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Introduction: Recent research on the gut deepens people's understanding of the role of gut microbe-metabolites in longevity. However, most of the longevity population is female, and the gut microbe-metabolites associated with longevity in women remain unknown. Here, we hypothesize that the gut microbe-metabolite levels differed between the longevity women (LW, age ≥90) and the elderly women (EW, 60 < age <90). Methods: We performed a cross-sectional study of 22 women in Guangxi longevity areas. 16S rRNA full-length sequencing, bioinformatic analysis, and nuclear magnetic resonance hydrogen spectra were determined to analyze the gut microbiota, microbial pathways, and fecal metabolites. We evaluated significant differences and relationships in gut microbe-metabolites and microbial pathways using the Mann-Whitney test and Spearman correlation, respectively. Results: The EW experienced gut dysbiosis characterized by a higher Firmicutes/Bacteroidetes (F/B) value. The LW showed a higher abundance of Bacteroides and Alistipes, which might support health maintenance. Moreover, LW enriched alanine, aspartate, and glutamate metabolism, histidine metabolism, and pyruvate metabolism, leading to major changes in histidine, fumaric acid, acetate, valine, and aspartate. Interestingly, the most valuable metabolic pathway based on differential fecal metabolites confirmed the KEGG microbial pathway "alanine, aspartate, and glutamate metabolism" enriched in LW. Impressively, Bacteroides and Alistipes were positively correlated with alanine, aspartate, and glutamate metabolism, thus improving the level of aspartate, which could be a particular pathway related to longevity. Conclusion: The enriched gut genus and microbial pathways in LW showed a significant correlation, which might mediate the production of metabolites related to longevity. [ABSTRACT FROM AUTHOR]

BACKGROUND: To fully investigate the effect of different stabilization methods on WBG in the same environment, we studied the effect of microwaving, baking, and extrusion on the nutritional, physicochemical, and processability properties of WBG and whole wheat bran‐germ noodle (WBGN). Principal component analysis was used to comprehensively evaluate the qualities of WBG and WBGN. Machine learning‐based research was conducted to predict the quality of WBGN based on the features of WBG. RESULTS: The results showed that three methods improved antioxidant ability, bound flavonoids, bound and total phenolics, and the processing properties in WBG (P < 0.05). Extruded‐WBG showed a lower polyphenol oxidase activity, lipase activity (35.02 ± 2.02 U and 20.29 ± 0.47 mg g−1) and particle size (54.08 ± 0.38 μm), and higher water hold capacity (2.60 ± 0.68%) and bound phenolic levels. The enhanced quantity of bound polyphenols had a major role in the increased antioxidant potential of WBGN. Extruded‐WBGN showed higher antioxidant ability for 2,2‐diphenyl‐1‐picrylhydrazyl (171.28 ± 3.16 μmol Trolox eq kg−1). The extruded‐WBGN had high concentrations of WBG aroma compounds, and low contents of bitterness and raw bran‐germ flavor compounds. Next, the enzymatic activity, powder properties, color, and antioxidant capacity of WBG were further utilized to predict the polyphenolic, flavonoids, flavor compounds, and antioxidant capacities of WBGN, where the R2 value of the model exceeded 0.90. The best comprehensive quality modification method of the WBG and WBGN was extrusion, followed by baking and microwaving. CONCLUSION: The present study shows that extrusion is a promising way to improve WBG into a nutritious and flavorful cereal food ingredient. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

As a traditional Chinese medicine, Eucommia ulmoides Oliver (E. ulmoides Oliv.) is an important medicinal plant, and its barks, male flowers, leaves, and fruits have high value of utilization. The seed meal of E. ulmoides Oliv. is the waste residue produced after oil extraction from seeds of E. ulmoides Oliv. Though the seed meal of E. ulmoides Oliv. is an ideal feed additive, its medicinal value is far from being developed and utilized. We identified six natural iridoid compounds from the seed meal of E. ulmoides Oliv., namely geniposidic acid (GPA), scyphiphin D (SD), ulmoidoside A (UA), ulmoidoside B (UB), ulmoidoside C (UC), and ulmoidoside D (UD). Six natural iridoid compounds were validated to have anti-inflammatory activities. Hence, six compounds were quantified at the optimum extracting conditions in the seed meal of E. ulmoides Oliv. by an established ultra-performance liquid chromatography (UPLC) method. Some interesting conversion phenomena of six tested compounds were uncovered by a systematic study of stability performed under different temperatures and pH levels. GPA was certified to be stable. SD, UA, and UC were only hydrolyzed under strong alkaline solution. UB and UD were affected by high temperature, alkaline, and strong acid conditions. Our findings reveal the active compounds and explore the quantitative analysis of the tested compounds, contributing to rational utilization for the seeds residues of E. ulmoides Oliv. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the effects of fucoidan (FU) and ferulic acid (FA) on the pasting, thermal, rheological, microstructural and moisture migration properties of potato starch (PS) gels. Pasting results showed that the presence of FU and FA significantly enhanced the thermal stability and resistance to breakdown, and inhibited the stickiness of starch, with the ternary system (PS-FU-FA) showing the best performance. Thermodynamic results indicated that the PS-FU-FA ternary system markedly reduced the retrogradation rate, with FA counteracting the aging phenomenon induced by FU. Rheological tests revealed that all gel systems exhibited weak gel and pseudoplastic fluid behaviors. FA increased the elasticity of PS gels, while FU and FU-FA reduced the viscoelasticity and thickening coefficient of PS, and improved its resistance to shear thinning. Scanning electron microscopy, infrared spectroscopy and low-field nuclear magnetic resonance results suggested that the changes in the above results were due to the interactions among FU, FA and PS, which increased the short-range order structure, and made the microstructure more uniform, compact and continuous, unfavorable for moisture movement, with better water-holding capacity and thermal stability. This study confirmed that the addition of FU and FA had positive effects on the gel properties of PS, providing new insights for the design strategy of starch-based foods, and promoting the practical application of FU, FA and PS in food industry. [Display omitted] • PS-FU-FA ternary system significantly retarded the aging process of PS gel. • PS-FU-FA gels displayed good pasting properties. • All gel systems exhibit weak gel and pseudoplastic fluid behaviors. • The microstructure of the PS-FU-FA gels was homogeneous and thick. • Water migration in PS gels was hampered by the presence of FU and FA. [ABSTRACT FROM AUTHOR]

Oxidized low-density lipoprotein (oxLDL)-induced endothelium injury promotes the development of atherosclerosis. It has been reported that homoplantaginin, a flavonoid glycoside from the traditional Chinese medicine Salvia plebeia R. Br., protected vascular endothelial cells by inhibiting inflammation. However, it is undetermined whether homoplantaginin affects atherosclerosis. In this study, we evaluated the effect of homoplantaginin and its derivative dihydrohomoplantagin on oxLDL-induced endothelial cell injury and atherosclerosis in apoE-/- mice. Our results showedthat both dihydrohomoplantagin and homoplantaginin inhibited apoptosis and the increased level of ICAM-1 and VCAM-1 in oxLDL-stimulated HUVECs and the plaque endothelium of apoE-/- mice. Additionally, both of them restricted atherosclerosis development of apoE-/- mice. Mechanistic studies showed that oxLDL-induced the increase in ROS production, phosphorylation of ERK and nuclear translocation of NF-κB in HUVECs was significantly inhibited by the compounds. Meanwhile, these two compounds promoted Nrf2 nuclear translocation and increased the anti-oxidation downstream HO-1 protein level in HUVECs and plaque endothelium. Notably, knockdown of Nrf2 by siRNA abolished the cell protective effects of compounds and antagonized the inhibition effects of them on ROS production and NF-κB activation in oxLDL-stimulated HUVECs. Collectively, dihydrohomoplantagin and homoplantaginin protected VECs by activating Nrf2 and thus inhibited atherosclerosis in apoE-/- mice. [ABSTRACT FROM AUTHOR]

