Treatment of a Patient with Acute Promyelocytic Leukemia with Multiple Isolated Relapses in the Central Nervous System: A Case Report and Mini-Review of the Literature.

The efficacy of therapeutics for acute promyelocytic leukemia (APL) has exhibited an increase in recent years. Only a few patients experience relapse, including extramedullary relapse, and in patients with extramedullary relapse, the central nervous system (CNS) is the most common site. To date, there is no expert consensus or clinical guidelines available for CNS relapse, at least to the best of our knowledge. The optimal therapeutic strategy and management options for these patients remain unclear. The present study reports the treatment of a patient with APL with multiple isolated relapses in the CNS. In addition, through a mini-review of the literature, the present study provides a summary of various reports of this disease and discusses possible treatment options for these patients.

Hydroxamate-Containing Bisphosphonates as Fosmidomycin Analogues: Design, Synthesis, and Proherbicide Activity.

Fosmidomycin (FOS) is a natural product inhibiting the DXR enzyme in the MEP pathway and has stimulated interest for finding more suitable FOS analogues. Herein, two series of FOS analogue hydroxamate-containing bisphosphonates as proherbicides were designed, with bisphosphonate replacing the phosphonic unit in FOS while retaining the hydroxamate (BPF series) or replacing it with retro-hydroxamate (BPRF series). The BPF series were synthesized through a three-step reaction sequence including Michael addition of vinylidenebisphosphonate, N-acylation, and deprotection, and the BPRF series were synthesized with a retro-Claisen condensation incorporated into the reaction sequence. Evaluation on model plants demonstrated several compounds having considerable herbicidal activities, and in particular, compound 8m exhibited multifold activity enhancement as compared to the control FOS. The proherbicide properties were comparatively validated. Furthermore, DXR enzyme assay, dimethylallyl pyrophosphate rescue, and molecular docking verified 8m to be a promising proherbicide candidate targeting the DXR enzyme. In addition, 8m also displayed good antimalarial activities.

Mucoid Degeneration of the Anterior Cruciate Ligament: Characteristics and Conservative Management.

Clinical and radiographic characteristics of mucoid degeneration of the anterior cruciate ligament (MD-ACL) were poorly documented in previous literature. And the optimal management strategy for MD-ACL remains unclear. Here, we summarized the characteristics associated with MD-ACL, and evaluated the clinical outcome of conservative management to MD-ACL.A total of 18 knees in 18 patients diagnosed with MD-ACL were collected and reviewed retrospectively. Sixteen patients underwent conservative management and two patients underwent arthroscopic surgery. Baseline demographic, clinical data, and pathologic changes of knee in magnetic resonance imaging (MRI) were recorded. Clinical outcome was evaluated with Visual Analogue Scale (VAS) and Oxford Knee Score (OKS).The most common clinical characteristic in patients with MD-ACL was knee pain (18/18), and seconded by mobility limitation (38.9%, 7/18). All patients presented a typical celery stalk sign with increased signal and diffuse thickening volume in the ACL in MRI. Thirteen patients companied with meniscus tear (72.2%, 13/18), and nine complicated with cartilage injury (50.0%, 9/18). Sixteen patients who underwent conservative treatment were followed up for 21.8 months, and a positive clinical outcome was observed with VAS decreasing from 5.3 ± 2.3 to 1.5 ± 1.9 and OKS decreasing from 27.5 ± 12.7 to 17.9 ± 11.8 (p < 0.001). The post-OKS score was highly correlated with age, duration of disease, and meniscus tear (r = 0.844, 0.707, and 0.474, p < 0.05, respectively). And the post-VAS highly correlated with age (r = 0.693, p < 0.05). Two patients who underwent arthroscopic surgery were followed up for 24.5 months, and the pain and function of knee was improved.Knee pain and meniscus tear was the main characteristic of MD-ACL in clinical and radiographic exam. Conservative treatment could be an alternative management for treatment of MD-ACL with positive clinical outcome. Old age, long duration of disease and complications from meniscus tears were associated with inferior outcome of conservative treatment for MD-ACL. LEVEL OF EVIDENCE: IV.

Design and synthesis of fosmidomycin analogs containing aza-linkers and their biological activity evaluation.

