Apoptosis is a highly-regulated, active process of cell death involved in development, homeostasis and aging. Dysregulation of apoptosis leads to pathological states, such as cancer, developmental ...anomalies and degenerative diseases. Osteoarthritis (OA), the most common chronic joint disease in the elderly population, is characterized by progressive destruction of articular cartilage, resulting in significant disability. Because articular cartilage depends solely on its resident cells, the chondrocytes, for the maintenance of extracellular matrix, the compromising of chondrocyte function and survival would lead to the failure of the articular cartilage. The role of subchondral bone in the maintenance of proper cartilage matrix has been suggested as well, and it has been proposed that both articular cartilage and subchondral bone interact with each other in the maintenance of articular integrity and physiology. Some investigators include both articular cartilage and subchondral bone as targets for repairing joint degeneration. In late-stage OA, the cartilage becomes hypocellular, often accompanied by lacunar emptying, which has been considered as evidence that chondrocyte death is a central feature in OA progression. Apoptosis clearly occurs in osteoarthritic cartilage; however, the relative contribution of chondrocyte apoptosis in the pathogenesis of OA is difficult to evaluate, and contradictory reports exist on the rate of apoptotic chondrocytes in osteoarthritic cartilage. It is not clear whether chondrocyte apoptosis is the inducer of cartilage degeneration or a byproduct of cartilage destruction. Chondrocyte death and matrix loss may form a vicious cycle, with the progression of one aggravating the other, and the literature reveals that there is a definite correlation between the degree of cartilage damage and chondrocyte apoptosis. Because current treatments for OA act only on symptoms and do not prevent or cure OA, chondrocyte apoptosis would be a valid target to modulate cartilage degeneration.
Defective apoptotic death of activated macrophages has been implicated in the pathogenesis of rheumatoid arthritis (RA). However, the molecular signatures defining apoptotic resistance of RA ...macrophages are not fully understood. Here, global transcriptome profiling of RA macrophages revealed that the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) critically regulates diverse pathologic processes in synovial macrophages including the cell cycle, apoptosis, and proliferation. Transcriptomic analysis of NFAT5-deficient macrophages revealed the molecular networks defining cell survival and proliferation. Proinflammatory M1-polarizing stimuli and hypoxic conditions were responsible for enhanced NFAT5 expression in RA macrophages. An in vitro functional study demonstrated that NFAT5-deficient macrophages were more susceptible to apoptotic death. Specifically, CCL2 secretion in an NFAT5-dependent fashion bestowed apoptotic resistance to RA macrophages in vitro. Injection of recombinant CCL2 into one of the affected joints of Nfat5+/- mice increased joint destruction and macrophage infiltration, demonstrating the essential role of the NFAT5/CCL2 axis in arthritis progression in vivo. Moreover, after intra-articular injection, NFAT5-deficient macrophages were more susceptible to apoptosis and less efficient at promoting joint destruction than were NFAT5-sufficient macrophages. Thus, NFAT5 regulates macrophage survival by inducing CCL2 secretion. Our results provide evidence that NFAT5 expression in macrophages enhances chronic arthritis by conferring apoptotic resistance to activated macrophages.
This single-center, retrospective study aimed to investigate the course and prognostic factors of patients with primary Sjögren syndrome-associated interstitial lung disease (pSS-ILD). We included ...120 pSS patients who underwent at least two high-resolution computed tomography (HRCT) scans between 2013 and 2021. Clinical symptoms, laboratory data, HRCT findings, and pulmonary function test results were collected. Two thoracic radiologists reviewed the HRCT findings. In patients with pSS without ILD at baseline (n = 81), no development of ILD was found on follow-up (median, 2.8 years). In patients with pSS-ILD (n = 39), total disease extent, extent of coarse reticulation, and traction bronchiectasis increased on HRCT, whereas the extent of ground glass opacity (GGO) decreased at follow-up (median, 3.2 years) (each p < 0.001). In progressive group of pSS-ILD (48.7%), the extent of coarse reticulation and coarseness score of fibrosis were increased at follow-up (p < 0.05). Usual interstitial pneumonia pattern on CT (OR, 15.237) and follow-up duration (OR, 1.403) were independent risk factors for disease progression in patients with pSS-ILD. In both progressive and non-progressive pSS-ILD, GGO decreased, whereas the extent of fibrosis increased even after treatment with glucocorticoid and/or immunosuppressants. In conclusion, progression occurred in approximately half of the pSS-ILD patients with slow gradual deterioration. Our study identified a definite group of progressive pSS-ILD who did not respond to current anti-inflammatory treatment.