Rapid characterization of chemical analogues in potentially toxic complex matrix was essential for prevention of accidental poisoning. On the basis of the fragment ions possessed not only the same retention times (RT) but the same drift times (DT) on liquid chromatography-ion mobility-mass spectrometry (LC-IM-MS), an alternating frames (AF)-data independent acquisition (DIA) was utilized for simultaneous detection and rapid match of precursor/product ions with a fast switch of low/high collision energy (CE). A diagnostic ions guided 2D-locating strategy was developed for identification of chemical analogues in potentially toxic herbal medicines using LC-IM-MS. Firstly, the 2D-locations (RT, DT) of diagnostic ions were screened from high-fragment IM-MS frames according to their m/z. Then, the correlated precursor ions were extracted from the complex background interference in low-fragment IM-MS frames based on diagnostic ions' 2D-locations. Finally, the remained ions were characterized using double-bond equivalent analysis combined with MS/MS fragment interpretation. Totally, 236 diterpene alkaloids including eight compounds with potential new esterification types were characterized in processed lateral roots of Aconitum carmichaelii Debx. Moreover, the LC-IM-MS distribution regularities of diterpene alkaloids with various chemical structure types were further investigated and discussed. This study presented an innovative idea for revealing the chemical basis related to the toxicities of potentially poisonous herbal medicines to ensure the medication safety. [ABSTRACT FROM AUTHOR]

Only problems that cannot be solved without representational changes can be regarded as pure insight problems; others are classified as pseudo-insight problems. Existing studies using neuroimaging have not yet distinguished between pure insight and pseudo-insight problems. This study is the first to investigate the brain mechanism of representational change via the remote associates test. Based on the homonymy of Chinese characters, we developed two sets of Chinese remote associates tests (CRATs). By comparing the brain activity of 30 adults during pure and pseudo-insight problem solving, we analysed the commonality and uniqueness of brain activation while solving these two insight problems. The results show that these two types of insight problem solving share the same brain activation area (i.e., the ventral precuneus and thalamus) and different operating areas. This study enhances our understanding of how representational change generates insight. [ABSTRACT FROM AUTHOR]

Past research found that similar appreciation for humor exists between spouses, but it is not certain whether this similarity between spouses also exists in kindhearted or malicious humor. The present study investigated the similarity of Taiwanese married couples' humor styles. Participants included 239 couples (mean age = 42.9 years) who had been married to each other for at least 10 years. We used a traditional Chinese edition of the Humor Styles Questionnaire to measure the humor style and clustered participants' humor styles in order to examine the similarity between spouses. The results show that husbands have higher tendencies toward aggressive (Cohen's d = 0.29, p <.01) and self-defeating (Cohen's d = 0.35, p <.01) humor styles than wives. Results from multilevel modeling indicate that spouses' aggressive (p <.001, confidence interval =.17,.41) and self-defeating (p <.01, confidence interval =.05,.30) humor styles acting as a valid predictor to the other spouses' negative humor styles. Furthermore, the results show that personal humor styles could be categorized into four clusters: positive humor endorsers, negative humor endorsers, general humor endorsers, and humor deniers. According to the clusters within spouse pairs, results show that similarities in humor styles exist between spouses (χ2 = 16.73, p =.01). The current study finds that most couples have similar humor styles and that a high proportion of married couples share the same humor clusters. [ABSTRACT FROM AUTHOR]

Although curcumin possesses anti-atherogenic and anti-inflammatory properties, its application is limited because of its low aqueous solubility and poor oral bioavailability. Recently, our group synthesized a novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly(ε-caprolactone) copolymer nanoparticle loading curcumin (Cur-NPs) which could improve solubility and release property of curcumin. In the present study, we further evaluated its anti-atherosclerotic effect in apolipoprotein E−/− mice. Our results demonstrated that the Cur-NPs significantly decreased atherosclerotic lesion areas and were more effective in stabilizing vulnerable plaques compared with free curcumin. The anti-atherosclerotic mechanisms of Cur-NPs include decreasing the number of introplaque microvessels, inhibiting the matrix metalloproteinase 2 and 9 activity, reducing the inflammatory response and regulating lipoprotein cholesterol metabolism more effectively compared with free curcumin. Furthermore, Cur-NPs could increase the amount of curcumin in the thoracic aorta and no significant toxicity was observed in the blood biochemical parameters in Cur-NPs-treated groups. Overall, our findings suggested that Cur-NPs could be a stabilized aqueous formulation for application with improved curcumin activity, which could be a potential treatment strategy for arteriosclerosis in the future. [ABSTRACT FROM AUTHOR]

Epimedium brevicornu Maxim has been used as a traditional herbal drug in China. In this study, the anti-inflammatory effects of E. brevicornu Maxim ethanol extract (EBME) were investigated in RAW264.7 macrophages and mice challenged with lipopolysaccharide (LPS). Results showed that EBME attenuated inflammation by decreasing the production of several proinflammatory mediators, such as nitric oxide (NO), prostaglandin (PG) E2, inducible nitric oxide synthase, and cyclooxygenase-2, in LPS-stimulated RAW264.7 macrophages. EBME increased the expression of heme oxygenase-1 (HO-1) and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2. The inhibitory effects of EBME on LPS-stimulated NO and PGE2 expression were partially reversed by HO-1 inhibitor. EBME also elicited an anti-inflammatory effect by inhibiting the production of tumor necrosis factor- α , interleukin (IL)-1 β , and IL-6 in LPS-induced peritonitis. Therefore, EBME exhibited anti-inflammatory effects in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Small-molecule inhibitors that block the Keap1-Nrf2 protein-protein interactions are being intensely pursued as a new therapeutic strategy for oxidative stress-related diseases, such as cancer, diabetes, Alzheimer's disease, arteriosclerosis, inflammation and myocarditis. However, there are not enough studies on antioxidant treatments using small molecules in myocarditis. We herein provided a series of novel hydronaphthoquinones as the Keap1-Nrf2 interaction inhibitors targeting LPS-induced myocarditis both in vitro and in vivo . These compounds were designed through an in-silico fragment growing approach based on our previous reported compound, S47 ( 1 ). The new compounds were predicted to form additional hydrogen bonds with the S363 residue, leading to higher inhibitory activity. Among these new derivatives, compounds S01 and S05 emerged as inhibitors with significant biochemical potency, as determined by fluorescent anisotropy assay and confirmed by surface plasmon resonance (SPR) and differential scanning fluorimetry (DSF) assays. These inhibitors can dose-dependently protect the H9c2 cardiac cells against LPS-induced injury (100% at 2 μM and 4 μM) and effectively prolong survival or save the life of LPS-injured mice. Mechanistic studies showed that these inhibitors could release Nrf2 in H9c2 cells and LPS-inflammatory mouse models and translocate into the nucleus in a dose-response manner, which significantly increased the downstream genes (HO-1, NQO-1) and the pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), while ROS production dramatically decreased. Their protective effects and the mechanism of action were further confirmed by siNrf2 transfected experiment. Collectively, the novel hydronaphthoquinones can be used as promising lead compounds for the study of Keap1-Nrf2 protein-protein interactions and further anti-myocarditis drug development. [ABSTRACT FROM AUTHOR]

Trace analysis of chemical analogues was always a hot topic and attracted the researchers' attentions. In this study, a database/multi-step filtering strategy was developed by using HPLC-Chip-MS system for comprehensive characterization of monacolin analogues in monascus -fermented rice product (MFRP). This strategy mainly included three steps, including chemical profile of MFRP by HPLC-Chip-MS, establishment of monacolin analogue database, multi-step filtering of monacolins based on modified mass defect filtering. All target compounds showed the symmetrical peak shapes and high MS response by using nanoflow HPLC-Chip-MS. According to the previous literature and experimental MS data, a database including 720 monacolin analogues was established. The original 522 ions in MFRP were automatically extracted by molecular feature extraction function. And then, through rectangular mass defect filtering and analogues distribution area filtering, 298 ions were further excluded. Finally, a total of 84 monacolins including 16 new compounds were unambiguously identified or tentatively characterized based on MS/MS information. In comparison with conventional mass defect filtering method, the proposed method was accurately able to exclude false positive results. The 438 false positive results were excluded in our study, while only 250 ones would be filtered out by using conventional method. This study provided a sensitive and powerful method for rapidly characterization of trace chemicals in complex matrix. [ABSTRACT FROM AUTHOR]