BACKGROUND: The enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway are attractive targets of a new mode of action for developing anti-infective drugs and herbicides, and inhibitors against 1-deoxy-d-xylulose 5-phosphate reductoisomerase (IspC), the second key enzyme in the pathway, have been intensively investigated; however, few works are reported regarding IspC inhibitors designed for new herbicide discovery. RESULTS: A series of fosmidomycin (FOS) analogs were designed with nitrogen-containing linkers replacing the trimethylene linker between the two active substructures of FOS, phosphonic acid and hydroxamic acid. Synthesis followed a facile three-step route of sequential aza-Michael addition of α-amino acids to dibenzyl vinylphosphonate, amidation of the amino acid carboxyl with O-benzyl hydroxylamine, and simultaneous removal of the benzyl protective groups. Biological activity evaluation of IspC and model plants revealed that some compounds had moderate enzyme and model plant growth inhibition effects. In particular, compound 10g, which has a N-(4-fluorophenylethyl) nitrogen-containing linker, exhibited the best plant inhibition activities, superior to the control FOS against the model plants Arabidopsis thaliana, Brassica napus L., Amaranthus retroflexus and Echinochloa crus-galli. A dimethylallyl pyrophosphate rescue assay on A. thaliana confirmed that both 10g and FOS exert their herbicidal activity by blocking the MEP pathway. This result consistent with molecular docking, which confirmed 10g and FOS binding to the IspC active site in a similar way. CONCLUSION: Compound 10g has excellent herbicidal activity and represents the first herbicide lead structure of a new mode of action that targets IspC enzyme in the MEP pathway. © 2023 Society of Chemical Industry.

Design, Synthesis and Bioactivity Evaluation of Heterocycle-Containing Mono- and Bisphosphonic Acid Compounds.

Fosmidomycin (FOS) is a naturally occurring compound active against the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) enzyme in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, and using it as a template for lead structure design is an effective strategy to develop new active compounds. In this work, by replacing the hydroxamate unit of FOS with pyrazole, isoxazole and the related heterocycles that also have metal ion binding affinity, while retaining the monophosphonic acid in FOS or replacing it with a bisphosphonic acid group, heterocycle-containing mono- and bisphosphonic acid compounds as FOS analogs were designed. The key steps involved in the facile synthesis of these FOS analogs included the Michael addition of diethyl vinylphosphonate or tetraethyl vinylidenebisphosphonate to ß-dicarbonyl compounds and the subsequent cyclic condensation with hydrazine or hydroxylamine. Two additional isoxazolinone-bearing FOS analogs were synthesized via the Michaelis-Becker reaction with diethyl phosphite as a key step. The bioactivity evaluation on model plants demonstrated that several compounds have better herbicidal activities compared to FOS, with the most active compound showing a 3.7-fold inhibitory activity on Arabidopsis thaliana, while on the roots and stalks of Brassica napus L. and Echinochloa crus-galli in a pre-emergence inhibitory activity test, the activities of this compound were found to be 3.2- and 14.3-fold and 5.4- and 9.4-fold, respectively, and in a post-emergency activity test on Amaranthus retroflexus and Echinochloa crus-galli, 2.2- and 2.0-fold inhibition activities were displayed. Despite the significant herbicidal activity, this compound exhibited a DXR inhibitory activity lower than that of FOS but comparable to that of other non-hydroxamate DXR inhibitors, and the dimethylallyl pyrophosphate rescue assay gave no statistical significance, suggesting that a different target might be involved in the inhibiting process. This work demonstrates that using bioisosteric replacement can be considered as a valuable strategy to discover new FOS analogs that may have high herbicidal activities.

Prediction formulae of sagittal alignment in thoracolumbar kyphosis secondary to ankylosing spondylitis after osteotomy.

