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Objectives: While the decision of abortion is undeniably complex, there are situations where it becomes a necessary choice. In such circumstances, a secure abortion procedure is essential to safeguard the physical and mental well-being of women. A uterine direct visualization system was designed to fulfill the requirements and this study undertook an assessment of the system's safety and effectiveness within a medical facility setting. Materials and methods: Induced abortion requested women in 17 institutions across the country between December 2016 and February 2017 were enrolled. Subjects were separated to the study and control group randomly. Induced abortion was conducted by a uterine direct visualization system and an ultrasound-guided system in the study and control group, respectively. The clinical indexes collected during intra- and post-procedures were analyzed and compared between groups. Results: Overall, 392 and 339 subjects were included in the study and control group, respectively. The baseline demographic and clinical characteristics were similar between two groups. Subjects in the study group had significant smaller number of uterine cavity entry (p

ObjectiveThis study aimed to evaluate perioperative antibiotic use for induced abortion and its association with lower genital tract infections (LGTI) two weeks post-surgery in China.MethodsWe conducted a prospective cohort study of women seeking induced abortion. We interviewed participants on the day of surgery and two weeks after, and evaluated preoperative tests, gynecological exams, perioperative antibiotic usage, postoperative vaginal microbiota, and LGTI diagnosis. Multivariate logistic regression was used to assess the association between the perioperative antibiotic use and LGTI risk.ResultsWe recruited 8,190 women undergoing induced abortion at 27 participating hospitals. Of these, 95% had gynecological exams, but over 80% lacked tests for vaginal microbiota, chlamydia, and gonorrhea. Approximately 20% of those examined had increased vaginal discharge and abnormal vaginal cleanliness. The positive rates for gram-positive rods, fungi, and trichomonas were 38.6, 2.4, and 0.3%, respectively. More than three-quarters (78.5%) of participants received antibiotics, mainly second-gen cephalosporins (36.8%) and nitroimidazoles (12.3%). LGTI rates two weeks post-surgery were 2.7% for antibiotic recipients and 3.1% for non-recipients, with no statistically significant difference (p > 0.05). Logistic regression showed no association between perioperative antibiotic use and LGTI risk (OR = 1.01, 95% CI 0.59–1.74). However, this risk increased with abnormal preoperative discharge tests (OR = 1.39, 95% CI 1.04–1.86).ConclusionMost Chinese women undergoing induced abortion used perioperative antibiotics, but this did not significantly reduce LGTI risk. Instead, this risk was related to abnormal preoperative discharge tests. Standardization of perioperative antibiotic use for induced abortion is recommended, and prophylactic treatment in Chinese abortion services warrants further investigation.

Abstract Endometrial regenerative cells (ERCs) are a new type of mesenchymal-like stromal cells, and their therapeutic potential has been tested in a variety of disease models. SDF-1/CXCR4 axis plays a chemotaxis role in stem/stromal cell migration. The aim of the present study was to investigate the role of SDF-1/CXCR4 axis in the immunomodulation of ERCs on the experimental colitis. The immunomodulation of ERCs in the presence or absence of pretreatment of SDF-1 or AMD3100 was examined in both in vitro cell culture system and dextran sulphate sodium-induced colitis in mice. The results showed that SDF-1 increased the expression of CXCR4 on the surface of ERCs. As compared with normal ERCs, the SDF-1-treated, CXCR4 high-expressing ERCs more significantly suppressed dendritic cell population as well as stimulated both type 2 macrophages and regulatory T cells in vitro and in vivo. Meanwhile, SDF-1-pretreated ERCs increased the generation of anti-inflammatory factors (e.g., IL-4, IL-10) and decreased the pro-inflammatory factors (e.g., IL-6, TNF-α). In addition, SDF-1-pretreated CM-Dil-labeled ERCs were found to engraft to injured colon. Our results may suggest that an SDF-1-induced high level of CXCR4 expression enhances the immunomodulation of ERCs in alleviating experimental colitis in mice.

Asherman’s Syndrome (AS) is an uncommon, acquired, and refractory gynecological disorder. Current treatment was still limited, and stem cell-based therapy has been proposed as a novel strategy for management of AS. Here, we conducted a meta-analysis of self-controlled clinical trials to assess the effectiveness and safety of stem cell-based therapy in Asherman syndrome patients who have failed in conventional treatment. We systematically searched PubMed, Embase, Cochrane, and Web of Science database (published up to October 3, 2020). Our main evaluation outcomes were menses improvement, endometrial thickness changes, pregnancy outcome, and side effects. All analyses were performed by using RevMan5.4 software. 427 studies were identified, eight of which were eligible and included in our analysis. Stem cell combined hormone therapy achieved a higher likelihood of improving menstruation (risk ratio [RR] 22.43, 95% CI: 8.03 to 62.68, P

Abstract Background The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)–induced acute liver injury (ALI). Methods An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.

Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive novel type of stem cell therapy. Previous studies have demonstrated that most ERCs accumulated in the lung after injection and are successfully used to treat diseases such as cardiac fibrosis. However, relevant studies of ERCs in idiopathic pulmonary fibrosis (IPF) have not been reported. The present study was designed to examine the effects of ERCs on bleomycin-induced pulmonary fibrosis. All IPF models in C57BL/6 mice were induced by administrating 5 mg/kg bleomycin in PBS intratracheally. ERCs were isolated from healthy female menstrual blood and were injected (1 million/mouse, i.v.) 24 hours after induction. Wet/dry weight ratio assay, hydroxyproline content, pathological and immunohistological changes, MDA content, T-SOD activity, cytokine profiles, and RT-qPCR analysis were assessed 2 weeks after disease induction. The results showed that ERC treatment significantly decreased the wet/dry ratio and reduced collagen deposition. Histological analyses, Masson staining, and hydroxyproline content analysis indicated that ERCs could reduce collagen fiber production. Immunohistochemical staining revealed lower expression of TGF-β after ERC treatment. Furthermore, mice treated with ERCs had lower levels of IL-1β and TNF-α, but a higher level of IL-10 in both the lung and serum. Gene expression analysis demonstrated that ERCs potently suppressed the proapoptotic gene Bax, while increasing the antiapoptotic gene Bcl-2 and antifibrosis genes HGF and MMP-9. Our results indicate that human ERCs protected the lung from pulmonary fibrosis in mice through immunosuppressive and antifibrosis effects. Moreover, these findings formed a foundation for the further use of ERCs in clinical treatment.

Many chronic, age-related disorders could be mitigated by enhancing the activity of enzymes that regulate biochemical signaling pathways, but all known modes of enzyme activation rely on allosteric binding sites, which have only been identified in less than 10% of proteins. Sirtuins (SIRT1-7) are nicotinamide adenine dinucleotide (NAD^{+})-dependent deacylases playing critical roles in lifespan and age-related diseases. The physiological importance of sirtuins and the reduction in their catalytic activity with the age-related decline in NAD^{+} levels have stimulated intense interest in designing sirtuin-activating compounds; however, except for substrate-specific allosteric SIRT1 activators, methodologies for rational design of sirtuin-activating compounds are lacking. Here, we introduce methods for the activation of such enzymes that do not rely on allosteric binding sites, and we demonstrate their successful application to the discovery of first-in-class activators of sirtuin enzymes. We establish how all-atom simulations of an enzyme’s active site under the potential of a small molecule modulator can be used to identify molecular properties that achieve desired changes in local enzyme conformational degrees of freedom conducive to the enhancement of catalytic activity. We apply computational high-throughput screening based on this biophysical model for activation of sirtuin enzymes to the major mitochondrial sirtuin SIRT3, which plays a critical role in age-related disorders but does not have a known allosteric site; we thereby identify first-in-class, nonallosteric activators of this enzyme. These compounds are the first reported steady-state activators of the major mitochondrial sirtuin enzyme, and they operate according to a mode of action not shared by any existing drug. Two such compounds can almost double the catalytic efficiency of SIRT3 with respect to NAD^{+}, thus compensating for the loss in SIRT3 activity that occurs due to the age-related decline in NAD^{+}, and they may be developed for therapeutic applications to combat multiple types of age-related disorders. These discoveries establish a foundation for the development of a new class of drugs that function through the activation of enzymes by modulation of local conformational ensembles.

Abstract Endurance exercise could attenuate obesity induced by high fat diet (HFD). Thus, the purpose of this study was to explore the crucial targets that play key roles in the improvement of body fat index (BFI) in obese mice by endurance exercise. Firstly, we constructed murine obesity models: High fat diet control (HFD) group, HFD exercise (HFE) group, normal chow diet control (NC) group, and normal chow diet exercise (NE) group. Next, we identified the BFI improvement related genes using differential gene analysis, and investigated these genes’ functional pathways using functional enrichment analysis. The qRT-PCR and western blot assays were used to determine the gene expression and protein expression, respectively. Gene set enrichment analysis was used to explore the potential pathways associated with endurance exercise in obese mice and Mitochondrial respiratory control ratio (RCR) assay was applied to determine the RCR in the liver tissues of mice. We discovered that endurance exercise remarkably reduced the body weights and BFI of HFD-induced obese mice. Runx1t1 was related to the improvement of BFI by endurance exercise in HFD-induced obese mice. Runx1t1 mRNA and protein levels in liver tissues were observably decreased in HFD mice compared to mice in HFE, NC and NE groups. Moreover, Glucagon signaling pathway that was associated with mitochondrial function was significantly activated in HFE mice. The Runx1t1 expression exhibited an observable negative correlation with Acaca in HFD mice. Moreover, the mitochondrial RCR level was significantly increased in HFE mice than that in HFD mice. In HFD-induced obese mice, Runx1t1 was implicated in the improvement of BFI via endurance exercise. Endurance exercise could improve mitochondrial dysfunction in obese mice by activating the Runx1t1.

