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BACKGROUND: Facet joint osteoarthritis (FJOA) is a prevalent condition contributing to low back pain, particularly in the elderly population. This study aimed to investigate the potential role of Cytokine Receptor-like Factor 1 (CRLF1) in FJOA pathogenesis and its therapeutic implications. METHODS: Bioinformatics analysis was utilized to identify CRLF1 as the target gene, followed by quantification of CRLF1 expression levels and joint degeneration degree using immunohistochemistry (IHC). In primary chondrocytes, the inhibition of CRLF1 expression by siRNA was performed, and Western blot analysis was conducted to evaluate the involvement of the extracellular matrix and MAPK/ERK signaling pathway. Flow cytometry was employed to assess the apoptosis rate of chondrocytes, while immunofluorescence (IF) was utilized to evaluate the localization of CRLF1, cleaved-caspase3, MMP13, COL2A1, and ERK. RESULTS: The expression of CRLF1 was found to be significantly elevated in FJOA tissues compared to normal tissues. Through the use of loss-of-function assays, it was determined that CRLF1 not only enhanced the rate of apoptosis in chondrocytes, but also facilitated the degradation of the extracellular matrix in vitro. Furthermore, CRLF1 was found to activate the ERK1/2 pathways. The pro-arthritic effects elicited by CRLF1 were mitigated by treatment with the MEK inhibitor U0126 in chondrocytes. CONCLUSION: These results suggest that CRLF1 enhances chondrocytes apoptosis and extracellular matrix degration in FJOA and thus may therefore be a potential therapeutic target for FJOA.
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Pentachlorophenol (PCP) is widely found in coastal environments and has various adverse effects, and its potential impact on coral reef ecosystems concerning. The scleractinian coral Montipora digitata was used for PCP stress experiments in this study. Phenotypes, physiological indicators, microbial diversity analysis and RNA sequencing were used to investigate the mechanisms underlying the responses of corals to acute and chronic PCP exposure. After 96 h of acute exposure, coral bleaching occurred at 1000 µg/LPCP and there was a significant decrease in Symbiodiniaceae density, Fv/Fm, and chlorophyll a content. Exposure to different concentrations of PCP significantly increased the content of malondialdehyde (MDA), leading to oxidative stress in corals. Chronic PCP exposure resulted in bleaching at 60 days, with the Fv/Fm significantly reduced to 0.461. Microbial diversity analysis revealed an increase in the abundance of potential pathogens, such as Vibrio, during acute PCP exposure and the emergence of the degrading bacterium Delftia during chronic PCP exposure. Transcriptional analysis showed that PCP exposure caused abnormal carbohydrate and amino acid metabolism in zooxanthella, which affected energy supply, induced immune responses, and disrupted symbiotic relationships. Corals respond to injury by boosting the expression of genes associated with signal transduction and immune response. Additionally, the expression of genes associated with environmental adaptation increased with chronic PCP exposure, which is consistent with the results of the microbial diversity analysis. These results indicate that PCP exposure might affect the balance of coral- zooxanthellae symbiosis in the stony coral M. digitata, impairing coral health and leading to bleaching.
Subject(s)
Anthozoa , Coral Reefs , Pentachlorophenol , Water Pollutants, Chemical , Anthozoa/physiology , Anthozoa/drug effects , Pentachlorophenol/toxicity , Animals , Water Pollutants, Chemical/toxicity , Oxidative StressABSTRACT
There is a complex high-dimensional nonlinear mapping relationship between the compressive strength of High-Performance Concrete (HPC) and its components, which has great influence on the accurate prediction of compressive strength. In this paper, an efficient robust software calculation strategy combining BP Neural Network (BPNN), Support Vector Machine (SVM) and Genetic Algorithm (GA) is proposed for the prediction of compressive strength of HPC. 8 features were extracted from the previous literature, and a compressive strength database containing 454 sets of data was constructed. The model was trained and tested, and the performance of 4 Machine Learning (ML) models, namely BPNN, SVM, GA-BPNN and GA-SVM, was compared. The results show that the coupled model is superior to the single model. Moreover, because GA-SVM has better generalization ability and theoretical basis, its convergence speed and prediction accuracy are better than GA-BPNN. Then Grey Relational Analysis (GRA) and Shapley analysis were used to verify the interpretability of the GA-SVM model, which showed that the water-binder ratio had the most significant influence on the compressive strength. Finally, the combination of multiple input variables to evaluate the compressive strength supplemented this research, and again verified the significant influence of water-binder ratio, providing reference value for subsequent research.
