Imaging extended single crystal lattice distortion fields with multi-peak Bragg ptychography.

Recent advances in phase-retrieval-based x-ray imaging methods have demonstrated the ability to reconstruct 3D distortion vector fields within a nanocrystal by using coherent diffraction information from multiple crystal Bragg reflections. However, these works do not provide a solution to the challenges encountered in imaging lattice distortions in crystals with significant defect content that result in phase wrapping. Moreover, these methods only apply to isolated crystals smaller than the x-ray illumination, and therefore cannot be used for imaging of distortions in extended crystals. We introduce multi-peak Bragg ptychography which addresses both challenges via an optimization framework that combines stochastic gradient descent and phase unwrapping methods for robust image reconstruction of lattice distortions and defects in extended crystals. Our work uses modern automatic differentiation toolsets so that the method is easy to extend to other settings and easy to implement in high-performance computers. This work is particularly timely given the broad interest in using the increased coherent flux in fourth-generation synchrotrons for innovative material research.

Efficacy of TNF-α Inhibitors in the Treatment of nr-axSpA: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

INTRODUCTION: A growing number of randomized controlled trials (RCTs) have demonstrated the effectiveness of tumor necrosis factor-α (TNF-α) inhibitors in treating non-radiographic axial spondyloarthritis (nr-axSpA). This study aimed to evaluate the efficacy of TNF-α inhibitors in the treatment of nr-axSpA. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were systematically searched for relevant RCTs using specific keywords up to June 2023. The primary outcome was the proportion of patients who achieved Assessment in SpondyloArthritis international Society 40% (ASAS40). Secondary outcomes included ASAS20, Bath Ankylosing Spondylitis Disease Activity Index 50% (BASDAI50), ASAS partial remission, and ASAS5/6. RESULTS: A total of eight RCTs involving 1,376 patients were included. Patients receiving anti-TNF therapy exhibited a higher rate of ASAS40 (pooled RR = 2.36; 95% CI: 1.63-3.42; p < 0.001). In addition, the TNF-α inhibitor group showed higher BASDAI50 rates (pooled RR = 2.06; 95% CI: 1.48-2.89), ASAS20 rates (pooled RR = 1.48; 95% CI: 1.31-1.67), ASAS partial remission rates (pooled RR = 2.33; 95% CI: 1.58-3.43), and ASAS5/6 rates (RR = 3.46; 95% CI: 2.05-5.83) than the placebo group. CONCLUSION: The TNF-α inhibitors were effective in treating nr-axSpA.

Antiplatelet Agents Inhibit Platelet Adhesion and Aggregation on Glass Surface Under Physiological Flow Conditions: Toward a Microfluidic Platelet Functional Assay Without Additional Adhesion Protein Modification.

ABSTRACT: As the pathogenesis of arterial thrombosis often includes platelet adhesion and aggregation, antiplatelet agents are commonly used to prevent thromboembolic events. Here, a new microfluidic method without additional adhesion protein modification was developed to quantify the inhibitory effect of antiplatelet drugs on the adhesion and aggregation behavior of platelets on glass surfaces under physiological flow conditions. Polydimethylsiloxane-glass microfluidic chips were fabricated by soft photolithography. Blood samples from healthy volunteers or patients before and after taking antiplatelet drugs flowed through the microchannels at wall shear rates of 300 and 1500 second -1 , respectively. The time to reach 2.5% platelet aggregation surface coverage (Ti), surface coverage (A 150s ), and mean fluorescence intensity (F 150s ) were used as quantitative indicators. Aspirin (80 µM) prolonged Ti and reduced F 150s . Alprostadil, ticagrelor, eptifibatide, and tirofiban prolonged Ti and reduced A 150s and F 150s in a concentration-dependent manner, whereas high concentrations of alprostadil did not completely inhibit platelet aggregation. Aspirin combined with ticagrelor synergistically inhibited platelet adhesion and aggregation; GPIb-IX-von Willebrand factor inhibitors partially inhibited platelet aggregation, and the inhibition was more pronounced at 1500 than at 300 second -1 . Patient administration of aspirin or (and) clopidogrel inhibited platelet adhesion and aggregation on the glass surface under flow conditions. This technology is capable of distinguishing the pharmacological effects of various antiplatelet drugs on inhibition of platelet adhesion aggregation on glass surface under physiological flow conditions, which providing a new way to develop microfluidic platelet function detection method without additional adhesive protein modification for determining the inhibitory effects of antiplatelet drugs in the clinical setting.

