Exhaled Anesthetic Xenon Regeneration by Gas Separation Using a Metal-Organic Framework with Sorbent-Sorbate Induced-Fit.

Noble gas xenon (Xe) is an excellent anesthetic gas, but its rarity, high cost and constrained production prohibits wide use in medicine. Here, we have developed a closed-circuit anesthetic Xe recovery and reusage process with highly effective CO2-specific adsorbent CUPMOF-5 that is promising to solve the anesthetic Xe supply problem. CUPMOF-5 possesses spacious cage cavities interconnected in four directions by confinement throat apertures of ~3.4 Å, which makes it an ideal molecular sieving of CO2 from Xe, O2, N2 with the benchmark selectivity and high uptake capacity of CO2. In-situ single-crystal X-ray diffraction (SCXRD) and computational simulation solidly revealed the vital sieving role of the confined throat and the sorbent-sorbate induced-fit strengthening binding interaction to CO2. CUPMOF-5 can remove 5% CO2 even from actual moist exhaled anesthetic gases, and achieves the highest Xe recovery rate (99.8%) so far, as verified by breakthrough experiments. This endows CUPMOF-5 great potential for the on-line CO2 removal and Xe recovery from anesthetic closed-circuits.

Role of Trace Cadmium Exposure on the Development of Occlusal Traumatic Temporomandibular Arthritis.

OBJECTIVE: To investigate whether heavy metal cadmium acts as a risk factor for temporomandibular joint disorder disease and to study its pathogenic mechanism. METHODS: A total of 57 rats were allocated into 6 distinct groups, distinguished by 2 interventions: occlusal elevation and cadmium water gavage. These groups included a blank control group, occlusal elevation group, occlusal elevation + 0.42 mg/mL cadmium water gavage group, occlusal elevation + 4.2 mg/mL cadmium water gavage group, no occlusal elevation + 0.42 mg/mL cadmium water gavage group, and no occlusal elevation + 4.2 mg/mL cadmium water gavage group. The impact of cadmium exposure on cartilage oxidative stress was evaluated through the assessment of SOD, CAT, GST, and GSH-Px enzyme activities. In addition, the influence of cadmium exposure on alterations in the extracellular matrix and inflammatory mediators was examined by analyzing the expression levels of type II collagen, protein aggregation polysaccharide, glycosaminoglycan, IL1ß, IL-6, and TNF-α. Histologic examination of the condylar process cartilage of rats in the occlusal elevation + cadmium water gavage group was conducted to ascertain the occurrence of osteoarthritis. RESULTS: The variance in the expression levels of inflammatory factors did not demonstrate statistical significance between the occlusal elevation group and the blank control group; however, statistical significance was observed between the occlusal elevation + cadmium water gavage group and both the control and occlusal elevation groups. CONCLUSION: The severity of inflammation and condylar lesions correlates directly with the concentration of cadmium.

Highly extensile approach for comminuted ulna coronoid process fractures with mini-plate fixation: a case series of 31 patients.

BACKGROUND: For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up. METHODS: Thirty-one patients diagnosed with coronoid fractures accompanied with a "terrible triad" or posteromedial rotational instability between April 2012 and October 2018 were included in the analysis. Anatomical reduction and mini-plate fixation of coronoid fractures were performed using an anterior minimally invasive approach. Patient-reported outcomes were evaluated using the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), and the visual analog score (VAS). The time of fracture healing and complications were recorded. RESULTS: The mean follow-up time was 26.7 months (range, 14-60 months). The average time to radiological union was 3.6 ± 1.3 months. During the follow-up period, the average elbow extension was 6.8 ± 2.9° while the average flexion was 129.6 ± 4.6°. According to Morrey's criteria, 26 (81%) elbows achieved a normal desired ROM. At the last follow-up, the mean MEPI score was 98 ± 3.3 points. There were no instances of elbow instability, elbow joint stiffness, subluxation or dislocation, infection, blood vessel complications, or nerve palsy. Overall, 10 elbows (31%) experienced heterotopic ossification. CONCLUSION: An anterior minimally invasive approach allows satisfactory fixation of coronoid fractures while reducing incision complications due to over-dissection of soft tissue injuries. In addition, this incision does not compromise the soft tissue stability of the elbow joint and allows the patient a more rapid return to rehabilitation exercises.

