WSTC on platelet apoptosis and oxidative stress in healthy middle-aged and elderly adults via a randomized double-blinded placebo-controlled crossover clinical trial (10 weeks in total). A total of 52 healthy middle-aged and elderly adults completed this trial. The results showed that WSTC could increase the serum total antioxidant capacity levels (p < 0.05) and decrease the serum malondialdehyde levels (p < 0.05) after a 4-week WSTC supplementation in healthy middle-aged and elderly adults. Platelet endogenous reactive oxygen species generation (p < 0.05), mitochondrial membrane potential dissipation (p < 0.05) and phosphatidylserine exposure (p < 0.05) were attenuated. In addition, our present study also found that WSTC could inhibit platelet aggregation and activation induced by collagen or ADP after intervention (p < 0.05), while having no effects on adverse events (p > 0.05). The results suggest that WSTC can inhibit oxidative stress and its related platelet apoptosis, which may provide a basis for the primary prevention of WSTC in ASCVD.

Background: This study aimed to investigate the biomechanical behaviors of polyether ether ketone (PEEK) and traditional materials (titanium and fiber) when used to restore tooth defects in the form of prefabricated post or customized post via computational modelling. Methods: First, the prototype of natural tooth, and the prototypes of prefabricated post and customized post were established, respectively, whilst the residual root was restored with dentin ferrule using reverse engineering methods. Then, the stress and strain of CFR-PEEK (PEEK reinforced by 30% carbon fiber) and pure PEEK (PEEK without any reprocessing) post were compared with those made in traditional materials using the three-dimensional finite element method. Results: From the stress point of view, compared with metal and fiber posts, CFR-PEEK and pure PEEK prefabricated post both demonstrated reduced post-core interface stress, post stress, post-root cement stress and root cement stress; moreover, CFR-PEEK and pure PEEK customized post demonstrated reduced post stress, post-root cement stress and root cement stress, while the strain of CFR-PEEK post was the closest to that of dentin. Conclusions: Compared with the traditional posts, both the CFR-PEEK and pure PEEK posts could reduce the risk of debonding and vertical root fracture, whether they were used as prefabricated posts or customized posts, but the biomechanical behavior of carbon fiber-reinforced CFR-PEEK restorations was the closest to dentin, no matter if they were used as prefabricated post or customized post. Therefore, the CFR-PEEK post could be more suitable to restore massive tooth defects. Pure PEEK needs filler reinforcement to be used for post-retained restoration.

Abstract Background Radiation exposure negatively affects the regenerative ability and makes reconstruction of bone defects after tumor section difficult. miR-34a is involved in radiation biology and bone metabolism. The aim of this study was to investigate whether miR-34a could contribute to bone regeneration in irradiated bone defects. Methods The expression of miR-34a was analyzed during the osteoblastic differentiation of irradiated BMSCs and bone formation in irradiated bone defects. miR-34a mimics and miR-34a inhibitor were used to upregulate or suppress the expression of miR-34a in BMSCs irradiated with 2 or 4 Gy X-ray radiation. In vitro osteogenesis and subcutaneous osteogenesis were used to assess the effects of miR-34a on the osteogenic ability of radiation-impaired BMSCs. Collagen-based hydrogel containing agomiR-34a or antagomiR-34a were placed into the 3-mm defects of irradiated rat tibias to test the effect of miR-34a on bone defect healing after irradiation. Results miR-34a was upregulated in the process of bone formation after irradiation. Transfecting radiation-impaired BMSCs with miR-34a mimics enhanced their osteoblastic differentiation in vitro by targeting NOTCH1. Overexpression of miR-34a enhanced the ectopic bone formation of irradiated BMSCs. In situ delivery of miR-34a promoted bone regeneration in irradiated bone defects. Conclusions miR-34a promoted the osteoblastic differentiation of BMSCs and enhanced the ectopic bone formation after irradiation. miR-34a promoted bone defect healing in irradiated rat tibias. miR-34a-targeted therapy might be a promising strategy for promoting the reconstruction of bone defects after radiotherapy.

Trimethylamine-N-oxide (TMAO) has recently been identified as an independent risk factor for atherosclerosis. The present study was to investigate the effects of ginger extract (GE) on plasma cholesterol and inflammation in TMAO-exacerbated hypercholesterolemic mice. Forty-five mice were assigned into five groups and fed a non-cholesterol diet, a high-cholesterol diet, or one of the three experimental high-cholesterol diets containing 1% GE, 0.2% TMAO, or 0.2% TMAO plus 1% GE for 12 weeks. Results showed that dietary TMAO increased plasma total cholesterol (TC). GE decreased plasma TC in both non-TMAO-fed and TMAO-fed mice, by up-regulating the expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) and promoting fecal excretion of total acidic sterols. GE also lowered plasma levels of proinflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and monocyte chemotactic protein 1 (MCP-1). It was concluded that GE could alleviate the TMAO-aggravated elevation in plasma TC and vascular inflammation in high cholesterol diet-fed mice.