Impact of rise and fall phases of shear on platelet activation and aggregation using microfluidics.

Blood flow disorders are often the result of the non-physiological narrowing of blood arteries caused by atherosclerosis and thrombus. The blood then proceeds through rising-peak-decreasing phases as it passes through the narrow area. Although abnormally high shear is known to activate platelets, the shear process that platelets undergo in small arteries is complex. Thus, understanding how each shear phase affects platelet activation can be used to improve antiplatelet therapy and decrease the risk of side effects like bleeding. Blood samples were sheared (68.8 ms,5200 s-1) in vitro by the microfluidic technique, and platelet activation levels (P-selectin and integrin αIIbß3) and von Willebrand factor (vWF) binding to platelets were analyzed by flow cytometry. Post-stenosis platelet aggregation was dynamically detected using microfluidic technology. We studied TXA2, P2Y12-ADP, and integrin αIIbß3-fibrinogen receptor pathways by adding antiplatelet drugs, such as acetylsalicylic acid (ASA, an active ingredient of aspirin that inhibits platelet metabolism), ticagrelor (hinders platelet activation), and tirofiban (blocks integrin αIIbß3 receptor) in vitro, respectively, to determine platelet activation function mediated by transient non-physiological high shear rates. We demonstrated that platelets can be activated under transient pathological high shear rates. The shear rise and fall phases influenced shear-induced platelet activation by regulating the binding of vWF to platelets. The degree of platelet activation and aggregation increased with multiple shear rise and fall phases. ASA did not inhibit shear-mediated platelet activation, but ticagrelor and tirofiban effectively inhibited shear-mediated platelet activation. Our data demonstrated that the shear rise and fall phases play an important role in shear-mediated platelet activation and promote platelet activation and aggregation in a vWF-dependent manner. Blocking integrin αIIbß3 receptor and hindering P2Y12-ADP were beneficial to reducing shear-mediated platelet activation.

The rapid change of shear rate gradient is beneficial to platelet activation.

Fluid shear plays a key role in hemostasis and thrombosis, and the purpose of this study was to investigate the effect of shear gradient change rate (SGCR) on platelet reactivity and von Willebrand factor (vWF) activity and its mechanism. In this study, we developed a set of microfluidic chips capable of generating different shear gradients and simulated the shear rate distribution in the flow field by COMSOL Multiphysics software. Molecular markers of platelet activation (P-selectin, activated GPIIb/IIIa, phosphatidylserine exposure, and monocyte-platelet aggregate formation) were analyzed by flow cytometry. Platelet aggregation induced by shear gradient was studied by a microfluidic experimental platform, and plasma vWF ristocetin cofactor (vWF: RCO) activity was investigated by flow cytometry. The expression of p-Akt was studied by Western blotting. The results showed that the faster the SGCR, the higher the expression of platelet p-Akt, and the stronger the platelet reactivity and vWF activity. This indicates that fluid shear stress can activate platelets and vWF in a shear gradient-dependent manner through the PI3K/AKT signal pathway, and the faster the SGCR, the more significant the activation effect.