Potential clinical applications of advanced genomic analysis in cerebral palsy.

Cerebral palsy (CP) has historically been attributed to acquired insults, but emerging research suggests that genetic variations are also important causes of CP. While microarray and whole-exome sequencing based studies have been the primary methods for establishing new CP-gene relationships and providing a genetic etiology for individual patients, the cause of their condition remains unknown for many patients with CP. Recent advancements in genomic technologies offer additional opportunities to uncover variations in human genomes, transcriptomes, and epigenomes that have previously escaped detection. In this review, we outline the use of these state-of-the-art technologies to address the molecular diagnostic challenges experienced by individuals with CP. We also explore the importance of identifying a molecular etiology whenever possible, given the potential for genomic medicine to provide opportunities to treat patients with CP in new and more precise ways.

TCFormer: Visual Recognition via Token Clustering Transformer.

Transformers are widely used in computer vision areas and have achieved remarkable success. Most state-of-the-art approaches split images into regular grids and represent each grid region with a vision token. However, fixed token distribution disregards the semantic meaning of different image regions, resulting in sub-optimal performance. To address this issue, we propose the Token Clustering Transformer (TCFormer), which generates dynamic vision tokens based on semantic meaning. Our dynamic tokens possess two crucial characteristics: (1) Representing image regions with similar semantic meanings using the same vision token, even if those regions are not adjacent, and (2) concentrating on regions with valuable details and represent them using fine tokens. Through extensive experimentation across various applications, including image classification, human pose estimation, semantic segmentation, and object detection, we demonstrate the effectiveness of our TCFormer. The code and models for this work are available at https://github.com/zengwang430521/TCFormer.

Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus.

Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats (220‒250 g) are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, 10 g/L in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.

Comparison of Short Curved Stems and Standard-length Single Wedged Stems for Cementless Total Hip Arthroplasty.

Purpose: The purpose of this study was to compare the clinical and radiographic outcomes with use of short-curved stems versus standard-length single wedged stems over a minimum follow-up period of five years. Materials and Methods: A retrospective study of primary total hip arthroplasties performed using the Fitmore® stem (127 hips, 122 patients) and the M/L taper® stem (195 hips, 187 patients) between October 2012 and June 2014 was conducted. The clinical and radiographic outcomes were obtained for evaluation over a minimum follow-up period of five years. Results: In both the Fitmore® and M/L taper® groups, the mean Harris hip score improved from 52.4 and 48.9 preoperatively to 93.3 and 94.5 at the final follow-up, respectively (P=0.980). The mean Western Ontario and McMaster Universities Osteoarthritis Index scores also improved from 73.3 and 76.8 preoperatively to 22.9 and 25.6 at the final follow-up, respectively (P=0.465). Fifteen hips (Fitmore®: 14 hips; M/L taper®: one hip, P<0.001) developed intraoperative cracks and were treated simultaneously with cerclage wiring. Radiography showed a radiolucent line in 24 hips in the Fitmore® group and 12 hips in the M/L taper® group (P=0.125). Cortical hypertrophy was detected in 29 hips (Fitmore® group: 28 hips; M/L taper® group: one hip, P<0.001). Conclusion: Similarly favorable clinical and radiographic outcomes were achieved with use of both short-curved stems and standard-length single wedged stems. However, higher cortical hypertrophy and a higher rate of femoral crack were observed with use of Fitmore® stems.

Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics.

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting.

Toward Enhancing Low Temperature Performances of Lithium-Ion Transport for Metal-Organic Framework-Based Solid-State Electrolyte: Nanostructure Engineering or Crystal Morphology Controlling.

