Search

ABSTRACTBackgroundTo find a new bedside method to monitor the anticoagulation effects of low-molecular-weight heparins (LMWHs) in patients with a high risk of venous thromboembolism (VTE).Research design and methodsA total of 32 hospitalized patients (aged ≥60 years) who were at high risk of VTE were assigned to receive subcutaneous LMWH for 5 to 14 days. Plasma anti-factor Xa (anti-Xa) activity was conducted by a chromogenic method, and the glass bead-activated whole blood clotting time (gb-ACT) value was obtained by a Sonoclot Analyzer.ResultsA correlation between the gb-ACT values and the anti-Xa levels was suggested (R = 0.447, p = 0.002), and it was stronger in the older group aged 80 years above (R = 0.467, p = 0.008) and in the group of patients with an eGFR of 30 ~ 60 mL/min (R = 0.565, p = 0.005). The area under the curve (AUC) for gb-ACT by receiver operating characteristic (ROC) curve evaluation was 0.725 (p = 0.011), and the gb-ACT >282.5s provided a sensitivity of 60% and specificity of 74% for anti-Xa >0.800 IU/ml.ConclusionsThe gb-ACT values detected by a Sonoclot Analyzer could act as a novel bedside method in the monitoring of LMWH anticoagulation.

CONTEXTE : On donne de facon empirique des agents antiviraux a certains patients atteints de la maladie a coronavirus 2019 (COVID-19). Dans le but d'appuyer la redaction de lignes directrices sur la prise en charge de la COVID-19, nous avons realise une revue systematique des benefices et des prejudices associes a 7 traitements antiviraux contre cette infection. METHODES : Nous avons effectue des recherches dans MEDLINE, Embase, le Cochrane Central Register of Controlled Trials (CENTRAL), PubMed et 3 bases de donnees chinoises (CNKI, Wanfang Data et SinoMed) jusqu'au 19 avril 2020, dans medRxiv et ChinaXiv jusqu'au 27 avril 2020, ainsi que dans Chongqing VIP jusqu'au 30 avril 2020. Nous avons selectionne des etudes sur la ribavirine, la chloroquine, l'hydroxychloroquine, l'umifenovir (Arbidol), le favipiravir, l'interferon et le lopinavir/ritonavir. Lorsqu'il n'y avait pas de donnees directes d'etudes sur la COVID-19, nous avons retenu des donnees indirectes d'etudes sur le syndrome respiratoire aigu severe (SRAS) et le syndrome respiratoire du Moyen-Orient (SRMO) pour l'analyse de l'efficacite, et d'etudes sur d'autres infections respiratoires virales aigues pour l'analyse de l'innocuite. RESULTATS : Le taux de deces chez les patients atteints d'une forme sans signe clinique de gravite de COVID-19 etait extremement bas, ce qui ne permet pas de conclure a un effet important sur la mortalite. Nous n'avons obtenu que des donnees de tres faible qualite indiquant que la plupart des traitements avaient peu ou pas de benefices sur les parametres a l'etude, quelle que soit la gravite de la COVID-19. Seule exception : le traitement au lopinavir/ritonavir, pour lequel nous avons obtenu des donnees de faible qualite faisant etat d'une reduction de la duree du sejour en unite de soins intensifs (difference des risques [DR] 5 jours de moins, intervalle de confiance [IC] de 95 % 0 a 9 jours) et de la duree d'hospitalisation (DR 1 jour de moins, IC de 95 % 0 a 2 jours). En ce qui concerne l'innocuite, les donnees etaient de faible ou de tres faible qualite, sauf pour le traitement au lopinavir/ ritonavir, ou des donnees de qualite moyenne laissaient supposer une augmentation probable de la diarrhee, des nausees et des vomissements. INTERPRETATION : A l'heure actuelle, rien ne prouve de facon convaincante que les traitements antiviraux apportent des benefices importants dans la lutte contre la COVID-19, bien que les donnees propres a chaque traitement n'excluent pas cette possibilite. D'autres essais randomises et controles menes aupres de patients atteints de la COVID-19 sont necessaires avant de pouvoir recourir a ces traitements en toute confiance., Au 30 avril 2020, la maladie a coronavirus 2019 (COVID-19) (1) etait a l'origine de plus de 3 millions de cas d'infection et de plus de 210 000 deces dans [...]