Spin-wave propagation in periodic magnetization-modulated cylindrical nanowires is studied by micromagnetic simulation. Spin wave scattering at the interface of two magnetization segments causes a spin-wave band structure, which can be effectively tuned by changing either the magnetization modulation level or the period of the cylindrical nanowire magnonic crystal. The bandgap width is oscillating with either the period or magnetization modulation due to the oscillating variation of the spin wave transmission coefficient through the interface of the two magnetization segments. Analytical calculation based on band theory is used to account for the micromagnetic simulation results. [ABSTRACT FROM AUTHOR]

Yinxing Mihuan Oral Solution (YMOS) has been widely applied for the treatment of coronary heart disease, angina pectoris, and cerebral ischemic disease in clinical practice. Nonetheless, the limited basic researches on quality analysis of YMOS remain a critical bottleneck that needs to be enhanced for better clinical applications. In this study, a total of 67 chemical components, including flavonoids, terpene lactones, nucleosides, etc., were tentatively characterized by ultra-high performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry, among which 34 compounds were further identified by comparison with reference substances. By adopting a methodologically validated method, we discovered that the quantitative estimate of multi-compounds in 22 batches of YMOS showed lot-to-lot consistency, and the additives in YMOS also met the corresponding regulations. Furthermore, five flavonol glycosides whose content presented a downward trend in the expired YMOS were focused. A systematic research on stability test focusing on the five targeted flavonol glycosides was performed under different temperatures and pH levels. It was found that ortho -diphenolic hydroxyl group on B-ring and the type of saccharide connected to 3-hydroxyl on C-ring play a pivotal role in the stability of the tested compounds. Subsequently, as the important compounds, ginkgolides A, B, and C in YMOS were simultaneously quantified with ultra performance liquid chromatography coupled with triple quadrupole mass spectrometry. In brief, this study performs a reliable chemical identification and provides a rapid and feasible method for the quality evaluation, which contributes to the in-depth investigation and safe application of YMOS for clinical uses. [Display omitted] • Chemical compounds in YMOS were globally identified by UHPLC-Q-Orbitrap-MS. • The content of bioactive compounds and additives in YMOS was evaluated by UPLC-PDA. • The flavonol glycosides presented significant downward trend in the expired YMOS. • The stability of five flavonol glycosides was investigated. [ABSTRACT FROM AUTHOR]

A wooden historic building located in Tibet, China, experienced structural damage when subjected to tourists visit. This kind of ancient building attends to too many visitors every day because heritage sites never fail to attract tourists. There should be a balance between accepting the visitors and the protection of historic buildings considering the importance of the cultural relics. In this paper, the singular spectrum analysis (SSA) is used for forecasting the number of tourist for the building management to exercise maintenance measures to the structure. The analyzed results can be used to control the tourist flow to avoid excessive pedestrian loading on the structure. The relationship between the measured acceleration from the structure and the tourist number is firstly studied. The root-mean-square (RMS) value of the measured acceleration in the passage route of the tourist is selected for forecasting future tourist number. The forecasting results from different methods are compared. The SSA is found slightly outperforms the autoregressive integrated moving average model (ARIMA), the X-11-ARIMA model and the cubic spline extrapolation in terms of the RMS error, mean absolute error and mean absolute percentage error for long-term prediction, whereas the opposite is observed for short-term forecasting. [ABSTRACT FROM AUTHOR]

Qi-Fu-Yin (QFY), a classical traditional Chinese medicine formula, is proven to have significant neuroprotective effects by modern pharmacological studies. However, the chemical constituents of QFY have not been fully explored. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF MS) was developed for comprehensive analysis of chemical constituents in QFY. By using characteristic ions and fragmentation rules, a reliable identification of 156 compounds was described here, including 69 triterpene saponins, 23 oligosaccharide esters, 22 flavanoids, 9 alkaloids, 9 phenolic acids, 8 phthalides, 7 phenylethanoid glycosides, 3 xanthones, 3 sesquiterpene lactones, 2 ionones and 1 iridoid glycoside. Twenty-six major compounds were then determined in a single run by UHPLC coupled with triple quadrupole tandem mass spectrometry (QQQ MS) with fast positive/negative polarity switching. It allows for the acquisition of MS data in both ionization modes from a single run. The proposed method was then validated in terms of linearity, accuracy, precision and recovery. The overall recoveries for 26 analytes ranged from 91.35% to 109.58%, with RSDs ranging from 0.82% to 4.83%. In addition, the content of 26 analytes in QFY prepared by five batches of herbal materials was also analyzed. These results demonstrated that our present method was effective and reliable for comprehensive quality evaluation of QFY. Meanwhile, the study might provide the chemical evidence for revealing the material basis of its therapeutic effects. [ABSTRACT FROM AUTHOR]

• A liquid chromatography-ion mobility-mass spectrometry method was established. • A 2-step filtering strategy integrated CCS interval predicting and MDF was developed. • Power regression was used to generate the CCS interval with 99% confidence level. • Totally, 172 isoquinoline alkaloid analogues were identified in four herbal samples. • False positive rates of integrated 2-step filtering and common MDF were compared. Rapid identification of chemical analogues in herbal medicines using liquid chromatography-mass spectrometry was an efficient tool for discoveries of potentially active ingredients. Multi-dimensional combination of various separation technologies could significantly enhance the capacities for detection of trace components and discrimination of multiple isomers. In this study, an integrated two-step filtering strategy on liquid chromatography-ion mobility tandem with quadrupole-time-of-flight mass spectrometry (LC-IM-QTOF MS) was developed for identification of analogues in complex matrixes. The extracted raw data were preliminarily filtered by a collision-cross section (CCS) interval generated from power regression with confidence level at 99% for prediction of analogues. Then, the remained ions were further screened using a mass defect filtering (MDF) window based on m/z and decimal m/z of potential skeletons and substituents. By applying this strategy, 86, 102, 73, and 57 isoquinoline alkaloids were identified in herbal materials of Coptis chinensis Franch (CC), C. deltoidea C.Y.Cheng et Hsiao (CD), C. teeta Wall (CT), and Corydalis yanhusuo W.T.Wang (CY). The integrated two-step filtering presented higher efficiencies on exclusion of the background interference and reducing the false-positive rates than previously reported approaches. This study facilitated the application of LC-IM-MS on small molecular analysis and promoted the discoveries of bioactive components of herbal medicines for further pharmacological researches and quality control. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the effect of surface roughness on the electrical characteristics in amorphous indium–gallium–zinc oxide (a-IGZO) thin-film transistors (TFTs) fabricating high-κ Sm2O3 gate dielectrics, prepared under different annealing temperatures. The high-κ Sm2O3 a-IGZO TFT device annealed at 200°C exhibited better electrical characteristics, including a large field effect mobility of 6.25cm2/Vs, small threshold voltage of 0.79V, low subthreshold swing of 354mV/decade, and high I on/I off ratio of 3.1×107. These results are attributed to the formation of smooth surface at the oxide/channel interface. Furthermore, the reliability of a Sm2O3 a-IGZO TFT device can be improved by oxygen annealing at low temperature. [Copyright &y& Elsevier]