Piperine is the major pungent ingredient in black and white peppers. The present study investigated plasma cholesterol-lowering activity of piperine and associated underlying mechanism in hypercholesterolemia hamsters. Thirty-two hamsters were assigned into four groups receiving one of four diets namely a non-cholesterol diet (NCD), a high-cholesterol diet (HCD), and the two HCD diets containing 0.03% (PL) and 0.06% (PH) piperine, respectively, for 6 weeks. Results showed that PL and PH diets significantly reduced plasma total cholesterol (TC) by 16–17%, and non-high-density lipoprotein cholesterol (non-HDL-C) by 24–25%, respectively. This was accompanied by 84–109% increase in fecal excretion of neutral sterols with down-regulation on gene expression of intestinal Niemann-Pick C1-like 1 protein (NPC1L1), acyl-CoA:cholesterol acyltransferase 2 (ACAT2), and microsomal triacylglycerol transport protein (MTP). It was concluded that plasma TC-lowering activity of piperine was mediated by reducing the intestinal cholesterol absorption via inhibition on gene expression of intestinal NPC1L1, ACAT and MTP.

The application of graphene oxide (GO)-based membranes combined with a quartz crystal microbalance (QCM) as a humidity sensor has attracted great interest over the past few years. Understanding the influence of the structure of the GO membrane (GOM) on the adsorption/desorption of water molecules and the transport mechanism of water molecules in the membrane is crucial for development of applications using GOM-based humidity sensors. In this paper, by investigating the effects of oxygen-containing groups, flake size and interlayer spacing on the performance of humidity sensing, it was found that humidity-sensing performance could be improved by rational membrane-structure design and the introduction of magnesium ions, which can expand the interlayer spacing. Therefore, a novel HGO&GO&Mg2+ structure prepared by uniformly doping magnesium ions into GO&HGO thin composite membranes was designed for humidity sensing from 11.3% RH to 97.3% RH. The corresponding sensor exhibits a greatly improved humidity sensitivity (~34.3 Hz/%RH) compared with the original pure GO-based QCM sensor (~4.0 Hz/%RH). In addition, the sensor exhibits rapid response/recovery times (7 s/6 s), low hysteresis (~3.2%), excellent repeatability and good stability. This research is conducive to understanding the mechanism of GOM-based humidity sensors. Owing to its good humidity-sensing properties, the HGO&GO&Mg2+ membrane-based QCM humidity sensor is a good candidate for humidity sensing.

Sox9 is an intrinsic transcription factor related to the determination and maintenance of chondrogenic lineage of bone marrow mesenchymal stem cells (BMSCs). In recent research, we have proved that fragmented chondrocyte aggregates (cell bricks) could promote chondrogenesis of BMSCs in vivo. However, it is still unknown whether the ratio of BMSCs/chondrocyte bricks has a significant influence on 3-D cartilage regeneration and related molecular mechanism. To address this issue, the current study subcutaneously injected three groups of cell complex with different rabbit BMSCs/chondrocyte bricks’ ratios (1 : 2, 1 : 1, and 2 : 1) into nude mice. Gross morphology observation, histological and immunohistochemical assays, biochemical analysis, gene expression analysis, and western blot were used to compare the influence of different BMSCs/chondrocyte bricks’ ratios on the properties of tissue-engineered cartilage and explore the related molecular mechanism. The constructs of 1 : 1 BMSCs/chondrocyte bricks, (B1CB1) group resulted in persistent chondrogenesis with appropriate morphology and adequate central nutritional perfusion without ossification. The related mechanism is that increased expression of Sox9 in the B1C1 group promoted chondrogenesis and inhibited the osteogenesis of BMSCs through upregulating Col-II as well as downregulating RUNX2 and downstream of Col-X and Col-I by upregulating Nkx3.2. This study demonstrated that BMSCs/chondrocyte bricks 1:1 should be a suitable ratio and the Sox9-Nkx3.2-RUNX2 pathway was a related mechanism which played an important role in the niche for stable chondrogenesis of BMSCs constructed by chondrocyte bricks and PRP.