Metal-organic frameworks (MOFs) have emerged as attractive candidates for Li+ conducting electrolytes due to their regular channels and controllable morphology, making their presence prominent in the field of solid-state lithium batteries. However, most MOF-based electrolytes are researched at or near room temperature, which poses a challenge to their practical applications at low temperatures. Herein, a thin layer flower-shaped 2D Cu-MOF (CuBDC-10)-based solid-state electrolytes (SSEs) for lithium-ion batteries (LIBs) are developed for facilitating Li+ transport at lower temperatures, which achieve an ion conductivity of 10-4 S cm-1 at -30 °C. The CuBDC-10-based SSE exhibits outstanding ionic conductivity over a wide temperature range of -40 to 100 °C (0.073-3.68 × 10-3 S cm-1). This work provides strategies for exploring MOF-based SSEs with high ionic transport performances at low temperatures.

TRIM71 mutations cause a neurodevelopmental syndrome featuring ventriculomegaly and hydrocephalus.

Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly, is one of the most common reasons for pediatric brain surgery. Recent studies have implicated lin-41 (lineage variant 41)/TRIM71 (tripartite motif 71) as a candidate CH risk gene, however, TRIM71 variants have not been systematically examined in a large patient cohort or conclusively linked with an OMIM syndrome. Through cross-sectional analysis of the largest assembled cohort of patients with cerebral ventriculomegaly, including neurosurgically-treated CH (totaling 2,697 parent-proband trios and 8,091 total exomes), we identified 13 protein-altering de novo variants (DNVs) in TRIM71 in unrelated children exhibiting variable ventriculomegaly, CH, developmental delay, dysmorphic features, and other structural brain defects including corpus callosum dysgenesis and white matter hypoplasia. Eight unrelated patients were found to harbor arginine variants, including two recurrent missense DNVs, at homologous positions in RPXGV motifs of different NHL domains. Seven additional patients with rare, damaging, unphased or transmitted variants of uncertain significance were also identified. NHL-domain variants of TRIM71 exhibited impaired binding to the canonical TRIM71 target CDKN1A; other variants failed to direct the subcellular localization of TRIM71 to processing bodies. Single-cell transcriptomic analysis of human embryos revealed expression of TRIM71 in early first-trimester neural stem cells of the brain. These data show TRIM71 is essential for human brain morphogenesis and that TRIM71 mutations cause a novel neurodevelopmental syndrome featuring ventriculomegaly and CH.

Coexistence of adeno-associated virus 2 with adenovirus 18 or herpesvirus may be associated with severe lingual papillomatosis in an immunocompromised individual.

Next-generation sequencing (NGS) has significantly improved the accuracy and efficiency of pathogen diagnosis for a wide range of diseases. In this study, viral metagenomics analysis was conducted on fecal and tissue samples from a 13-year-old recipient of hematopoietic stem cell transplantation (HSCT) afflicted with severe lingual papillomatosis. The analysis revealed a high abundance of adeno-associated virus 2 (AAV2), alongside potential helper viruses, herpesvirus type 1 (HSV-1), and the uncommon adenovirus serotype 18 (AdV18). Although a direct causal relationship was not definitively established, the concurrence of these viruses indicated a plausible link to the development of severe lingual papillomatosis in immunocompromised individuals. Notably, the study generated a complete genome sequence of AdV18, offering insights into adenovirus genetic variability, origin, and pathogenicity. Noteworthy findings include three amino acid substitutions in the polymerase and one in the hexon, distinguishing them from previously published strains of AdV18. Phylogenetic analysis unveiled a close relationship between both the polymerase and hexon regions of AdV18 in our study and previously reported AdV18 sequences. This study underscores the pivotal role of comprehensive viral scrutiny in elucidating infections among HSCT patients with lingual papillomatosis.

Hydrogen Sulfide Ameliorates Heart Aging by Downregulating Matrix Metalloproteinase-9.

