Comparison of Polyethylene Wear before and after Hip Revision with Liner Exchange Fixed with the Original Locking Mechanism

<div><p>Objective</p><p>To compare the wear of conventional ultra-high molecular weight polyethylene (CUHMWPE) and highly cross-linked polyethylene (HCLPE) in hip revision with liner exchange fixed with original locking mechanism using analysis of history medical data.</p><p>Methods</p><p>From Jan. 1, 2000, to Dec. 31, 2007, 26 patients (with 29 involved hips) underwent liner exchange revision fixed with the original locking mechanism due to wear of CUHMWPE and/or osteolysis. The mean age was 53 ± 9 years at the time of the primary total hip arthroplasty (THA) and 64 ± 9 years at the revision. The exchanged liners (Marathon, Depuy) were made of HCLPE. Annual X-rays were used to measure linear wear and osteolysis. The annual linear penetration was measured using PolyWare® software (Draftware Inc.). Annual Harris Hip Scores(HSS) were recorded.</p><p>Results</p><p>The mean follow-up time between the primary and revision THAs was 11 ± 2 years and 8 ± 2 years after revision. The mean Harris Hip Score(HHS) before primary THA, 1 year after primary THA, before revision and 1 year after revision was 43±5, 85±5, 71±6, 83±7 individually. The mean penetration of the CUHMWPE and HCLPE liners occurring in the first year were 0.44 ± 0.28 mm and 0.38 ± 0.14 mm, respectively (p = 0.211). The mean annual linear penetration of CUHMWPE and HCLPE from the second year onward were 0.29±0.09 mm and 0.08 ± 0.03 mm respectively (p <0.01). All THAs with CUHMWPE showed osteolysis on acetabular and/or femoral side before revision. No HCLPE liner showed osteolysis at the last follow-up. Conclusion: The CUHMWPE liner had a significantly higher wear rate than did the HCLPE liner. The HCLPE liner showed a satisfactory liner penetration rate after revision with isolated liner exchange fixed with the original locking mechanism.</p></div

Penetration of CUHMWPE and HCLPE liners before and after revision.

<p>Penetration of CUHMWPE and HCLPE liners before and after revision.</p

DNN acceleration in vehicle edge computing with mobility-awareness: A synergistic vehicle–edge and edge–edge framework

In recent years, vehicular networks have seen a proliferation of applications and services such as image tagging, lane detection, and speech recognition. Many of these applications rely on Deep Neural Networks (DNNs) and demand low-latency computation. To meet these requirements, Vehicular Edge Computing (VEC) has been introduced to augment the abundant computation capacity of vehicular networks to complement limited computation resources on vehicles. Nevertheless, offloading DNN tasks to MEC (Multi-access Edge Computing) servers effectively and efficiently remains a challenging topic due to the dynamic nature of vehicular mobility and varying loads on the servers. In this paper, we propose a novel and efficient distributed DNN Partitioning And Offloading (DPAO), leveraging the mobility of vehicles and the synergy between vehicle–edge and edge–edge computing. We exploit the variations in both computation time and output data size across different layers of DNN to make optimized decisions for accelerating DNN computations while reducing the transmission time of intermediate data. In the meantime, we dynamically partition and offload tasks between MEC servers based on their load differences. We have conducted extensive simulations and testbed experiments to demonstrate the effectiveness of DPAO. The evaluation results show that, compared to offloaded all tasks to MEC server, DPAO reduces the latency of DNN tasks by 2.4x. DPAO with queue reservation can further reduce the task average completion time by 10%.</p

Silica Nanoparticles Promote the Megakaryocyte Maturation and Differentiation: Potential Implications for Hematological Homeostasis

Silica nanoparticles (SiO2 NPs) have been widely applied in diverse areas, thus causing the extensive release through multiple routes. Their toxicological effects, especially for the disturbance in hematological homeostasis, have raised public concern. Considering the detrimental role of excessive platelets in many cardiovascular diseases, the regulation of platelet formation offers a unique aspect for studying the blood compatibility of nanomaterials. In this study, the effects of SiO2 NPs with four sizes (80, 120, 200, and 400 nm) were investigated on the maturation and differentiation of the megakaryocytes into platelets. The results showed that SiO2 NPs promoted megakaryocyte development as manifested by the occurrence of irregular cell morphology, enlargement of cell size, increases in DNA content and DNA ploidy, and formation of spore-like protrusions. The expression of megakaryocyte-specific antigen (CD41a) was up-regulated, due to SiO2 NP treatments. The correlation analysis of SiO2 NP size with the above test bioindicators showed that the smaller the SiO2 NPs were, the stronger effects they induced. Moreover, exposure to SiO2 NPs induced the up-regulation of both GATA-1 and FLI-1, while the transcriptional expressions of aNF-E2 and fNF-E2 remained unchanged. The significant positive correlation of GATA-1 and FLI-1 with megakaryocytic maturation and differentiation suggested their crucial roles in the SiO2 NP-promoted effect. The finding herein provided new insight into the potential health risk of SiO2 NPs by perturbing the platelet-involved hematological homeostasis

