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1.
BMC Musculoskelet Disord ; 25(1): 522, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970051

ABSTRACT

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.


Subject(s)
Bone Plates , Elbow Joint , Fracture Fixation, Internal , Fractures, Comminuted , Range of Motion, Articular , Ulna Fractures , Humans , Male , Female , Ulna Fractures/surgery , Ulna Fractures/diagnostic imaging , Fracture Fixation, Internal/methods , Fracture Fixation, Internal/instrumentation , Middle Aged , Adult , Fractures, Comminuted/surgery , Fractures, Comminuted/diagnostic imaging , Elbow Joint/surgery , Elbow Joint/diagnostic imaging , Elbow Joint/physiopathology , Treatment Outcome , Retrospective Studies , Follow-Up Studies , Minimally Invasive Surgical Procedures/methods , Minimally Invasive Surgical Procedures/instrumentation , Fracture Healing , Aged , Patient Reported Outcome Measures , Young Adult
2.
EBioMedicine ; 106: 105229, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970919

ABSTRACT

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.

3.
Angew Chem Int Ed Engl ; : e202407840, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953248

ABSTRACT

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.

4.
Virol Sin ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38914259

ABSTRACT

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.

5.
ACS Appl Mater Interfaces ; 16(26): 33954-33962, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38904988

ABSTRACT

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.

6.
Article in English | MEDLINE | ID: mdl-38884920

ABSTRACT

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.

7.
Hip Pelvis ; 36(2): 120-128, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38825821

ABSTRACT

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.

8.
Article in English | MEDLINE | ID: mdl-38863438

ABSTRACT

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.

9.
Brain ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833623

ABSTRACT

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.

10.
Proc Natl Acad Sci U S A ; 121(27): e2314702121, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38916997

ABSTRACT

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.


Subject(s)
Cilia , Hydrocephalus , Microtubules , Animals , Hydrocephalus/genetics , Hydrocephalus/pathology , Hydrocephalus/metabolism , Humans , Mice , Microtubules/metabolism , Male , Cilia/metabolism , Cilia/pathology , Female , Katanin/metabolism , Katanin/genetics , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/pathology , Autism Spectrum Disorder/metabolism , Neurons/metabolism , Ependyma/metabolism , Ependyma/pathology , ATPases Associated with Diverse Cellular Activities/genetics , ATPases Associated with Diverse Cellular Activities/metabolism , Pyramidal Cells/metabolism , Pyramidal Cells/pathology
11.
Nat Commun ; 15(1): 4489, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802385

ABSTRACT

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.

12.
Integr Zool ; 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704846

ABSTRACT

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.

13.
Accid Anal Prev ; 203: 107636, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38776837

ABSTRACT

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.


Subject(s)
Accidents, Traffic , Automobile Driving , Cities , Deep Learning , Image Processing, Computer-Assisted , Neural Networks, Computer , Humans , Accidents, Traffic/prevention & control , Image Processing, Computer-Assisted/methods
14.
Mol Divers ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38683490

ABSTRACT

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.

15.
Chem Commun (Camb) ; 60(41): 5369-5390, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38687504

ABSTRACT

Solid-state electrolytes (SSEs) are the key materials in the new generation of all-solid-state lithium ion/metal batteries. Metal-organic frameworks (MOFs) are ideal materials for developing solid electrolytes because of their structural diversity and porous properties. However, there are several significant issues and obstacles involved, such as lower ion conductivity, a smaller ion transport number, a narrower electrochemical stability window and poor interface contact. In this review, a comprehensive analysis and summary of the unique ion-conducting behavior of MOF-based electrolytes in rechargeable batteries are presented, and the different design principles of MOF-based SSEs are classified and emphasized. Accordingly, four design principles for achieving these MOF-based SSEs are presented and the influence of SSEs combined with MOFs on the electrochemical performance of the batteries is described. Finally, the challenges in the application of MOF materials in lithium ion/metal batteries are explored, and directions for future research on MOF-based electrolytes are proposed. This review will deepen the understanding of MOF-based electrolytes and promote the development of high-performance solid-state lithium ion/metal batteries. This review not only provides theoretical guidance for research on new MOF-based SSE systems, but also contributes to further development of MOFs applied to rechargeable batteries.