PURPOSE: Aging contributes significantly to cardiovascular diseases and cardiac dysfunction, leading to the upregulation of matrix metalloproteinase-9 (MMP-9) in the heart and a significant decrease in hydrogen sulfide (H2S) content, coupled with impaired cardiac diastolic function. This study explores whether supplementing exogenous hydrogen sulfide during aging ameliorates the decline in H2S concentration in the heart, suppresses MMP-9 expression, and improves the age-associated impairment in cardiac morphology and function. METHODS: We collected plasma from healthy individuals of different ages to determine the relationship between aging and H2S and MMP-9 levels through Elisa detection and liquid chromatography-tandem mass spectrometry (LC/MC) detection of plasma H2S content. Three-month-old mice were selected as the young group, while 18-month-old mice were selected as the old group, and sodium hydrosulfide (NaHS) was injected intraperitoneally from 15 months old until 18 months old as the old + NaHS group. Plasma MMP-9 content was detected using Elisa, plasma H2S content, cardiac H2S content, and cystathionine gamma-lyase (CSE) activity were detected using LC/MC, and cardiac function was detected using echocardiography. Heart structure was assessed using hematoxylin and eosin staining, Masone staining was used to detect the degree of cardiac fibrosis, while western blot was used to detect the expression of MMP-9, CSE, and aging marker proteins. Knockdown of MMP-9 and CSE in H9c2 cells using small interfering RNA was carried out to determine the upstream-downstream relationship between MMP-9 and CSE. RESULTS: H2S content in the plasma of healthy individuals decreases with escalating age, whereas MMP-9 level rises with age progression. Aging leads to a decrease in H2S levels in the heart and plasma of mice, severe impairment of cardiac diastolic function, interstitial relaxation, and fibrosis of the heart. Supplementing with exogenous H2S can improve these phenomena. CONCLUSION: H2S maintains the structure and function of the heart by inhibiting the expression of MMP-9 during the aging process.

The effects of grassland degradation on the genetic structure of a small mammal.

Grassland degradation is challenging the health of grassland ecosystems globally and causing biodiversity decline. Previous studies have demonstrated the impact of grassland degradation on the abundance and behavior of small mammals. Little is known about how it affects the genetic structure of gregarious mammals in the wild. This study explores the effects of grassland degradation on the genetic structure of a small burrowing mammal, plateau pika (Ochotona curzoniae). We used nine microsatellite loci to analyze the genetic diversity and genetic differentiation between colonies and genetic relatedness between individuals within the colony. We found that pikas in severely degraded grasslands had a significantly higher genetic diversity within colonies, a higher level of gene flow between colonies, and a lower genetic differentiation between colonies compared to pikas in less degraded grasslands. Individuals within colonies had a significantly lower genetic relatedness in severely degraded grasslands than in less degraded grasslands. This study has provided potential evidence of a significant impact of grassland degradation on the genetic structure of pikas, which has caused a breakdown of their kin-selected colony structure.

Whole-soil warming leads to substantial soil carbon emission in an alpine grassland.

The sensitivity of soil organic carbon (SOC) decomposition in seasonally frozen soils, such as alpine ecosystems, to climate warming is a major uncertainty in global carbon cycling. Here we measure soil CO2 emission during four years (2018-2021) from the whole-soil warming experiment (4 °C for the top 1 m) in an alpine grassland ecosystem. We find that whole-soil warming stimulates total and SOC-derived CO2 efflux by 26% and 37%, respectively, but has a minor effect on root-derived CO2 efflux. Moreover, experimental warming only promotes total soil CO2 efflux by 7-8% on average in the meta-analysis across all grasslands or alpine grasslands globally (none of these experiments were whole-soil warming). We show that whole-soil warming has a much stronger effect on soil carbon emission in the alpine grassland ecosystem than what was reported in previous warming experiments, most of which only heat surface soils.

The dynamic-static dual-branch deep neural network for urban speeding hotspot identification using street view image data.