What is the context? Recent studies have shown that fluid shear stress plays a key role in platelet activation and thrombosis. However, its mechanism and effect have not been fully elucidated.The development of microfluidic chip technology enables people to study platelet function in a precisely controlled flow field environment.Previous studies have shown that the PI3K-AKT signal pathway may be a mechanically sensitive signal transduction pathway.What is new?In this study, we designed a microfluidic model with different narrow geometry, and controlled the injection pump to perfuse fluid at the same flow rate, so that the platelets flowing through the model experienced the flow field environment of different shear gradients.We studied the activities of platelets and von Willebrand factor in different flow fields and explored their signal transduction pathways.What is the impact? Our results suggest that vascular stenosis does increase platelet activity and the risk of thrombosis. However, its ability to activate platelets is not only related to the peak shear rate and shear time, but also closely related to the decreasing rate of shear gradient. Even if the peak shear rate at the stenosis is the same, the faster the shear rate decreases, the higher the reactivity of platelets and von Willebrand factor, which may be mediated by the PI3K-AKT signal pathway. This study not only helps clinicians to judge the risk of thrombosis in patients with atherosclerosis or percutaneous coronary intervention, but also helps us to better understand the mechanism of shear-induced platelet activation.

Evaluating the impact of transient shear stress on platelet activation, adhesion, and aggregation with microfluidic chip technique.

BACKGROUND: When nonphysiological stenosis occurs, the transient high shear stress formed in vessels increases the risk of thrombosis and is a potential factor for cardiovascular diseases. But the platelet adhesion and aggregation behavior at nonphysiological post-stenosis and its affecting factors are not fully understood yet. METHODS: In this experiment, platelet aggregation on collagen and fibrinogen at different shear stresses and different hematocrits were observed by microfluidic technology. Platelet activation (P-selectin, glycoprotein IIb/IIIa) and monocyte-platelet aggregate (MPA) levels under different shear stresses were analyzed by flow cytometry. RESULTS: On fibrinogen, platelets aggregate more at higher shear stress conditions. While on collagen, it becomes more difficult for platelets to form stable aggregation at higher shear stress conditions. If platelets adhere initially at low shear stress, stable platelet aggregation can be formed at subsequent high shear stress. Moreover, when the shear stress increases, platelet activity markers (P-selectin, glycoprotein IIb/IIIa and MPAs) increase significantly. Hematocrit affects the degree of platelet aggregation, and the influence of hematocrit is obvious at high shear stress. CONCLUSION: Transient high shear stress (46 ms) can effectively activate platelets. Platelet aggregation behavior was different for coated fibrinogen and collagen protein. Stable platelet adhesion at post-stenosis is more dependent on fibrinogen and platelet aggregation is stable on both fibrinogen and collagen. Hematocrit can significantly affect the formation of platelet aggregation.

Methodologic Quality and Pharmacotherapy Recommendations for Patient Blood Management Guidelines for Cardiac Surgery on Cardiopulmonary Bypass.

Patient blood management (PBM) guidelines for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) have increased during the past decade, and pharmacotherapy plays an important role in PBM. In the face of the undefined consistency in the methodologic quality and pharmacotherapy recommendations across multiple guidelines, this study exclusively evaluated methodologies of the related guideline development process, and compiled medication recommendations of PBM for cardiac surgery patients. PBM guidelines for cardiac surgery under CPB were searched through some mainstream literature and guideline databases from database establishment to May 15, 2023. Nine guidelines meeting inclusion criteria were included in this study. The quality of the guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. "Stakeholder involvement" received the lowest mean score of 49.38% in the AGREE II scoring among the guidelines. PBM for cardiac surgery patients spans the perioperative phase. Drug therapy strategies of PBM for cardiac surgery patients involve anemia therapy, perioperative administration of antithrombotic drugs, intraoperative anticoagulation, and the use of hemostatic drugs. Unlike for adults, there is less evidence about the management of antithrombotic drugs and hemostatic drugs for pediatric cardiac surgery patients. Recombinant activated factor VII (rFVIIa) and desmopressin (DDAVP) are not recommended after pediatric cardiac surgery, whereas prothrombin complex concentrate could be considered in clinical trials. As for the controversies regarding the administration of rFVIIa and DDAVP after adult cardiac surgery by different societies, clinicians should exercise their clinical judgment based on individual patient features.

