Activation of STAT6 by STING is critical for antiviral innate immunity.

STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs. Phosphorylated STAT6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing. Virus-induced STAT6 activation is detected in all cell-types tested, in contrast to the cell-type specific role of STAT6 in cytokine signaling, and Stat6(-/-) mice are susceptible to virus infection. Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum.

Adjacent segment degeneration after single- and double-level cervical total disc replacement: a cohort with an over 12-year follow-up.

PURPOSE: To characterize the change of adjacent segment degeneration (ASD) after cervical total disc replacement (CTDR) with more than 12-year follow-up, and identify the risk factors for ASD. METHOD: This process included 75 patients underwent CTDR from February 2004 to December 2012, with the follow-up of 151.9 ± 36.0 (m). The artificial disc included ProDisc-C, Prestige-LP and Mobi-C. ASD was followed up at 1 week, 6 months, 1 year, 2 years, 5 years, 10 years after CTDR and at the endpoint of June 2022. The radiographic measurements were cervical mobility, intervertebral disc height (IDH), cervical lordosis and balance status. The complications were implant migration, subsidence and heterotopic ossification (HO). RESULTS: Cervical mobility in adjacent segments, IDH and lordosis showed no statistical differences between ASD and NASD group. Balance status, subsidence and migration showed no relationship with ASD. Postoperative ASD increased at 6 m and especially between 6 m to 2y. There was no difference between the incidence of upper ASD and lower ASD all the time and few ASD-related reoperation. The majority of adjacent segments were C4/5 (33.6%) and C6/7 (34.2%), and ASD of C5/6 had the highest incidence (61.5%). Cox regression showed ASD was not related to the types of prosthesis or operated numbers. Generalized estimating equations (GEE) analysis showed severe HO had a higher (2.68 times) probability to suffer from ASD. CONCLUSIONS: After over 12-year follow-up of CTDR, the occurrence of ASD and HO had temporal synchronization. ASD was not merely a natural progression but with the pathological process such as HO.

Effects of Training and Calibration Data on Surface Electromyogram-Based Recognition for Upper Limb Amputees.

Surface electromyogram (sEMG)-based gesture recognition has emerged as a promising avenue for developing intelligent prostheses for upper limb amputees. However, the temporal variations in sEMG have rendered recognition models less efficient than anticipated. By using cross-session calibration and increasing the amount of training data, it is possible to reduce these variations. The impact of varying the amount of calibration and training data on gesture recognition performance for amputees is still unknown. To assess these effects, we present four datasets for the evaluation of calibration data and examine the impact of the amount of training data on benchmark performance. Two amputees who had undergone amputations years prior were recruited, and seven sessions of data were collected for analysis from each of them. Ninapro DB6, a publicly available database containing data from ten healthy subjects across ten sessions, was also included in this study. The experimental results show that the calibration data improved the average accuracy by 3.03%, 6.16%, and 9.73% for the two subjects and Ninapro DB6, respectively, compared to the baseline results. Moreover, it was discovered that increasing the number of training sessions was more effective in improving accuracy than increasing the number of trials. Three potential strategies are proposed in light of these findings to enhance cross-session models further. We consider these findings to be of the utmost importance for the commercialization of intelligent prostheses, as they demonstrate the criticality of gathering calibration and cross-session training data, while also offering effective strategies to maximize the utilization of the entire dataset.

The Pillar Effect of Large-Size Alkaline Ions on the Electrochemical Stability of Sodium Manganese Hexacyanoferrate for Sodium-Ion Batteries.

Sodium manganese hexacyanoferrate (NaMnHCF) is an attractive candidate as a cathode material for sodium-ion batteries due to its low cost and high energy density. However, its practical application is hindered by poor electrochemical stability caused by the Jahn-Teller effect of Mn and the unstable structure of NaMnHCF. Here, this paper aims to address this issue by introducing highly stable AMnHCF (where A = K, Rb, or Cs) through a facile method to composite with NaMnHCF. The findings reveal that all AMnHCFs have a "pillar effect" on the crystal structure of NaMnHCF. It is observed that the degree of pillar effect varies depending on the specific AMnHCF used. The less electrochemically inactive the alkaline ion is and the greater the degree of compositing with NaMnHCF, the more dramatic the pillar effect. KMnHCF shows limited pillar effect due to its rough composition with NaMnHCF and the loss of K+ upon (de)intercalation. RbMnHCF has lower electrochemical activity and can be better composited with NaMnHCF. On the other hand, CsMnHCF exhibits the strongest pillar effect due to the inactivation of Cs+ and the excellent coherent structure formed by CsMnHCF and NaMnHCF. This research provides a new perspective on stabilizing NaMnHCF with other alkaline elements.