Heavy Exposure of Waste Collectors to Polycyclic Aromatic Hydrocarbons in a Poor Rural Area of Middle China

Manual collection and open-air incineration of waste materials is a common practice in rural regions of China and beyond. Low-temperature combustion of rubber and plastic waste generates high levels of airborne polycyclic aromatic hydrocarbons (PAHs). We investigated ten urinary hydroxylated PAH metabolites (OH-PAHs), the oxidative damage biomarker (8-hydroxy-deoxyguanosine, 8-OHdG), and four serum biomarkers including gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) in 41 waste collectors and 122 control subjects residing in the same or a distant rural village in Henan Province. The level of PAH metabolites in urine (median: 17.24 μg/g Cre) was twice that of controls living in the same area without an occupational history involving waste collection (median: 8.16 μg/g Cre) and thrice that of controls living 30 km away (median: 6.07 μg/g Cre). The concentrations of OH-PAHs were positively associated with urinary 8-OHdG levels (β = 0.283, <i>p</i> < 0.05). Serum GGT and ALT were slightly increased in waste collectors. Urinary 8-OHdG levels were similar in one-year and longer-term workers, suggesting that rubber and plastic waste collection/incineration carries a high PAH exposure risk. These data provide solid baseline information, emphasizing the importance of monitoring the long-term health outcomes of waste collectors and changes in exposure patterns associated with rural development and regulation of waste disposal

Table_1_Comprehensive Analysis of the Transcriptome-wide m6A Methylome in Lung Adenocarcinoma by MeRIP Sequencing.xlsx

N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic mRNAs. There is increasing evidence that m6A plays a key role in tumor progression, so it is important to analyze m6A modifications within the transcriptome-wide in lung adenocarcinoma (LUAD). Three pairs of LUAD samples and tumor-adjacent normal tissues were obtained from the South University of Science and Technology Hospital. And then methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to identify differential m6A modifications between tumor and tumor-adjacent normal tissues. We identified 4041 aberrant m6A peaks, of which 1192 m6A peaks were upregulated and 2849 m6A peaks downregulated. It was found that genes with the dysregulated m6A peaks were enriched in the pathways in cancer, Rap1 signaling pathway, and insulin resistance. Additionally, 612 genes with abnormal regulation of m6A peaks and RNA expression were identified by combining MeRIP-seq and RNA-seq data. Through KEGG analysis, the 612 genes were enriched in cancer-related signaling pathways, such as the cGMP-PKG signaling pathway, and the Rap1 signaling pathway. What’s more, GSEA enrichment analysis showed these genes were enriched in cell cycle phase transition, cell division, cellular response to DNA damage stimulus, and chromosome organization. To further explore the relationship between differential m6A modified genes and clinical parameters of LUAD patients, we searched The Cancer Genome Atlas (TCGA) and identified 2 genes (FCRL5 and GPRIN1) that were associated with the prognosis and diagnosis of LUAD patients. Furthermore, we found a positive correlation between GPRIN1 and m6A reader YTHDF1 in the GEPIA2 database. It was verified that YTHDF1 binds to GPRIN1 mRNA and regulates its expression. Our study results suggest that m6A modification plays important role in the progression and prognosis of LUAD and maybe a potential new therapeutic target for LUAD patients in the future.</p

Prevention of Remifentanil Induced Postoperative Hyperalgesia by Dexmedetomidine via Regulating the Trafficking and Function of Spinal NMDA Receptors as well as PKC and CaMKII Level In Vivo and In Vitro