Associations of glyphosate exposure and serum sex steroid hormones among 6-19-year-old children and adolescents.

Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6-19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E2 (TT/E2) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E2 in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E2, FAI, and TT (p trend <0.05) was observed in female adolescents for the highest quartile of urinary glyphosate compared to the lowest quartile. However, no similar association was observed among male adolescents. Our findings suggest that exposure to glyphosate at the current level may decrease the levels of sex steroids in adolescents, particularly female adolescents. Considering the cross-sectional study design, further research is needed to confirm our findings.

Gut microbiota dysbiosis links chronic apical periodontitis to liver fibrosis in nonalcoholic fatty liver disease: Insights from a mouse model.

AIM: In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis. METHODOLOGY: Sixteen 7-week-old male apolipoprotein E knockout (apoE-/-) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography-mass spectrometry (LC-MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues. RESULTS: Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group. CONCLUSION: This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.

Sonic-assisted antibacterial photodynamic therapy: a strategy for enhancing lateral canal disinfection.

BACKGROUND: Bacterial infections in lateral canals pose challenges for root canal treatment. This in vitro study aims to evaluate the antibacterial efficacy of sonic-assisted methylene blue mediated antimicrobial photodynamic therapy (MB-aPDT) against Enterococcus faecalis (E. faecalis) in infected lateral canals. METHODS: Sixty-five premolars infected with E. faecalis in lateral canals were randomly divided into five groups (n = 13) and treated with : (1) 5.25% NaOCl (positive control); (2) Saline (negative control); (3) Sonic-assisted MB-aPDT; (4) 3% NaOCl + MB-aPDT; (5) 3% NaOCl + sonic-assisted MB-aPDT, respectively. The antibacterial efficacy was evaluated by the colony- counting method (CCM) and scanning electronic microscope (SEM). RESULTS: Both 5.25% NaOCl and the 3% NaOCl + sonic-assisted MB-aPDT exhibited the most effective while comparable antibacterial effects without significant statistical difference (P > 0.05). Furthermore, the antibacterial effect of the 3% NaOCl + MB-aPDT group was significantly higher compared to that of the sonic-assisted MB-aPDT group (P < 0.05). The SEM results demonstrated notable morphological alterations in E. faecalis across all experimental groups, except for the negative control group. CONCLUSION: The concentration of NaOCl can be reduced to a safe level while preserving its antibacterial efficacy through the synergism with the sonic-assisted MB-aPDT in this study.

Oligomeric Remodeling by Molecular Glues Revealed Using Native Mass Spectrometry and Mass Photometry.

Molecular glues stabilize interactions between E3 ligases and novel substrates to promote substrate degradation, thereby facilitating the inhibition of traditionally "undruggable" protein targets. However, most known molecular glues have been discovered fortuitously or are based on well-established chemical scaffolds. Efficient approaches for discovering and characterizing the effects of molecular glues on protein interactions are required to accelerate the discovery of novel agents. Here, we demonstrate that native mass spectrometry and mass photometry can provide unique insights into the physical mechanism of molecular glues, revealing previously unknown effects of such small molecules on the oligomeric organization of E3 ligases. When compared to well-established solution phase assays, native mass spectrometry provides accurate quantitative descriptions of molecular glue potency and efficacy while also enabling the binding specificity of E3 ligases to be determined in a single, rapid measurement. Such mechanistic insights should accelerate the rational development of molecular glues to afford powerful therapeutic agents.

Brown adipose tissue is not associated with cachexia or increased mortality in a retrospective study of patients with cancer.