Z-shaped folding wings have the potential to enhance the flight performance of an aircraft, contingent upon its mission requirements. However, the current scope of research on unmanned aerial vehicles (UAVs) with Z-shaped folding wings primarily focuses on the analysis of their folding structure and aeroelasticity-related vibrations. Computational fluid dynamics methods and dynamic meshing are employed to examine the folding process of Z-shaped folding wings. By comparing the steady aerodynamic characteristics of Z-shaped folding wings with those of conventional wings, this investigation explores the dynamic aerodynamic properties of Z-shaped folding wings at varying upward folding speeds. The numerical findings reveal that the folding of Z-shaped folding wings reduces the lift-to-drag ratio, yet simultaneously diminishes the nose-down pitching moment, thereby augmenting maneuverability. Concerning unsteady aerodynamics, the transient lift and drag coefficients of the folded wing initially increase and subsequently decrease as the folding angle increases at small angles of attack. Likewise, the nose-down pitching moment exhibits the same pattern in response to the folding angle. Additionally, the aerodynamic coefficients experience a slight decrease during the initial half of the folding process with increasing folding speed. Once the wing reaches approximately 40°~45° of folding, there is an abrupt change in the transient aerodynamic coefficients. Notably, this abrupt change is delayed with higher folding speeds, eventually converging to similar values across different folding speeds.

Background: Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia-reperfusion injury (IRI) were examined.Methods: Renal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30 min, followed by reperfusion for 48 h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2 h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48 h of renal reperfusion.Results: Here, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-α, IFN-γ and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4(+) and CD8(+) T cell populations, while the percentage of splenic CD4(+)CD25(+) regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice.Conclusions: This study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients. [ABSTRACT FROM AUTHOR]

In order to solve the problems of limited installation space and strict additional quality, the effects of internal distributed nonlinear energy sinks (NES) considering optimal locations on a composite truss core sandwich plate are investigated in this paper. Choose five NESs here and inset them in the different places of the sandwich plate to suppress the vibration of the plate, which is excited by a half-wave shock. The coupled dynamic equations of the system are derived by the principle of conservation of energy. Then, the vibration-control performances of five NESs are discussed by numerical simulation. The distributions of the five NESs are analyzed, and the optimal position distributions are obtained. Based on the optimal location, the transient responses of the system are studied. Moreover, the performances of five NESs and a single NES are compared in different dimensions. Finally, it is found that the selection of parameters has a great impact on the effectiveness of the five NESs. The new distribution way is introduced to improve the suppression effects of the five NESs in the sandwich plate.

A new strategy for diversity-oriented direct glycosylation of bioactive small molecules was developed. This reaction features (-)-β-pinene as acid scavenger and work with glycosyl iodides under mild conditions. With the aid of RP-HPLC and chiral SFC separation techniques, the new direct glycosylation proved effective at gram scale on bioactive small molecules including AZD6244, podophyllotoxin, paclitaxel, and docetaxel. Interesting glycoside derivatives were efficiently created with good yields and 1,2-cis selectivity. [ABSTRACT FROM AUTHOR]

A method of modal parameter identification of structures using reconstructed displacements was proposed in the present research. The proposed method was developed based on the stochastic subspace identification (SSI) approach and used reconstructed displacements of measured accelerations as inputs. These reconstructed displacements suppressed the high-frequency component of measured acceleration data. Therefore, in comparison to the acceleration-based modal analysis, the operational modal analysis obtained more reliable and stable identification parameters from displacements regardless of the model order. However, due to the difficulty of displacement measurement, different types of noise interferences occurred when an acceleration sensor was used, causing a trend term drift error in the integral displacement. A moving average low-frequency attenuation frequency-domain integral was used to reconstruct displacements, and the moving time window was used in combination with the SSI method to identify the structural modal parameters. First, measured accelerations were used to estimate displacements. Due to the interference of noise and the influence of initial conditions, the integral displacement inevitably had a drift term. The moving average method was then used in combination with a filter to effectively eliminate the random fluctuation interference in measurement data and reduce the influence of random errors. Real displacement results of a structure were obtained through multiple smoothing, filtering, and integration. Finally, using reconstructed displacements as inputs, the improved SSI method was employed to identify the modal parameters of the structure.