The tumor suppressor Adenomatous polyposis coli (APC) negatively regulates Wnt signaling through its activity in the destruction complex. APC binds directly to the main effector of the pathway, β-catenin (βcat, Drosophila Armadillo), and helps to target it for degradation. In vitro studies demonstrated that a nonphosphorylated 20-amino-acid repeat (20R) of APC binds to βcat through the N-terminal extended region of a 20R. When phosphorylated, the phospho-region of an APC 20R also binds βcat and the affinity is significantly increased. These distinct APC--βcat interactions suggest different models for the sequential steps of destruction complex activity. However, the in vivo role of 20R phosphorylation and extended region interactions has not been rigorously tested. Here we investigated the functional role of these molecular interactions by making targeted mutations in Drosophila melanogaster APC2 that disrupt phosphorylation and extended region interactions and deletion mutants missing the Armadillo binding repeats. We tested the ability of these mutants to regulate Wnt signaling in APC2 null and in APC2 APC1 double-null embryos. Overall, our in vivo data support the role of phosphorylation and extended region interactions in APC2's destruction complex function, but suggest that the extended region plays a more significant functional role. Furthermore, we show that the Drosophila 20Rs with homology to the vertebrate APC repeats that have the highest affinity for bcat are functionally dispensable, contrary to biochemical predictions. Finally, for some mutants, destruction complex function was dependent on APC1, suggesting that APC2 and APC1 may act cooperatively in the destruction complex. [ABSTRACT FROM AUTHOR]

Abstract: Lipopolysaccharide (LPS)-induced vascular endothelial cell (VEC) dysfunction is an important contributing factor in vascular diseases. Recently, we found that LPS impaired VEC by inducing autophagy. Our previous researches showed that a butyrolactone derivative, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) selectively protected VEC function. The objective of the present study is to investigate whether and how 3BDO inhibits LPS-induced VEC autophagic injury. Our results showed that LPS induced autophagy and led to increase of reactive oxygen species (ROS) and decrease of mitochondrial membrane potential (MMP) in Human umbilical vein vascular endothelial cells (HUVECs). Furthermore, LPS significantly increased p8 and p53 protein levels and the nuclear translocation of p53. All of these effects of LPS on HUVECs were strongly inhibited by 3BDO. Importantly, the ROS scavenger N-acetylcysteine (NAC) could inhibited LPS-induced autophagy and knockdown of p8 by RNA interference inhibited the autophagy, p53 protein level increase, the translocation of p53 into nuclei and the ROS level increase induced by LPS in HUVECs. The data suggested that 3BDO inhibited LPS-induced autophagy in HUVECs through inhibiting the ROS overproduction, the increase of p8 and p53 expression and the nuclear translocation of p53. Our findings provide a potential tool for understanding the mechanism underlying LPS-induced autophagy in HUVECs and open the door to a novel therapeutic drug for LPS-induced vascular diseases. [Copyright &y& Elsevier]

Photoactive enzymes have been proposed as promising catalysts in photocontrolled reversible addition–fragmentation chain transfer (RAFT) polymerization. However, only a few enzymes have the photoactive properties suitable for initiating RAFT polymerization. Herein, we synthesize nanozymes with uniform and well-defined nanostructures through coassembly of albumin and photosensitizer. The resulting nanozymes feature the absorption bands of the monomeric photosensitizer, facilitating efficient light capture and electron transfer, which lead to high conversion efficiencies in photocontrolled RAFT polymerization. Importantly, the nanozymes show good reusability in multiple rounds of polymerizations and precise controllability of activation and deactivation of the reactions. This work represents the first realization of photoactive nanozymes that can be used for photocontrolled RAFT polymerization and thus will conceivably promote the rational design and catalytic applications of functional nanozymes. [Display omitted] • Nanozymes were constructed by coassembly of albumin and photosensitizer. • The nanozymes show uniform and well-defined nanostructures. • The photosensitizer in the nanozymes is in a monomeric state. • The nanozymes show high conversion efficiencies in RAFT polymerization. • The nanozymes have good reusability and precise controllability in polymerization. [ABSTRACT FROM AUTHOR]

• A rapid, sensitive and selective UHPLC-MS/MS method was developed and validated. • Twenty components were quantified in rat plasma and brain orally administrated by JWQFY. • These results were further applied to pharmacokinetic and brain distribution studies. • Six compounds were considered as the potential effective components of JWQFY. A rapid ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-QqQ MS/MS) approach with high sensitivity and selectivity was developed for the quantification of twenty compounds, including 9 saponins, 8 flavonoids, 2 oligosaccharide esters and 1 phenolic acid, in rat plasma and brain, which was administrated intragastrically with Jia-Wei-Qi-Fu-Yin (JWQFY), Mass spectrometric detection was operated under multiple reaction monitoring (MRM) mode. All calibration curves possessed good linearity with correlation coefficients (r2) higher than 0.9916 in their respective linear ranges. For intra- and inter-day precision, all the relative standard deviations (RSDs) at different levels were less than 14.68 %. Based on the UHPLC-QqQ MS/MS quantitative results, pharmacokinetic study and brain distribution of multiple components in JWQFY was then successfully performed. As a result, constituents with discrepancy structures showed diverse pharmacokinetic and distribution characteristics. For instance, ferulic acid (phenolic acid), 3, 6′-disinapoyl sucrose and tenuifoliside A (oligosaccharide esters) showed short T max (< 10 min), whereas the T max of ginsenosides Rb 1 , Rb 2 and Rc (ppd-type terpenoid saponins) were much longer (> 4 h). Besides, ferulic acid, epimedin C, icariin, glycyrrhizin, ginsenoside Rb 1 and ginsenoside Rg 1 were considered as the potential effective ingredients of JWQFY because of their relatively high exposure to blood and brain. Our study would provide relevant information for discovery of pharmacodynamic ingredients, as well as further action mechanisms investigations of JWQFY. [ABSTRACT FROM AUTHOR]

A great deal of clinical research has sought to describe and suggest remedies for the client dropout phenomenon. However, few studies have addressed the equally pervasive, yet often ignored, non-engagement problem. An exploratory study was conducted to understand why many clients fail to engage in family therapy services after they have completed the initial intake. The results of the study suggest that therapist gender and experience level, clinic policies regarding videotaping sessions, family concerns, and changes in the presenting problem prior to the first session, had an impact on potential clients’ decision to engage in therapy. Implications and future research are discussed. [ABSTRACT FROM AUTHOR]

Large eddy simulation of rotating channel and ribbed channel flows with and without heat transfer is reported. The rotation axis is parallel to the spanwise direction of the parallel plate channel. An implicit finite-volume scheme was used to solve the preconditioned time-dependent filtered Navier–Stokes equations using a dynamic subgrid-scale model to account for the subgrid-scale effects. The distribution of mean velocity and mean temperature were influenced by system rotation, transforming from a symmetric profile into a non-symmetric profile. The shift of peak values was toward the stable side of the channel.Near the stable (leading) side, the turbulent intensities and heat transfer were suppressed, but turbulence was enhanced with increasing shear stress and turbulent kinetic energy near the unstable (trailing) side. [Copyright &y& Elsevier]

Objective: The Da Vinci Robot is the most advanced micro-control system in endoscopic surgical instruments and has gained a lot of valuable experience today. However, the technical feasibility and oncological safety of the robot over open surgery are still uncertain. This work is to systematically evaluate the efficacy of the unilateral axillary approach for robotic surgery compared to open surgery for differentiated thyroid carcinoma. Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were utilized to search for relevant literatures of robotic thyroid surgery using unilateral axillary approach compared to open thyroid surgery, and a meta-analysis was performed using RevMan software version 5.3. Statistical analysis was performed through Mantle-Haenszel and inverse variance methods. Results: Twelve studies with a total of 2660 patients were included in the meta-analysis. The results showed that compared with the open group, the robotic group had a longer total thyroidectomy time, shorter hospital stay, less intraoperative bleeding, more postoperative drainage, fewer retrieved central lymph nodes, and higher cosmetic satisfaction (all P < 0.05). In contrast, temporary and permanent laryngeal recurrent nerve injury, temporary and permanent hypoparathyroidism or hypocalcemia, brachial plexus nerve injury, number of retrieved central lymph nodes, number of retrieved lymph nodes in the lateral cervical region, number of lymph node metastases in the lateral cervical region, hematoma, seroma, lymphatic leak, stimulated thyroglobulin (sTg) and unstimulated thyroglobulin (uTg), and the number and recurrence rate of patients with sTg <1ng/ml were not statistically different between the two groups (P > 0.05). Conclusions: The unilateral axillary approach for robotic thyroid surgery may achieve outcomes similar to those of open surgery. Further validation is required in a prospective randomized controlled trial. [ABSTRACT FROM AUTHOR]

Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE−/− mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis. [Display omitted] • Endothelial NECC2 promotes the development of atherosclerosis. • NECC2 contributes to oxLDL-induced endothelial oxidative damage. • NECC2-induced Cav-1 phosphorylation via Tyk2 promotes oxLDL accumulation in VECs. • Compound YF-307 inhibits endothelial oxidative damage and atherosclerosis. [ABSTRACT FROM AUTHOR]

• A modified mass defect filtering strategy with four detailed steps was developed. • The strategy was applied to analysis procyanidins in grape seed extracts with IM-MS. • Collision cross-sections of 769 procyanidin ions were measured at single field. • The trendlines of procyanidin ions were predicted using multi-model regression. • The tendency of collision cross-sections with various factors was discussed. Polymers, widely existing in food or dietary materials, have been attracting researchers, facing challenges, and needing effective strategies on targeted characterization in complex matrixes. A modified data filtering strategy (including locating with drift time and m / z ranges, multiple mass defect filtering, validating MS information, and evaluating MS/MS spectra) was developed and applied for procyanidins in the grape seed extracts (GSE) using drift tube ion mobility-mass spectrometry. The procyanidin ions' trendlines were predicted by multi-model regression. Their collision cross-sections (CCSs) were calculated using single-field methods. Totally, 769 CCSs belonging to 686 procyanidins with polymer degrees at 1–15 were characterized. The exponent regression was the most reasonable model (r 2 ≥ 0.9379) to reveal the trendlines. The change tendency of CCSs with their polymer degrees, charge states, and linkage types were investigated. This study provided an innovative strategy for targeted characterization of polymers in complex matrixes. [ABSTRACT FROM AUTHOR]

Autophagy is a process in which cells degrade intracellular substances and play a variety of roles in cells, such as maintaining intracellular homeostasis, preventing cell overgrowth, and removing pathogens. It is highly conserved during the evolution of eukaryotic cells. So far, the study of autophagy is still a hot topic in the field of cytology. Ferroptosis is an iron‐dependent form of cell death, accompanied by the accumulation of reactive oxygen species and lipid peroxides. With the deepening of research, it has been found that ferroptosis, like autophagy, is involved in the occurrence and development of cardiovascular diseases. The relationship between autophagy and ferroptosis is complex, and the association between the two in cardiovascular disease remains to be clarified. This article reviews the mechanism of autophagy and ferroptosis and their correlation, and discusses the relationship between them in cardiovascular diseases, which is expected to provide new and important treatment strategies for cardiovascular diseases. Significance statement: Autophagy and ferroptosis are hot topics in the field of cell biochemistry, both of which are closely related to the occurrence and development of cardiovascular diseases. As the molecular mechanisms of autophagy and ferroptosis become more clear in cells, the two seem to intersect in some places, especially in related studies of cardiovascular diseases. If the interaction between autophagy and ferroptosis can be clarified, it will provide novel therapeutic strategies for alleviating related diseases. [ABSTRACT FROM AUTHOR]

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR‐T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR‐T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR‐T cell therapy, and considers future outlooks for research development. Significance statement: The necessity and importance of chimeric antigen receptor (CAR) T cells and their therapeutic efficiency in treating diseases other than cancer, mainly cardiovascular diseases, have emerged in recent years. However, there is still room for advancement in the current models of CAR‐T cell therapy. This paper highlights the evolution and roadblocks of CAR‐T technology at different levels, from technical concerns to clinical outcomes, in an attempt to improve the therapeutic efficiency of CAR‐T cell therapy in this area. [ABSTRACT FROM AUTHOR]

K-ras (Kirsten ras GTPase) mutations are oncogenic events frequently observed in many cancer types especially in pancreatic cancer. Although mitochondrial dysfunction has been associated with K-ras mutation, the molecular mechanisms by which K-ras impacts mitochondria and maintains metabolic homeostasis are not fully understood. In this study, we used two K-ras inducible cell systems, human pancreatic epithelial/ K-rasG12D (HPNE/K-rasG12D) and human embryonic kidney cells with tetracycline repressorT-Rex/K-rasG12V, to evaluate the role of oncogenic K-ras in regulating mitochondrial function. Among a panel of genes known to affect mitochondria, only the expression of OPA3 (optic atrophy protein 3) was consistently up-regulated by K-ras activation in both cell lines. Importantly, high expression of OPA3 was also observed in clinical pancreatic cancer tissues. Genetic knockdown of OPA3 caused a significant decrease of energy metabolism, manifested by a suppression of oxygen consumption rate (OCR) and a decrease in cellular ATP content, leading to inhibition of cell proliferation capacity and reduced expression of epithelial–mesenchymal transition (EMT) markers. Our study suggests that OPA3 may promote cellular energy metabolism and its up-regulation in K-ras-driven cancer is likely a mechanism to offset the negative impact of K-ras on mitochondria to maintain energy homeostasis. As such, OPA3 could be a potential target to kill cancer cells with K-ras mutations. [ABSTRACT FROM AUTHOR]

As a clinically effective traditional Chinese medicine injection (TCMI), Shuanghuanglian injection (SHLI) is widely used in the treatment of upper respiratory tract infection and pneumonia. However, the shortage of quality analysis is a limitation that remains to be improved in the clinical application of SHLI. In this study, taking advantage of ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC/Q-Orbitrap-MS), 31 chemical components (eight organic acids, eleven flavonoids, five iridoid glycosides, four phenylethanoid glycosides, and three lignans) in SHLI were characterized, among which 22 components were unambiguously identified by reference compounds. The brief prediction results of network pharmacology indicated that the 22 targeted components may have anti-inflammatory, antibacterial, antiviral, and immunomodulatory activities. Using multiwavelength switching method, the 22 targeted components were quantified by ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) after the methodological validation. Based on the successfully established method, the total content of 22 components in 20 batches of SHLIs was efficiently determined with a slight variation between 10.25 and 11.28 mg/mL, which accounted for 38.7% in total solid of SHLI. This study performed a reliable chemical identification and provided a rapid and effective method for quality analysis, which contributed to the in-depth investigation and application of SHLI. [ABSTRACT FROM AUTHOR]

• Fascaplysin, a natural angiogenesis inhibitor, activated vascular endothelial cell (VEC) autophagy. • Fascaplysin induced VEC autophagy via ROS and p8, an mTOR independent pathway. • Inhibition of VEC autophagy could enhance the cell death and the anti-angiogenesis activity of fascaplysin. Fascaplysin is a natural product isolated from marine sponges that exhibits broad anticancer activity. Previous studies revealed that fascaplysin-induced apoptosis and angiogenesis inhibition in vascular endothelial cells contributed to its anticancer activity. Accumulating evidence indicates that autophagy plays a significant role in mediating the function of vascular endothelial cells (VECs) and the response to cancer therapy. However, the effect of fascaplysin on VEC autophagy and the role of autophagy in fascaplysin-induced vascular endothelial cell apoptosis and angiogenesis inhibition are not clear. The present study found that fascaplysin induced autophagy in vascular endothelial cells. Suppression of autophagy using a pharmacological inhibitor (3-methyladenine) or RNA interference of an essential autophagy gene (ATG5) enhanced the cell death and anti-angiogenesis activity of fascaplysin. We further found that fascaplysin significantly increased p8 protein and reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential but had no effect on the mTOR pathway in VECs. Notably, the ROS scavenger N-acetylcysteine inhibited fascaplysin-induced autophagy and increased p8 protein level. Knockdown of p8 by using RNA interference inhibited the autophagy but increased the level of ROS in VECs. Taken together, these data indicated that fascaplysin activated autophagy as a cytoprotective response via ROS and p8 in VECs. Our findings provided important insight into the response of VECs to fascaplysin and may be useful for improving the anticancer efficacy of fascaplysin. [ABSTRACT FROM AUTHOR]