Perioperative risk factors related to complications of lumbar spine fusion surgery in elderly patients.

PURPOSE: To analyze the perioperative risk factors related to lumbar spine fusion surgery in elderly patients. METHODS: 202 elderly patients (age range 77-92 years old) who have underwent lumbar spinal fusion surgeries between January 2019 and June 2021 were retrospectively investigated. Information of age, sex, comorbidity, fixation segments, operation time, surgical blood loss and perioperative complications during hospitalization were collected. Risk factors for complications were analyzed. Student's t-test, chi-square test, Mann-Whitney U­test and multivariate generalized linear models were used. RESULTS: In this study, 31 patients presented complications (15.3%) in these elderly patients with an average age of 79.1 years, including 1 patient with intraoperative complication and 30 patients with postoperative complications; and 2 out of 31 patients (1%) died. The elderly patients were divided into group A (24 patients) with major postoperative complications and group B (178 patients) without major postoperative complications. Major postoperative complications were significantly associated with age (univariate analysis, t = 3.92, P < 0.001; multivariate analysis, OR = 1.323, 95%CI 1.126-1.554, P = 0.001), but not significantly associated with other factors tested (sex, comorbidity, fixation segments, operation time, surgical blood loss). Then 173 patients (range 77-81 years) were selected and the rate of major postoperative complications of each age from 78 to 81 years was compared with that of 77 years patients, respectively. We found that the ratios of complications at 80 years (OR = 10.000, P = 0.019) and 81 years (OR = 10.000, P = 0.009) were higher than the ratio at 77 years. CONCLUSIONS: Although with great progress of medical technology, increasing age was still the independent risk factor for major postoperative complications in elderly patients undergoing lumbar spinal fusion surgery. As for the incidence of major postoperative complications, 80 and 81 years old patients was 10 folds higher than that of 77 years old patients, reminding us to pay more attention to 80 years old and even older patients.

Atmospheric wet and dry depositions of polycyclic aromatic compounds in a megacity of Southwest China.

The dry and wet depositions of polycyclic aromatic hydrocarbons (PAHs) and related derivatives have rarely been characterized separately. Parent, oxygenated and nitrated PAHs (PAHs, OPAHs and NPAHs) have been measured in monthly-averaged wet and dry deposition samples collected from January to December 2019 in urban Chongqing. The annual average concentrations of Æ©17PAHs, Æ©9OPAHs and Æ©9NPAHs in wet deposition samples were 457 ± 375, 1311 ± 1416 and 8.25 ± 10.2 ng/L, respectively, with significant monthly variations introduced by rainfall and air-borne particle deposition. Most PAHs species were associated with the particulate phase in wet deposition, while OPAHs and NPAHs were mainly distributed in the dissolved phase, probably due to the lower octanol-water partitioning coefficient of N/OPAHs than that of PAHs. Annual deposition fluxes of PAHs, OPAHs and NPAHs in dry deposition were 25264, 25310 and 388 ng/m2/yr, respectively, higher than those in wet deposition (9869, 24083 and 207 ng/m2/yr). This indicates that PACs, especially PAHs, were removed from the atmosphere mainly via dry deposition. The contributions of wet deposition to total deposited PACs were larger for months with higher precipitation and for PACs with higher molecular weight. Composition pattern and temporal variation results indicated that wet deposition fluxes were mainly affected by precipitation-related particle deposition and chemical properties (e.g., water solubility), while dry deposition fluxes were affected more by factors such as gas/particle partitioning, particle size distribution and physicochemical properties of PACs. Principle component analysis combined with diagnostic ratios revealed that PACs in atmospheric deposition samples were from vehicle emission (48.6%), coal combustion (13.4%), petrogenic source (5.9%) and secondary formation (32.1%).

The compensatory mechanisms for global sagittal balance in degenerative spinal kyphosis patients: a radiological analysis of muscle-skeletal associations.