Betanin, a water-soluble nitrogenous pigment, is found to exert various health benefits including anti-oxidative, anti-inflammatory, anti-hyperglycemic and cardioprotective effects. However, the roles of betanin in platelet function is completely unknown. In the present study we investigated the effects of betanin-enriched red beet extract on human platelet physiology in vitro and explored the underlying mechanism. The results showed that betanin significantly and dose-dependently reduced platelet P-selectin, CD63, CD40L expression and PAC-1 binding, inhibited ATP secretion and platelet aggregation. Meanwhile, betanin didn’t prolong tail bleeding time in C57BL/6 mice. Western blot results demonstrated that betanin attenuated platelet Akt and P38 MAPK phosphorylation induced by thrombin. Taken together, betanin could attenuate platelet function without affecting bleeding time, and this effect is potentially mediated by inhibition of Akt and P38 MAPK phosphorylation. Our findings suggest that betanin could be considered as a candidate agent for the prevention of platelet-associated thromboembolic CVDs.

Abstract Background The reconstruction of bone defects is often impaired by radiotherapy since bone quality is compromised by radiation. This study aims to investigate the therapeutic efficacy of the composite cell sheets-bone marrow mesenchymal stem cell (BMSC) sheets cocultured with endothelial progenitor cells (EPCs)-in the healing of irradiated bone defects and the biological effects of EPCs on the osteogenic properties of BMSC sheets. Methods BMSCs and EPCs were isolated from rat bone marrow. BMSCs were used to form cell sheets by the vitamin C inducing method. EPCs were seeded on BMSC sheets to make EPCs–BMSC sheets. Osteogenesis of EPCs–BMSC sheets and BMSC sheets were tested. In vitro osteogenesis tests included ALP, Alizarin Red S, Sirius Red staining, qRT-PCR and Western blot analysis after 3 and 7 days of osteogenic incubation. Subcutaneous osteogenesis was tested by H&E staining and immunohistochemical staining 8 weeks after transplantation. EPCs–BMSC sheets and BMSC sheets were used in the 3 mm defects of non-irradiated and irradiated rat tibias. Micro-CT and histological analysis were used to test the healing of bone defects 4 and 8 weeks after transplantation. Results EPCs–BMSC sheets showed enhanced osteogenic differentiation in vitro with increased expression of osteoblastic markers and osteogenesis related staining compared with BMSC sheets. In subcutaneous osteogenesis test, EPCs–BMSC sheets formed larger areas of new bone and blood vessels. The EPCs–BMSC group had the highest volume of newly formed bone in the defect area of irradiated tibias. Conclusions EPCs improved the osteogenic differentiation of BMSC Sheets and enhanced the ectopic bone formation. EPCs–BMSC sheets promoted bone healing in irradiated rat tibias. EPCs–BMSC sheets are potentially useful in the reconstruction of bone defect after radiotherapy.

In this paper, a novel secure data transmission scheme using chaotic compressed sensing, which has inherent encryption property without additional cost, is proposed based on a T-way Bernoulli shift chaotic system. In the proposed scheme, the Bernoulli chaotic sensing matrix (BCsM) is generated by the Bernoulli shift chaotic sequence. We prove that the BCsM meets the restricted isometry property with overwhelming probability, which guarantees good sensing performance. Compared with the state-of-the-art sensing matrices, such as the Gaussian sensing matrix, the BCsM has low complexity and is easily implemented in hardware. Meanwhile, we investigate the recovery performance, robustness, and security of the proposed scheme and show that the proposed scheme can ensure efficient secure data transmission against additive noise and malicious attacks. The proposed scheme is perfectly effective for large-scale, long-term data transmission with high energy efficiency and strong security.

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.

Little is known about which currently available a priori dietary indexes provide best guidance for reducing cardiometabolic risk factors (CMRF) among hyperlipidemic patients. This study was designed to compare the associations between four a priori dietary indexes, including Diet Balance Index (DBI-16), Chinese Healthy Eating Index (CHEI), Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH) and CMRF among hyperlipidemic patients. A total of 269 participants were enrolled into the cross-sectional study. DBI-16, CHEI, MDS, and DASH scores were calculated using established methods. CMRF was measured using standard methods. DBI-total scores (DBI-TS) were inversely associated with triglyceride concentrations and TC:HDL-C ratio, and positively associated with HDL-C and ApoA1 concentrations (all p < 0.05), while the results for DBI-low bound scores (DBI-LBS) were opposite. DBI-high bound scores (DBI-HBS) and DASH scores were positively and inversely associated with glucose concentrations, respectively (both p < 0.05). Higher diet quality distance (DQD) was positively associated with higher TC, LDL-C and ApoB concentrations, and TC:HDL-C and LDL-C:HDL-C ratios, and lower HDL-C and ApoA1 concentrations and ApoA1:ApoB ratio (all p < 0.05). CHEI scores were inversely associated with triglyceride concentrations (p = 0.036). None of the dietary indexes was associated with blood pressures. DBI-16 provided most comprehensive evaluations of the overall diet quality and balance for optimizing cardiometabolic health among hyperlipidemic individuals.