To construct and validate prediction formulae of sagittal alignment in thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) after osteotomy. A total of 115 AS patients who suffered from thoracolumbar kyphosis and underwent osteotomy were enrolled, with 85 patients in derivation group and 30 patients in validation group. Radiographic parameters were measured on lateral radiographs, including thoracic kyphosis, lumbar lordosis (LL), T1 pelvic angel (TPA), sagittal vertical axis (SVA), osteotomized vertebral angle, pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and PI and LL mismatch (PI-LL). Prediction formulae of SS, PT, TPA and SVA were established; and their effectiveness was evaluated. There was no significant difference in baseline characteristics between the two groups (p > 0.05). In derivation group, LL and PI-LL were correlated with SS, and were then used to establish the prediction formula of SS[SS = - 12.791-0.765 × (LL) + 0.357 × (PI-LL), R2 = 68.3%]; PI and PI-LL were correlated with PT, and the prediction formula of PT were thus established[PT = 12.108 + 0.402 × (PI-LL) + 0.252 × (PI), R2 = 56.8%]; PT, PI-LL and LL were correlated with TPA, and were used to establish the prediction formula of TPA[TPA = 0.225 + 0.597 × (PT) + 0.464 × (PI-LL)-0.161 × (LL), R2 = 87.4%]; PT, PI-LL and age were correlated with SVA, and were used to establish the prediction formula of SVA[SVA = 36.157 + 2.790 × (PI-LL) + 1.657 × (Age)-1.813 × (PT), R2 = 41.5%]. In validation group, the predictive SS, PT, TPA and SVA were basically consistent with corresponding real values; and the mean error between predictive values and real values was of 1.3° in SS, 1.2° in PT, 1.1° in TPA and 8.6 mm in SVA. Postoperative SS, PT, TPA and SVA could be predicted with PI and the planned LL and PI-LL using prediction formulae, providing a method for AS kyphosis to plan postoperative sagittal alignment. Change of pelvic posture after osteotomy was quantitatively evaluated using the formulae.

A Sequential Electrospinning of a Coaxial and Blending Process for Creating Double-Layer Hybrid Films to Sense Glucose.

This study presents a glucose biosensor based on electrospun core-sheath nanofibers. Two types of film were fabricated using different electrospinning procedures. Film F1 was composed solely of core-sheath nanofibers fabricated using a modified coaxial electrospinning process. Film F2 was a double-layer hybrid film fabricated through a sequential electrospinning and blending process. The bottom layer of F2 comprised core-sheath nanofibers fabricated using a modified process, in which pure polymethacrylate type A (Eudragit L100) was used as the core section and water-soluble lignin (WSL) and phenol were loaded as the sheath section. The top layer of F2 contained glucose oxidase (GOx) and gold nanoparticles, which were distributed throughout the polyvinylpyrrolidone K90 (PVP K90) nanofibers through a single-fluid blending electrospinning process. The study investigated the sequential electrospinning process in detail. The experimental results demonstrated that the F2 hybrid film had a higher degradation efficiency of ß-D-glucose than F1, reaching a maximum of over 70% after 12 h within the concentration range of 10-40 mmol/L. The hybrid film F2 is used for colorimetric sensing of ß-D-glucose in the range of 1-15 mmol/L. The solution exhibited a color that deepened gradually with an increase in ß-D-glucose concentration. Electrospinning is flexible in creating structures for bio-cascade reactions, and the double-layer hybrid film can provide a simple template for developing other sensing nanomaterials.

Ultrasmall Enzyme-Powered Janus Nanomotor Working in Blood Circulation System.

Injectable chemically powered nanomotors may revolutionize biomedical technologies, but to date, it is a challenge for them to move autonomously in the blood circulation system and they are too large in size to break through the biological barriers therein. Herein, we report a general scalable colloidal chemistry synthesis approach for the fabrication of ultrasmall urease-powered Janus nanomotors (UPJNMs) that have a size (100-30 nm) meeting the requirement to break through the biological barriers in the blood circulation system and can efficiently move in body fluids with only endogenous urea as fuel. In our protocol, the two hemispheroid surfaces of eccentric Au-polystyrene nanoparticles are stepwise grafted with poly(ethylene glycol) brushes and ureases via selective etching and chemical coupling, respectively, forming the UPJNMs. The UPJNMs have lasting powerful mobility with ionic tolerance and positive chemotaxis, while they are able to be dispersed steadily and self-propelled in real body fluids, as well as demonstrate good biosafety and a long circulation time in the blood circulation system of mice. Thus, the as-prepared UPJNMs are promising as an active theranostics nanosystem for future biomedical applications.

Effect of quercetin and oil water separation system on formation of ß-carboline heterocyclic amines during frying process of braised chicken drumsticks.

