A meet-up of acetyl phosphate and c-di-GMP modulates BldD activity for development and antibiotic production.

Actinobacteria are ubiquitous bacteria undergoing complex developmental transitions coinciding with antibiotic production in response to stress or nutrient starvation. This transition is mainly controlled by the interaction between the second messenger c-di-GMP and the master repressor BldD. To date, the upstream factors and the global signal networks that regulate these intriguing cell biological processes remain unknown. In Saccharopolyspora erythraea, we found that acetyl phosphate (AcP) accumulation resulting from environmental nitrogen stress participated in the regulation of BldD activity through cooperation with c-di-GMP. AcP-induced acetylation of BldD at K11 caused the BldD dimer to fall apart and dissociate from the target DNA and disrupted the signal transduction of c-di-GMP, thus governing both developmental transition and antibiotic production. Additionally, practical mutation of BldDK11R bypassing acetylation regulation could enhance the positive effect of BldD on antibiotic production. The study of AcP-dependent acetylation is usually confined to the control of enzyme activity. Our finding represents an entirely different role of the covalent modification caused by AcP, which integrated with c-di-GMP signal in modulating the activity of BldD for development and antibiotic production, coping with environmental stress. This coherent regulatory network might be widespread across actinobacteria, thus has broad implications.

Protein acylation links metabolism and the control of signal transduction, transcription regulation, growth, and pathogenicity in Actinobacteria.

Actinobacteria have a complex life cycle, including morphological and physiological differentiation which are often associated with the biosynthesis of secondary metabolites. Recently, increased interest in post-translational modifications (PTMs) in these Gram-positive bacteria has highlighted the importance of PTMs as signals that provide functional diversity and regulation by modifying proteins to respond to diverse stimuli. Here, we review the developments in research on acylation, a typical PTM that uses acyl-CoA or related metabolites as donors, as well as the understanding of the direct link provided by acylation between cell metabolism and signal transduction, transcriptional regulation, cell growth, and pathogenicity in Actinobacteria.

High accuracy, compact 3D face imaging method based on translational and online-switchable phase-shifting fringe projection.

In this paper, a compact, cost-effective, and fast translational online-switchable phase-shifting fringe (TOPF) projector is designed and fabricated for high accuracy three-dimensional (3D) face imaging. Compared with the conventional mechanical projectors, the main difference is that it utilizes a translational approach instead of a rotational one to achieve a better balance in terms of size, speed, accuracy, and cost. To mitigate the inconsistency of the motor's step size and ensure the stability of phase-shifting, an optical encoder-based feedback control mechanism is employed. Additionally, to address the random phase shift errors induced by mechanical motion, a fast, generalized phase-shifting algorithm with unknown phase shifts (uPSAs) that can calculate arbitrary phase shifts is proposed. Finally, a 3D imaging system consisting of the TOPF projector and two cameras is constructed for experimental validation. The feasibility, effectiveness, and precision of our proposed method are substantiated through the reconstruction of a static facial model and a dynamic real face.

Phase retrieval from single-shot square wave fringe based on image denoising using deep learning.

Fringe-structured light measurement technology has garnered significant attention in recent years. To enhance measurement speed while maintaining a certain level of accuracy using binary fringe, this paper proposes a phase retrieval method with single-frame binary square wave fringe. The proposed method utilizes image denoising through deep learning to extract the phase, enabling the use of a trained image denoiser as a low-pass filter, which adaptively replaces the manual selection of the appropriate band-pass filter. The results demonstrate that this method achieves higher reconstruction accuracy than the traditional single-frame algorithm while preserving more object details.

Theoretical analysis and experimental investigation of the Floyd-Steinberg-based fringe binary method with offset compensation for accurate 3D measurement.

Digital fringe projection (DFP) with defocused binary fringe patterns has the ability to overcome the projector nonlinearity and achieve a high-speed 3D measurement. The Floyd-Steinberg (FS) dithering technique is one of the most commonly adopted binary fringe coding methods due to its relatively high measurement accuracy. Nevertheless, we found that the FS binary fringe would cause a fixed error in the recovered phase, which is proven to be invariable for various defocusing levels and various phase-shift steps according to the analysis of the phase error based on noise model of phase-shifting profilometry. It means that FS binary fringe would have a certain offset in space, compared with standard sinusoidal fringe, which is verified to be essentially constant for different fringe pitches through simulation and experiment. This offset would distort the 3D geometry of the tested target for monocular systems relying on triangulation, which needs to be compensated to improve 3D measurement accuracy. Experiments are presented to demonstrate the enhanced 3D result after compensation.

Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2.

BACKGROUND: Osteoarthritis (OA) is the most common articular disorder, leading to joint malfunction and disability. Although the incidence of OA is increasing globally, the treatment of OA is very limited. LncRNA CIR has been implicated in OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in chondrogenic differentiation. METHODS: Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry was used to analyze the surface markers of hUC-MSCs. Various culture conditions and corresponding staining assays were employed to assess the differentiation abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to measure expression levels of related genes and proteins such as lncRNA CIR, ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and chromatin immunoprecipitaion assay were performed to analyze the interactions of lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter. RESULTS: hUC-MSCs exhibited MSCs features and could differentiate into chondrocytes under specific conditions. LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown lncRNA CIR on chondrogenic differentiation. CONCLUSION: LncRNA CIR suppresses chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could inhibit ATOH8 expression that functions to promote chondrogenic differentiation through EZH2-mediated epigenetic modifications.

Distiboranes based on ortho-phenylene backbones as bidentate Lewis acids for fluoride anion chelation.

As part of our efforts in the chemistry of main group platforms that support anion sensing and transport, we are now reporting the synthesis of anitmony-based bidentate Lewis acids featuring the o-C6F4 backbone. These compounds can be easily accessed by reaction of the newly synthesized o-C6F4(SbPh2)2 (5) with o-chloranil or octafluorophenanthra-9,10-quinone, affording the corresponding distiboranes 6 and 7 of general formula o-C6F4(SbPh2(diolate))2 with diolate = tetrachlorocatecholate for 6 and octafluorophenanthrene-9,10-diolate for 7, respectively. While 6 is very poorly soluble, its octafluorophenanthrene-9,10-diolate analog 7 readily dissolves in CH2Cl2 and undergoes swift conversion into the corresponding fluoride chelate complex [7-µ2-F]- which has been isolated as a [nBu4N]+ salt. The o-C6H4 analog of 7, referred to as 8, has also been prepared. Although less Lewis acidic than 7, 8 also forms a very stable fluoride chelate complex ([8-µ2-F]-). Altogether, our experiental results, coupled with computational analyses and fluoride anion affinity calculations, show that 7 and 8 are some of the strongest antimony-based fluoride anion chelators prepared to date. Another notable aspect of this work concerns the use of the octafluorophenanthrene-9,10-diolate ligand and its ablity to impart advantageous solubility and Lewis acidity properties.

Pelvic dimension as a predictor of ureteral injury in gynecological cancer surgeries.

BACKGROUND: Ureteral injury is an intractable complication in gynecological cancer surgeries. Identifying risk factors can ensure safety of the ureters intraoperatively. A narrow pelvis is known to exert extra difficulties in pelvic surgeries. However, whether pelvic dimension can affect the risk of ureteral injury in gynecological cancer surgeries is poorly understood. We aimed to evaluate the association between pelvic dimension and the risk of ureteral injury during gynecological cancer surgeries. METHODS: All patients who had undergone gynecological cancer surgeries were searched from January 2011 to July 2017. We included patients with ureteral injury who had available data of abdominal and pelvic computed tomography for measuring pelvic dimensions. Multivariate condition logistic analysis was used to identify the risk factors independently correlated with ureteral injury in gynecological cancer surgeries. RESULTS: A total of 43 cases with 86 controls were included in this study. We discovered that a longer anteroposterior diameter of the mid-pelvis (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13, P = 0.019) and a shorter transverse diameter of the mid-pelvis (OR 0.92, 95% CI 0.86-0.98, P = 0.013) were associated with ureteral injury in gynecological cancer surgeries. In laparoscopic analysis, a longer anteroposterior diameter of the mid-pelvis (OR 1.11, 95% CI 1.00-1.24, P = 0.041) was a risk factor for ureteral injury. In the analysis of open surgery, a longer transverse diameter of the mid-pelvis (OR 0.79, 95% CI 0.66-0.93, P = 0.006) was a protective factor for ureteral injury. CONCLUSIONS: This study demonstrated that mid-pelvis dimensions were associated with ureteral injury, but the observed differences were too small. In addition, pelvic inlet dimensions did not appear to relate with ureteral injury. Thus, these pelvimetry measures could not be beneficial in assessing the risk of ureteral injury in gynecological cancer surgeries.

Acetylation of translation machinery affected protein translation in E. coli.