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Self-supported Ru-doped NiMoO4 (Ru-NiMoO4) is synthesized on commercial NiMo foam. The Ru-NiMoO4 exhibits extremely high performance for electrocatalytic hydrogen evolution with a small overpotential of 170.6 mV to afford a current density of 1000 mA cm-2, and excellent durability for 150 hours in alkaline solution.
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OBJECTIVE: Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. METHODS: Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. RESULTS: The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. CONCLUSION: Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.
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An exploding foil initiator system (EFIs) is essential in modern weaponry for its safety and reliability. As the main component of EFIs, the performance of the switch is critical to EFIs. In this study, a planar three-electrode trigger switch was designed and fabricated using the Flexible Printed Circuits (FPC) process. Subsequently, the performance of the FPC switch was tested. The results show that the self-breakdown voltage of the FPC switch is stable. In addition, an FPF switch with a 0.6 mm main electrode gap demonstrated consistency, with delay times below 31.75 ns, and a jitter ranging from 1.7 ns to 10.94 ns at 900 V to 1200 V, evidencing the FPC switches' reliability and uniform performance across various voltages. Compared to the Micro-Electro-Mechanical Systems (MEMS) switches of similar dimensions, the FPC switches achieved a faster high-current attainment with less inductance, showing a 5% reduction in loop inductance. The repetitive testing results demonstrate that the FPC switch maintains consistent output performance, with stable peak currents, peak current time, and delay time over 50 action cycles, highlighting its repeatability. The FPC switch was assembled with an EFI chip and capacitor into an integrated system, which was subsequently able to successfully detonate HNS-IV at 1000 V/0.22 µF, proving the FPC switch's potential in low inductance applications.
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To enhance the energy efficiency of exploding foil initiator systems (EFIs) and mitigate energy loss due to ablation in the bridge-wing regions, a low-energy bridge-wing-thickened EFI chip was designed and fabricated. Computational analysis revealed that increasing the thickness of the bridge flanks significantly reduces ablation within the bridge region during the electrical explosion. The refinement of the design led to the adoption of a bridge flank thickness of 19 µm, with the bridge area dimensions specified as 0.25 mm × 0.25 mm × 4 µm. This bridge-wing-thickened EFI chip was produced by employing micro-electro-mechanical systems (MEMS) technology and underwent rigorous performance evaluations. The empirical results closely matched the computational predictions, thereby corroborating the precision of the proposed model in simulating the temperature distribution seen during the explosion process. Notably, this enhanced EFI design achieves a flyer velocity of 3800 m/s at a condition of 900 V/0.22 µF, signifying a significant advancement in EFI system efficiency and performance.
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Osteoarthritis (OA) is a low-grade, nonspecific inflammatory disease that affects the entire joint. This condition is characterized by synovitis, cartilage erosion, subchondral bone defects, and subpatellar fat pad damage. There is mounting evidence demonstrating the significance of crosstalk between synovitis and cartilage destruction in the development of OA. To comprehensively explore the phenotypic alterations of synovitis and cartilage destruction, it is important to elucidate the crosstalk mechanisms between chondrocytes and synovial cells. Furthermore, the updated iteration of single-cell sequencing technology reveals the interaction between chondrocyte and synovial cells. In the present review, the histological and pathological alterations between cartilage and synovium during OA progression are described, and the mode of interaction and molecular mechanisms between synovial cells and chondrocytes in OA, both of which affect the OA process mainly by altering the inflammatory environment and cellular state, are elucidated. Finally, the current OA therapeutic approaches are summarized and emerging therapeutic targets are reviewed in an attempt to provide potential insights into OA treatment.
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The rumen is divided into multiple rumen sacs based on anatomical structure, and each has its unique physiological environment. Tarim wapiti preserved roughage tolerance after domestication, and adaptation to the desertified environment led to the development of a unique rumen shape and intraruminal environment. In this work, six Tarim wapiti were chosen and tested for fermentation parameters, microbes, and histomorphology in four rumen areas (Dorsal sac, DS; Ventral sac, VS; Caudodorsal blind sac, CDBS; Caudoventral blind sac, CVBS). Tarim wapiti's rumen blind sac had better developed rumen histomorphology, the ventral sac was richer in VFAs, and the dominant bacteria varied most notably in the phylum Firmicutes, which was enriched in the caudoventral blind sac. The ventral sac biomarkers focused on carbohydrate fermentation-associated bacteria, the dorsal sac focused on N recycling, and the caudoventral blind sac identified the only phylum-level bacterium, Firmicutes; we were surprised to find a probiotic bacterium, Bacillus clausii, identified as a biomarker in the ventral sac. This research provides a better understanding of rumen fermentation parameters, microorganisms, and histomorphology in the Tarim wapiti rumen within a unique ecological habitat, laying the groundwork for future regulation targeting the rumen microbiota and subsequent animal production improvement.