The effect of quercetin and oil water separation system on the formation of heterocyclic amines (HAs) was investigated during the frying process of braised chicken drumsticks. The results showed that two ß-carboline HAs (ß-CHAs) were detected in the chicken samples: 9H-pyrido [3,4-b] indole (Norharman) and1-methyl-9H-pyrido [3,4-b] indole (Harman). ß-CHAs content in the chicken samples increased as the cycle times of the frying oil rose (P < 0.05). The addition of quercetin and use of oil water separation system significantly inhibited the formation of Harman (27.3% and 28.2%; P < 0.05) and Norharman (28.7% and 64.1%; P < 0.05), respectively, and the combined use of the two treatments had a better effect (47.0% and 80.2%; P < 0.05). It can be attributed to the lower consumption of ß-CHAs precursors (tryptophan) and reduced generation of the intermediates (carbonyl compounds and 1,2,3,4-Tetrahydro-ß-carboline-3-carboxylic acid). This provides a promising way for reducing ß-CHAs during the frying process of braised chicken products.

Optimal immediate sagittal alignment for kyphosis in ankylosing spondylitis following corrective osteotomy.

Purpose: To investigate the optimal immediate sagittal alignment of kyphosis in ankylosing spondylitis (AS) following corrective osteotomy. Methods: Seventy-seven AS patients who underwent osteotomy were enrolled. Radiographic parameters, including global kyphosis (GK), lumbar lordosis (LL), T1 spinopelvic inclination (T1SPI), sagittal vertical axis (SVA), T1 pelvic angle (TPA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and PI and LL mismatch (PI-LL), were collected. The clinical outcome was evaluated using the Scoliosis Research Society-22 (SRS-22) questionnaire and Oswestry Disability Index (ODI). At the final follow-up, SVA > 5 cm was regarded as sagittal imbalance, and a total ODI ≤ 20 or total SRS-22 score ≥4 was considered to indicate a good clinical outcome. Results: Seventy-seven patients with an average age of 37.4 ± 8.6 years were followed up for 29.4 ± 4.2 months. At the final follow-up, GK, LL, PT, SS, TPA, and T1SPI showed some degree of correction loss (P < 0.05). The follow-up parameters could be predicted with the immediate postoperative parameters through their linear regression equation (P < 0.05). The postoperative immediate T1SPI, TPA, SVA, and PI were also highly correlated with the clinical outcome (ODI and/or SRS-22) at the final follow-up (P < 0.05). Based on the relationship, the optimal immediate sagittal alignment for obtaining good clinical outcome was determined: T1SPI ≤ 0.9°, TPA ≤ 31.5°, and SVA ≤ 9.3cm. AS patients with PI ≤ 49.2° were more likely to achieve the optimal alignment and obtained lower ODI and a lower incidence of sagittal imbalance than those with PI > 49.2° at the final follow-up (P < 0.05). Conclusion: Postoperative immediate parameters could be used to predict the final follow-up parameters and clinical outcome. The optimal postoperative immediate sagittal alignment of AS patients was T1SPI ≤ 0.9°, TPA ≤ 31.5°, and SVA ≤ 9.3 cm, providing a reference for kyphosis correction and a means for clinical outcome evaluation. Patients with a lower PI (≤49.2°) were more likely to achieve optimal alignment and obtain satisfactory clinical outcomes.

Preoperative prediction of sagittal imbalance in kyphosis secondary to ankylosing spondylitis after one-level three-column osteotomy.

BACKGROUND: This study aimed to determine preoperative predictors for sagittal imbalance in kyphosis secondary to ankylosing spondylitis (AS) after one-level three-column osteotomy. METHODS: A total of 55 patients with AS who underwent one-level three-column osteotomy were enrolled. The patients were divided into two groups according to sagittal vertical axis (SVA) value at the final follow-up (group A: SVA > 5 cm; group B: SVA ≤ 5 cm). The radiographic measures included global kyphosis, lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sacral slope, T1 pelvic angle (TPA), SVA, osteotomized vertebral angle and PI and LL mismatch (PI - LL). Postoperative clinical outcomes were evaluated using Scoliosis Research Society-22 questionnaire (SRS-22) and Oswestry Disability Index (ODI). RESULTS: Fifty-five AS patients had an average follow-up of 30.6 ± 10.2 months (range 24-84 months). Group A had larger preoperative and postoperative LL, PT, PI - LL, TPA and SVA values compared with group B (P < 0.05), and no significant differences were found in ODI and SRS-22 scores between the two groups (P > 0.05). Preoperative LL, PT, PI - LL, TPA, and SVA values were positively correlated with the follow-up SVA value (P < 0.05). Among them, TPA > 40.9°, PI - LL > 32.5° and SVA > 13.7 cm were the top three predictors with the best accuracy to predict sagittal imbalance. Immediate postoperative SVA value of ≤ 7.4 cm was a key factor in reducing the risk of sagittal imbalance during follow-up. CONCLUSIONS: Preoperative TPA > 40.9°, PI - LL > 32.5° and SVA > 13.7 cm could predict sagittal imbalance in AS kyphosis after one-level three-column osteotomy, and additional osteotomies were recommended for this condition. Immediate postoperative SVA ≤ 7.4 cm was an optimal indicator for preventing sagittal imbalance. LEVEL OF EVIDENCE: IV.