Reversible lysine acetylation (RLA) of translation machinery components, such as ribosomal proteins (RPs) and translation factors (TFs), was identified in many microorganisms, while knowledge of its function and effect on translation remains limited. Herein, we show that translation machinery is regulated by acetylation. Using the cell-free translation system of E. coli, we found that AcP-driven acetylation significantly reduced the relative translation rate, and deacetylation partially restored the translation activity. Hyperacetylation caused by intracellular AcP accumulation or carbon/nitrogen fluctuation (carbon overflow or nitrogen limitation) modulated protein translation in vivo. These results uncovered a critical role of acetylation in translation regulation and indicated that carbon/nitrogen imbalance induced acetylation of ribosome in E. coli and dynamically affected translation rate via a global, uniform manner. KEY POINTS: • Acetylation of translation machinery directly regulated global translation. • K618 of EF-G, K411, and K464 of S1 are the key points influencing translation rate. • Carbon/nitrogen imbalance triggers AcP-dependent acetylation.

A High-Performance Face Illumination Processing Method via Multi-Stage Feature Maps.

In recent years, Generative Adversarial Networks (GANs)-based illumination processing of facial images has made favorable achievements. However, some GANs-based illumination-processing methods only pay attention to the image quality and neglect the recognition accuracy, whereas others only crop partial face area and ignore the challenges to synthesize photographic face, background and hair when the original face image is under extreme illumination (Image under extreme illumination (extreme illumination conditions) means that we cannot see the texture and structure information clearly and most pixel values tend to 0 or 255.). Moreover, the recognition accuracy is low when the faces are under extreme illumination conditions. For these reasons, we present an elaborately designed architecture based on convolutional neural network and GANs for processing the illumination of facial image. We use ResBlock at the down-sampling stage in our encoder and adopt skip connections in our generator. This special design together with our loss can enhance the ability to preserve identity and generate high-quality images. Moreover, we use different convolutional layers of a pre-trained feature network to extract varisized feature maps, and then use these feature maps to compute loss, which is named multi-stage feature maps (MSFM) loss. For the sake of fairly evaluating our method against state-of-the-art models, we use four metrics to estimate the performance of illumination-processing algorithms. A variety of experimental data indicate that our method is superior to the previous models under various illumination challenges in illumination processing. We conduct qualitative and quantitative experiments on two datasets, and the experimental data indicate that our scheme obviously surpasses the state-of-the-art algorithms in image quality and identification accuracy.

Effects of AURKA-mediated degradation of SOD2 on mitochondrial dysfunction and cartilage homeostasis in osteoarthritis.

This study aimed to investigate the mechanism of the ubiquitinase Aurora kinase A (AURKA) in the occurrence of osteoarthritis (OA) by mediating mitochondrial stress. Bioinformatic predictions revealed 2247 differentially expressed genes (DEGs) in the normal and OA tissues. According to the UbiNet database, 39 DEGs that code for ubiquitination enzymes was screened. AURKA was highly expressed in OA tissues and cells. AURKA interference inhibited the elevation of matrix metalloproteinase-13 (MMP-13). (MMP13), sex determining region Y-box 9 (Sox9), and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) expression and the reduction of collagen type IIα (Col2a1) and Aggrecan expression in interleukin-1 ß (IL-1ß) induced chondrocytes. The animal experiments proved that depleting AURKA could repress the occurrence of OA. Superoxide dismutase 2 (SOD2) was determined to be AURKA ubiquitination substrate via AURKA expression and bioinformatic prediction experiments. SOD2 expression was lower in OA tissues, but higher in normal joint tissues. AURKA interference activates SOD2. Meanwhile, the IP results confirmed that AURKA could bind to SOD2 and degrade it through K48 ubiquitination. Modification and overexpression of AURKA reduce SOD2 levels. AURKA interference can reverse the reactive oxygen species elevation caused by SOD2 overexpression or lysine-48 (K48) mutation, respectively, leading to mitochondrial dysfunction. Furthermore, AURKA silencing suppressed the occurrence of OA induced by mitochondrial activation. These findings suggest that ubiquitination of AURKA lowers SOD2 expression and affects mitochondrial dysfunction to repress the occurrence of OA. The results of the current study reveal that AURKA ubiquitination influences mitochondrial dysfunction and suppresses the occurrence of OA via degradation of SOD2. These data reveal novel potential targets for OA treatment.

Antitumor efficacy of PARP inhibitors in homologous recombination deficient carcinomas.