Tonicity-responsive enhancer-binding protein (TonEBP; nuclear factor of activated T cells 5) is a transcription factor that responds to changes in osmolality. However, recent studies have shown that ...it also modulates immune responses under inflammatory conditions independently of hyperosmolality. Fibronectin fragments (FN-fs), which are abundant in the synovial fluid of patients with osteoarthritis (OA), induce expression of matrix metalloproteinases (MMPs) via the toll-like receptor-2 (TLR-2) signaling pathway. In this study we examined whether TonEBP is involved in 29-kDa FN-f-induced expression of MMPs. The expression of TonEBP was significantly higher in human osteoarthritis compared with normal cartilage samples. 29-kDa FN-f affected the expression of MMPs 1, 3, and 13 via TonEBP, and expression and nuclear accumulation of TonEBP were induced by activation of the phospholipase C/NF-κB/MAPK signaling pathway and, in particular, modulated by TLR-2. In addition, 29-kDa FN-f induced the expression of osmoregulatory genes, including Tau-T, SMIT, and AR, as well as voltage-dependent calcium channels via the TonEBP/TLR-2 signaling pathway. These results show that 29-kDa FN-f upregulates MMPs in chondrocytes via the TLR-2/TonEBP signaling pathway.
Muscle development and lipid accumulation in muscle critically affect meat quality of livestock. However, the genetic factors underlying myofiber-type specification and intramuscular fat (IMF) ...accumulation remain to be elucidated. Using two independent intercrosses between Western commercial breeds and Korean native pigs (KNPs) and a joint linkage-linkage disequilibrium analysis, we identified a 488.1-kb region on porcine chromosome 12 that affects both reddish meat color (a*) and IMF. In this critical region, only the MYH3 gene, encoding myosin heavy chain 3, was found to be preferentially overexpressed in the skeletal muscle of KNPs. Subsequently, MYH3-transgenic mice demonstrated that this gene controls both myofiber-type specification and adipogenesis in skeletal muscle. We discovered a structural variant in the promotor/regulatory region of MYH3 for which Q allele carriers exhibited significantly higher values of a* and IMF than q allele carriers. Furthermore, chromatin immunoprecipitation and cotransfection assays showed that the structural variant in the 5'-flanking region of MYH3 abrogated the binding of the myogenic regulatory factors (MYF5, MYOD, MYOG, and MRF4). The allele distribution of MYH3 among pig populations worldwide indicated that the MYH3 Q allele is of Asian origin and likely predates domestication. In conclusion, we identified a functional regulatory sequence variant in porcine MYH3 that provides novel insights into the genetic basis of the regulation of myofiber type ratios and associated changes in IMF in pigs. The MYH3 variant can play an important role in improving pork quality in current breeding programs.
The composition of the wastewater matrix influences the oxidation potential of ozonation, a technique widely recognized efficient removal of micropollutants. Here, we developed a chemical kinetic ...model to determine the ozone dose required to minimize bromate production in wastewater containing bromine ions while achieving target removal rates. In wastewater ozonation, ozone decomposition comprises instantaneous ozone consumption and subsequent decomposition at first-order reaction rates. Under the injection condition of 1.5 g O3/g dissolved organic carbon (DOC), the instantaneous ozone demand was 62.7% of the injection concentration, and it increased proportionally with increasing injected ozone concentration. Ozone and hydroxyl radical exposures were proportional to the initial ozone dose, while hydroxyl radical exposure was proportional to ozone exposure, and the deviation was relatively high at 1.0–1.5 g O3/g DOC. The calculated hydroxyl radical exposure was 3.0 × 10−10 to 5.3 × 10−10 M s. Ozone and hydroxyl radicals are highly correlated with the ratio of ozone dose to organic matter concentration. Therefore, a trace substance removal rate evaluation model combined with the ROH, O3 model and a bromate generation model were also considered. For ibuprofen, the ozone dose for achieving the target removal rate of 80% while maintaining the bromate concentration below 50 μg L−1 was suitable in the operating range of 0.86 g O3/g DOC or more. The proposed method provides a practical operation strategy to calculate the appropriate ozone dose condition from the target compound removal rate prediction and bromate generation models considering the ratio of ozone dose to organic matter concentration in the incoming wastewater.
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•A model predictive control strategy of wastewater ozonation was proposed.•Its aim is to minimize bromate generation during industrial wastewater treatment.•Ozone exposure was quantified considering ozone degradation features.•The model was applied to organic substances having low reactivity with ozone.
Taste and odor (T&O) compounds present in natural water bodies could originate from algae. In this study, alga-generated compounds that can cause T&O issues in water, such as geosmin (GE), ...2-Methylisoborneol (MIB), 2,4,6-Trichloroanisole (TCA), 2-Methylbenzofuran (MB), 2-Isopropyl-3-methoxypyrazine (IPMP), 2-Isobutyl-3-methoxypyrazine (IBMP), cis-3-Hexenyl acetate (HA), trans,trans-2,4-Heptadienal (HD), trans,cis-2,6-Nonadienal (ND), and trans-2-Decenal (DN), were determined through solid-phase microextraction coupled with gas chromatography/mass spectrometry (HS-SPME GC/MS) and electronic tongue (E-tongue), and the results from the two techniques were compared. Although HS-SPME GC/MS facilitates the detection and quantification of T&O compounds with high precision and accuracy, the sample preparation and handling is difficult and the analysis time (1 h) is longer than those of other analytical methods. E-tongue can be used as an alternative analytical method for water quality analysis and risk management because it enables controlled and rapid analysis (3 min) of T&O compounds in water at a low cost. Notably, principal component analysis indicated that E-tongue can discriminate and quantify eight T&O compounds at as low as 0.02 μg L−1 concentration. Further, partial least squares analysis confirmed that the sensor exhibits high sensitivity to concentration changes. The sensors with the highest variable importance in projection scores were determined to be SCS (1.39 and 1.38) for GE and MIB, CTS (1.34) for IPMP, CPS (1.33) for IBMP, AHS (1.42) for HA, ANS (1.22) for HD, and NMS (1.14 and 1.19) for ND and DN.