Descending serotonergic (5-HT) projections originating from the raphe nuclei form an important input to the spinal cord that control basic locomotion. The molecular signals that control this projection pattern are currently unknown. Here, we identify Semaphorin7A (Sema7A) as a critical cue that restricts serotonergic innervation in the spinal cord. Sema7A deficient mice show a marked increase in serotonergic fiber density in all layers of the spinal cord while the density of neurons expressing the corresponding 5-HTR2α receptor remains unchanged. These alterations appear to be successfully compensated as no obvious changes in rhythmic locomotion and skilled stepping are observed in adult mice. When the system is challenged with a spinal lesion, serotonergic innervation patterns in both Sema7A-deficient and -competent mice evolve over time with excessive innervation becoming most pronounced in the dorsal horn of Sema7A-deficient mice. These altered serotonergic innervation patterns correlate with diminished functional recovery that predominantly affects rhythmic locomotion. Our findings identify Sema7A as a critical regulator of serotonergic circuit formation in the injured spinal cord. [ABSTRACT FROM AUTHOR]

Ion mobility coupled with mass spectrometry (IM-MS), an emerging technology for analysis of complex matrix, has been facing challenges due to the complexities of chemical structures and original data, as well as low-efficiency and error-proneness of manual operations. In this study, we developed a structural similarity networking assisted collision cross-section prediction interval filtering (SSN-CCSPIF) strategy. We first carried out a structural similarity networking (SSN) based on Tanimoto similarities among Morgan fingerprints to classify the authentic compounds potentially existing in complex matrix. By performing automatic regressive prediction statistics on mass-to-charge ratios (m/z) and collision cross-sections (CCS) with a self-built Python software, we explored the IM-MS feature trendlines, established filtering intervals and filtered potential compounds for each SSN classification. Chemical structures of all filtered compounds were further characterized by interpreting their multidimensional IM-MS data. To evaluate the applicability of SSN-CCSPIF, we selected Ginkgo biloba extract and dripping pills. The SSN-CCSPIF subtracted more background interferences (43.24%∼43.92%) than other similar strategies with conventional ClassyFire criteria (10.71%∼12.13%) or without compound classification (35.73%∼36.63%). Totally, 229 compounds, including eight potential new compounds, were characterized. Among them, seven isomeric pairs were discriminated with the integration of IM-separation. Using SSN-CCSPIF, we can achieve high-efficient analysis of complex IM-MS data and comprehensive chemical profiling of complex matrix to reveal their material basis. [Display omitted] • Multi-molecules were classified by fingerprints-based structural similarity networking (SSN). • A Python software was built for IM-MS feature filtering by CCS prediction interval (CCSPIF). • Each classification of potential compounds was rapidly filtered from IM-MS data of GBE and GBDP. • Totally, 229 compounds were identified by performing SSN-CCSPIF on UHPLC-IM-QTOF MS. • Eight potential new compounds without previous reports were tentatively characterized. [ABSTRACT FROM AUTHOR]

Increasing evidence has confirmed that long non-coding RNAs (lncRNAs) serve critical roles in the development of a large number of human malignancies, including glioma. Several previously published studies have reported that the lncRNA retinal non-coding RNA3 (RNCR3; also termed LINC00599) exerts important roles in certain human malignancies; however, the precise biological role and underlying molecular mechanisms of RNCR3 in the development of glioma are yet to be fully elucidated. In the present study, it was revealed that the expression of RNCR3 was increased in glioma tissues compared with in corresponding adjacent normal tissues. Furthermore, increased levels of RNCR3 expression were associated with tumor progression and poor survival rates of patients with glioma. In addition, the U87 and U251 cell lines were selected to investigate the biological function and potential mechanisms of RNCR3 in glioma, and it was observed that RNCR3 knockdown led to an impairment of the proliferative and invasive abilities of cells; furthermore, G1 phase arrest was induced in glioma cells in vitro. Finally, the results of western blot analyses revealed that knockdown of RNCR3 led to a decrease in the expression levels of phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β), without any clear effect on the expression levels of total Akt and GSK-3β. Collectively, these results suggested that RNCR3 is able to regulate cell proliferation, the cell cycle and cell invasion in glioma, potentially via the Akt/GSK-3β signaling pathway. [ABSTRACT FROM AUTHOR]

Loss of estrogen receptor (ER) pathway activity promotes breast cancer progression, yet how this occurs remains poorly understood. Here, we show that serine starvation, a metabolic stress often found in breast cancer, represses estrogen receptor alpha (ERa) signaling by reprogramming glucose metabolism and epigenetics. Using isotope tracing and time-resolved metabolomic analyses, we demonstrate that serine is required to maintain glucose flux through glycolysis and the TCA cycle to support acetyl-CoA generation for histone acetylation. Consequently, limiting serine depletes histone H3 lysine 27 acetylation (H3K27ac), particularly at the promoter region of ER pathway genes including the gene encoding ERα, ESR1. Mechanistically, serine starvation impairs acetyl-CoA-dependent gene expression by inhibiting the entry of glycolytic carbon into the TCA cycle and down-regulating the mitochondrial citrate exporter SLC25A1, a critical enzyme in the production of nucleocytosolic acetyl-CoA from glucose. Consistent with this model, total H3K27ac and ERα expression are suppressed by SLC25A1 inhibition and restored by acetate, an alternate source of acetyl-CoA, in serine-free conditions. We thus uncover an unexpected role for serine in sustaining ER signaling through the regulation of acetyl-CoA metabolism. [ABSTRACT FROM AUTHOR]

It is a long‐standing challenge to exploit cellular uptake mechanisms to deliver desired cargo into cells, for example, specific drugs or gene editing techniques. This study introduces a bioinspired material approach where nanoparticles are presented at the ventral side of cells adhering to engineered extracellular matrices. The effect of matrix stiffness on cell adhesion and mechanics, as well as on particle internalization by clathrin‐mediated endocytosis (CME), is investigated for varying particle size and surface functionalization. The results presented here show that substrate stiffness affects both cell adhesion and particle internalization, with softer substrates promoting higher levels of particle uptake. However, the activation of the CME pathway, either mechanically by particle size or functionally by receptor binding, regulates the sensitivity of cellular particle uptake to matrix stiffness. Finally, adeno‐associated viruses as the leading platform for therapeutic gene delivery are used as model cargo to showcase the importance of considering multiple components when designing delivery systems. These findings indicate that particle uptake is a multifaceted process that can be improved by the appropriate combination of extracellular environment mechanics and cargo properties. [ABSTRACT FROM AUTHOR]

Malus toringoides (Rehd.) Hughes (Rosaceae) is used as a traditional folk medicine in the Tibet autonomous region of China to treat hypertension, hyperglycemia, and hyperlipidemia. However, few modern pharmacological data on the use of this plant against diabetic syndrome are available. In this study, we examined the vascular protection provided by a 70% ethanol extract of M. toringoides (EMT) in human umbilical vein endothelial cells (HUVECs) grown in high-glucose medium and in a high-fat diet/streptozotocin-induced rat diabetes model. EMT significantly suppressed the expression of cell adhesion molecules in both HUVECs and diabetic rats. EMT also inhibited activation of the CX3CL1/CX3CR1 axis and the nuclear factor kappa B (NF-κB) signaling pathway in vivo and in vitro. The results provide a significant information on the vasoprotective properties of M. toringoides that may contribute to the development and application of related herbal medicines. [ABSTRACT FROM AUTHOR]