PARP inhibitors (PARPis) have remarkable antitumor activity in BRCA mutant ovarian carcinoma. Emerging evidence has shown that responses to PARPis are not limited to BRCA mutant tumors, but could expand to other homologous recombination deficiency (HRD) carcinomas. However, relatively little is known about the efficacy of PARPis in patients with HRD when compared to non-HRD carriers. In this systematic review, 13 clinical trials were included and analyzed for the treatment effect of PARPis on progression free survival (PFS) and overall survival (OS) for HRD (BRCA mutant HRD, n = 697; BRCA wild-type HRD, n = 478) vs. non-HRD (n = 1,417) patients. Pooled analyses of the effect of PARPis in both ovarian and nonovarian carcinoma groups showed significantly higher PFS rates at 6 months and 12 months (PFS6 and PFS12) in the HRD subgroup, as compared to the non-HRD subgroup. Within the HRD subgroup, the BRCA-mutant population achieved significantly higher PFS6 (OR: 2.29, 95% CI: 1.03-5.08) and PFS12 (OR: 1.95, 95% CI: 1.26-3.01) when compared to BRCA wild-type patients. Furthermore, within BRCA wild-type carcinomas, mutations in other HRD-related genes also led to increased PFS6 (OR: 1.72, 95% CI: 1.27-2.43) and PFS12 (OR: 1.85, 95% CI: 1.31-2.62), as compared to non-HRD counterparts. Therefore, patients with HRD carcinomas exhibited pronounced PFS advantages upon treatment with PARPis, as compared to non-HRD carcinomas. In addition to BRCA mutations, other non-BRCA HRD-related aberrations may serve as novel biomarkers for the prediction of PARPi efficacy.

Phosphate regulator PhoP directly and indirectly controls transcription of the erythromycin biosynthesis genes in Saccharopolyspora erythraea.

BACKGROUND: The choice of phosphate/nitrogen source and their concentrations have been shown to have great influences on antibiotic production. However, the underlying mechanisms responsible for this remain poorly understood. RESULTS: We show that nutrient-sensing regulator PhoP (phosphate regulator) binds to and upregulates most of genes (ery cluster genes) involved in erythromycin biosynthesis in Saccharopolyspora erythraea, resulting in increase of erythromycin yield. Furthermore, it was found that PhoP also directly interacted with the promoter region of bldD gene encoding an activator of erythromycin biosynthesis, and induced its transcription. Phosphate limitation and overexpression of phoP increased the transcript levels of ery genes to enhance the erythromycin production. The results are further supported by observation that an over-producing strain of S. erythraea expressed more PhoP than a wild-type strain. On the other hand, nitrogen signal exerts the regulatory effect on the erythromycin biosynthesis through GlnR negatively regulating the transcription of phoP gene. CONCLUSIONS: These findings provide evidence that PhoP mediates the interplay between phosphate/nitrogen metabolism and secondary metabolism by integrating phosphate/nitrogen signals to modulate the erythromycin biosynthesis. Our study reveals a molecular mechanism underlying antibiotic production, and suggests new possibilities for designing metabolic engineering and fermentation optimization strategies for increasing antibiotics yield.

Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism.

In cells of all domains of life, reversible lysine acetylation modulates the function of proteins involved in central cellular processes such as metabolism. In this study, we demonstrate that the nitrogen regulator GlnR of the actinomycete Saccharopolyspora erythraea directly regulates transcription of the acuA gene (SACE_5148), which encodes a Gcn5-type lysine acetyltransferase. We found that AcuA acetylates two glutamine synthetases (GlnA1 and GlnA4) and that this lysine acetylation inactivated GlnA4 (GSII) but had no significant effect on GlnA1 (GSI-ß) activity under the conditions tested. Instead, acetylation of GlnA1 led to a gain-of-function that modulated its interaction with the GlnR regulator and enhanced GlnR-DNA binding. It was observed that this regulatory function of acetylated GSI-ß enzymes is highly conserved across actinomycetes. In turn, GlnR controls the catalytic and regulatory activities (intracellular acetylation levels) of glutamine synthetases at the transcriptional and posttranslational levels, indicating an autofeedback loop that regulates nitrogen metabolism in response to environmental change. Thus, this GlnR-mediated acetylation pathway provides a signaling cascade that acts from nutrient sensing to acetylation of proteins to feedback regulation. This work presents significant new insights at the molecular level into the mechanisms underlying the regulation of protein acetylation and nitrogen metabolism in actinomycetes.