BACKGROUND: Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes. RESULTS: In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting. INTERPRETATION: To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence., As of Apr. 30, 2020, coronavirus disease 2019 (COVID-19) (1) has resulted in more than 3 million cases and more than 210 000 deaths worldwide. (2) The World Health Organization [...]

Dumbbell- and bola-shaped amphiphiles are commonly expected to self-assemble into vesicles with condensed hydrophobic domains due to the dominant hydrophobic interaction. In this work, we examined the assemblies of the dumbbell-shaped AC60-AC60amphiphile, with two carboxylic acid-functionalized fullerenes (AC60) polar head groups linked by an organic tether, and found that they assemble into hollow, spherical blackberry-type structures with porous surfaces, judged by their smaller assemblies in organic solvents with higher polarity and in aqueous solutions with high pH. We attribute the formation of blackberry structures to the organic tether that may be too short to fill up a condensed hydrophobic domain, as confirmed by all-atom simulations. This is further proved by noticing that several bola-type macromolecules with hydrophilic polyethylene glycol (PEG) chain being the linker and no hydrophobic components, AC60-PEG-AC60, can also self-assemble into hollow, spherical assemblies and demonstrate similar pH response as the assemblies from AC60-AC60dumbbells. Therefore, we conclude that the driving force of the self-assembly for these dumbbell- or bola-shaped molecules is counterion-mediated attraction from the two AC60head groups rather than the hydrophobic interaction due to the organic linkers. The so-formed blackberry structures here, as well-studied before in other systems, possess porous surfaces, making these charged amphiphiles a valuable model for designing stable nanocontainers with controllable porosity to the change of the environment.

Time reliability (TR) is a critical factor that affects the efficiency and service quality of the urban rail transit network (URTN). However, previous studies have not incorporated TR into the evaluation of URTN station importance, focusing instead on basic centrality measures. Therefore, this paper proposes a new metric of station-based TR for evaluating and ranking URTN station importance. The new metric in combination with traditional centrality measures was used by the weighted Technique for Order of Preference by Similarity to Ideal Solution (weighted TOPSIS) to identify the combined significance level of individual URTN station importance and rank them accordingly. To investigate the performance of this method, we exploit deliberate attacks on the top-ranked stations through different methods. A case study of Beijing’s URTN during the morning peak hour showed that the proposed method is generally a better indicator for identifying station importance in maintaining network connectivity. The case study also demonstrated the feasibility and validity of the model. This study can provide recommendations for the planning and operation of rail transit systems and can inform the effective design of station protection strategies.

In order to investigate the microstructure evolution, tensile deformation mechanism and strengthening mechanism of Ni36Co30Fe11Cr11Al8Nb4high entropy alloy (HEA), the alloy samples were prepared by directional solidification at different solidification rates (5, 10, 20, 50 and 100 μm/s). Results indicate that the microstructure of the directionally solidified Ni36Co30Fe11Cr11Al8Nb4HEA is composed of primary bulky dendrites (FCC1phase) and inter-dendritic lamellar structures which consist of the Laves phase and the Nb-enriched FCC2phase. With the increase of solidification rate, the dendrites are refined, the volume fraction of inter-dendritic lamellar structure decreases, and Laves phase accumulates at the grain boundaries. Since FCC2phase has lower nucleation barriers, the nucleation and growth of FCC2phase are preferential to those of Laves phase in the inter-dendrite region. Tensile results indicate that the directionally solidified Ni36Co30Fe11Cr11Al8Nb4HEA possesses the highest ultimate tensile strength and fracture strain at 5 μm/s, which are 740.15 MPa and 35.23 %, respectively. The microscopic deformation behavior shows that FCC1phase yields first, followed by FCC2and Laves phases in sequence during tensile deformation. The moderately strong FCC2phase coordinates the large inherent strength gap between FCC1and Laves phases to avoid stress concentration and maintain ductility. FCC2- Laves interface plays a significant role in hindering dislocation movement and increasing the strength, the overall interfacial strengthening stress is estimated to be 9.1 GPa.