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A metabolic bone disease characterized by decreased bone formation and increased bone resorption is osteoporosis. It can cause pain and fracture of patients. The elderly are prone to osteoporosis and are more vulnerable to osteoporosis. In this study, radiomics are extracted from computed tomography (CT) images to screen osteoporosis in the elderly. Collect the plain scan CT images of lumbar spine, cut the region of interest of the image and extract radiomics features, use Lasso regression to screen variables and adjust complexity, use python language to model random forests, support vector machines, K nearest neighbor, and finally use receiver operating characteristic curve to evaluate the performance of the model, including precision, recall, accuracy and area under the curve (AUC). For the model, 14 radiolomics features were selected. The diagnosis performance of random forest model and support vector machine is good, all around 0.9. The AUC of K nearest neighbor model in training set and test set is 0.828 and 0.796, respectively. We selected the plain scan CT images of the elderly lumbar spine to build radiomics features model, which has good diagnostic performance and can be used as a tool to assist the diagnosis of osteoporosis in the elderly.
Subject(s)
Lumbar Vertebrae , Osteoporosis , Support Vector Machine , Tomography, X-Ray Computed , Humans , Aged , Osteoporosis/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Female , Male , Aged, 80 and over , Middle Aged , RadiomicsABSTRACT
PURPOSE OF REVIEW: Intervertebral disc degeneration is the primary etiology of low back pain and radicular pain. This review examines the roles of crucial chemokines in different stages of degenerative disc disease, along with interventions targeting chemokine function to mitigate disc degeneration. RECENT FINDINGS: The release of chemokines from degenerated discs facilitates the infiltration and activation of immune cells, thereby intensifying the inflammatory cascade response. The migration of immune cells into the venous lumen is concomitant with the emergence of microvascular tissue and nerve fibers. Furthermore, the presence of neurogenic factors secreted by disc cells and immune cells stimulates the activation of pain-related cation channels in the dorsal root ganglion, potentially exacerbating discogenic and neurogenic pain and intensifying the degenerative cascade response mediated by chemokines. Gaining a deeper comprehension of the functions of chemokines and immune cells in these processes involving catabolism, angiogenesis, and injury detection could offer novel therapeutic avenues for managing symptomatic disc disease.
Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Low Back Pain , Humans , Intervertebral Disc Degeneration/therapy , Intervertebral Disc/metabolism , Low Back Pain/etiology , Chemokines/metabolism , Ganglia, SpinalABSTRACT
Shoreline cities are influenced by both urban-scale processes and land-water interactions, with consequences on heat exposure and its disparities. Heat exposure studies over these cities have focused on air and skin temperature, even though moisture advection from water bodies can also modulate heat stress. Here, using an ensemble of model simulations covering Chicago, we find that Lake Michigan strongly reduces heat exposure (2.75°C reduction in maximum average air temperature in Chicago) and heat stress (maximum average wet bulb globe temperature reduced by 0.86°C) during the day, while urbanization enhances them at night (2.75 and 1.57°C increases in minimum average air and wet bulb globe temperature, respectively). We also demonstrate that urban and lake impacts on temperature (particularly skin temperature), including their extremes, and lake-to-land gradients, are stronger than the corresponding impacts on heat stress, partly due to humidity-related feedback. Likewise, environmental disparities across community areas in Chicago seen for skin temperature are much higher (1.29°C increase for maximum average values per $10,000 higher median income per capita) than disparities in air temperature (0.50°C increase) and wet bulb globe temperature (0.23°C increase). The results call for consistent use of physiologically relevant heat exposure metrics to accurately capture the public health implications of urbanization.
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Electrochemical nitrate reduction to ammonia (NH3) not only provides a promising strategy for green NH3 synthesis, but also removes harmful nitrates from water. Herein, a Cu-doped FeP electrocatalyst was prepared for nitrate reduction, which achieved a high NH3 faradaic efficiency of 92.5% and a high NH3 yield of 0.787 mmol h-1 cm-2 in a neutral electrolyte, greatly surpassing its FeP counterpart.
