Circular RNAs (circRNAs) are endogenous non‑coding RNAs implicated in atherosclerosis. The aim of the present study was to explore the function of circRNA‑0044073 in atherosclerosis. Reverse ...transcription quantitative polymerase chain reaction assays were used to measure the expression levels of circRNA‑0044073, microRNA (miRNA/miR)‑107, janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), B‑cell lymphoma 2 (Bcl‑2) and v‑myc avian myelocytomatosis viral oncogene homolog (c‑myc) in in blood cells from patients with atherosclerosis. RNA pull‑down and luciferase reporter assays were then used to determine the association between circRNA and miR expression, and miR and gene expression, respectively. Matrigel invasion assay and flow cytometry were used to analyze cell invasion and cell cycle. Western blot analysis and ELISA were used to evaluate the expression levels of proteins. It was identified that the expression of circRNA‑0044073 was upregulated and the expression of miR‑107 was downregulated in atherosclerotic blood cells. Overexpression of circRNA‑0044073 promoted the proliferation of human vascular smooth muscle cells (HUVSMCs) and human vascular endothelial cells (HUVECs), while overexpression of miR‑107 inhibited their proliferation. In addition, circRNA‑0044073 suppressed the levels of miR‑107 via a sponge mechanism. Lipopolysaccharide (LPS) affected the proliferation of HUVSMCs and HUVECs, and also resulted in changes in circRNA‑0044073 expression levels. CircRNA‑0044073 promoted the proliferation and invasion of HUVSMCs and HUVECs in spite of the opposite effect observed with LPS treatment. The JAK/STAT signaling pathway was activated in patients with atherosclerosis. CircRNA‑0044073 favored the activation of the JAK/STAT signaling pathway and inflammation in HUVSMCs and HUVECs. These data indicate that circRNA‑0044073 is upregulated in atherosclerosis and promotes the proliferation and invasion of cells by targeting miR‑107 and activating the JAK/STAT signaling pathway, potentially offering a target for novel treatment strategies against atherosclerosis.
Background Insufficient clinical data exist to determine whether provision of oral nutritional supplements during dialysis can improve survival in hypoalbuminemic maintenance hemodialysis patients. ...Study Design Retrospective matched-cohort study. Setting & Participants All oral nutritional supplement program–eligible in-center maintenance hemodialysis patients with albumin level ≤3.5 g/dL in quarter 4 of 2009 without oral nutritional supplements in the prior 90 days at Fresenius Medical Care, North America facilities. Quality Improvement Plan Monitored intradialytic oral nutritional supplements were provided to eligible maintenance hemodialysis patients upon physician order, to continue for a year or until serum albumin level was ≥4.0 g/dL. Outcome Mortality (including deaths and withdrawals), followed up until December 31, 2010. Measurements Both an intention-to-treat (ITT) and an as-treated analysis was performed using a 1:1 geographic region and propensity score–matched study population (using case-mix, laboratory test, access type, 30-day prior hospitalization, and incident patient status) comparing patients treated with intradialytic oral nutritional supplements with usual-care patients. Cox models were constructed, unadjusted and adjusted for facility standardized mortality ratio and case-mix and laboratory variables. Results The ITT and as-treated analyses both showed lower mortality in the oral nutritional supplement group. The conservative ITT models with 5,227 matched pairs had 40% of controls subsequently receiving oral nutritional supplements after January 1, 2010 (because many physicians delayed participation), with comparative death rates of 30.1% versus 30.4%. The corresponding as-treated (excluding crossovers) death rates for 4,289 matched pairs were 30.9% versus 37.3%. The unadjusted ITT mortality HR for oral nutritional supplement use was 0.95 (95% CI, 0.88-1.01), and the adjusted HR was 0.91 (95% CI, 0.85-0.98); the corresponding as-treated HRs were 0.71 (95% CI, 0.66-0.76) and 0.66 (95% CI, 0.61-0.71) before and after adjustment, respectively. Limitations Limited capture of oral nutritional supplement intake outside the facility and potential residual confounding from unmeasured variables, such as dietary intake. Conclusions Maintenance hemodialysis patients with albumin levels ≤3.5 g/dL who received monitored intradialytic oral nutritional supplements showed survival significantly better than similar matched patient controls, with the as-treated analysis highlighting the potentially large effect of this strategy in clinical practice.