The Model Dimensionality and Its Impacts on the Strategic and Policy Outcomes in IAMs the Findings from the RICE2020 Model.

This paper studies the impacts of regional breakdowns or model dimensionality on the model's optimal solutions. Using the United States (USA) and China (CHN) as the experimental subject, we test the various solutions related to USA and CHN, such as the Cournot-Nash equilibrium and the Lindahl equilibrium, in the RICE2020 model under three regional breakdowns. Their solutions' invariance and variances across different model dimensionalities indicate that modeling dimensionality may play a role in the strategic interactions among the regions in GHG mitigation. The simulation results also point out the pitfalls of the model comparisons across IAMs for climate change.

Hybrid Films Prepared from a Combination of Electrospinning and Casting for Offering a Dual-Phase Drug Release.

One of the most important trends in developments in electrospinning is to combine itself with traditional materials production and transformation methods to take advantage of the unique properties of nanofibers. In this research, the single-fluid blending electrospinning process was combined with the casting film method to fabricate a medicated double-layer hybrid to provide a dual-phase drug controlled release profile, with ibuprofen (IBU) as a common model of a poorly water-soluble drug and ethyl cellulose (EC) and polyvinylpyrrolidone (PVP) K60 as the polymeric excipients. Electrospun medicated IBU-PVP nanofibers (F7), casting IBU-EC films (F8) and the double-layer hybrid films (DHFs, F9) with one layer of electrospun nanofibers containing IBU and PVP and the other layer of casting films containing IBU, EC and PVP, were prepared successfully. The SEM assessments demonstrated that F7 were in linear morphologies without beads or spindles, F8 were solid films, and F9 were composed of one porous fibrous layer and one solid layer. XRD and FTIR results verified that both EC and PVP were compatible with IBU. In vitro dissolution tests indicated that F7 were able to provide a pulsatile IBU release, F8 offered a typical drug sustained release, whereas F9 were able to exhibit a dual-phase controlled release with 40.3 ± 5.1% in the first phase for a pulsatile manner and the residues were released in an extended manner in the second phase. The DHFs from a combination of electrospinning and the casting method pave a new way for developing novel functional materials.

Aqueous lithium chloride solution as a non-toxic bactericidal and fungicidal disinfectant for air-conditioning systems: Efficacy and mechanism.

Airborne pathogenic bacteria and fungi transmitted through air-conditioning (AC) systems have been identified as a major public health risk. Air scrubbing is a promising liquid-based air disinfection technique that captures and inactivates airborne pathogens in liquid disinfectants. However, owing to the drawbacks of irritating odor and toxicity, the commonly-used chemical disinfectants cannot be employed for AC systems. This study aimed to unveil the inactivation performance and mechanism of non-toxic and chemically stable aqueous lithium chloride (LiCl) solution-the popular liquid desiccant in the AC systems-as a user-friendly disinfectant. Four prominent airborne pathogenic bacteria and fungi were exposed to the LiCl solution under various conditions. The inactivation effects were quantified with fluorescence-staining-based confocal microscopy and verified with the pathogens' membrane integrity variations, intracellular substance leakage, and morphological changes. Results showed that LiCl solution was remarkably efficient in inactivating the pathogens within 60 min, with an efficacy of 35.2-96.2%. The solution's inactivation ability was promoted by increasing the temperatures and concentrations; however, it appeared insensitive to exposure time over 30 min. We then explored the inactivation mechanism of LiCl solution by assessing cellular protein leakages and compared the inactivation rates with those of NaCl solution. The extracellular protein increased by over 470% after being exposed to LiCl solution. The inactivation rate was also considerably higher than in NaCl solution under the same osmotic pressure (24.79 MPa). We suggest that apart from osmotic pressure, the inactivation is reinforced by Li+-specific properties, including its strong water attraction that deprived the solvation shells of microbial protein and caused protein denaturation. We propose that aqueous LiCl solution may act as a user-friendly disinfectant for air-scrubbing due to its attractive characteristics, including its non-toxicity, odorless nature, and chemical stability. These findings may open up a "green" way to disinfect airborne pathogens and safeguard public health.