GntR Family Regulator DasR Controls Acetate Assimilation by Directly Repressing the acsA Gene in Saccharopolyspora erythraea.

The GntR family regulator DasR controls the transcription of genes involved in chitin and N-acetylglucosamine (GlcNAc) metabolism in actinobacteria. GlcNAc is catabolized to ammonia, fructose-6-phosphate (Fru-6P), and acetate, which are nitrogen and carbon sources. In this work, a DasR-responsive element (dre) was observed in the upstream region of acsA1 in Saccharopolyspora erythraea This gene encodes acetyl coenzyme A (acetyl-CoA) synthetase (Acs), an enzyme that catalyzes the conversion of acetate into acetyl-CoA. We found that DasR repressed the transcription of acsA1 in response to carbon availability, especially with GlcNAc. Growth inhibition was observed in a dasR-deleted mutant (ΔdasR) in the presence of GlcNAc in minimal medium containing 10 mM acetate, a condition under which Acs activity is critical to growth. These results demonstrate that DasR controls acetate assimilation by directly repressing the transcription of the acsA1 gene and performs regulatory roles in the production of intracellular acetyl-CoA in response to GlcNAc.IMPORTANCE Our work has identified the DasR GlcNAc-sensing regulator that represses the generation of acetyl-CoA by controlling the expression of acetyl-CoA synthetase, an enzyme responsible for acetate assimilation in S. erythraea The finding provides the first insights into the importance of DasR in the regulation of acetate metabolism, which encompasses the regulatory network between nitrogen and carbon metabolism in actinobacteria, in response to environmental changes.

Modulating the σ-Accepting Properties of an Antimony Z-type Ligand via Anion Abstraction: Remote-Controlled Reactivity of the Coordinated Platinum Atom.

In search of ligand platforms, which can be used to remotely control the catalytic activity of a transition metal, we have investigated the coordination noninnocence of ambiphilic L2/Z-type ligands containing a trifluorostiborane unit as a Lewis acid. The known dichlorostiboranyl platinum complex (( o-(Ph2P)C6H4)2SbCl2)PtCl (1) reacts with TlF in the presence of acetonitrile (MeCN) and cyclohexyl isocyanide (CyNC) to afford the trifluorostiborane platinum complexes 2 ((( o-(Ph2P)C6H4)2SbF3)Pt-NCMe) and 3 ((( o-(Ph2P)C6H4)2SbF3)Pt-CNCy), respectively. Formation of these complexes, which results from a redistribution of the halide ligands about the dinuclear core, affects the nature of the Pt-Sb bond. The latter switches from covalent in 1 to polar covalent (or dative) in 2 and 3 where the trifluorostiborane moiety engages the platinum center in a Pt → Sb interaction. The polarity of the Pt-Sb bond can be modulated further by abstraction of an antimony-bound fluoride ligand using B(C6F5)3. These reactions afford the cationic complexes [(( o-(Ph2P)C6H4)2SbF2)Pt-NCMe]+ ([5]+) and [(( o-(Ph2P)C6H4)2SbF2)Pt-CNCy]+ ([6]+) which have been isolated as [BF(C6F5)3]- salts. These complexes possess a highly Lewis acidic difluorostibonium moiety, which exerts an intense draw on the electron density of the platinum center. As a result, the latter becomes significantly more electrophilic. In the case of [5]+, which contains a labile acetonitrile ligand, this increased electrophilicity translates into increased carbophilicity as reflected by the ability of this complex to promote enyne cyclization reactions. These results demonstrate that the coordination noninnocence of antimony Z-ligands can be used to adjust the catalytic activity of an adjoining metal center.

Extraordinary Redox Activities in Ladder-Type Conjugated Molecules Enabled by B ← N Coordination-Promoted Delocalization and Hyperconjugation.