Acute lung injury (ALI) is characterized by dysfunction of the alveolar epithelial membrane caused by acute inflammation and tissue injury. Qingwenzhike (QWZK) prescription has been demonstrated to ...be effective against respiratory viral infections in clinical practices, including coronavirus disease 2019 (COVID-19) infection. So far, the chemical compositions, protective effects on ALI, and possible anti-inflammatory mechanisms remain unknown.
In this study, the compositions of QWZK were determined
the linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap MS). To test the protective effects of QWZK on ALI, an ALI model induced by lipopolysaccharide (LPS) in rats was used. The effects of QWZK on the LPS-induced ALI were evaluated by pathological changes and the number and classification of white blood cell (WBC) in bronchoalveolar lavage fluid (BALF). To investigate the possible underlying mechanisms, the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1), interleukin-1β (IL-1β), interleukin-18 (IL-18), and immunoregulatory-related factors interferon-γ (IFN-γ) were detected by ELISA. Furthermore, the expression of Toll-like receptor 4 (TLR4), p-IKKα/β, IKKα, IKKβ, p-IκBα, IκBα, p-NF-κB, nuclear factor-κB (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, pro-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), and β-actin were tested by Western blot.
A total of 99 compounds were identified in QWZK, including 33 flavonoids, 23 phenolic acids, 3 alkaloids, 3 coumarins, 20 triterpenoids, 5 anthraquinones, and 12 others. ALI rats induced by LPS exhibited significant increase in neutrophile, significant decrease in lymphocyte, and evidently thicker alveolar wall than control animals. QWZK reversed the changes in WBC count and alveolar wall to normal level on the model of ALI induced by LPS. ELISA results revealed that QWZK significantly reduced the overexpression of proinflammatory factors IL-6, TNF-α, MCP-1, IL-1β, IL-18, and IFN-γ induced by LPS. Western blot results demonstrated that QWZK significantly downregulated the overexpression of TLR4, p-IKKα/β, p-IκBα, p-NF-κB, NLRP3, cleaved caspase-1, and ASC induced by LPS, which suggested that QWZK inhibited TLR4/NF-κB signaling pathway and NLRP3 inflammasomes.
The chemical compositions of QWZK were first identified. It was demonstrated that QWZK showed protective effects on ALI induced by LPS. The possible underlying mechanisms of QWZK on ALI induced by LPS was
inhibiting TLR4/NF-kB signaling pathway and NLRP3 inflammasome activation. This work suggested that QWZK is a potential therapeutic candidate for the treatments of ALI and pulmonary inflammation.
Through laboratory experiments and thermodynamic calculation, the chemical composition and morphology of inclusion and grain size in the cast melt are comprehensively characterized herein. The ...results show the evolution of Al2O3 inclusion formed by Al deoxidation in the gear steel 20CrNiMo follows the route of Al2O3 → CeAlO3 → Ce2O2S → Ce2O2S + CeS, and thus the nucleation core of complex CemnS sulfides changes from CeAlO inclusion to CeOS inclusion with the increase in Ce addition. Moreover, grain size of gear steel 20CrNiMo treated by Ce addition decreases from 491.4 to 164.0 μm, because both the Ce2O2S and CeS form with Ce addition and have potential to be effective heterogeneous nucleation agents for the primary δ‐ferrite during the solidification process of gear steel 20CrNiMo. And statistical results show that the percentage of small inclusion with a diameter less than 3 μm are, respectively, 64.4%, 86.5%, 96.4%, 93.6%, and 75.6% in the steel samples with Ce content of 0, 13, 31, 77, and 203 ppm. Thus, the recommended Ce content to achieve fine inclusions and solidification structure of gear steel 20CrNiMo is 31 ppm.
The effect of Ce on the inclusion and grain structure of gear steel 20CrNiMo is investigated. The evolution route of inclusions in steel after Ce addition is analyzed, and the mechanism is discussed. In addition, the reason for the grain refinement after adding Ce to the steel is also analyzed.