The visual information regarding the road environment can influence drivers' perception and judgment, often resulting in frequent speeding incidents. Identifying speeding hotspots in cities can prevent potential speeding incidents, thereby improving traffic safety levels. We propose the Dual-Branch Contextual Dynamic-Static Feature Fusion Network based on static panoramic images and dynamically changing sequence data, aiming to capture global features in the macro scene of the area and dynamically changing information in the micro view for a more accurate urban speeding hotspot area identification. For the static branch, we propose the Multi-scale Contextual Feature Aggregation Network for learning global spatial contextual association information. In the dynamic branch, we construct the Multi-view Dynamic Feature Fusion Network to capture the dynamically changing features of a scene from a continuous sequence of street view images. Additionally, we designed the Dynamic-Static Feature Correlation Fusion Structure to correlate and fuse dynamic and static features. The experimental results show that the model has good performance, and the overall recognition accuracy reaches 99.4%. The ablation experiments show that the recognition effect after the fusion of dynamic and static features is better than that of static and dynamic branches. The proposed model also shows better performance than other deep learning models. In addition, we combine image processing methods and different Class Activation Mapping (CAM) methods to extract speeding frequency visual features from the model perception results. The results show that more accurate speeding frequency features can be obtained by using LayerCAM and GradCAM-Plus for static global scenes and dynamic local sequences, respectively. In the static global scene, the speeding frequency features are mainly concentrated on the buildings and green layout on both sides of the road, while in the dynamic scene, the speeding frequency features shift with the scene changes and are mainly concentrated on the dynamically changing transition areas of greenery, roads, and surrounding buildings. The code and model used for identifying hotspots of urban traffic accidents in this study are available for access: https://github.com/gwt-ZJU/DCDSFF-Net.

Out-of-equilibrium interactions and collective locomotion of colloidal spheres with squirming of nematoelastic multipoles.

Many living and artificial systems show similar emergent behavior and collective motions on different scales, starting from swarms of bacteria to synthetic active particles, herds of mammals, and crowds of people. What all these systems often have in common is that new collective properties like flocking emerge from interactions between individual self-propelled or driven units. Such systems are naturally out-of-equilibrium and propel at the expense of consumed energy. Mimicking nature by making self-propelled or externally driven particles and studying their individual and collective motility may allow for deeper understanding of physical underpinnings behind collective motion of large groups of interacting objects or beings. Here, using a soft matter system of colloids immersed into a liquid crystal, we show that resulting so-called nematoelastic multipoles can be set into a bidirectional locomotion by external oscillating electric fields. Out-of-equilibrium elastic interactions between such colloidal objects lead to collective flock-like behaviors emerging from time-varying elasticity-mediated interactions between externally driven propelling particles. Repulsive elastic interactions in the equilibrium state can be turned into attractive interactions in the out-of-equilibrium state under applied external electric fields. We probe this behavior at different number densities of colloidal particles and show that particles in dense dispersions collectively select the same direction of a coherent motion due to elastic interactions between near neighbors. In our experimentally implemented design, their motion is highly ordered and without clustering or jamming often present in other colloidal transport systems, which is promising for technological and fundamental-science applications, like nano-cargo transport, out-of-equilibrium assembly, and microrobotics.

Application of 18ß-glycyrrhetinic acid in the structural modification of natural products: a review.

18ß-Glycyrrhetinic acid (GA) is an oleane-type pentacyclic triterpene saponin obtained from glycyrrhizic acid by removing 2 glucuronic acid groups. GA and its analogues are active substances of glycyrrhiza aicd, with similar structure and important pharmacological effects such as anti-inflammatory, anti-diabetes, anti-tumor and anti-fibrosis. Although GA combined compounds are in the clinical trial stages, its application potential is severely restricted by its low bioavailability, water solubility and membrane permeability. In this article, synthetic methods and structure-activity relationships (SARs) of GA derivatives from 2018 to present are reviewed based on pharmacological activity. It is hoped that this review can provide reference for the future development of potential GA preclinical candidate compounds, and furnish ideas for the development of pentacyclic triterpenoid lead compounds.

Investigation of peri-implant diseases prevalence and related risk indicators in patients with treated severe periodontitis over 4 years after restoration.