A Cu-catalyzed diastereoselective [3 + 2] cycloaddition of 2-arylaziridines and cyclic silyl dienol ethers was developed to efficiently construct fused-[5,n] carbocyclic pyrrolidines, which are widespread in bioactive natural products. Mechanistic studies revealed that the high diastereoselectivity of this transformation arose from a sequential retro aza-Michael/epimerization/aza-Michael process. Taking advantage of this newly developed method, the first total syntheses of pancratinines B and C were concisely realized.

A variety of prosthetic ankles have been successfully developed to reproduce the locomotor ability for lower limb amputees in daily lives. However, they have not been shown to sufficiently improve the natural gait mechanics commonly observed in comparison to the able-bodied, perhaps due to over-simplified designs of functional musculoskeletal structures in prostheses. In this study, a flexible bionic ankle prosthesis with joints covered by soft material inclusions is developed on the basis of the human musculoskeletal system. First, the healthy side ankle–foot bones of a below-knee amputee were reconstructed by CT imaging. Three types of polyurethane rubber material configurations were then designed to mimic the soft tissues around the human ankle, providing stability and flexibility. Finite element simulations were conducted to determine the proper design of the rubber materials, evaluate the ankle stiffness under different external conditions, and calculate the rotation axes of the ankle during walking. The results showed that the bionic ankle had variable stiffness properties and could adapt to various road surfaces. It also had rotation axes similar to that of the human ankle, thus restoring the function of the talocrural and subtalar joints. The inclination and deviation angles of the talocrural axis, 86.2° and 75.1°, respectively, as well as the angles of the subtalar axis, 40.1° and 29.9°, were consistent with the literature. Finally, dynamic characteristics were investigated by gait measurements on the same subject, and the flexible bionic ankle prosthesis demonstrated natural gait mechanics during walking in terms of ankle angles and moments.

Postoperative cognitive dysfunction (POCD) is a major postoperative complication. Triggering receptor expressed on myeloid cells 2 (TREM2) exerts a neuroprotective function against neuro-inflammatory responses. The present study investigated the role of TREM2 in anesthesia and surgery-induced cognitive impairment and the potential related mechanism. Our results revealed that TREM2 was downregulated, coupled with activation of the NLRP3 inflammasome and subsequent IL-1β expression on postoperative day 3. A corresponding decline in PSD-95 and BDNF was found at the same time point. The key regulator of mitophagy PINK1 and Parkin protein levels were significantly decreased following surgery and anesthesia. TREM2 overexpression partially reversed postoperative cognitive impairment and enhanced PSD-95 and BDNF expression. TREM2 overexpression also improved mitophagy function and inhibited activation of the NLRP3 inflammasome and associated production of IL-1β. Our findings demonstrate that TREM2 rescues anesthesia and surgery-induced spatial learning and memory impairment and neuro-inflammation in aged C57/BL6 mice, which may be at least partially mediated through the activation of mitophagy and subsequent inhibition of the NLRP3 inflammasome.

Purpose: In proton radiotherapy, the precise estimation of a beam profile is essential for improving the dose deposited in the target tissues in clinical treatment planning. An accurate beam range is determined based on the stopping power ratio (SPR) of the tissues and beam energy. This study investigated the potential of a spectral computed tomography (CT) based on a fast kV-switching dual-energy technique to predict the SPR for proton radiotherapy. Methods: We scanned 11 types of tissue equivalents (CIRS phantom) and derived the electron density and the effective atomic number from spectral CT to predict the SPR using the method proposed by Hünemohr et al. We investigated the influence of energy pairs on SPR prediction accuracy and compared three scan modes on spectral CT and single-energy CT (SECT). Results: The prediction accuracy of SPR on spectral CT was within 0.79% (except for the lungs). The divergence of the lungs exhibited a defect in the phantom. Meanwhile, we revealed that the energy pairs had a negligible effect on SPR estimation. Additionally, we demonstrated that the gemstone spectral imaging (GSI) mode on spectral CT owned the most accurate prediction compared with the mono-energetic mode on spectral CT and the normal mode on SECT. Conclusion: Spectral CT in GSI mode was shown to be an effective instrument for predicting SPR, which contributes to the accurate prediction of SPR using spectral CT and expands the application of spectral CT.