Although brown fat is strongly associated with a constellation of cardiometabolic benefits in animal models and humans, it has also been tied to cancer cachexia. In humans, cancer-associated cachexia increases mortality, raising the possibility that brown fat in this context may be associated with increased cancer death. However, the effect of brown fat on cancer-associated cachexia and survival in humans remains unclear. Here, we retrospectively identify patients with and without brown fat on fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) scans obtained as part of routine cancer care and assemble a cohort to address these questions. We did not find an association between brown fat status and cachexia. Furthermore, we did not observe an association between brown fat and increased mortality in patients with cachexia. Our analyses controlled for confounding factors including age at cancer diagnosis, sex, body mass index, cancer site, cancer stage, outdoor temperature, comorbid conditions (heart failure, type 2 diabetes mellitus, coronary artery disease, hypertension, dyslipidemia, cerebrovascular disease), and ß-blocker use. Taken together, our results suggest that brown fat is not linked to cancer-associated cachexia and does not worsen overall survival in patients with cachexia.NEW & NOTEWORTHY This study finds that brown fat is not linked to cancer-associated cachexia. Moreover, this work shows that brown fat does not worsen overall survival in patients with cachexia.

Effects of amygdalin on ferroptosis and oxidative stress in diabetic retinopathy progression via the NRF2/ARE signaling pathway.

Oxidative stress has been involved in the pathogenesis of diabetic retinopathy (DR). Amygdalin is an effective component of bitter almond that exhibits excellent antioxidant properties. We explored the effects of amygdalin on ferroptosis and oxidative stress in high-glucose (HG)-stimulated human retinal endothelial cells (HRECs) via the NRF2/ARE pathway. HG-stimulated HRECs were used to establish a DR model. Cell viability was evaluated using the MTT assay. The release of lactate dehydrogenase was used to evaluate cell toxicity. The protein levels of NRF2, NQO1, and HO-1 were detected using western blotting. The GSH, GSSG, GPX4, SOD, CAT, MDA, and Fe2+ levels in the HRECs were also detected. Flow cytometry was used to detect reactive oxygen species (ROS) using a fluorescent probe. Immunofluorescence staining was performed to detect NRF2 expression. The results revealed that HG stimulation decreased the levels of GSH, GPX4, SOD, and CAT but increased those of MDA, ROS, GSSG, and Fe2+ in HRECs. Ferrostatin-1 treatment reversed the effects of HG stimulation, whereas erastin aggravated these effects. Amygdalin treatment relieved HG-induced injury in HRECs. Amygdalin treatment promoted the nuclear transport of NRF2 in HG-stimulated HRECs. NQO1 and HO-1 levels were upregulated in HG-stimulated HRECs after amygdalin treatment. An inhibitor of NRF2 reversed the effects of amygdalin. Therefore, amygdalin treatment inhibited ferroptosis and oxidative stress in HG-stimulated HRECs by activating the NRF2/ARE signaling pathway.

Novel Antiplatelet Activity of Ginsenoside Re Through the Inhibition of High Shear Stress-Induced Platelet Aggregation.

ABSTRACT: Bleeding is one of the most serious side effects of antiplatelet drugs. Efforts have been made to find new antiplatelet agents without bleeding complications. Shear-induced platelet aggregation (SIPA) occurs only under pathological conditions and is a promising target for overcoming bleeding problems. This work demonstrates that the ginsenoside Re selectively inhibits platelet aggregation induced by high shear stress. Human platelets were exposed to high shear stress using microfluidic chip technology, and aggregation, activation, and phosphatidylserine (PS) exposure were measured. The Von Willebrand Ristocetin Cofactor (vWF:RCo) assay and western blot were used to evaluate the effect of the vWF-GPⅠb/PI3K/Akt signal pathway. The coagulation and bleeding risk were evaluated by measuring the coagulation parameters PT, APTT, TT, and thromboelastography. The 3-dimensional morphology of platelet aggregates was observed by a microscopic 3-dimensional imaging. Re was a potent inhibitor of SIPA, with an IC 50 of 0.071 mg/mL. It effectively blocked shear stress-induced platelet activation without any significant toxicity. It was highly selective against SIPA, effectively inhibiting vWF-GPIb and the downstream PI3K/Akt signaling pathway. Most importantly, Re did not affect normal blood coagulation and did not increase the risk of bleeding. In conclusion, Re inhibits platelet activation through the inhibition of the vWF-GPIb/PI3K/Akt pathway. Thus, it might be considered as a new antiplatelet drug in the prevention of thrombosis without increasing the risk of bleeding.