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Heterosigma akashiwo (H. akashiwo) is recognized as a harmful algal bloom (HABs) species with a global distribution, capable of posing significant threats to marine ecosystems, particularly when spread through ship ballast water. This investigation focused on elucidating the inactivation kinetics and underlying mechanism of H. akashiwo through a combined ultraviolet irradiation and peroxydisulfate (UV/PDS) process. The results demonstrated a strong synergistic effect within the UV/PDS system, resulting in an inactivation of 0.78-ln and 2.67-ln within 40 min of UV and UV/PDS processes. The principal agents accountable for inactivation were identified as sulfate radicals (â¢SO4-) and hydroxyl radical (â¢OH), which exhibited a synergistic effect in the UV/PDS process. Furthermore, the study observed a negatively impact of seawater pH and salinity on the efficiency of inactivation. UV/PDS caused oxidative stress on algal cells, initially involving the participation of antioxidant enzymes in counteracting cellular damage, but this protective mechanism diminished as the reaction duration extended. The UV/PDS treatment not only inflicted damage upon H. akashiwo's photosynthetic system but also caused the extracellular release of DNA and algal organic matter (AOM) due to damaged cell membranes. Transcriptome analysis provided a molecular biology perspective on the cellular inactivation process. Upregulation of genes linked to photosynthesis and oxidative phosphorylation suggested a potential elevation in energy metabolism. In contrast, genes associated with cellular and metabolic processes, including glycolysis and the tricarboxylic acid cycle (TCA cycle), exhibited downregulation. Moreover, this treatment exerted an inhibitory influence on RNA polymerase and protein synthesis, resulting in the reduced expression of genetic information.
Subject(s)
Disinfection , Ecosystem , Ultraviolet Rays , Antioxidants , Cell MembraneABSTRACT
Reconstructions of ocean oxygenation are critical for understanding the role of respired carbon storage in regulating atmospheric CO2. Independent sediment redox proxies are essential to assess such reconstructions. Here, we present a long magnetofossil record from the eastern Indian Ocean in which we observe coeval magnetic hardening and enrichment of larger, more elongated, and less oxidized magnetofossils during glacials compared to interglacials over the last ~900 ka. Our multi-proxy records of redox-sensitive magnetofossils, trace element concentrations, and benthic foraminiferal Δδ13C consistently suggest a recurrence of lower O2 in the glacial Indian Ocean over the last 21 marine isotope stages, as has been reported for the Atlantic and Pacific across the last glaciation. Consistent multi-proxy documentation of this repeated oxygen decline strongly supports the hypothesis that increased Indian Ocean glacial carbon storage played a significant role in atmospheric CO2 cycling and climate change over recent glacial/interglacial timescales.
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BACKGROUND: Spinal cord injury (SCI) is a devastating disease that can lead to tissue loss and neurological dysfunction. TNIP2 is a negative regulator of NF-κB signaling due to its capacity to bind A20 and suppress inflammatory cytokines-induced NF-κB activation. However, the anti-inflammatory role of TNIP2 in SCI remains unclear. Our study's intention was to evaluate the effect of TNIP2 on the inflammatory response of microglia after spinal cord injury in rats. METHODS: HE staining and Nissl staining were performed on day 3 following SCI to analyze the histological changes. To further investigate the functional changes of TNIP2 after SCI, we performed immunofluorescence staining experiments. The effect of LPS on TNIP2 expression in BV2 cells was examined by western blot. The levels of TNF-α, IL-1ß, and IL-6 in spinal cord tissues of rats with SCI and in BV2 cells with LPS were measured by using qPCR. RESULTS: TNIP2 expression was closely associated with the pathophysiology of SCI in rats, and TNIP2 was involved in regulating functional changes in microglia. TNIP2 expression was increased during SCI in rats and that overexpression of TNIP2 inhibited M1 polarization and pro-inflammatory cytokine production in microglia, which might ultimately protect against inflammatory responses through the MAPK and NF-κB signaling pathways. CONCLUSIONS: The present study provides evidence for a role of TNIP2 in the regulation of inflammation in SCI and suggests that induction of TNIP2 expression alleviated the inflammatory response of microglia.
Subject(s)
Adaptor Proteins, Signal Transducing , NF-kappa B , Spinal Cord Injuries , Animals , Rats , Inflammation/metabolism , Lipopolysaccharides , Microglia/metabolism , NF-kappa B/metabolism , Signal Transduction , Spinal Cord/metabolism , Spinal Cord Injuries/metabolism , Adaptor Proteins, Signal Transducing/metabolismABSTRACT
Electrochemical conversion of nitrate to NH3 not only eliminates nitrate pollution in the environment, but also produces highly valuable NH3. Herein, Cu-doped Co3O4 with abundant oxygen vacancies (Cu-Co3O4-x) was prepared on carbon cloth. The as-fabricated Cu-Co3O4-x can selectively reduce nitrate to NH3 with high Faraday efficiencies (around 90%) and a large NH3 yield of 0.83 mmol h-1 cm-2 in a neutral electrolyte.