Aims: This study aims to explore early intensive lipid-lowering therapy in patients with non- ST-segment elevation acute coronary syndrome (NSTE-ACS). Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease. Due to many reasons, the need for early intensive lipid-lowering therapy is far from being met in Chinese NSTE-ACS patients at high risk of recurrent ischaemic events. Objective: This study evaluates the feasibility, safety and efficacy of starting evolocumab in hospitals to lower LDL-C levels in Chinese patients with NSTE-ACS. Methods: In this prospective cohort study initiated by researchers, 334 consecutive patients with NSTEACS who had sub-standard LDL-C levels (LDL-C ≥2.3 mmol/L after regular oral statin treatment for at least 4 weeks; or LDL-C ≥3.2 mmol/L without regular oral statin treatment) were included. Patients who agreed to treatment with evolocumab (140 mg subcutaneously every 2 weeks, initiated in hospital and used for 12 weeks after discharge) were enrolled in the evolocumab group (n=96) and others in the control group (n=238). All enrolled patients received regular statin treatment (atorvastatin 20 mg/day or rosuvastatin 10 mg/day; doses unchanged throughout the study). The primary endpoint was the change in LDL-C levels from baseline to week 12. Results: Most patients (67.1%) had not received regular statin treatment before. In the evolocumab group, LDL-C levels decreased significantly at week 4 and remained stable at week 8 and 12 (all p<0.001). At week 12, the LDL-C percentage change from baseline in the evolocumab group was - 79.2±12.7% (from an average of 3.7 to 0.7 mmol/L), while in the control group, it was -37.4±15.4% (from an average of 3.3 to 2.0 mmol/L). The mean difference between these 2 groups was -41.8% (95% CI -45.0 to -38.5%; p<0.001). At week 12, the proportion of patients with LDL-C levels <1.8 mmol/L and 1.4 mmol/L in the evolocumab group was significantly higher than in the control group (96.8 vs 36.1%; 90.6 vs 7.1%; both p<0.001). The incidences of adverse events and cardiovascular events were similar in both the groups. Conclusion: In this prospective cohort study, we evaluated the early initiation of evolocumab in NSTEACS patients in China. Evolocumab combined with statins significantly lowered LDL-C levels and increased the probability of achieving recommended LDL-C levels, with satisfactory safety and good tolerance.

We report a complex coacervate formed by a 2.5 nm-diameter, rigid uranyl peroxide molecular cluster (Li68K12(OH)20)[UO2(O2)OH]60, U6060–) and SrCl2salt in dilute aqueous solutions, including its location in the phase diagram, composition, rheological features, and critical conditions for phase transitions. In this coacervate, the Sr2+cations are a major building component, and the coacervate phase covers a substantial region of the phase diagram. This coacervate demonstrates features that differ from traditional coacervates formed by oppositely charged long-chain polyelectrolytes, especially in its formation mechanism, dehydration, enhancement of mechanical strength with increasing ionic strength, and the change of salt partition preference into the coacervate and supernatant phases with ionic strength.

Supplemental Digital Content is available in the text.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. During the ongoing COVID-19 epidemic, most hospitals have postponed elective surgeries. However, some emergency surgeries, especially for trauma patients, are inevitable. For patients with suspected or confirmed COVID-19, a standard protocol addressing preoperative preparation, intraoperative management, and postoperative surveillance should be implemented to avoid nosocomial infection and ensure the safety of patients and the health care workforce. With reference to the guidelines and recommendations issued by the National Health Commission and Chinese Society of Anesthesiology, this article provides recommendations for anesthesia management of trauma and emergency surgery cases during the COVID-19 pandemic.