BACKGROUND: The position of the head relative to the spine can be used to evaluate the true global balance in patients with degenerative spinal kyphosis (DSK). However, it is still not clear how the position of the head is related to the spinal-pelvic parameters and lumbar muscles, which are most commonly considered. METHODS: Sixty-seven patients with DSK admitted in the hospital from January 2017 to January 2019 were retrospectively analyzed. All patients had whole spine X-ray and lumbar MRI. The head position parameters include: the angles of both lines joining the center of acoustic meati (CAM) to the center of the bi-coxofemoral axis (BA) (CAM-BA) and the most superior point of dentiform apophyse of C2 odontoid (OD) to BA (OD-BA) with the vertical line; the distance between the vertical line passing CAM and the posterior upper edge of the S1 (CAM-SVA). The spinal parameters include: C7 sagittal vertical axis (C7-SVA), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), and lumbar lordosis (LL). The pelvic parameters include: pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS). The relative cross-sectional area (RCSA) of bilateral multifidus, erector spinae and psoas muscle at L3/4 and L4/5 segments were measured. The correlations between head position parameters and the spinal-pelvic parameters and RCSA of lumbar muscles were analyzed, respectively. RESULTS: Significant positive correlations were found between each two of CAM-SVA, C7-SVA, CAM-BA and OD-BA (p < 0.001). SS was found to be significantly positively correlated with CAM-BA (r = 0.377, p = 0.034) and OD-BA (r = 0.402, p = 0.023). CAM-BA was found to be significantly negatively correlated with TK (r = - 0.367, p = 0.039). Significant positive correlations were found between RCSA of multifidus at L3/4 level and CAM-SVA (r = 0.413, p = 0.021), CAM-BA (r = 0.412, p = 0.019) and OD-BA (r = 0.366, p = 0.04). CONCLUSIONS: Our study showed that the head position relative to the spine were significantly correlated to some spinal-pelvic parameters, and the lower lumbar multifidus muscle. The compensatory mechanisms of the global sagittal balance status should also involve the head position area.

Activation of GSDMD contributes to acute kidney injury induced by cisplatin.

Cisplatin is one of the most effective antitumor agents, but its clinical use is highly limited by its severe side effects, especially nephrotoxicity. Recently, the active form of gasdermin D (GSDMD), termed GSDMD-N, was identified to mediate pyroptotic inflammatory cell death in several diseases. However, the role of the GSDMD-N fragment in cisplatin-induced acute kidney injury (AKI) remains unclear. In the present study, we found that pyroptosis was induced by cisplatin in both mouse kidney tissues and renal tubular epithelial cells, accompanied by increased expression of the GSDMD-N fragment. In GSDMD knockout mice with cisplatin-induced AKI, we found that cisplatin-induced loss of renal function, renal tubular injury, and inflammation was significantly attenuated compared with wild-type mice. Furthermore, the GSDMD-N fragment was overexpressed by an established rapid plasmid tail vein injection approach to evaluate the role of this cleaved form of GSDMD in AKI. As expected, mice with GSDMD-N fragment overexpression in the kidney were more susceptible to cisplatin-induced AKI than control mice, as evidenced by further elevated serum levels of blood urea nitrogen and creatinine, aggravated renal pathology, increased expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, and enhanced renal inflammatory cytokine secretion, which indicates a pathogenic role of GSDMD-N in cisplatin-induced AKI by triggering cell pyroptosis. Similar results were also observed in renal tubular epithelial cells overexpressing the GSDMD-N fragment. Thus these findings suggested that the activation of GSDMD contributes to cisplatin-induced AKI, possibly through triggering pyroptosis.

Publisher Correction: Regioselective surface encoding of nanoparticles for programmable self-assembly.

In the version of this Article originally published, the diblock copolymer structure in Fig. 2a showed a single bond between the carbon and the oxygen atoms; it should have been a double bond. This has been corrected in all versions of the Article.

Regioselective surface encoding of nanoparticles for programmable self-assembly.

Surface encoding of colloidal nanoparticles with DNA is fundamental for fields where recognition interaction is required, particularly controllable material self-assembly. However, regioselective surface encoding of nanoparticles is still challenging because of the difficulty associated with breaking the identical chemical environment on nanoparticle surfaces. Here we demonstrate the selective blocking of nanoparticle surfaces with a diblock copolymer (polystyrene-b-polyacrylic acid). By tuning the interfacial free energies of a ternary system involving the nanoparticles, solvent and copolymer, controllable accessibilities to the nanoparticles' surfaces are obtained. Through the modification of the polymer-free surface region with single-stranded DNA, regioselective and programmable surface encoding is realized. The resultant interparticle binding potential is selective and directional, allowing for an increased degree of complexity of potential self-assemblies. The versatility of this regioselective surface encoding strategy is demonstrated on various nanoparticles of isotropic or anisotropic shape and a total of 24 distinct complex nanoassemblies are fabricated.