The introduction of B ← N coordinate bond-isoelectronic to C-C single bond-into π-systems represents a promising strategy to impart exotic redox and electrochromic properties into conjugated organic molecules and macromolecules. To achieve both reductive and oxidative activities using this strategy, a cruciform ladder-type molecular constitution was designed to accommodate oxidation-active, reduction-active, and B ← N coordination units into a compact structure. Two such compounds (BN-F and BN-Ph) were synthesized via highly efficient N-directed borylation. These molecules demonstrated well-separated, two reductive and two oxidative electron-transfer processes, corresponding to five distinct yet stable oxidation states, including a rarely observed boron-containing radical cation. Spectroelectrochemical measurements revealed unique optical characteristics for each of these reduced/oxidized species, demonstrating multicolor electrochromism with excellent recyclability. Distinct color changes were observed between each redox state with clear isosbestic points on the absorption spectra. The underlying redox mechanism was elucidated by a combination of computational and experimental investigations. Single-crystal X-ray diffraction analysis on the neutral state, the oxidized radical cation, and the reduced dianion of BN-Ph revealed structural transformations into two distinct quinonoid constitutions during the oxidation and reduction processes, respectively. B ← N coordination played an important role in rendering the robust and reversible multistage redox properties, by extending the charge and spin delocalization, by modulating the π-electron density, and by a newly established hyperconjugation mechanism.

Acetyl-CoA synthetases of Saccharopolyspora erythraea are regulated by the nitrogen response regulator GlnR at both transcriptional and post-translational levels.

Saccharopolyspora erythraea has three AMP-forming acetyl-CoA synthetases (Acs) encoded by acsA1, acsA2, and acsA3. In this work, we found that nitrogen response regulator GlnR can directly interact with the promoter regions of all three genes and can activate their transcription in response to nitrogen availability. The typical GlnR-binding boxes were identified in the promoter regions. Moreover, the activities of three Acs enzymes were modulated by the reversible lysine acetylation (RLA) with acetyltransferase AcuA and NAD+ -dependent deacetylase SrtN. Interestingly, GlnR controlled the RLA by directly activating the expression of acuA and srtN. A glnR-deleted mutant (ΔglnR) caused a growth defect in 10 mM acetate minimal medium, a condition under which RLA function is critical to control Acs activity. Overexpression of acuA reversed the growth defect of ΔglnR mutant. Total activity of Acs in cell-free extracts from ΔglnR strain had a 4-fold increase relative to that of wildtype strain. Western Blotting showed that in vivo acetylation levels of Acs were influenced by nitrogen availability and lack of glnR. These results demonstrated that GlnR regulated acetyl-CoA synthetases at transcriptional and post-translational levels, and mediated the interplay between nitrogen and carbon metabolisms by integrating nitrogen signals to modulate the acetate metabolism.

[12]aneN3-based lipid with naphthalimide moiety for enhanced gene transfection efficiency.

Three cationic lipids derived from [12]aneN3 modified with naphthalimide (1a), oleic acid (1b) and octadecylamine (1c) were designed and synthesized. In vitro transfection showed that all these liposomes can deliver plasmid DNA into the tested cell lines. Among these liposomes, 1a gave the best transfection efficiency (TE) in A549 cells, which was higher than that of lipofectamine 2000. More importantly, the TE of 1a was dramatically increased in the presence of 10% serum. These results suggested that 1a might be a promising non-viral gene vector, and also give further insight for developing novel high performance gene delivery agents.

Hysteroscopy after repeated implantation failure of assisted reproductive technology: A meta-analysis.

We conducted this meta-analysis to explore the prognostic value of outpatient (or office) hysteroscopy (OH) preceding in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles in women who had experienced repeated implantation failure (RIF), particularly in regard to the conflicting evidence reported by previous studies. Two reviewers independently searched Pubmed, MEDLINE, Web of Science, Cochrane Library and Embase to identify all publications of clinical trials of hysteroscopy with or without endometrial biopsy in RIF patients. The primary outcome measures were clinical pregnancy rate (CPR) and live birth rate (LBR). Pooled relative ratios (RRs) with 95% confidence intervals (CIs) were calculated. Publication bias was detected using funnel plots and Egger's regression tests. Six eligible studies comprising 4143 patients were included. The CPR and LBR were both significantly higher in RIF patients with OH than RIF patients without OH (CPR: RR 1.34, 95% CI 1.14-1.57, P < 0.05; LBR: RR 1.29, 95% CI 1.03-1.62, P < 0.05). Subgroup analysis revealed a significant association between OH and CPR in Asia (CPR: RR 1.49, 95% CI 1.31-1.69; P < 0.05) rather than in Europe (CPR: RR 1.08, 95% CI 0.93-1.26; P = 0.291). However, there was no evidence of a significant difference in either CPR or LBR between the normal and abnormal OH groups (CPR: RR 0.92, 95% CI 0.83-1.02, P = 0.12; LBR: RR 0.76, 95% CI 0.37-1.56, P = 0.450). Hysteroscopy may potentially improve pregnancy outcomes in patients with RIP.