<div><p>Remifentanil-induced secondary hyperalgesia has been demonstrated in both animal experiments and clinical trials. Enhancement of N-methyl-D-aspartate (NMDA) receptor trafficking as well as protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMKII) have been reported to be involved in the induction and maintenance of central sensitization. In the current study, it was demonstrated that dexmedetomidine could prevent remifentanil-induced hyperalgesia (RIH) via regulating spinal NMDAR-PKC-Ca²⁺/ CaMKII pathway in vivo and in vitro. We firstly investigated the effect of dexmedetomidine, a highly selective α2-adrenergic receptor agonist, on mechanical and thermal hyperalgesia using a rat model of RIH. NMDA receptor subunits (NR1, NR2A and NR2B) expression and membrane trafficking as well as PKC and CaMKII expression in spinal cord L4–L5 segments were measured by Western blot analysis. The expression of NMDA receptor subunits (NR1, NR2A and NR2B) were also detected by immunohistochemistry. Further more, the effect of dexmedetomidine on NMDA receptor current amplitude and frequency in spinal cord slices were investigated by whole-cell patch-clamp recording. We found that remifentail infusion at 1.2 μg.kg⁻¹.min⁻¹ for 90 min caused mechanical and thermal hyperalgesia, up-regulated NMDA receptor subunits NR1 and NR2B expression in both membrane fraction and total lysate as well as increased PKC and CaMKII expression in spinal cord dorsal horn. Subcutaneously injection of dexmedetomidine at the dose of 50 μg/kg at 30 min before plantar incision significantly attenuated remifentanil-induced mechanical and thermal hyperalgesia from 2 h to 48 h after infusion, and this was associated with reversal of up-regulated NR1 and NR2B subunits in both membrane fraction and total lysate as well as increased PKC and CaMKII expression in spinal cord dorsal horn. Furthermore, remifentanil incubation increased amplitude and frequency of NMDA receptor-induced current in dorsal horn neurons, which was dose-dependently attenuated by dexmedetomidine. These results suggest that dexmedetomidine can significantly ameliorate RIH via modulating the expression, membrane trafficking and function of NMDA receptors as well as PKC and CaMKII level in spinal dorsal horn, which present useful insights into the mechanistic action of dexmedetomidine as a potential anti-hyperalgesic agents for treating RIH.</p></div

Exploring Prenatal Exposure to Halogenated Compounds and Its Relationship with Birth Outcomes Using Nontarget Analysis

Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks

Pollution Trees: Identifying Similarities among Complex Pollutant Mixtures in Water and Correlating Them to Mutagenicity

There are relatively few tools available for computing and visualizing similarities among complex mixtures and in correlating the chemical composition clusters with toxicological clusters of mixtures. Using the “intersection and union ratio (IUR)” and other traditional distance matrices on contaminant profiles of 33 specific water samples, we used “pollution trees” to compare these mixtures. The “pollution trees” constructed by neighbor-joining (NJ), maximum parsimony (MP), and maximum likelihood (ML) methods allowed comparison of similarities among these samples. The mutagenicity of each sample was then mapped to the “pollution tree”. The IUR-distance-based measure proved effective in comparing chemical composition and compound level differences between mixtures. We found a robust “pollution tree” containing seven major lineages with certain broad characteristics: treated municipal water samples were different from raw water samples and untreated rural drinking water samples were similar with local water sources. The IUR-distance-based tree was more highly correlated to mutagenicity than were other distance matrices, i.e., MP/ML methods, sampling group, region, or water type. IUR-distance-based “pollution trees” may become important tools for identifying similarities among real mixtures and examining chemical composition clusters in a toxicological context

DataSheet1_Nrf2−/− regulated lung DNA demethylation and CYP2E1 DNA methylation under PM2.5 exposure.docx

Cytochrome P450 (CYP450) can mediate fine particulate matter (PM2.5) exposure leading to lung injury. Nuclear factor E2-related factor 2 (Nrf2) can regulate CYP450 expression; however, the mechanism by which Nrf2−/− (KO) regulates CYP450 expression via methylation of its promoter after PM2.5 exposure remains unclear. Here, Nrf2−/− (KO) mice and wild-type (WT) were placed in a PM2.5 exposure chamber (PM) or a filtered air chamber (FA) for 12 weeks using the real-ambient exposure system. The CYP2E1 expression trends were opposite between the WT and KO mice following PM2.5 exposure. After exposure to PM2.5,CYP2E1 mRNA and protein levels were increased in WT mice but decreased in KO mice, and CYP1A1 expression was increased after exposure to PM2.5 in both WT and KO mice. CYP2S1 expression decreased after exposure to PM2.5 in both the WT and KO groups. We studied the effect of PM2.5 exposure on CYP450 promoter methylation and global methylation levels in WT and KO mice. In WT and KO mice in the PM2.5 exposure chamber, among the methylation sites examined in the CYP2E1 promoter, the CpG2 methylation level showed an opposite trend with CYP2E1 mRNA expression. The same relationship was evident between CpG3 unit methylation in the CYP1A1 promoter and CYP1A1 mRNA expression, and between CpG1 unit methylation in the CYP2S1 promoter and CYP2S1 mRNA expression. This data suggests that methylation of these CpG units regulates the expression of the corresponding gene. After exposure to PM2.5, the expression of the DNA methylation markers ten-eleven translocation 3 (TET3) and 5-hydroxymethylcytosine (5hmC) was decreased in the WT group but significantly increased in the KO group. In summary, the changes in CYP2E1, CYP1A1, and CYP2S1 expression in the PM2.5 exposure chamber of WT and Nrf2−/− mice might be related to the specific methylation patterns in their promoter CpG units. After exposure to PM2.5, Nrf2 might regulate CYP2E1 expression by affecting CpG2 unit methylation and induce DNA demethylation via TET3 expression. Our study revealed the underlying mechanism for Nrf2 to regulate epigenetics after lung exposure to PM2.5.</p