Portable ultrasonic humidifier exacerbates indoor bioaerosol risks by raising bacterial concentrations and fueling pathogenic genera.

Portable ultrasonic humidifiers are frequently used in heating rooms to ease air dryness. However, it has also posed serious health concerns such as "humidifier fever" because the bioaerosol concentration and community in the humidified space may alter quickly before the occupants could even notice. We compared the microbial proliferation rates in the humidifiers' reservoirs filled with three commonly used water types and investigated the impacts of the ultrasonic humidifiers on the temporal concentration, size distribution, and community variations of indoor bacterial and fungal aerosols during two-week humidification. The concentration of indoor bacterial aerosols increased exponentially, concentrating in the respiratory size ranges (≤1.1 µm), and was proportional to the humidification level, which soon exceeded 1000 CFU/m3 in one week (at RH = 70%), while the fungal concentration always remained low (≤177 CFU/m3 ). The indoor bioaerosol community, significantly associated with the humidifier water, was substantially distorted after humidification and dominated by the pathogenic Pseudomonas spp. (40.50%), Brevundimonas spp. (3.02%), Acinetobacter spp. (0.98%) and Legionella spp. (0.69%). Our results show that ultrasonic humidification contaminates indoor air by raising bacterial concentrations and fueling the pathogenic genera. To minimize the exposure risks, occupants should avoid long-term and excessive humidification (RH ≥ 70%) and clean the ultrasonic humidifier weekly.

CircRNA LRP6 promotes high-glucose induced proliferation and migration of vascular smooth muscle cells through regulating miR-545-3p/HMGA1 signaling axis.

OBJECTIVE: The dysfunction of vascular smooth muscle cells (VSMCs) has been revealed to be closely linked with the pathogenesis of cardiovascular diseases in diabetes. Recently, circular RNAs (circRNAs) were found to regulate the behaviors of VSMCs. Here, we attempted to study the role of circLRP6 in VSMCs under diabetes condition. METHODS: Human VSMCs were cultured under the condition of normal glucose (NG) or high glucose (HG). VSMC viability and proliferation were estimated by CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. VSMC migration and invasion were assessed via wound-healing and transwell experiments. Protein expression of HMGA1 was measured in VSMCs using western blot and immunofluorescence analysis. Relative expressions of circLRP6, miR-545-3p, and HMGA1 mRNA were estimated in VSMCs using qRT-PCR. The co-localization of circLRP6 and miR-545-3p was verified by fluorescence in situ hybridization (FISH) analysis. Binding sequence of miR-545-3p in circLRP6 or HMGA1 was predicted using StarBase tool, and verified by RNA immunoprecipitation and dual-luciferase reporter experiments. RESULTS: HG exposure promoted VSMC proliferation, migration and invasion, upregulated the circLRP6 expression, and downregulated HMGA1 expression. Knockdown of circLRP6 or overexpression of miR-545-3p abrogated the HG-caused VSMC proliferation, migration and invasion. CircLRP6 severed as a miR-545-3p sponge, and HMGA1 was targeted by miR-545-3p. MiR-545-3p inhibitor blocked the suppressive effects of si-circLRP6 on VSMC in the presence of HG. CONCLUSION: These findings suggest that circRNA LRP6 promotes HG-induced VSMC proliferation and migration through regulating miR-545-3p/HMGA1 signaling axis.

Angiotensin (1-7) Alleviates Postresuscitation Myocardial Dysfunction by Suppressing Oxidative Stress Through the Phosphoinositide 3-Kinase, Protein Kinase B, and Endothelial Nitric Oxide Synthase Signaling Pathway.