Background/purpose: History of periodontitis is a well-documented risk indicator of peri-implantitis. However, the influence of severity of periodontitis is still unclear, especially for severe periodontitis. This study was aimed to investigate the prevalence of peri-implant disease and analyze the risk indicators in patients with treated severe periodontitis. Materials and methods: A total of 182 implants from 88 patients (44 males and 44 females) with severe periodontitis with a mean fellow-up period of 76.5 months were enrolled in this study. Patient and implant information, and periodontal and peri-implant conditions were collected to evaluate the prevalence of peri-implant disease and risk indicators. Results: The prevalence of peri-implantitis was 9.1% and 6.6% at the patient-level and implant-level. The prevalence of peri-implant mucositis was 76.1% and 51.1% at the patient-level and implant-level. Risk indicators of peri-implantitis included older age (OR: 1.132), poor proximal cleaning habits (OR: 14.218), implants in anterior area (OR: 10.36), poor periodontal disease control (OR: 12.76), high peri-implant plaque index (OR: 4.27), and keratinized tissue width (KTW)＜2 mm (OR: 19.203). Conclusion: Implants in patients with severe periodontitis after periodontal treatment and maintenance show a low prevalence (9.1%) of peri-implantitis and a relatively high prevalence (76.2%) of peri-implant mucositis. Patient age, peri-implant proximal cleaning habits, implant position, periodontal disease control, peri-implant plaque index, and KTW are associated with prevalence of peri-implantitis.

Trimethylamine-N-oxide aggravated the sympathetic excitation in D-galactose induced aging rats by down-regulating P2Y12 receptor in microglia.

This study aimed to determine whether trimethylamine N-oxide (TMAO) was involved in sympathetic activation in aging and the underlying mechanisms. Our hypothesis is TMAO reduces P2Y12 receptor (P2Y12R) and induces microglia-mediated inflammation in the paraventricular nucleus (PVN), then leading to sympathetic activation in aging. This study involved 18 young adults and 16 old adults. Aging rats were established by injecting D-galactose (D-gal, 200 mg/kg/d) subcutaneously for 12 weeks. TMAO (120 mg/kg/d) or 1% 3, 3-dimethyl-l-butanol (DMB) was administrated via drinking water for 12 weeks to investigate their effects on neuroinflammation and sympathetic activation in aging rats. Plasma TMAO, NE and IL-1ß levels were higher in old adults than in young adults. In addition, standard deviation of all normal to normal intervals (SDNN) and standard deviation of the average of normal to normal intervals (SDANN) were lower in old adults and negatively correlated with TMAO, indicating sympathetic activation in old adults, which is associated with an increase in TMAO levels. Treatment of rats with D-gal showed increased senescence-associated protein levels and microglia-mediated inflammation, as well as decreased P2Y12R protein levels in PVN. Plasma TMAO, NE and IL-1ß levels were increased, accompanied by enhanced renal sympathetic nerve activity (RSNA). While TMAO treatment exacerbated the above phenomenon, DMB mitigated it. These findings suggest that TMAO contributes to sympathetic hyperactivity in aging by downregulating P2Y12R in microglia and increasing inflammation in the PVN. These results may provide promising new target for the prevention and treatment of aging and aging-related diseases.

Endothelial lincRNA-p21 alleviates cerebral ischemia/reperfusion injury by maintaining blood-brain barrier integrity.

Blood-brain barrier (BBB) disruption is increasingly recognized as an early contributor to the pathophysiology of cerebral ischemia/reperfusion (I/R) injury, and is also a key event in triggering secondary damage to the central nervous system. Recently, long non-coding RNA (lncRNA) have been found to be associated with ischemic stroke. However, the roles of lncRNA in BBB homeostasis remain largely unknown. Here, we report that long intergenic non-coding RNA-p21 (lincRNA-p21) was the most significantly down-regulated lncRNA in human brain microvascular endothelial cells (HBMECs) after oxygen and glucose deprivation/reoxygenation (OGD/R) treatment among candidate lncRNA, which were both sensitive to hypoxia and involved in atherosclerosis. Exogenous brain-endothelium-specific overexpression of lincRNA-p21 could alleviate BBB disruption, diminish infarction volume and attenuate motor function deficits in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Further results showed that lincRNA-p21 was critical to maintain BBB integrity by inhibiting the degradation of junction proteins under MCAO/R and OGD/R conditions. Specifically, lincRNA-p21 could inhibit autophagy-dependent degradation of occludin by activating PI3K/AKT/mTOR signaling pathway. Besides, lincRNA-p21 could inhibit VE-cadherin degradation by binding with miR-101-3p. Together, we identify that lincRNA-p21 is critical for BBB integrity maintenance, and endothelial lincRNA-p21 overexpression could alleviate cerebral I/R injury in mice, pointing to a potential strategy to treat cerebral I/R injury.