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Overexpression of survivin is frequently observed in human malignancies and is associated with poor prognosis. The present study found that survivin is highly expressed in nasopharyngeal carcinoma (NPC) tumor tissues. Depleting survivin with shRNA inhibited cell viability, colony formation, and in vivo tumorigenesis of NPC cells. With a natural product screening, we identified Butein as a potential anti-tumor compound for NPC by reducing survivin protein level. Butein shortened the half-life of survivin and enhanced ubiquitination-mediated degradation. The mechanism study showed that Butein promoted the interaction between survivin and E3 ligase Fbxl7, and the knockdown of Fbxl7 compromised Butein-induced survivin ubiquitination. Butein suppressed the Akt-Wee1-CDK1 signaling and decreased survivin Thr34 phosphorylation, facilitating E3 ligase Fbxl7-mediated survivin ubiquitination and degradation. Moreover, Butein exhibited a strong in vivo anti-tumor activity, as the tumor volume of Butein-treated xenografts was reduced significantly. Butein alone or combined with cisplatin (CDDP) overcame chemoresistance in NPC xenograft tumors. Overall, our data indicate that Butein is a promising anti-tumor agent for NPC treatment. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Xin Dong and Wenbin Liu. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-21839-4, published online 30 November 2022 In the original version of this Article, Xin Dong was incorrectly affiliated with 'Department of Head and Neck Surgery, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China'. [Extracted from the article]

Structural topology optimization has gained widespread attention due to more possibilities of innovative structural design. The current research focus/hotspots, application areas, main research scholars, institutions and the countries involved in structural topology optimization are visually presented through clustering and visual analysis based on CiteSpace. The four metric dimensions of the literatures in this paper are as follows: annual quantity of papers and core countries, core authors and co-authors' institutions, hotspots and burst terms, and the highly co-cited papers. The results show the research hotspots in this field are concentrated on keywords such as "level set method", "sensitivity analysis", "homogenization", "genetic algorithm", etc. Regarding the research frontier, "moving morphable component (MMC)", "additive manufacturing (AM)" and "deep learning" are hot topics. In addition, Y. Sui, Z. Kang and O. Sigmund, etc. have high publications. M. Bendsøe and O. Sigmund have high citations. Dalian University of Technology, Technical University of Denmark, etc. are prominent institutions. Moreover, China accounts for more than 34% in the terms of original WOS literatures following by the USA and Australia. This paper could identify structural topology optimization development patterns for the scholars concerned with this field, especially novices, to quickly focus and track the research priorities. [ABSTRACT FROM AUTHOR]

Structural topology optimization has gained widespread attention due to more possibilities of innovative structural design. The current research focus/hotspots, application areas, main research scholars, institutions and the countries involved in structural topology optimization are visually presented through clustering and visual analysis based on CiteSpace. The four metric dimensions of the literatures in this paper are as follows: annual quantity of papers and core countries, core authors and co-authors' institutions, hotspots and burst terms, and the highly co-cited papers. The results show the research hotspots in this field are concentrated on keywords such as "level set method", "sensitivity analysis", "homogenization", "genetic algorithm", etc. Regarding the research frontier, "moving morphable component (MMC)", "additive manufacturing (AM)" and "deep learning" are hot topics. In addition, Y. Sui, Z. Kang and O. Sigmund, etc. have high publications. M. Bendsøe and O. Sigmund have high citations. Dalian University of Technology, Technical University of Denmark, etc. are prominent institutions. Moreover, China accounts for more than 34% in the terms of original WOS literatures following by the USA and Australia. This paper could identify structural topology optimization development patterns for the scholars concerned with this field, especially novices, to quickly focus and track the research priorities. [ABSTRACT FROM AUTHOR]

Recent experimental study shows that the pre-lithiated MoS2 monolayer exhibits an enhanced electrochemical performance, coulombic efficiency of which is 26% higher than the pristine MoS2 based anode. The underlying mechanism of such significant enhancement, however, has not yet been addressed. By means of density functional theory (DFT) calculations, we systematically investigated the adsorption and diffusion behavior of lithium (Li) atoms on the MS2 (M = Mo, W, V) monolayers. On the pre-lithiated MS2 monolayers, the adsorption energy of extra Li ions are not significantly changed, implying the feasibility of multilayer adsorption. Of importance, the Li diffusion barriers on pre-lithiated MS2 are negligibly small because of the charge accumulation between the diffusing Li ions and the pre-lithiating Li layer. Correspondingly, we report that the pre-lithiation should be a general treatment which can be employed on many transition-metal di-chalcogenides to improve their storage capacities and charge-discharge performance in Li ion batteries. In addition, we propose that the pre-lithiated VS2 may serve as an outstanding anode material in LIBs. [ABSTRACT FROM AUTHOR]

Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H2O2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H2O2-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX's cardioprotection effect. [ABSTRACT FROM AUTHOR]

To investigate the ratio of mitochondrial DNA to genomic DNA (mt/gDNA) in embryo culture medium as a possible predictor for embryonic development and pregnancy outcome, we collected a total of 93 embryo biopsy specimens from 52 women at the corresponding Day 3 (D3) and Day 5 (D5) embryo culture medium of in vitro fertilization. With the multiple annealing and looping-based amplification cycles method of next-generation sequencing for whole genome amplification, we examined the karyotype of the biopsy samples and the mt/gDNA ratio in the culture medium. Results showed that the ratio of mt/gDNA had an upward trend with decreasing trophectoderm levels with no significant difference. At the same time, from D3 to D5, the mt/gDNA ratio in the medium of embryos that failed to become blastocysts showed an upward trend, and the mt/gDNA ratio of medium from embryos that reached blastulation with successful pregnancy showed a decreasing trend, but the differences were not statistically significant. We conclude that there is a certain correlation between mt/gDNA ratio and early embryonic development, but it does not reach a level that can be used as a clinical predictor. [ABSTRACT FROM AUTHOR]

Prolonged ischemia can result in apoptotic death of vascular endothelial cells and lead to ischemic vascular diseases including vascular dementia, arteriosclerosis and brain oedema. Finding protective strategies to prevent this is therefore an urgent mission. Recent studies have shown that dysregulation of microRNAs (miRNAs) can lead to imbalance of Bcl-2 family proteins and mitochondrial dysfunction, leading to further damage of vascular cells under ischemic conditions. However, whether miRNAs can be used as a drug target for treating vascular diseases is not fully understood. In this study, we observed that the natural product 2,4,5-trihydroxybenzaldehyde (TDB) could effectively inhibit vascular cell apoptosis following oxygen-glucose deprivation/reperfusion (OGD/R) by maintaining mitochondrial membrane potential (MMP) and suppressing activation of the mitochondria-dependent caspase-9/3 apoptosis pathway. Furthermore, we identified miR-34a, a crucial negative regulator of Bcl-2, as a target for the protective effect of TDB on vascular cells. TDB-induced suppression of miR-34a resulted in a significant upregulation of Bcl-2 protein, MMP maintenance, and the survival of vascular cells following OGD/R. Our findings suggest that targeting miR-34a with the natural product TDB may provide a novel strategy for the treatment of ischemic vascular injuries, and demonstrate the therapeutic potential in targeting miRNAs using appropriate small molecules. [ABSTRACT FROM AUTHOR]

In this report, a facile and effective one-pot oxidation-assisted dealloying protocol has been developed to massively synthesize monolithic core-shell architectured nanoporous copper@cuprous oxide nanonetworks (C-S NPC@Cu2O NNs) by chemical dealloying of melt-spun Al 37 at.% Cu alloy in an oxygen-rich alkaline solution at room temperature, which possesses superior photocatalytic activity towards photodegradation of methyl orange (MO). The experimental results show that the as-prepared nanocomposite exhibits an open, bicontinuous interpenetrating ligament-pore structure with length scales of 20 ± 5 nm, in which the ligaments comprising Cu and Cu2O are typical of core-shell architecture with uniform shell thickness of ca. 3.5 nm. The photodegradation experiments of C-S NPC@Cu2O NNs show their superior photocatalytic activities for the MO degradation under visible light irradiation with degradation rate as high as 6.67 mg min−1 gcat−1, which is a diffusion-controlled kinetic process in essence in light of the good linear correlation between photodegradation ratio and square root of irradiation time. The excellent photocatalytic activity can be ascribed to the synergistic effects between unique core-shell architecture and 3D nanoporous network with high specific surface area and fast mass transfer channel, indicating that the C-S NPC@Cu2O NNs will be a promising candidate for photocatalysts of MO degradation. [ABSTRACT FROM AUTHOR]

Osteoporosis, characterized by bone mass reduction and increased fractures, has become a global health problem that seriously affects the health of people, especially postmenopausal women; however, the current pathogenesis of postmenopausal osteoporosis (PMOP) has not been thoroughly elucidated to date. In this study, bilateral ovariectomy was performed to establish an OVX mouse model of osteoporosis. UPLC-Q-TOF-MS-based lipidomics in combination with metabolomics were used to analyze the femur tissue of osteoporosis mice. We found that 11 polar metabolites and 93 lipid metabolites were significantly changed and were involved in amino acid metabolism, nucleotide metabolism and lipid metabolism. Among the lipids, fatty acyls, glycerolipids, glycerophospholipids, sphingolipids and sterols showed robust changes. These results revealed that several metabolic disorders caused by changes in the hormone levels in OVX, especially disordered lipid metabolism, are closely related to the imbalance between bone resorption and formation and may underlie the development of PMOP. The data generated via lipidomics and metabolomics presented in this study shows good applicability and wide coverage in the construction of the metabolic profile of bone tissue. Therefore, this approach may provide the pathway focusing and data support at the metabolite level for the in-depth mechanism of PMOP. [ABSTRACT FROM AUTHOR]