16.
Hepatology ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38557779

ABSTRACT

BACKGROUND AND AIMS: In the classical form of α1-antitrypsin deficiency, a misfolded variant α1-antitrypsin Z accumulates in the endoplasmic reticulum of liver cells and causes liver cell injury by gain-of-function proteotoxicity in a sub-group of affected homozygotes but relatively little is known about putative modifiers. Here, we carried out genomic sequencing in a uniquely affected family with an index case of liver failure and 2 homozygous siblings with minimal or no liver disease. Their sequences were compared to sequences in well-characterized cohorts of homozygotes with or without liver disease, and then candidate sequence variants were tested for changes in the kinetics of α1-antitrypsin variant Z degradation in iPS-derived hepatocyte-like cells derived from the affected siblings themselves. APPROACH AND RESULTS: Specific variants in autophagy genes MTMR12 and FAM134A could each accelerate the degradation of α1-antitrypsin variant Z in cells from the index patient, but both MTMR12 and FAM134A variants were needed to slow the degradation of α1-antitrypsin variant Z in cells from a protected sib, indicating that inheritance of both variants is needed to mediate the pathogenic effects of hepatic proteotoxicity at the cellular level. Analysis of homozygote cohorts showed that multiple patient-specific variants in proteostasis genes are likely to explain liver disease susceptibility at the population level. CONCLUSIONS: These results validate the concept that genetic variation in autophagy function can determine susceptibility to liver disease in α1-antitrypsin deficiency and provide evidence that polygenic mechanisms and multiple patient-specific variants are likely needed for proteotoxic pathology.

17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 532-540, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660863

ABSTRACT

OBJECTIVE: To investigate the molecular mechanism of proteolytic cleavage of unusually large von Willebrand Factor(ULVWF) on endothelial cells by ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats-13) in the absence of fluid shear stress, so as to provide a theoretical basis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP) and other thrombotic disorders. METHODS: The ADAMTS13-mediated proteolysis of ULVWF on the surface of endothelial cells in the absence of fluid shear stress was observed through immunofluorescence microscopy. The variation in VWF antigen levels in the conditioned media were determined by ELISA assay. The levels of VWF and the proteolytic fragments released into the conditioned media were determined by ELISA assay and Western blot in the absence and presence of fluid shear stress or FVIII. The effect of ADAMTS13-mediated ULVWF cleavage on the normal distribution of plasma VWF multimers was evaluated by multimer analysis. Histamine stimulated human umbilical vein endothelial cells (HUVECs) were incubated with ADAMTS13 and various N- and C-terminally truncated mutants. Then the ULVWF that maintained binding to the cells were observed through immunofluorescence microscopy and the soluble ULVWF released from endothelial cells was determined by ELISA, so as to demonstrate the domains of ADAMTS13 required for proteolysis of ULVWF on endothelial cells. RESULTS: The ULVWF strings on the endothelial cell surface were rapidly proteolyzed by recombinant and plasma ADAMTS13 in the absence of fluid shear stress. This proteolytic processing of ULVWF depended on incubation time and ADAMTS13 concentration, but not shear stress and FVIII. The distribution of VWF releaseded by ADAMTS13-mediated proteolysis was quite similar to that secreted by endothelial cells under histamine stimulation, suggesting the ULVWF cleavage occured at the cell surface. The proteolysis of the ULVWF on endothelial cells required the Cys-rich(CysR) and spacer domains, but not the TSP1 2-8 and CUB domains of ADAMTS13. CONCLUSION: The ULVWF polymers on endothelial cells are sensitive to ADAMTS13-mediated cleavage even in the absence of fluid shear stress. The findings provide novel insight into the molecular mechanism of ADAMTS13-mediated ULVWF cleavage at the cellular level and may contribute to understanding of the pathogenesis of TTP and other thrombotic disorders.


Subject(s)
ADAMTS13 Protein , Endothelial Cells , Stress, Mechanical , von Willebrand Factor , Humans , ADAM Proteins/metabolism , ADAMTS13 Protein/metabolism , Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells , Proteolysis , Purpura, Thrombotic Thrombocytopenic/metabolism , von Willebrand Factor/chemistry , von Willebrand Factor/metabolism
19.
Elife ; 122024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647539

ABSTRACT

Warming and precipitation anomalies affect terrestrial carbon balance partly through altering microbial eco-physiological processes (e.g., growth and death) in soil. However, little is known about how such processes responds to simultaneous regime shifts in temperature and precipitation. We used the 18O-water quantitative stable isotope probing approach to estimate bacterial growth in alpine meadow soils of the Tibetan Plateau after a decade of warming and altered precipitation manipulation. Our results showed that the growth of major taxa was suppressed by the single and combined effects of temperature and precipitation, eliciting 40-90% of growth reduction of whole community. The antagonistic interactions of warming and altered precipitation on population growth were common (~70% taxa), represented by the weak antagonistic interactions of warming and drought, and the neutralizing effects of warming and wet. The members in Solirubrobacter and Pseudonocardia genera had high growth rates under changed climate regimes. These results are important to understand and predict the soil microbial dynamics in alpine meadow ecosystems suffering from multiple climate change factors.


Subject(s)
Soil Microbiology , Tibet , Rain , Climate Change , Bacteria/growth & development , Bacteria/metabolism , Soil/chemistry , Temperature , Grassland , Droughts
20.
J Dent Sci ; 19(2): 894-899, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38618128

ABSTRACT

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.

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