Based on the structures of unmanned aerial vehicle (UAV) wings, nonlinear dynamic analysis of macrofiber composite (MFC) laminated shells is presented in this paper. The effects of piezoelectric properties and aerodynamic forces on the dynamic stability of the MFC laminated shell are studied. Firstly, under the flow condition of ideal incompressible fluid, the thin airfoil theory is employed to calculate the effects of the mean camber line to obtain the circulation distribution of the wings in subsonic air flow. The steady aerodynamic lift on UAV wings is derived by using the Kutta–Joukowski lift theory. Then, considering the geometric nonlinearity and piezoelectric properties of the MFC material, the nonlinear dynamic model of the MFC laminated shell is established with Hamilton’s principles and the Galerkin method. Next, the effects of electric field, external excitation force, and nonlinear parameters on the stability of the system are studied under 1 : 1 internal resonance and the effects of material parameters on the natural frequency of the structure are also analyzed. Furthermore, the influence of the aerodynamic forces and electric field on the nonlinear dynamic responses of MFC laminated shells is discussed by numerical simulation. The results indicate that the electric field and external excitation have great influence on the structural dynamic responses.

Across all families of enzymes, only a dozen or so distinct classes of non-natural small molecule activators have been characterized, with only four known modes of activation among them. All of these modes of activation rely on naturally evolved binding sites that trigger global conformational changes. Among the enzymes that are of greatest interest for small molecule activation are the seven sirtuin enzymes, nicotinamide adenine dinucleotide (NAD+)-dependent protein deacylases that play a central role in the regulation of healthspan and lifespan in organisms ranging from yeast to mammals. However, there is currently no understanding of how to design sirtuin-activating compounds beyond allosteric activators of SIRT1-catalyzed reactions that are limited to particular substrates. Here, we introduce a general mode of sirtuin activation that is distinct from the known modes of enzyme activation. Based on the conserved mechanism of sirtuin-catalyzed deacylation reactions, we establish biophysical properties of small molecule modulators that can in principle result in enzyme activation for diverse sirtuins and substrates. Building upon this framework, we propose strategies for the identification, characterization and evolution of hits for mechanism-based enzyme activating compounds.

This work presents the nonlinear dynamical analysis of a multilayer d31 piezoelectric macrofiber composite (MFC) laminated shell. The effects of transverse excitations and piezoelectric properties on the dynamic stability of the structure are studied. Firstly, the nonlinear dynamic models of the MFC laminated shell are established. Based on known selected geometrical and material properties of its constituents, the electric field of MFC is presented. The vibration mode-shape functions are obtained according to the boundary conditions, and then the Galerkin method is employed to transform partial differential equations into two nonlinear ordinary differential equations. Next, the effects of the transverse excitations on the nonlinear vibration of MFC laminated shells are analyzed in numerical simulation and moderating effects of piezoelectric coefficients on the stability of the system are also presented here. Bifurcation diagram, two-dimensional and three-dimensional phase portraits, waveforms phases, and Poincare diagrams are shown to find different kinds of periodic and chaotic motions of MFC shells. The results indicate that piezoelectric parameters have strong effects on the vibration control of the MFC laminated shell.

Sirtuins are key regulators of many cellular functions including cell growth, apoptosis, metabolism, and genetic control of age-related diseases. Sirtuins are themselves regulated by their cofactor nicotinamide adenine dinucleotide (NAD+) as well as their reaction product nicotinamide (NAM), the physiological concentrations of which vary during the process of aging. Nicotinamide inhibits sirtuins through the so-called base exchange pathway, wherein rebinding of the reaction product to the enzyme accelerates the reverse reaction. We investigated the mechanism of nicotinamide inhibition of human SIRT3, the major mitochondrial sirtuin deacetylase, in vitro and in silico using experimental kinetic analysis and Molecular Mechanics-Poisson Boltzmann/Generalized Born Surface Area (MM-PB(GB)SA) binding affinity calculations with molecular dynamics sampling. Through experimental kinetic studies, we demonstrate that NAM inhibition of SIRT3 involves apparent competition between the inhibitor and the enzyme cofactor NAD+, contrary to the traditional characterization of base exchange as noncompetitive inhibition. We report a model for base exchange inhibition that relates such kinetic properties to physicochemical properties, including the free energies of enzyme-ligand binding, and estimate the latter through the first reported computational binding affinity calculations for SIRT3:NAD+, SIRT3:NAM, and analogous complexes for Sir2. The computational results support our kinetic model, establishing foundations for quantitative modeling of NAD+/NAM regulation of mammalian sirtuins during aging and the computational design of sirtuin activators that operate through alleviation of base exchange inhibition.