Association between visceral fat area and serum uric acid in Chinese adults: A cross-sectional study.

BACKGROUND AND AIMS: Hyperuricemia has become a vital public health problem affecting the health of residents. The visceral fat area (VFA) is closely related to many chronic diseases. However, the association between VFA and hyperuricemia within the Chinese adult population remains nebulous. The aim of the research is to assess the relationship between VFA and serum uric acid levels. METHODS AND RESULTS: From June 2020 to June 2021, a total of 340 Chinese adults (240 in the control group and 100 in the hyperuricemia group) were recruited from the physical examination center of Hongqi Hospital Affiliated to Mudanjiang Medical University. General demographic characteristics were collected by questionnaire. VFA was measured by a body composition analyzer, and serum biochemical indices were detected by clinical laboratory. VFA in the hyperuricemia group was higher than in the control group (P＜0.05). Further, VFA demonstrated a positive correlation with serum uric acid level (rs = 0.370, P＜0.001). To further explore this relationship, we divided the VFA into quartiles (＜P25, P25-P50, P50-P75, ≥P75). Upon comparison with the ＜P25 group, we found the VFA in the P25-P50, P50-P75, and ≥P75 groups to be associated with a substantially escalated risk of hyperuricemia, even after adjusting for age, gender, body weight, fasting plasma glucose, calcium, alanine transaminase, urea, alkaline phosphatase, and γ-glutamyltransferase. The OR and 95% CI were 2.547 (1.023, 6.341), 3.788 (1.409, 10.187) and 3.723 (1.308, 10.595), respectively (P＜0.05). CONCLUSION: VFA has a positive correlation with serum uric acid levels and may serve as a crucial predictive marker for hyperuricemia.

Is oxidative stress involved in the hepatic inflammatory response to apical periodontitis? A comparative study in normal and hyperlipidaemic rat.

AIM: The aim of the study was to explore the involvement of oxidative stress (OS) in the hepatic inflammation induced by apical periodontitis (AP). Periapical, systemic and hepatic reaction to AP under hyperlipidaemia was also investigated. METHODOLOGY: A total of 16 male Sprague-Dawley rats were fed with a hyperlipidaemic diet (HD) whereas another 16 rats with a normal diet (ND). After 9 weeks, the first molars of the right maxilla and mandible of 8 HD and 8 ND rats were exposed to induce AP (ND, ND + AP, HD and HD + AP group). After 5 weeks, rats were euthanized, the haematological tissue was collected directly from the heart, and serum levels of inflammatory cytokines were measured. Liver tissue was analysed by haematoxylin-eosin and Masson staining, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect mRNA expression of inflammatory cytokines. Serum, periapical, and hepatic OS parameters including total oxidant status (TOS), total antioxidant capacity (TAOC) and oxidative stress index (OSI) were measured by enzyme-linked immunosorbent assay (ELISA). The area of AP lesion in the right maxilla or mandible was radiographically assessed. Student's t-test was performed on the periapical data. A one-way analysis of variance and the Kruskal-Wallis test were analysed for others. RESULTS: The HD + AP group had a larger AP lesion in the maxilla, compared with the ND + AP group (p < .05). The ND + AP group presented higher serum interleukin (IL)-18, IL-1ß, TOS, OSI levels, lower serum TOAC levels, higher hepatic tumour necrosis factor (TNF)-α mRNA expression and higher hepatic TOS, and OSI levels, compared with the ND group (p < .05). The HD + AP group had lower serum IL-4 level, higher serum IL-1ß level, and higher hepatic IL-6 and transforming growth factor (TGF) -ß1 mRNA expression, compared with the HD group (p < .05). CONCLUSIONS: Apical periodontitis could activate systemic and liver inflammation by promoting serum IL-18, 1L-1ß, TOS and OSI expression, enhancing hepatic TOS and OSI expression and inhibiting serum TOAC expression. AP under hyperlipidaemia led to more profound periapical bone destruction in the maxilla and elicit systemic and liver inflammatory responses through elevating serum levels of IL-1ß, descending serum IL-4 level and improving hepatic IL-6 and TGF-ß1 expression.