ABSTRACT: There is increasing evidence that angiotensin (1-7) [Ang (1-7)] is an endogenous biologically active component of the renin-angiotensin system. However, the role of the Ang (1-7)-MasR axis in postresuscitation myocardial dysfunction (PRMD) and its associated mechanism are still unclear. In this study, we investigated the effect of the Ang (1-7)-MasR axis on myocardial injury after cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation. We established a model of oxygen/glucose deprivation-reperfusion in myocardial cells in vitro and a rat model of cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation in vivo. The cell apoptosis rate and the expression of the superoxide anion 3-nitrotyrosine were decreased in the Ang (1-7) group in vitro and in vivo. The mean arterial pressure was decreased, whereas +LVdp/dtmax and -LVdp/dtmax were increased in rats in the Ang (1-7) group. The mRNA and protein levels of Ang II type 1 receptor, MasR, phosphoinositide 3-kinase, protein kinase B, and endothelial nitric oxide synthase were increased in the Ang (1-7) group in vivo. These results indicate that the Ang (1-7)-MasR axis can alleviate PRMD by reducing myocardial tissue damage and oxidative stress through activation of the phosphoinositide 3-kinase-protein kinase B-endothelial nitric oxide synthase signaling pathway and provide a new direction for the clinical treatment of PRMD.

Effect of Nanobubbles on the Flotation Performance of Oxidized Coal.

In this study, the effects of air bubbles and nanobubbles on flotation performance and kinetics of oxidized coal were investigated. The surface properties of the coal sample before and after oxidation were characterized by a scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). The nanobubbles on highly oriented pyrolytic graphite (HOPG) were observed by an atomic force microscope (AFM). The interaction between coal and conventional bubbles in the absence and presence of nanobubbles was explained by induction time. Flotation results showed that oxidized coal flotation in the presence of nanobubbles resulted in 10% higher combustible matter recovery than conventional air bubble flotation. Moreover, it was found that the flotation of oxidized coal in the absence and presence of nanobubbles can be best described using the first-order model with the rectangular model. AFM images analysis showed that a large number of nanobubbles were produced and attached to the oxidized coal surface. The induction times of the oxidized coal in the absence and presence of nanobubbles were 1000 and 39 ms, respectively, indicating that the existence of nanobubbles effectively promotes the interaction between oxidized coal and macroair bubbles. In addition, the agglomeration between oxidized coal particles also occurred spontaneously in the presence of nanobubbles, which was helpful in improving the combustible matter recovery and flotation rate of oxidized coal.

Self-preservation strategy for approaching global warming targets in the post-Paris Agreement era.

A strategy that informs on countries' potential losses due to lack of climate action may facilitate global climate governance. Here, we quantify a distribution of mitigation effort whereby each country is economically better off than under current climate pledges. This effort-sharing optimizing approach applied to a 1.5 °C and 2 °C global warming threshold suggests self-preservation emissions trajectories to inform NDCs enhancement and long-term strategies. Results show that following the current emissions reduction efforts, the whole world would experience a washout of benefit, amounting to almost 126.68-616.12 trillion dollars until 2100 compared to 1.5 °C or well below 2 °C commensurate action. If countries are even unable to implement their current NDCs, the whole world would lose more benefit, almost 149.78-791.98 trillion dollars until 2100. On the contrary, all countries will be able to have a significant positive cumulative net income before 2100 if they follow the self-preservation strategy.

Increased glycoprotein acetylation is associated with high cardiac event rates: Analysis using coronary computed tomography angiography.

OBJECTIVE: Glycoprotein acetylation (GlycA), an emerging inflammatory biomarker, has been used as an indicator of cardiovascular disease. Our research aimed to evaluate the correlation between GlycA and coronary artery disease (CAD) using coronary computed tomography angiography (CCTA). METHODS: In the present study, a total of 342 patients were enrolled, and each of them underwent CCTA. The correlation between GlycA and major adverse cardiac events (MACE) was detected via Cox's proportional hazards models. Based on differences in the GlycA level, patients were categorized into three groups (T1, T2, and T3). RESULTS: Compared with the group with the lowest GlycA level (T1), the group with the highest GlycA level (T3) exhibited stronger atherosclerotic pressure involving the extent of atherosclerotic plaque and risk of obstructive CAD. In addition, the patients in the T3 group had a greater chance of experiencing MACE and higher all-cause mortality than those in the T1 group. Among patients without CAD who underwent CCTA, those with high GlycA levels experienced elevated atherosclerotic stress and heightened risk of MACE compared with those with low GlycA levels. CONCLUSION: These results suggest that serum GlycA is significantly associated with the long-term clinical results of patients with no known CAD undergoing CCTA. The risks of death and experiencing MACE increase among patients with high GlycA levels.