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Background: To reveal candidate genes and the molecular genetic mechanism underlying primary feather color trait in ducks, a genome-wide association study (GWAS) for the primary feather color trait was performed based on the genotyping-by-sequencing (GBS) technology for a native Chinese female duck, Longyan Shan-ma ducks. Methods: Blood genomic DNA from 314 female Longyan Shan-ma duck were genotyped using GBS technology. A GWAS for the primary feather color trait with genome variations was performed using an univariate linear mixed model based on all SNPs in autosomes. Results: Seven genome-wide significant single nucleotide polymorphisms (SNPs, Bonferroni-adjusted p-value <8.03 × 10-7) within the introns of the genes STARD9, ZNF106, SLC7A5, and BANP genes were associated with the primary feather color trait. Twenty-two genome-wide suggestive SNPs (Bonferroni-adjusted p-value <1.61 × 10-5) of 17 genes (besides ZNF106 and SLC7A5) were also identified. Seven SNPs were located at one 0.22 Mb region (38.65-38.87 Mb) on chromosome 5, and six SNPs were located at one 0.31 Mb region (19.53-19.84 Mb) on chromosome 11. The functions of STARD9, SLC7A5, BANP, LOC101798015, and IPMK were involved pigmentation and follicle development, especially, STARD9 upregulated expression in black feather (haplotype-CCCC) bulb tissue compared with in pockmarked feather (haplotype-TGTT) bulb tissue, implicating these genes as candidate genes for primary feather color trait. Conclusion: The preliminarily findings suggested candidate genes and regions, and the genetic basis of primary feather color trait in a female duck.
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>80 % of applied pesticides in agriculture will enter the soil and be exposed to soil animals. Little is known about the stereoselective metabolic effects of epoxiconazole (EPO) on soil animals. In this study, EPO-mediated stereoselective enrichment, biotransformation, oxidative stress, detoxification, and global metabolic profiles in earthworms were investigated by exposure to EPO and its enantiomers at 1 mg/kg and 10 mg/kg doses. Preferential enrichment of (-)-EPO was observed, and the five transformation products (TPs) exhibited the chemically specific stereoselective accumulation with inconsistent configurations. Biochemical markers related to reactive oxygen species (ROS) and detoxification (·OH- content, SOD, CAT, GST, and CYP450 enzymes) showed a significant stereoselective activation overall at the low-level exposure (p-value <0.05). Based on untargeted metabolomic analysis, the steroid biosynthesis and ROS-related biotransformation, glutathione metabolism, TCA cycle, amino acid metabolism, purine and pyrimidine metabolism of earthworms were significantly interfered with by EPO and its enantiomer exposure. More pronounced stereoselectivity was observed at the level of the global metabolic profile, while comparable levels of metabolic perturbations were identified at the individual metabolite level. This study provides novel insights into the stereoselective effects of the chiral fungicide EPO, and valuable evidence for soil environmental risk assessments.
Subject(s)
Fungicides, Industrial , Oligochaeta , Soil Pollutants , Animals , Oligochaeta/metabolism , Fungicides, Industrial/metabolism , Soil Pollutants/metabolism , Reactive Oxygen Species/metabolism , Soil/chemistry , Oxidative Stress , BiotransformationABSTRACT
Purpose: To compare the clinical outcomes and radiological parameters of patients undergoing percutaneous vertebroplasty (PVP) versus those undergoing percutaneous vertebral-disc plasty (PVDP) for back pain, segmental instability, and kyphosis due to thoracolumbar very severe osteoporotic vertebral compression fractures (vsOVCFs). Methods: This prospective randomized controlled study included elderly patients with thoracolumbar vsOVCFs. All the patients were randomly allocated into the PVP group (who underwent conventional PVP) and the PVDP group (who underwent PVP combined percutaneous cement discoplasty). The visual analogue scale (VAS), Oswestry Disability Index (ODI), local kyphosis angle, and disc height were recorded preoperatively and postoperatively. Results: Significant postoperative improvements in the VAS, ODI, and the local kyphosis angle (LKA) were shown, compared with the preoperative values in both groups (p < 0.05). The average VAS, ODI, and LKA for patients in the PVP group were increased compared to those in the PVDP group observed at the last follow-up (p < 0.05). The DHA, DHP, and LKA were seen to be maintained in the PVDP group at the last follow-up (p > 0.05). The change was significantly lower in the PVDP group at the last follow-up in those parameters (p < 0.05). Conclusion: PVDP may be a feasible and effective technique for the treatment of very severe OVCFs, that can restore intervertebral height, provide segmental stabilizing and relieve back pain in the short term.