Malus toringoides (Rehd.) Hughes (MT) leaves are traditionally used as a medicine for treating or preventing cardiovascular disease in Tibet. In addition to the effect of this medicinal plant on thrombosis, we tested its effect on dyslipidemia in a hypolipidemic rat model. A total of 60 healthy Sprague-Dawley rats were randomly divided into six groups, as follows: normal control, model control, simvastatin groups, and MT low-, medium-, and high-dose groups. The normal controls were fed with a normal diet, whereas all other groups were fed with a high-fat diet. After 6 weeks, the high-fat diet had induced hyperlipidemia in the rats, which were then orally administered with different doses of MT leaf extract (50, 100, and 200 mg/kg) for an additional 6 weeks. Serum levels of total cholesterol (TC), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-c and HDL-c, respectively), as well as the antioxidant capacity of glutathione peroxidase (GSHP-x), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured at the end of the study. MT significantly reduced serum TC, TG, and LDL-c and increased the HDL-c content in MT-treated rats compared with the model group. These changes were dose dependent. MT treatment also significantly elevated the activity of SOD and GSHP-x, and decreased the serum levels of MDA compared with untreated hyperlipidemic rats, thereby increasing serum antioxidant capacity. In addition, MT reduced liver steatosis in hyperlipidemic rats. Overall, MT exerts considerable hypolipidemic and antioxidant properties. [ABSTRACT FROM AUTHOR]

Regorafenib significantly prolongs overall survival in patients with metastatic colorectal cancer (mCRC), but the overall clinical efficacy of regorafenib remains quite limited. Combination chemotherapy is a potentially promising approach to enhance anticancer activity, overcome drug resistance, and improve disease-free and overall survival. The current study investigates the antitumor activity of regorafenib in combination with lapatinib in preclinical models of human CRC. Our results show improved antitumor efficacy when regorafenib is combined with lapatinib both in vitro and in vivo. Furthermore, pharmacokinetic analyses revealed that regorafenib and lapatinib do not influence on each plasma concentration. The finding that regorafenib in combination with lapatinib have synergistic activity warrants further clinical investigation of this beneficial combination as a potential treatment strategy for CRC patients. [ABSTRACT FROM AUTHOR]

Objective Femoral component overhang in total knee arthroplasty ( TKA) has been reported in previous studies. The purpose of this study was to evaluate the effect of femoral component flexion implantation on mediolateral bone-prosthetic fit in TKA. Methods Virtual prosthesis implantations were performed on computed tomographic models of 10 Chinese knees with femoral prostheses of the Advance Medial-Pivot knee system (MicroPort Orthopedics, Arlington, TN, USA), with the femoral component positioned at 0°, 3°, or 6° of flexion in the sagittal plane. For each degree of flexion implantation, the differences between the knee and femoral component models on the lateral and medial sides at trochlea (zone 1), anterior-distal condyle (zone 2), posterior-distal condyle (zone 3), and posterior condyle (zone 4) were measured. Positive difference values indicate component overhang, and negative difference values indicate component underhang. The values of component overhang (underhang) in each zone were statistically analyzed across the 3° of flexion implantation. Results With a greater degree of flexion implantation, overhang was reduced and even changed to underhang. With 0° of flexion implantation, an overhang exceeding 3 mm existed mainly on the medial side of zone 1 (5.81 mm) and the lateral side of zone 2 (3.39 mm). With 3° of flexion, overhang exceeding 3 mm was observed only on the medial side of zone 1 (3.10 mm), and underhang was observed only on the medial side of zone 4 (−0.32 mm). No overhang exceeding 3 mm was observed for 6° of flexion, while underhang was observed except on the lateral sides of zone 2 (1.32 mm) and zone 4 (1.10 mm) and on the medial side of zone 1 (1.54 mm). A significant difference in overhang values on the lateral and medial sides of zone 1 was observed between 0 and 6° of flexion ( P < 0.05). Conclusion The present study demonstrated that femoral component flexion implantation by 3° can reduce excessive overhang, although 3.10 mm of overhang remained at the medial side of zone 1. Conversely, 6° of flexion implantation can avoid 3 mm of overhang for any zone, but increases the risk of underhang. Slight flexion implantation may be an effective alternative technique to prevent excessive component overhang, especially in the trochlea and anterior region of the distal condyle, in Chinese patients with standard TKA prostheses. [ABSTRACT FROM AUTHOR]

The tumor suppressor Adenomatous polyposis coli (APC) has roles in both Wnt signaling and in actin and microtubule organization. Within the cell, APC proteins have been reported to localize in the cytoplasm, at the cell cortex and in the nucleus. How these localizations relate to the functions of the protein is an aspect of APC biology that is poorly understood. Using Drosophila S2 cells, we have dissected the structural and functional requirements for the cortical localization of Drosophila APC2. Here, we show that both the Armadillo repeats and a novel C-terminal domain are necessary for the cortical localization of APC2 in S2 cells and in the embryo, and that neither domain alone is sufficient for this localization. Furthermore, we show that the Armadillo repeats mediate self-association of APC2 molecules. To test the function of the cortical localization of APC2, we asked whether an APC2 protein deleted for the C-terminal localization domain could rescue APC mutant defects in Wnt signaling and actin organization in the Drosophila embryo. We show that although cortical localization is required for the APC2 function in organizing actin, cortical localization is dispensable for its role in regulating Wnt signaling. [ABSTRACT FROM AUTHOR]

The rearrangement of cytoskeletal elements is essential for many cellular processes. The tumor suppressor Adenomatous polyposis coli (APC) affects the function of microtubules and actin, but the mechanisms by which it does so are not well understood. Here we report that Drosophila syncytial embryos null for Apc2 display defects in the formation and extension of pseudocleavage furrows, which are cortical actin structures important for mitotic fidelity in early embryos. Furthermore, we show that the formin Diaphanous (DIA) functions with APC2 in this process. Colocalization of APC2 and DIA peaks during furrow extension, and localization of APC2 to furrows is DIA-dependent. Furthermore, APC2 binds DIA directly through a region of APC2 not previously shown to interact with DIA-related formins. Consistent with these results, reduction of dia enhances actin defects in Apc2 mutant embryos. Thus, an APC2-DIA complex appears crucial for actin furrow extension in the syncytial embryo. Interestingly, EB1, a microtubule +TIP and reported partner of vertebrate APC and DIA1, may not function with APC2 and DIA in furrow extension. Finally, whereas DIA-related formins are activated by Rho family GTPases, our data suggest that the APC2-DIA complex might be independent of RHOGEF2 and RHO1. Furthermore, although microtubules play a role in furrow extension, our analysis suggests that APC2 and DIA function in a novel complex that affects actin directly, rather than through an effect on microtubules. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of new formylpiperazine-based ferroptosis inhibitors was designed and synthesized. • These derivatives were evaluated for their effects against Erastin-induced ferroptosis HUVECs. • Compound 26 to have better anti-ferroptosis activity and microsomal stability than Fer-1. • Compound 26 is a promising lead compound for treating ferroptosis-related vascular diseases. In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26 , showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases. [ABSTRACT FROM AUTHOR]

In the present study, the critical role of the meteorological condition in a persistent extreme haze episode that occurred in Guanzhong basin of China on December 16 to 25, 2013 has been investigated. Analyses of the large-scale meteorological conditions on 850 hPa during the episode have been performed using the NCEP FNL data set, indicating that synoptic situations generally facilitate the accumulation of pollutants either in horizontal or vertical directions in the basin. The FLEXPART model has been utilized to illustrate the pollutant transport patterns during the episode, further showing the dominant role of synoptic conditions in accumulation of pollutants in the basin. Detailed meteorological conditions, such as temperature inversion, and low-level horizontal wind speed also contribute to the extreme haze episode. In addition, the WRF-CHEM model has been used to evaluate the responses of the surface PM 2.5 level to the emission mitigation. Generally, the predicted PM 2.5 spatial patterns and temporal variations agree well with the observations at the ambient monitoring sites. Sensitivity studies show that the emissions in the basin need to be mitigated by more than 91% to meet the excellent level of the China National Air Quality Standard under the extremely unfavorable meteorological conditions, demonstrating that it is imperative to implement stringent controls on emissions to improve the air quality. [ABSTRACT FROM AUTHOR]