Metal/metalloid complexes have been commonly used in medicine as either therapeutic or diagnostic agents. Understanding the molecular mechanisms of action of metallodrugs is crucial for the development of more effective metallodrugs. Metalloproteomics serve as important tools for systematic analysis of metal-bound proteins within a cell or tissue type. Inductively coupled plasma mass spectrometry (ICP-MS), has been widely employed by metalloproteomic approaches. We summarize the latest progress of ICP-MS-based metalloproteomic approaches for the identification of putative protein targets of anticancer and antibacterial metallodrugs with the purpose of exploring their molecular mechanisms of action. The approach can also play a role in systems biology and precision medicine.Metal/metalloid complexes have been commonly utlized in medicine for therapeutics and diagnostics. Inductively coupled plasma mass spectrometry (ICP-MS) has been widely applied to unveil the molecular mechanisms of metallodrugs. This review focuses on the most recent applications of ICP-MS based metalloproteomic approaches in characterizing potential protein targets of anticancer and antibacterial metallodrugs and subsequently exploring their molecular mechanisms.

BACKGROUND:Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19.METHODS:We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes.RESULTS:In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting.INTERPRETATION:To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

Background: Gadolinium-based nanoparticles (GdNPs) are clinically used agents to increase the radiosensitivity of tumor cells. However, studies on the mechanisms and biological modeling of GdNP radio-enhancement are still preliminary. This study aims to investigate the mechanism of radio-enhancement of GdNPs for kilovoltage photons using Monte Carlo (MC) simulations, and to establish local effect model (LEM)-based biological model of GdNP radiosensitization. Methods: The spectrum and yield of secondary electrons and dose enhancement around a single GdNP and clustered GdNPs were calculated in a water cube phantom by MC track-structure simulations using TOPAS code. We constructed a partial shell-like cell geometry model of pancreatic cancer cell based on transmission electron microscope (TEM) observations. LEM-based biological modeling of GdNP radiosensitization was established based on the MC-calculated nano-scale dose distributions in the cell model to predict the cell surviving fractions after irradiation. Results: The yield of secondary electrons for GdNP was 0.16% of the yield for gold nanoparticle (GNP), whereas the average electron energy was 12% higher. The majority of the dose enhancement came from the contribution of Auger electrons. GdNP clusters had a larger range and extent of dose enhancement than single GdNPs, although GdNP clustering reduced radial dose per interacting photon significantly. For the dose range between 0 and 8 Gy, the surviving fraction predicted using LEM-based biological model laid within one standard deviation of the published experimental results, and the deviations between them were all within 25%. Conclusions: The mechanism of radio-enhancement of GdNPs for kilovoltage photons was investigated using MC simulations. The prediction results of the established LEM-based biological model for GdNP radiosensitization showed good agreement with published experimental results, although the deviation of simulation parameters can lead to large disparity in the results. To our knowledge, this was the first LEM-based biological model for GdNP radiosensitization.

Ankylosing spondylitis (AS) is an autoimmune disease with complex inflammatory mechanism. The aim of this study is to apply the methods of bibliometrics and knowledge mapping to analyze the research trends and hot spots of B cells intervention in inflammatory mechanism of AS. Global published articles on B-cells intervention in inflammatory mechanism of AS were retrieved from the Web of Science (WOS) database from 2004 to 2023. CiteSpace 6.1.R6 software was used to conduct the visualization analysis of countries, authors, institutions, references and keywords in this field. A total of 359 related articles were collected. Since 2004, the number of articles published in the field of B cells intervention in inflammatory mechanism of AS has shown a fluctuating upward trend. The 29 core authors are part of a research group centered on Bowness, Paul and Breban, Maxime. The main research institutions are Anhui Med Univ and Charite. Co-citation analysis reveals that research in this field is currently focused on “intergenic region” and “bone mineral density.” Keyword analysis shows that the current research hotspots and trends in this field mainly focus on the cellular immune mechanism, humoral immune mechanism and clinical application value of B cells intervention in inflammatory mechanism of AS. In the past 20 years, the research on the mechanism of B cells intervention in AS inflammation has focused on B cells intervention in AS inflammation through humoral and cellular immune mechanisms. The future research focus may tend to use B cells as a new therapeutic target for AS.

Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation. In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. We demonstrate that dynamic changes in O-GlcNAcylation are required for osteoclastogenesis. Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages, whereas its downregulation is required for osteoclast maturation. At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. TNFα fosters the dynamic regulation of O-GlcNAcylation to promote osteoclastogenesis in inflammatory arthritis. Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption.

Cardiac structural remodeling, including cardiomyocyte apoptosis, interstitial fibrosis, and inflammation, appears to be a key event associated with the progression of left ventricular hypertrophy and heart failure. Asiatic acid (AA) is a triterpenoid compound extracted from Centella asiaticathat exhibits antiapoptotic, antifibrotic, and anti-inflammatory activities. In the present study, a transverse aortic constriction (TAC) model was created in mice to mimic the progression of hypertrophy (2 weeks post-TAC) and heart failure (4 weeks post-TAC) to investigate whether the potential therapeutic drug AA ameliorates hypertrophy progression and which mechanisms are involved in this amelioration. Our results demonstrated that AA markedly inhibited the process of progression induced by pressure overload. The increases cardiomyocyte apoptosis and interstitial fibrosis, and inflammatory responses were significantly suppressed by AA. Our investigation revealed that this inhibitory effect was mediated by blocking the activation of both mitochondrial and death receptor-dependent apoptotic signaling pathways. Additional experiments demonstrated that AA attenuated fibrosis by blocking both transforming growth factor-β1/Smad and interleukin-6, signaling activation. Consequently, these findings indicated that AA attenuated pathological cardiac structural remodeling and preserved cardiac function via multiple intracellular signaling pathways in response to cardiac stimuli.

AbstractObjectivesTo investigate whether genetic variants in methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase (MTHFD) genes are associated with risk of congenital cardiac disease.BackgroundAccumulative evidence suggests that hyperhomocysteinaemia is associated with risk of congenital cardiac disease. Inherited polymorphisms in key folate metabolic pathway genes, MTHFRand MTHFD, may influence the efficiency of folate metabolism and plasma level of homocysteine.MethodsA two-stage case?control study of congenital cardiac disease was conducted by genotyping MTHFRc.1793G>A and four other variants ? MTHFRc.677C>T, c.1298A>C, and MTHFDc.1958G>A, c.401C>T ? in a Chinese population consisting of 1033 congenital cardiac disease patients and 1067 non-congenital cardiac disease patients.ResultsThe variant genotypes of MTHFRc.1793GA/AA were associated with a significantly decreased risk of congenital cardiac disease in two stages combined, with an adjusted odds ratio of 0.67 and a 95% confidence interval of 0.54?0.84 (p = 0.0004). In comparison with wild-type homozygote c.1793GG, the effect was significant in isolated perimembranous ventricular septal defect patients with an adjusted odds ratio of 0.60 and a 95% confidence interval of 0.43?0.83 (p = 0.0003).ConclusionThese findings indicate that MTHFRc.1793G>A may have a role in susceptibility to sporadic congenital cardiac disease.

Mobile edge computing (MEC) meets the high-bandwidth and ultra-low-latency requirements of mobile networks and improves communication reliability by reducing the networks’ load. In this study, we study a wireless powered MEC system, which includes an access point (AP) and two mobile devices. The endurance of mobile devices can be effectively enhanced using the wireless power transfer technology and user cooperation. However, during user cooperation, a closer user assists a farther user with forwarding tasks by sharing the same bandwidth, which causes interference. To overcome the interference issue, the closer user can instead assist other users in forwarding tasks by using a different bandwidth. We aim to minimize the power of the AP by joint power and bandwidth optimization while satisfying the delay and users’ computational tasks. Simulation results show that the proposed user collaboration method can overcome user interference, reduce energy consumption, and improve user performance compared with the baseline policies.