Gut microbiota may mediate the impact of chronic apical periodontitis on atherosclerosis in apolipoprotein E-deficient mice.

AIM: There are growing evidences linking chronic apical periodontitis (CAP) to atherosclerosis. Gut microbiota is found to be involved in the development of atherosclerosis. Recent studies have shown that CAP could change the diversity and composition of the gut microbiota. It was therefore, we hypothesized that gut microbiota and its metabolites could mediate the impact of CAP on atherosclerosis. METHODOLOGY: Twenty-four 5-week-old lipoprotein E knockout (apoE-/- ) mice were randomly divided into four groups: the CAP group, Con group, Co-CAP (cohoused with CAP) and Co-Con (cohoused with Con) group. In the CAP group, sterile cotton wool containing P. gingivalis was placed into the exposed pulp chamber, followed by coronal resin-based composite restoration of the bilateral maxillary first and second molars. In the Con group, a sham operation was performed. Biweekly, mice in the CAP group were anaesthetised to check the sealing of coronal access. Meanwhile, the animals in the Con group were anaesthetised. The cohousing approach was used to introduce gut microbiota from the CAP and Con groups into the Co-CAP and Co-Con groups, respectively. Alterations in the abundance and diversity of the gut microbiota were detected using 16S rRNA sequencing, Oil-red O staining was used to demonstrate the extent of lesions, and serum levels of trimethylamine N-oxide (TMAO), and immunohistochemistry of flavin-containing monooxygenase 3 (FMO3) in liver were used to assess TMAO-related metabolic alterations. RESULTS: Alterations of alpha and beta diversity were shown both in the CAP and the Co-CAP groups. Moreover, the percentage of atherosclerotic lesion area increased in the CAP and Co-CAP groups (p < .05). Linear discriminant analysis effect size (LEfSe) at the family level found the increases of Lachnospiraceae and Ruminococcaceae (p < .05), which were positively correlated with serum TMAO levels (p < .05). In the redundancy analysis technique (RDA), serum levels of TMAO were positively associated with the atherosclerotic lesions. Co-occurrence analysis revealed that the relative abundances of Lachnospiraceae and Porphyromonadacae were positively correlated with both the percentage of lesion area and TMAO level (p < .05). CONCLUSION: Thus, within the limitations of this study, the data suggest that the gut microbiota can mediate the effects of CAP on atherosclerosis.

A new sandwich-type electrochemiluminescence sensor based on HPSNs-NH2@Au NPs and AuPdPt NPs for determination of α(2,3)-sial-Gs.

A novel sandwich-type "on-off" electrochemiluminescence (ECL) biosensor for the determination of α(2,3)-sial-Gs was designed. Specifically, amino-functionalized porous silica nanoparticles (HPSNs-NH2) were first prepared and then decorated with gold nanoparticles (Au NPs) to form HPSNs-NH2@Au NP nanocomposite, which exhibited a strong ability to enhance ECL intensity with K2S2O8 as co-reactant (signal-on) and could immobilize the target-specific binding molecules of maackia amurensis lectin (MAL). Additionally, AuPdPt trimetallic nanoparticles were prepared to serve as a quenched ECL signal indicator (signal-off) with the ability of capturing the target non-specific binding molecules of 3-aminophenylboronic acid (APBA) to form a signal label. The sandwich-type ECL biosensor was constructed based on the structure of MAL-α(2,3)-sial-Gs-APBA and achieved a determination toward α(2,3)-sial-Gs with a wide linear range from 1 fg mL-1 to 10 ng mL-1 and a low detection limit of 0.5 fg mL-1. Furthermore, the proposed ECL biosensor showed satisfactory selectivity, stability, and reproducibility for α(2,3)-sial-Gs determination.