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•Rapid and simple analysis with E-tongue detected ten taste and odor (T&O) compounds.•Principal component analysis was used to process the E-tongue results.•Mixtures of eight T&O compounds showed some overlaps.•E-tongue could detect changes in T&O concentration of as low as 0.02 μg L−1.
We report a breath hydrogen analyzer based on Pd-coated SnO2 nanorods (Pd-SnO2 NRs) sensor integrated into a miniaturized gas chromatography (GC) column. The device can measure a wide range of ...hydrogen (1–100 ppm), within 100 s, using a small volume of human breath (1 mL) without pre-concentration. Especially, the mini-GC integrated with Pd-SnO2 NRs can detect 1 ppm of H2, as a lower detection limit, at a low operating temperature of 152 °C. Furthermore, when the breath hydrogen analyzer was exposed to a mixture of interfering gases, such as carbon dioxide, nitrogen, methane, and acetone, it was found to be capable of selectively detecting only H2. We found that the Pd-SnO2 NRs were superior to other semiconducting metal oxides that lack selectivity in H2 detection. Our study reveals that the Pd-SnO2 NRs integrated into the mini-GC device can be utilized in breath hydrogen analyzers to rapidly and accurately detect hydrogen due to its high selectivity and sensitivity.
This study applied a method for estimating chlorine decay constant (k) in urban water distribution systems using fluorescence excitation–emission matrix spectroscopy-parallel factor analysis ...(FEEM-PARAFAC), considering that it accounts for the influence of organic matter in the target area. The simultaneous impacts of seasonal variations on chlorine consumption and dissolved organic matter (DOM) composition were investigated for a year in three full-scale water distribution systems in I city (areas S, K, and G). Bulk decay constants (kb) were obtained through bottle tests, and the kb value was observed to differ by season and significantly affected by temperature. It exhibited its highest value, 0.794 d−1, in summer at area G. As a result of analyses through F-EEM-PARAFAC, it was determined that the components of the target raw water were humic-like and tryptophan-like. The quantitative analysis of organic substances through PARAFAC revealed that area G had the highest score (C1+C2) than other areas. 11.568, 10.578, and 11.771 in summer at areas S, K, and G, respectively. The model equations were derived such that the significant (R2 = 0.85–0.95) correlation between the C1 and C2 model scores and total chlorine decay constants (kt) verified via PARAFAC analysis of the target raw water was considered. Furthermore, a method for obtaining the wall decay constants at a target point based on the correlation equation was investigated.
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•To model the chlorine decay in a water distribution network, the reaction rates of chlorine with the water and pipe wall demands must be considered.•The proposed method of estimating the reaction constant with FEEM-PARAFAC is a practical tool to maintain the residual chlorine in urban water distribution system.
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•We report on a breath-isoprene analyzer based on a gas chromatography column with catalyst-coated In2O3 thin films.•We found that Pd-coated In2O3 thin films were superior to Au- and ...Pt-coated films.•The analyzer was able to selectively detect isoprene in air within 2 min at 196 °C.•The detection limit was 0.4 ppb, which is the lowest level reported to date.•Our study demonstrates that the analyzer can be utilized to rapidly and accurately detect isoprene in breath.
Monitoring breath isoprene concentration plays a role in non-invasive diagnosis of blood-cholesterol levels. In this study, we developed a highly sensitive and selective isoprene analyzer based on a Pd-coated In2O3 thin film integrated in a miniaturized gas chromatography column. To improve the sensing performance, the In2O3 thin films were fabricated with high uniformity and crystallinity using a dual-ion-beam sputtering system, and various metal catalysts (Au, Pt, and Pd) were loaded on the film surface. Among them, the Pd catalyst afforded the highest sensing reaction and the lowest detection limit (approximately 0.4 ppb), which is the best performance ever reported. It also significantly lowered the optimal operating temperature of the sensor from 432 °C to 196 °C. The excellent isoprene sensing performance of the Pd-coated In2O3 film can be attributed to the high density of oxygen vacancies, efficient reduction-reoxidation of PdO, and the Mars-van-Krevelen catalytic reaction. We further optimized the isoprene sensing performance of a Pd-coated In2O3 film by varying the Pd thickness and discovered that 1 nm of Pd deposition showed the optimal status of discontinuous islands for sensing. We expect that our device can be applied to a portable breath isoprene analyzer.
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