It is reported that salvianolic acid B, a bioactive phenolic compound contained in the root of
Salvia miltiorrhiza, exhibits a much stronger activity in free radical scavenging and antioxidance than ...those of vitamin E. When a conventional refluxing method is adopted to extract salvianolic acid B from the root, in which the materials are subjected to higher temperature and longer time, the yield of this phenolic compound is lower due to the possibility of its hydrolysis to tanshinol. However, a higher extraction yield can be achieved over a shorter time period and lower temperature when an ultrasound-assisted extraction method is used. This paper investigated the parameters influencing the extraction of salvianolic acid B. Factors such as extraction time, frequency of the ultrasound, the ratio of solvent to material, and types of extraction solvent were examined. A comparison was also conducted between conventional refluxing and ultrasound-assisted extraction. Results showed that the optimal parameters to extract salvianolic acid B from the root of
S. miltiorrhiza were as follows: ultrasonic frequency: 45
Hz; solvent: 60% aqueous ethanol; extraction temperature: 30
°C; extraction time duration: 25 min.; ratio of solvent to material: 20:1 (v/w, ml/g). Under these conditions, the yield of salvianolic acid B was 5.17
mg/g (33.93
mg/g) higher than those with conventional refluxing method (28.76
mg/g), indicating that the efficiency and the yield of ultrasound-assisted extraction method are higher than reflux method, and the hydrolysis of salvianolic acid B to tanshinol is effectively avoided.
This paper determines the influencing factors of architectural acoustic environment comfort assessment from the perspective of green building acoustic environment comfort, and constructs a two-by-two ...comparison judgment matrix for each questionnaire survey result. Through the consistency test of the judgment matrix, the weights of the factors influencing the comfort of the building sound environment are obtained, and the construction of the assessment model of the comfort of the building sound environment is completed. Based on the architectural acoustic environment comfort assessment model, optimization variables are selected and multi-objective optimization is used to determine the objective function and constraints of architectural acoustic environment comfort. The comfort of the acoustic environment of the campus building is evaluated and analyzed through simulation analysis. The results show that the two measurement points, point 8 and point 15, located on the north side of the library and information building and the center courtyard, respectively, have relatively low continuous sound pressure levels
of 51.7 dB and 44.4 dB, respectively, which are relatively favorable for the creation of a comfortable acoustic environment. Improving the building arrangement through the multi-objective optimization method under the acoustic environment assessment model can provide good environmental protection for people’s daily lives and work.
This study focuses on the urban landscape design of city A, and uses information fusion technology to evaluate. Through the analysis of the measured data by the entropy weighting method and the ...ensemble optimal weighting method, and compared with the established index system, the results reveal the weights of different landscape elements. Regarding ecological landscape, the CR value was 0.003, in which landscape diversity and green space rate were the leading indicators, and the weights were 0.2976. The weights of landscape dominance and uniformity were relatively medium, both of which were 0.1579. In the evaluation of aesthetic landscape, the CR value was 0.0309, and the highway alignment and urban landscape indicators in the urban landscape were the most important, with a weight of 0.2044, while the weight of the indication information was the lowest, only 0.0266. The CR value of the cultural landscape was 0.0518, of which the weight of scenic connectivity was the highest (0.5559), followed by the number and scale of scenic spots (0.3537), and the weight of historical and cultural elements was the lowest (0.0904). In the past few years, landscape design has accounted for the most significant proportion of landscape construction investment, especially reaching a peak of about 57,000 yuan in 2022. From 2018 to 2022, the cumulative investment in urban landscape design is about 246664 yuan.
Background Hemodialysis (HD) access is considered a critical and actionable determinant of morbidity, with a growing literature suggesting that initial HD access type is an important marker of ...long-term outcomes. Accordingly, we examined HD access during the incident dialysis period, focusing on infection risk and successful fistula creation during the first dialysis year. Study Design Longitudinal cohort. Setting & Participants All US adults admitted to Fresenius Medical Care North America facilities within 15 days of first maintenance dialysis session between January 1 and December 31, 2007. Predictor Vascular access type at HD therapy initiation. Outcomes Vascular access type at 90 days and at the end of the first year on HD therapy, bloodstream infection within the first year by access type, and catheter complication rate. Results Of 25,003 incident dialysis patients studied, 19,622 (78.5%) initiated dialysis with a catheter; 4,151 (16.6%), with a fistula; and 1,230 (4.9%), with a graft. At 90 days, 14,105 (69.7%) had a catheter, 4,432 (21.9%) had a fistula, and 1,705 (8.4%) had a graft. Functioning fistulas and grafts at dialysis therapy initiation had first-year failure rates of 10% and 15%, respectively. Grafts were seldom replaced by fistulas (3%), whereas 7,064 (47.6%) of all patients who initiated with a catheter alone still had only a catheter at 1 year. Overall, 3,327 (13.3%) patients had at least one positive blood culture during follow-up, with the risk being similar between the fistula and graft groups, but approximately 3-fold higher in patients with a catheter ( P <0.001 for either comparison). Nearly 1 in 3 catheters (32.5%) will require tissue plasminogen activator use by a median of 41 days, with 59% requiring more than one tissue plasminogen activator administration. Limitations Potential underestimation of bacteremia because follow-up blood culture results did not include samples sent to local laboratories. Conclusions In a large and representative population of incident US dialysis patients, catheter use remains very high during the first year of HD care and is associated with high mechanical complication and bloodstream infection rates.