The root tuber and rhizome of Curcuma longa L., abbreviated, respectively, as RCL and RHCL, are used as different medicines in China. In this work, volatile oils were extracted from RCL and RHCL. Then, gas chromatography–mass spectrometry (GC–MS) was used for RCL and RHCL volatile oils analysis, and 45 compounds were identified. The dominant constituents both in volatile oils of RCL and RHCL were turmerone, (−)-zingiberene, and β-turmerone, which covered more than 60% of the total area. The chromatographic fingerprint similarities between RCL and RHCL were not less than 0.943, indicating that their main chemical compositions were similar. However, there were also some compounds that were varied in RCL and RHCL. Based on the peak area ratio of 45 compounds, the RCL and RHCL samples were separated into principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Then, 20 compounds with a variable importance for the projection (VIP) value of more than 1 were the high potential contributors for RCL and RHCL differences. Furthermore, ferric ion-reducing antioxidant power (FRAP) assay results demonstrated that the volatile oils of RCL and RHCL had antioxidant activities. This study provided the material basis for the research of volatile components in RCL and RHCL and contributed to their further pharmacological research and quality control. [ABSTRACT FROM AUTHOR]

Background: Moschus is a rare and precious natural medicine. Due to the properties of resources scarcity and expensive price of natural musk, artificial musk has been developed as substitute materials in some prescriptions. Rapid and accurate identification of natural or artificial musk in complex traditional Chinese medicine (TCM) preparations is also a challenge. Method: A strategy from non-targeted to targeted gas chromatography-mass spectrometry (GC–MS) metabolomics was developed for discrimination of natural and artificial musk. Firstly, GC–MS-based non-targeted analysis combined with chemometrics was used to find the potential chemical markers to distinguish natural musk and artificial musk. Subsequently, targeted metabolomics was used to analyze musk in preparations with multiple reaction monitoring (MRM) mode by use gas chromatography coupled with triple quadrupole mass spectrometry (GC-QQQ MS). Results: Two chemical markers named prasterone and androsterone have been selected and could be detected in all Compound Pien Tze Huang preparations (CPZHs) containing artificial musk, while the CPZHs containing natural musk did not detect two markers with S/N (signal to noise ratio) less than 3. Conclusion: Our work provides an applicable approach to select the practical chemical markers for the assessment of musk in preparations to realize the traceability of musk in TCM and improve the quality control of musk-containing preparations. [ABSTRACT FROM AUTHOR]

The studies of differences in life history and suitability of both water temperatures and trophic levels among rotifer sibling species improve our understanding of speciation, sibling species coexistence and possible niche differentiation over space and time, and consequences for the functioning of ecosystems induced by climate change and eutrophication. We collected Brachionus calyciflorus from Lake Baixiang and Lake Kongque, two tropical shallow lakes, in Xishuangbanna city, Yunnan, China, clonally cultured them in laboratory, and found that the B. calyciflorus complex contains two sibling species named sibling species BNA13 and BNB3 by phylogenetic analysis, and investigated the life-table parameters of the two sibling species BNA13 and BNB3 at four temperatures (16, 20, 24 and 28°C) and four algal densities (0.5, 1.0, 2.0 and 4.0×106 cells.mL−1). The results showed that the responses to increasing temperature and algal density for each of the life-table parameters differed with rotifer sibling species. Sibling species, temperature, algal density and their interactions almost all significantly affected the durations of juvenile period, embryonic development, reproductive period, post-reproductive period, mean lifespan, net reproductive rate, generation time and intrinsic rate of population growth. Sibling species significantly affected the age-specific survivorship. Temperature, algal density and their interaction and the interaction of sibling species and temperature significantly affected the age-specific fecundity. Regardless of the effects of temperature and algal density, the durations of juvenile period, embryonic development, reproductive period, post-reproductive period and mean lifespan, age-specific survivorship, net reproductive rate and generation time of the B. calyciflorus sibling species BNA13 were greater than those of BNB3, but the intrinsic rate of population growth of BNA13 was lower than those of BNB3. This suggests that the two B. calyciflorus sibling species adopted variable life history strategies, low population growth and high survivorship for sibling species BNA13, and high population growth and low survivorship for sibling species BNB3. Both the intrinsic rates of population growth of BNA13 and BNB3 were the highest at 28°C and 4.0×106 cells.mL−1 algal density, indicating that some adaptations of the B. calyciflorus sibling species BNA13 and BNB3 in tropical shallow lakes to water temperatures and trophic levels were similar, and they have the potential for coexistence in single waterbody of higher temperature and higher trophic level. [ABSTRACT FROM PUBLISHER]

Sphingosylphosphorylcholine (SPC), an important cardiovascular mediator derived from sphingomyelin that has atheroprotective effects via actions on vascular endothelial cells (VECs) at normal levels in vivo. However, the underlying mechanism is not well known. To clarify this question, we first investigated the effect of SPC on VEC apoptosis and autophagy induced by deprivation of serum and fibroblast growth factor 2 (FGF-2). SPC at 5-20 µM inhibited apoptosis and induced autophagy in vitro. To understand the underlying mechanism, we investigated the role of integrin β4 in SPC-induced autophagy in VECs. SPC significantly decreased the level of integrin β4, whereas overexpression of integrin β4 inhibited SPC-induced autophagy. Moreover, knockdown of integrin β4 promoted VEC autophagy. To understand the downstream factors of integrin β4 in this process, we observed the effects of SPC on phosphatidylcholine-specific phospholipase C (PC-PLC) activity and level of p53. PC-PLC activity and p53 level in cytoplasm was decreased during autophagy induced by SPC, and knockdown of integrin β4 inhibited the activity of PC-PLC and the cytoplasmic level of p53. SPC may promote autophagy via integrin β4. Moreover, PC-PLC and p53 may be the downstream factors of integrin β4 in autophagy of VECs deprived of serum and FGF-2. J. Cell. Physiol. 226: 2827-2833, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objective: To compare rapid prototyping technology (RP tech) in revision total hip arthroplasty (RTHA) with traditional examination methods and to see how they are different in evaluating acetabular anatomy and designing surgical procedure. Methods: From February 2014 to March 2018, 43 RTHA patients with complex acetabulum defects were enrolled in this prospective study regardless of age or gender. Incomplete and unclear data were excluded. Three types of radiographic examination were performed on each patient before the revision surgery. Four groups of evaluations were designed: (i) X‐ray; (ii) computed tomography (CT‐scan); (iii) RP tech; and (iv) CT‐aided RP tech. Discrepancies between preoperative radiographic analysis and intra‐operative findings were separately compared by a team of surgeons. Premade surgical plans based on each evaluation method were compared with the final surgical procedure. The compliance of anatomic evaluation and surgical plan‐design based on 3D RP tech and traditional radiographs were ranked manually by a of team surgeons into: (i) complete accordance; (ii) general accordance; and (iii) undetermined structure/procedure. The difference in ranks between RP tech and traditional radiographic methods were analyzed with a nonparametric Kruskal‐Wallis test. P < 0.05 was considered significant. Multiple adjustments were taken for the statistical tests level according to the Bonferroni method. Results: For anatomic analysis, the accordance in four groups of evaluating methods differed from each other (P < 0.05) except for the comparison of RP tech and CT‐aided RP tech. RP tech displayed better anatomic evaluating accuracy than traditional methods (X‐ray and CT) with the "complete accordance" rates of these groups being 88.37%, 4.65% and 27.91%, respectively. But CT‐aided RP tech did not improve accuracy significantly compared with using RP tech individually, although the value seems high in the CT‐aided RP group with the "complete accordance" rate of 95.35%. For surgery design, RP tech significantly showed better applicable surgical design compared with X‐ray and CT (P < 0.05), and the "complete accordance" rates were 88.37%, 6.98% and 23.26%, but no significant difference was observed between RP tech and CT‐aided RP tech, and the "complete accordance" rate of CT‐aided RP tech group was 97.67%. RP tech showed remarkable improvement in bone defect assessment and surgical plan design. Conclusion: Using RP technology improved both sensibility and accuracy in acetabular defect evaluation with better locating and evaluating efficiency compared with X‐ray and CT‐scans. It also improved surgical schedule designing in complex acetabular defecting revision surgery. In particularly complex cases, CT aided RP tech may increase the accuracy of RP tech. [ABSTRACT FROM AUTHOR]