Active Soil Nitrifying Communities Revealed by In Situ Transcriptomics and Microcosm-Based Stable-Isotope Probing.

Long-term nitrogen field fertilization often results in significant changes in nitrifying communities that catalyze a key step in the global N cycle. However, whether microcosm studies are able to inform the dynamic changes in communities of ammonia-oxidizing bacteria (AOB) and archaea (AOA) under field conditions remains poorly understood. This study aimed to evaluate the transcriptional activities of nitrifying communities under in situ conditions, and we found that they were largely similar to those of 13C-labeled nitrifying communities in the urea-amended microcosms of soils that had received different N fertilization regimens for 22 years. High-throughput sequencing of 16S rRNA genes and transcripts suggested that Nitrosospira cluster 3-like AOB and Nitrososphaera viennensis-like AOA were significantly stimulated in N-fertilized fresh soils. Real-time quantitative PCR demonstrated that the significant increase of AOA and AOB in fresh soils upon nitrogen fertilization could be preserved in the air-dried soils. DNA-based stable-isotope probing (SIP) further revealed the greatest labeling of Nitrosospira cluster 3-like AOB and Nitrosospira viennensis-like AOA, despite the strong advantage of AOB over AOA in the N-fertilized soils. Nitrobacter-like nitrite-oxidizing bacteria (NOB) played more important roles than Nitrospira-like NOB in urea-amended SIP microcosms, while the situation was the opposite under field conditions. Our results suggest that long-term fertilization selected for physiologically versatile AOB and AOA that could have been adapted to a wide range of substrate ammonium concentrations. It also provides compelling evidence that the dominant communities of transcriptionally active nitrifiers under field conditions were largely similar to those revealed in 13C-labeled microcosms.IMPORTANCE The role of manipulated microcosms in microbial ecology has been much debated, because they cannot entirely represent the in situ situation. We collected soil samples from 20 field plots, including 5 different treatments with and without nitrogen fertilizers for 22 years, in order to assess active nitrifying communities by in situ transcriptomics and microcosm-based stable-isotope probing. The results showed that chronic N enrichment led to competitive advantages of Nitrosospira cluster 3-like AOB over N. viennensis-like AOA in soils under field conditions. Microcosm labeling revealed similar results for active AOA and AOB, although an apparent discrepancy was observed for nitrite-oxidizing bacteria. This study suggests that the soil microbiome represents a relatively stable community resulting from complex evolutionary processes over a large time scale, and microcosms can serve as powerful tools to test the theory of environmental filtering on the key functional microbial guilds.

Effect of bandgap alignment on the photoreduction of CO2 into methane based on Cu2O-decorated CuO microspheres.

Semiconductors' band gap alignment is important for the photoreduction of CO2 to methane. In the paper, two kinds of Cu2O-decorated CuO microspheres composed with nanoflakes were prepared by using two different methods. Their electron behaviors were studied from the XPS spectra and photoelectrochemical measurements. Both samples are p-type CuO covered with an amount of Cu2O nanoparticles on their surface. Combined with their bandgaps and flat band potentials, CuO-Mic has a well-matched bandgap alignment between Cu2O and CuO, which is favorable for the separation of photogenerated electron-hole pairs. Those photogenerated carriers are beneficial for the conversion of CO2 to CH4, as an 8-electron process for the conversion of CO2 to CH4 will consume more photogenerated electrons for the chemical reactions than that of the 2-electron process for CO2 reduction to CO. Therefore, CuO-Mic has much better photocatalytic activity for CO2 reduction to CH4 with a CH4 yield ten times higher than that of CuO-Hyd under a visible light irradiation, the CO yields of the CO2 reduction are identical.

Inhibition of mitochondrial activity ameliorates atherosclerosis in ApoE-/- mice via suppressing vascular smooth cell activation and macrophage foam cell formation.