To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples. [ABSTRACT FROM AUTHOR]

Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is refractory to chemotherapies, necessitating novel effective agents. The lysosome inhibitor Bafilomycin A1 (BafA1) at high concentrations displays cytotoxicity in a variety of cancers. Here we show that BafA1 at nanomolar concentrations suppresses HCC cell growth in both 2 dimensional (2D) and 3D cultures. BafA1 induced cell cycle arrest in the G1 phase and triggered Cyclin D1 turnover in HCC cells in a dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) dependent manner. Notably, BafA1 induced caspase-independent cell death in HCC cells by impairing autophagy flux as demonstrated by elevated LC3 conversion and p62/SQSTM1 levels. Moreover, genetic ablation of LC3 significantly attenuated BafA1-induced cytotoxicity of HCC cells. We further demonstrate that pharmacological down-regulation or genetic depletion of p38 MAPK decreased BafA1-induced cell death via abolishment of BafA1-induced upregulation of Puma. Notably, knockdown of Puma impaired BafA1-induced HCC cell death, and overexpression of Puma enhanced BafA1-mediated HCC cell death, suggesting a role for Puma in BafA1-mediated cytotoxicity. Interestingly, pharmacological inhibition of JNK with SP600125 enhanced BafA1-mediated cytotoxicity both in vitro and in xenografts derived from HCC cells. Taken together, our data suggest that BafA1 may offer potential as an effective therapy for HCC. [ABSTRACT FROM AUTHOR]

TNF receptor-associated factor 6 (TRAF6) is a key hub protein involved in Toll-like receptor-dependent inflammatory signaling pathway, and it recruits additional proteins to form multiprotein complexes capable of activating downstream NF-κB inflammatory signaling pathway. Ubiquitin-proteasome system (UPS) plays a crucial role in various protein degradations, such as TRAF6, leading to inhibitory effects on inflammatory response and immunologic function. However, whether ubiquitination-dependent TRAF6 degradation can be used as a novel anti-inflammatory drug target still remains to be explored. FMHM, a bioactive natural small molecule compound extracted from Chinese herbal medicine Radix Polygalae, suppressed acute inflammatory response by targeting ubiquitin protein and inducing UPS-dependent TRAF6 degradation mechanism. It was found that FMHM targeted ubiquitin protein via Lys48 site directly induced Lys48 residue-linked polyubiquitination. This promoted Lys48 residue-linked polyubiquitin chain formation on TRAF6, resulting in increased TRAF6 degradation via UPS and inactivation of downstream NF-κB inflammatory pathway. Consequently, FMHM down-regulated inflammatory mediator levels in circulation, protected multiple organs against inflammatory injury in vivo, and prolong the survival of endotoxemia mouse models. Therefore, FMHM can serve as a novel lead compound for the development of TRAF6 scavenging agent via ubiquitination-dependent mode, which represents a promising strategy for treating inflammatory diseases. [ABSTRACT FROM AUTHOR]

We have devised a novel amplification strategy based on isothermal strand-displacement polymerization reaction, which was termed multiple cross displacement amplification (MCDA). The approach employed a set of ten specially designed primers spanning ten distinct regions of target sequence and was preceded at a constant temperature (61-65 °C). At the assay temperature, the double-stranded DNAs were at dynamic reaction environment of primer-template hybrid, thus the high concentration of primers annealed to the template strands without a denaturing step to initiate the synthesis. For the subsequent isothermal amplification step, a series of primer binding and extension events yielded several single-stranded DNAs and single-stranded single stem-loop DNA structures. Then, these DNA products enabled the strand-displacement reaction to enter into the exponential amplification. Three mainstream methods, including colorimetric indicators, agarose gel electrophoresis and real-time turbidity, were selected for monitoring the MCDA reaction. Moreover, the practical application of the MCDA assay was successfully evaluated by detecting the target pathogen nucleic acid in pork samples, which offered advantages on quick results, modest equipment requirements, easiness in operation, and high specificity and sensitivity. Here we expounded the basic MCDA mechanism and also provided details on an alternative (Single-MCDA assay, S-MCDA) to MCDA technique. [ABSTRACT FROM AUTHOR]