The protective role of curcumin in human dental pulp stem cells stimulated by lipopolysaccharide via inhibiting NF-κB p65 phosphorylation to suppress NLRP3 inflammasome activation.

OBJECTIVES: This study aims to investigate the anti-inflammatory effect of curcumin and underlying mechanisms regarding the modulation of the nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome in human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: The impact of curcumin on the viability of hDPSCs was evaluated. The effect of curcumin on the expression of IL-1ß and NLRP3 in hDPSCs stimulated by lipopolysaccharide (LPS) was assessed. Then, LPS-primed hDPSCs were pre-treated with curcumin before ATP triggering NLRP3 inflammasome activation, and NLRP3 inflammasome-related mediators were assessed. The mechanism of curcumin inactivation of LPS plus ATP-induced inflammasome associated with NF-κB pathway was explored. The NF-κB pathway related pro-inflammatory mediators at mRNA and protein levels were evaluated. The expression of NF-κB p65 and phosphorylation p65 was visualized after curcumin or NF-κB inhibitor administrating respectively in hDPSCs with an activated NLRP3 inflammasome. Statistical analysis was performed. RESULTS: While curcumin at the concentration of 0.5-5 µM showed no obvious impact on the viability of hDPSCs, it significantly decreased IL-1ß and NLRP3 mRNA expression in LPS-induced hDPSCs in a dose-dependent manner. Curcumin significantly inhibited the LPS plus ATP-primed NLRP3 inflammasome activation in hDPSCs (NLRP3, ASC, caspase-1, and IL-1ß). Curcumin evidently attenuated the LPS plus ATP-induced expression of NF-κB pathway-related pro-inflammatory mediators (IL-6, IL-8, TNF-α, and COX-2). Furthermore, curcumin effectively reduced p65 phosphorylation, which acts as an NF-κB inhibitor in hDPSCs with an activated NLRP3 inflammasome. CONCLUSIONS: Curcumin pre-treatment may exert an anti-inflammatory role via inactivation of the NLRP3 inflammasome by inhibiting NF-κB p65 phosphorylation in cultured hDPSCs. CLINICAL RELEVANCE: Curcumin may have therapeutic potential in pulp inflammation.

A mixed-reality stimulator for lumbar puncture training: a pilot study.

BACKGROUND: The simulation is one of the basic methods of medical education, which is often used for procedural skills training. However, the existing simulator lacks internal anatomical landmarks. The study developed a mixed-reality stimulator and evaluated its usability and feasibility in lumbar puncture training. METHODS: The study recruited 40 subjects, including medical students, residents and faulty with varied levels of experience. Before training, participants completed the questionnaire about the basic information and watched a presentation about mixed reality. After practicing on mixed-reality stimulator, which provided internal anatomical structure, the examination was carried out and the results were documented. At the end of the training, trainees completed a survey of MR technology. RESULTS: In this study, participants generally believed that the MR technology was very realistic (90%), and that the presentation of internal anatomy could help the operation (95%). Moreover, 72.5% and 75%, respectively, strongly agreed that the MR technology promoted learning and should be used in medical training. After this training, the success rate of puncture and the puncture time were significantly improved in experienced and non-experienced participants. CONCLUSION: The existing simulator was easy to be transformed into MR simulator. This study showed the usability and feasibility of MR simulator in lumbar puncture training. As a potentially good tool to simulated medical skills training, next, MR technology would be developed and evaluated in more clinical skills teaching scenarios.