BACKGROUND: Atherosclerosis involves disorders in lipoprotein metabolism and inflammation. Mitochondrial dysfunction plays a critical role in promoting cell apoptosis, inflammation, and oxidative stress involved in the progress of atherosclerosis. Whereas the direct effect of mitochondrial activity modulation on atherogenesis remains unclear. This study evaluated the effect of a mitochondrial complex inhibitor on atherosclerosis in ApoE-deficient mice as well as the potential mechanisms. METHODS AND RESULTS: We treated ApoE-deficient mice with mitochondrial complex I inhibitor rotenone in the western diet and found that rotenone attenuated early and advanced atherosclerosis with no effect on serum lipoprotein levels. Mechanistic investigation showed that rotenone suppressed primary macrophage foam cell formation possibly by suppressing CD36. In addition, we also found that the inhibitory effect of rotenone on VSMC proliferation and migration possibly by targeting the PI3K/AKT signaling. Consistently, mitochondrial complex III inhibitor azoxystrobin also exhibited similar actions as rotenone in VSMCs but not in macrophages. CONCLUSIONS: Inhibition of mitochondrial activity could significantly attenuate atherosclerosis possibly by modulating CD36-mediated macrophage foam cell formation and PI3K/AKT signaling pathway-associated VSMC activation. Targeting mitochondrial activity might be the potential therapeutic strategy for atherosclerosis.

Estrogen-related receptor-α mediates puromycin aminonucleoside-induced mesangial cell apoptosis and inflammatory injury.

Glomerular diseases are the leading cause of chronic kidney disease, and mesangial cells (MCs) have been demonstrated to be involved in the pathogenesis. Puromycin aminonucleoside (PAN) is a nephrotoxic drug that induces glomerular injury with elusive mechanisms. The present study was undertaken to investigate the role of PAN in MC apoptosis, as well as the underlying mechanism. Here we found that PAN induced MC apoptosis accompanied by declined cell viability and enhanced inflammatory response. The apoptosis was further evidenced by increments of apoptosis regulator BAX (BAX) and caspase-3 expression. In line with the apoptotic response in MCs following PAN treatment, we also found a remarkable induction of estrogen-related receptor-α (ERRα), an orphan nuclear receptor, at both mRNA and protein levels. Interestingly, ERRα silencing by an siRNA approach resulted in an attenuation of the apoptosis and inflammatory response caused by PAN. More importantly, overexpression of ERRα in MCs significantly triggered MC apoptosis in line with increased BAX and caspase-3 expression. In PAN-treated MCs, ERRα overexpression further aggravated PAN-induced apoptosis. In agreement with the in vitro study, we also observed increased ERRα expression in line with enhanced apoptotic response in renal cortex from PAN-treated rats. These data suggest a detrimental effect of ERRα on PAN-induced MC apoptosis and inflammatory response, which could help us to better understand the pathogenic mechanism of MC injury in PAN nephropathy.

Association between back muscle degeneration and spinal-pelvic parameters in patients with degenerative spinal kyphosis.

BACKGROUND: The paraspinal and psoas muscles have been considered to be essentially important for stabilizing the spinal column, and the muscle degeneration was found to exist in degenerative spinal kyphosis (DSK) patients. However, it is still not clear the relationship between muscle degeneration and spinal-pelvic alignment. The purpose of this study was to determine the correlations between the individual muscle degeneration at each lumbar spinal level and spinal-pelvic parameters in DSK patients. METHODS: The imaging data of 32 patients with DSK were retrospectively analyzed. The fat infiltration (FI) and relative cross-sectional area of muscle (RCSA) were quantitatively measured for multifidus (MF), erector spinae (ES) and psoas (PS) at each spinal level from L1/2 to L5/S1. The correlations were analyzed between RCSA and the sagittal vertical axis (SVA), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT) and pelvic incidence (PI). RESULTS: The FI of MF and ES at L3/4, L4/5 and L5/S1 were higher than that at L1/2 and L2/3. The FI of PS at L4/5 and L5/S1 were lower than that of L1/2, L2/3 and L3/4. The RCSA of ES and PS from L1/2 to L5/S1 gradually increased, whereas the RCSA of ES from L1/2 to S5/S1 gradually decreased. The RCSA of MF at the L1/2 level was negatively correlated SVA (r = - 0.397,p = 0.024); the RCSA at L3/4, L4/5 and L5/S1 levels were negatively correlated with TK (r = - 0.364, p = 0.04; r = - 0.38, p = 0.032; r = - 0.432, p = 0.014); the RCSA at L4/5 level was positively correlated with LL (r = 0.528, p = 0.002). The RCSA of ES at L3/4 and L4/5 levels were positively correlated with PI (r = 0.377, p = 0.037) and SS (r = 0.420, p = 0.019). CONCLUSIONS: FI of MF and ES at lower lumbar level is higher than that at upper level, but FI of PS at upper lumbar level is higher than that at lower level. MF and ES have different roles for maintaining the sagittal spinal-pelvic balance.