The decrease of vitamin D plays a critical role in diabetes mellitus (DM)-induced oxidative stress and vascular endothelial injury. Therefore, we investigated the effect and mechanism of ...25-hydroxyvitamin D3 (25 (OH) D3) on oxidative stress and ferroptosis induced by high glucose in human retinal microvascular endothelial cells (hRMVECs). And the objective of this paper was to propose a new strategy for the prevention and treatment of diabetic retinopathy (DR).
First, hRMVECs were transfected with mimics NC or miR-93. After that, cells were treated with 100 nM / 500 nM 25 (OH) D3 and then cultured in a high glucose (30 mM) environment. Subsequently, qRT-PCR was employed to detect the expression level of miR-93; CCK-8 for the proliferation of cells in each group; biochemical tests for the level of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH) and ferrous ion (Fe
); and Western blot for the expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and SLC7A11).
Under a high glucose environment, 25 (OH) D3 at 100 nM/500 nM could significantly promote the proliferation of hRMVECs, remarkably decrease the level of intracellular ROS/MDA, and up-regulate the level of GSH. Besides, 25 (OH) D3 greatly reduced Fe
level in the cells while increased protein level of GPX4 and SLC7A11. Subsequently, we found that high glucose induced miR-93 expression, while 25 (OH) D3 markedly decreased high glucose-induced miR-93 overexpression. Furthermore, overexpression of miR-93 inhibited the functions of 25 (OH) D3 by activating ROS (ROS and MDA were up-regulated while GSH was down-regulated) and inducing Fe
(Fe
level was up-regulated while GPX4 and SLC7A11 level was down-regulated) in cells.
25 (OH) D3 may inhibit oxidative stress and ferroptosis in hRMVECs induced by high glucose via down-regulation of miR-93.
Background Low serum magnesium levels in patients with kidney disease have been linked to increased mortality. This study investigated whether similar associations existed in maintenance hemodialysis ...(HD) patients. Study Design Cohort study. Setting & Participants All Fresenius Medical Care North America in-center HD patients with available serum magnesium measurements were studied. The initial exploratory study in 21,534 HD patients evaluated associations among serum magnesium level, dialysate magnesium concentration, and mortality from April 2007 through June 2008. The follow-up study in 27,544 HD patients evaluated associations between serum magnesium levels and mortality over 1 year (January through December 2008). Predictors The primary predictor was serum magnesium level, with adjustment for case-mix (age, sex, race, diabetes, and dialysis vintage and additionally for follow-up study: body surface area and vascular access) and laboratory variables (albumin, hemoglobin, phosphorus, equilibrated Kt/V, potassium, calcium, and intact parathyroid hormone values). Outcome Primary outcome variable was 1-year mortality risk, evaluated using Cox proportional hazards models. Results Among 21,534 HD patients in the exploratory study, there were 3,682 deaths. Higher dialysate magnesium level was associated with higher serum magnesium level ( R = 0.22; P < 0.001). Patients with the lowest serum magnesium levels (<1.30 mEq/L) were at highest risk for death (HR, 1.63; 95% CI, 1.30-1.96; reference serum magnesium, 1.60-<1.90 mEq/L). Among 27,544 HD patients in the follow-up study, there were 4,531 deaths. In Cox proportional hazards models, there was a linear decline in death risk from the lowest to the highest serum magnesium category, with the best survival at serum magnesium levels ≥ 2.50 mEq/L (HR, 0.68; 95% CI, 0.56-0.82). However, risk estimates were attenuated with case-mix and lab adjustment. This pattern was consistent within diabetes subgroups and for cardiovascular or noncardiovascular causes of death. Limitations Observational study with cross-sectional serum magnesium measurements and no information for oral magnesium intake. Conclusions Elevated serum magnesium levels > 2.10 mEq/L were associated with better survival than low serum magnesium levels < 1.30 mEq/L in HD patients. Prospective studies may determine whether manipulation of low serum magnesium levels affects survival.
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