Abstract Irradiated bone has a greater risk of implant failure than nonirradiated bone. The purpose of this study was to investigate the influence of cell sheets composed of co-cultured bone marrow mesenchymal stromal cells (BMSCs) and endothelial progenitor cells (EPCs) on implant osseointegration in irradiated bone. Cell sheets (EPCs, BMSCs or co-cultured EPCs and BMSCs) were wrapped around titanium implants to make cell sheet-implant complexes. The co-cultured group showed the highest osteogenic differentiation potential in vitro, as indicated by the extracellular matrix mineralization and the expression of osteogenesis related genes at both mRNA and protein levels. The co-cultured cells promoted ectopic bone formation as indicated by micro-computed tomography (Micro-CT) and histological analysis. In the irradiated tibias of rats, implants of the co-cultured group showed enhanced osseointegration by Micro-CT evaluation and histological observation. Co-cultured EPCs and BMSCs also up-regulated the expression of osteogenesis related genes in bone fragments in close contact with implants. In conclusion, cell sheets of co-cultured EPCs and BMSCs could promote osseous healing around implants and are potentially useful to improve osseointegration process for patients after radiotherapy.

This paper focuses on image compressive sensing (CS). As the intrinsic properties of natural images, nonlocal self-similarity and sparse representation have been widely used in various image processing tasks. Most existing image CS methods apply either self-adaptive dictionary (e.g., principle component analysis (PCA) dictionary and singular value decomposition (SVD) dictionary) or fixed dictionary (e.g., discrete cosine transform (DCT), discrete wavelet transform (DWT), and Curvelet) as the sparse basis, while single dictionary could not fully explore the sparsity of images. In this paper, a Hybrid NonLocal Sparsity Regularization (HNLSR) is developed and applied to image compressive sensing. The proposed HNLSR measures nonlocal sparsity in 2D and 3D transform domain simultaneously, and both self-adaptive singular value decomposition (SVD) dictionary and fixed 3D transform are utilized. We use an efficient alternating minimization method to solve the optimization problem. Experimental results demonstrate that the proposed method outperforms existing methods in both objective evaluation and visual quality.

The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = −0.177, p < 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80; p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism.

Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 1–4 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity.

Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities was observed. The results show that the microporous structures with micropore diameters of 10–60 µm did not influence the initial adherent fibroblast number; however, those with diameters of 40 and 50 µm improved the spread, actin stress fiber organization, proliferation and fibronectin secretion of the fibroblasts. The microporous structures with micropore diameters of 40–50 µm may be promising for application in the percutaneous part of an implant.

Abstract Bone marrow mesenchymal stem cells (BMMSCs) are capable of differentiating into multiple cell types and regulating immune cell response. However, the mechanisms that govern the immunomodulatory properties of BMMSCs are still not fully elucidated. Here we show that telomerase‐deficient BMMSCs lose their capacity to inhibit T cells and ameliorate the disease phenotype in systemic sclerosis mice. Restoration of telomerase activity by telomerase reverse transcriptase (TERT) transfection in TERT−/− BMMSCs rescues their immunomodulatory functions. Mechanistically, we reveal that TERT, combined with β‐catenin and BRG1, serves as a transcriptional complex, which binds the FAS ligand (FASL) promoter to upregulate FASL expression, leading to an elevated immunomodulatory function. To test the translational value of these findings in the context of potential clinical therapy, we used aspirin treatment to upregulate telomerase activity in BMMSCs, and found a significant improvement in the immunomodulatory capacity of BMMSCs. Taken together, these findings identify a previously unrecognized role of TERT in improving the immunomodulatory capacity of BMMSCs, suggesting that aspirin treatment is a practical approach to significantly reduce cell dosage in BMMSC‐based immunotherapies.

Polyether-ether-ketone (peek) is one of the most common materials used for load-bearing orthopedic devices owing to its radiolucency and favorable mechanical properties. However, current smooth-surfaced peek implants can lead to fibrous capsule formation. To overcome this issue, here, peek specimens with well-defined internal cross-linked structures (macropore diameters of 1.0−2.0 mm) were fabricated using a three-dimensional (3D) printer, and an acid-etched microporous surface was achieved using injection-molding technology. The cell adhesion properties of smooth and microporous peek specimens was compared in vitro through a scanning electron microscope (SEM), and the soft tissue responses to the both microporous and cross-linked structure of different groups were determined in vivo using a New Zealand white rabbit model, and examined through histologic staining and separating test. The results showed that the acid-etched microporous surface promoted human skin fibroblasts (HSF) adherence, while internal cross-linked structure improved the ability of the peek specimen to form a mechanical combination with soft tissue, especially with the 1.5 mm porous specimen. The peek specimens with both the internal cross-linked structure and external acid-etched microporous surface could effectively promote the close integration of soft tissue and prevent formation of fibrous capsules, demonstrating the potential for clinical application in surgical repair.