Parkin Modulates ERRα/eNOS Signaling Pathway in Endothelial Cells.

BACKGROUND/AIMS: Although a number of reports documented the important role of parkin in mitophagy, emerging evidence also indicated additional functions of parkin besides mitophagy. The present study was undertaken to investigate the role of parkin in the regulation of ERRα/eNOS pathway in endothelial cells (ECs). METHODS: Mouse aortic endothelial cells (MAECs) and cardiac muscle HL-1 cells were transfected with parkin plasmid or siRNA. ERRα inhibitor XCT-790, autophagy inhibitor 3-MA and Bafilomycin A1, and caspase inhibitor Z-VAD-FMK were used to block autophagy or apoptosis. Western blotting was performed to examine the protein levels. Flow cytometry was applied to determine the cell apoptosis and ROS production. Mitochondrial membrane potential was measured using JC-1 and TMRM. Immunoprecipitation was performed to confirm the parkin effect on ERRα ubiquitination. RESULTS: Overexpression of parkin resulted in a significant reduction of total-eNOS and p-eNOS in parallel with the downregulation of ERRα (a regulator of eNOS) protein and the enhancement of ERRα ubiquitination. To test the role of ERRα in regulating eNOS in this experimental setting, we treated ECs with ERRα inhibitor and found a decrement of total-eNOS and p-eNOS. On the contrary, overexpression of ERRα increased the levels of total-eNOS and p-eNOS. Meanwhile, parkin overexpression induced mitochondrial dysfunction and cell apoptosis in both ECs and HL-1 cells. Finally, we confirmed that the parkin effect on the regulation of eNOS was independent of the autophagy and apoptosis. CONCLUSION: These findings suggested that parkin overexpression downregulated eNOS possibly through the ubiquitination of ERRα in endothelial cells.

Role of dihydroartemisinin in regulating prostaglandin E2 synthesis cascade and inflammation in endothelial cells.

Endothelial cells (ECs) are crucial in maintaining vascular homeostasis. Endothelial dysfunction was involved in many cardiovascular diseases (CVDs). Recently, antimalarial medicine artemisinin and its derivatives including dihydroartemisinin (DHA) were found to be beneficial in some diseases including CVDs. Prostaglandin (PG) E2 is a known inflammatory mediator and plays important roles in cardiovascular system. This study was to investigate the role of DHA in regulating cyclooxygenase (COX)/PGE synthase (PGES)/PGE2 cascade and inflammation in ECs. After DHA treatment, the mRNA and protein levels of COX-2 were strikingly upregulated in time- and dose-dependent manners. In contrast, COX-1 was significantly downregulated. As expected, inhibition of COX-1 or COX-2 further reduced PGE2 production after DHA treatment. Moreover, DHA enhanced microsomal PGE2 synthase (mPGES)-2 and moderately modulated cytosolic PGE2 synthase (cPGES) with no effect on mPGES-1 expression. Importantly, DHA significantly reduced PGE2 levels in line with the upregulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH, a key enzyme for prostaglandin degradation). Lastly, we observed that DHA not only reduced the PGE2 levels in tumor necrosis factor-α (TNF-α)-treated ECs but also blunted the upregulation of inflammatory cytokines of interleukin (IL)-6 and IL-1ß induced by TNF-α or PGE2. These findings demonstrated an important role of DHA in regulating PGE2 synthesis cascade and inflammation in ECs, suggesting a potential of DHA for the treatment of inflammatory vascular diseases.

[Research progress of the uremic toxin indoxyl sulfate in cardiovascular complication of end-stage renal diseases].

Cardiovascular disease is one of the most common complications and the main cause of death in patients with chronic kidney disease. Uremic toxins are the primary cause of cardiovascular disease in renal insufficiency. In patients with chronic kidney disease, the protein-bound uremic toxins represented by indoxyl sulfate are difficult to be removed by conventional dialysis and are extremely toxic. In recent years, studies have confirmed that the occurrence of cardiovascular disease induced by chronic kidney disease is closely related to the accumulation of indoxyl sulfate. Indoxyl sulfate can induce oxidative stress to cause endothelial injury, smooth muscle cell proliferation and migration, and promote the occurrence of atherosclerosis, thereby affecting multiple systems throughout the body. This article reviews the research progress of uremic toxin indoxyl sulfate in end-stage renal diseases associated cardiovascular diseases.