In wireless multi-hop networks, instead of using the traditional store-and-forward method, the relay nodes can exploit the network coding idea to encode and transmit the packets in the distributed coding-aware routing (DCAR) mechanisms, which can decrease the transmission number and achieve higher throughput. However, depending on the primary coding conditions of DCAR, the DCAR-type schemes may not only detect more coding opportunities, but also lead to an imbalanced distribution of the network load. Especially, they are not energy efficient in more complex scenarios, such as wireless ad-hoc networks. In this paper, to solve these shortcomings, we propose a constrained coding-aware routing (CCAR) mechanism with the following benefits: (1) by the constrained coding conditions, the proposed mechanism can detect good coding opportunities and assure a higher decoding probability; (2) we propose a tailored “routing + coding„ discovery process, which is more lightweight and suitable for the CCAR scheme; and (3) by evaluating the length of the output queue, we can estimate the states of coding nodes to improve the efficient coding benefit. To those ends, we implement the CCAR scheme in different topologies with the ns-2 simulation tool. The simulation results show that a higher effective coding benefit ratio can be achieved by the constrained coding conditions and new coding benefit function. Moreover, the CCAR scheme has significant advantages regarding throughput, average end-to-end delay, and energy consumption.

A new dibenzylbutyrolactone lignan named matairesinol 4′-O-β-d-cellobioside (1), together with a known compound (7R, 8S)-dihydrodehydrodiconiferyl alcohol (2) was isolated from Caulis Trachelospermi. The extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, and its main components trachelogenin (3), nortrachelogenin (4), matairesinol (5) showed moderate inhibiting activities on NF-κB signaling pathway induced by TNFα, with the IC50 values of 17.7 μg/mL, 17.9 μM, 49.4 μM and 29.1 μM, respectively.

A new flavonol glycoside, namely quercetin 3-O-[α-d-apiofuranosyl(1–5)-β-d-apiofuranosyl(1–2)]-α-l-rhamnopyranosyl(1–6)-β-d-glucopyranoside (1), was isolated from glandless cotton seeds together with the known compounds quercetin 3-O-α-l-rhamnopyranosyl(1–2)-[α-l-rhamnopyranosyl(1–6)]-β-d-glucopyranoside (manghaslin, 2), kaempferol 3-O-β-d-apiofruranosyl(1–2)-β-d-glucopyranoside (3) and kaempferol 3-O-α-l-rhamnopyranosyl(1–6)-β-d-glucopyranoside (4). It is interesting that the tetrasaccharide fragment of 1 contained both a β-apiosyl and an unusual α-apiosyl group.

In traditional medicine, Bauhinia glauca subsp. hupehana has long been used as an analgesic agent in China. The aim of this study was to evaluate the antinociceptive activity of the ethanol extract of the aerial parts of B. glauca subsp. hupehana (BHE) in rats and its chemical fingerprint. The antinociceptive activity of BHE was assessed in mice using chemically and heat-induced pain models, such as the acetic acid-induced writhing, hot plate, tail-flick and glutamate tests. Naltrexone hydrochloride, a non-selective opioid receptor antagonist, was utilized to determine the involvement of the opioid system. In addition to this, the involvements of the cGMP and ATP-sensitive K+ channel pathways were also detected using methylene blue and glibenclamide. The oral administration of BHE (at doses of 50, 100 and 200 mg/kg) produced significant and dose-related inhibitions in both the chemically and heat-induced pain models. Interestingly, in the abdominal constriction test, when the dose of BHE was increased to 800 mg/kg (p.o., n = 10), the inhibition rate was 100%. The antinociceptive mechanism may involve the cGMP pathway and ATP sensitive K+ channel pathway. The central antinociceptive effect was not antagonized by naltrexone. One phenolic acid, one lignin and five flavonoids were isolated from BHE. The antinociceptive activity of BHE was most likely due to the presence of the flavonoids. The acute toxicity results showed that BHE was safe at a high dose (2 g/kg, p.o.). The current investigation demonstrates that B. glauca subsp. hupehana is a potential candidate for the development of novel, non-opioid, analgesic phytomedicines.