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The mechanical relaxation of metallic Zr46.75Ti8.25Cu7.5Ni10Be27.5 supercooled liquid has been measured by dynamic mechanical analysis. The relaxation behaviors are found to fit well the Kohlrausch–Williams–Watts equation in time domain as well as the Havriliak–Negami equation in frequency domain. Characteristic quantities relaxation time and time–temperature superposition are among the properties also exhibited. The metallic supercooled liquid is found to have common relaxation characteristics of the nonmetallic glass-forming supercooled liquids, demonstrating a connection of the underlying physics for quite different classes of glass formers. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fourteen new dammarane-type saponins isolated from G. pentaphyllum. • Three dammarane-type saponins and one cucurbitane-type saponin exhibited satisfactory Sirt1 agonist activity. • Candidate drugs towards Sirt agonist may be discovered. Gynostemma pentaphyllum (Thunb.) Makino (Cucurbitaceae family) is a perennial creeping plant with a common Chinese name of "south ginseng". To date, more than 250 individual saponins with dammarane-type skeleton have been isolated from G. pentaphyllum. The purpose of this study was the isolation and structural characterization of novel, minor gypenosides from G. pentaphyllum and evaluation of their Sirt1 agonist activity. Individual saponins from G. pentaphyllum were isolated and purified by a variety of chromatography techniques, and their structures were elucidated by means of various spectroscopic analysis and comparision with the reported data. Sirt1 enzyme activity detection kit was used to preliminarily evaluate the Sirt1 agonist activity of thirty three individual saponins purified from G. pentaphyllum. Fourteen new triterpenoid saponins named gypenoside CII-CXV (1 – 14) along with twenty six known compounds (15 – 40) were isolated from G. pentaphyllum. Thirty three of all the isolates were screened for Sirt1 agonist activity, and the results showed that three dammarane-type saponins (2 , 18 , 37) and one cucurbitane-type saponin 33 exhibited satisfactory Sirt1 agonist activity. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule Sirt1 agonist and facilitate their utilization as "south ginseng". [ABSTRACT FROM AUTHOR]

Accurate and timely diagnosis of Listeria monocytogenes (L. monocytogenes), a well-known foodborne pathogen with a serious threat to human life and health, is critical for managing bacterial infections and food quality. Here, we report a genosensor platform based on DNA biofunctionalized superparamagnetic nickel colloidal nanocrystal clusters (SNCNCs) coupling with "IS-primer" amplification reaction (ISAR) for rapid, ultrasensitive and specific L. monocytogenes detection. Specifically, the catalytic activity of SNCNCs was identified. After three-step modification, the signal unit was formed by immobilizing AuNPs and hairpin probes on the surface of SNCNCs, achieving enhanced catalytic activity, leading to the reduction of a colorimetric substrate 4-nitrophenol (4-NP). The in-situ signal amplification of target RNA on the surface of SNCNCs coupling with ISAR showed high sensitivity and a detection limit of 1.50 × 10-3 ng mL-1 under optimized conditions. As SNCNCs can bind and lyse bacteria, this genosensor can detect live L. monocytogenes without RNA extraction, with a detection limit of 3.80 × 102 CFU mL-1. Furthermore, the system could also detect L. monocytogenes in artificially contaminated milk samples within 6 h. These results indicate the great potential of our method for sensitive, specific, convenient and low-cost bacterial detection in food, environment and clinics. [Display omitted] • The catalytic activity of SNCNCs is discovered. • SNCNCs coupling with ISAR is applied to detection for the first time. • The genosensor can detect live bacteria without preprocessing (3.8 ×102 CFU mL-1). • The genosensor shows excellent specificity and sensitivity in contaminated milk. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fourteen new dammarane-type saponins isolated from G. pentaphyllum. • Three dammarane-type saponins remarkably reduced PCSK9 expression at 10 μM concentration. • Candidate drugs towards PCSK9 inhibitors may be discovered. Gynostemma pentaphyllum (Thunb.) Makino has a long history as food and diary supplement in China. At present, there are some products for hyperlipidemia in the market, including G. pentaphyllum tea, healthy wine and healthy food. In order to discover proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fourteen new triterpenoid saponins named gypenoside LXXXVIII-CI (1 – 14) along with six known compounds (15 – 20) were isolated from G. pentaphyllum. Their structures were elucidated by means of various spectroscopic techniques. Eight isolates were evaluated the inhibitory effect on PCSK9 in HepG2 cells. The results showed that three dammarane-type glycosides (2 , 3 , 15) remarkably reduced PCSK9 expression at 10 μM concentration. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule PCSK9 inhibitors and facilitate their utilization as functional food ingredients. [ABSTRACT FROM AUTHOR]

Anoectochilus roxburghii is a well-known and valuable traditional Chinese herb due to various medicinal and functional benefits. In-depth investigation is necessary to discover active ingredients and expand its application. In this study, four new compounds (1-4) along with ten known compounds (5-14) were isolated from the ethanol extract of A.roxburghii. Their structures were elucidated by spectroscopic data interpretation. The isolates were screened for their inhibitory activities on the production of NO in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Among them, compounds 5, 6, 9, 10, 12, 13 and 14 exhibited significant anti-inflammatory activity through inhibiting the release of NO., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: This study aimed to investigate whether physical activity (PA) is associated with a lower risk of subsequently developing chronic obstructive pulmonary disease (COPD)., Methods: We conducted this population-based longitudinal follow-up study in a community in Taiwan. This study recruited 61,446 subjects who had participated in the Keelung Community-based Integrated Screening Program (KCIS) between 2005 and 2012. During their participation in KCIS, they were provided with structured questionnaires to collect their baseline characteristics, including weekly PA time. After excluding subjects diagnosed with COPD before they joined KCIS and/or who provided incomplete lifestyle data, 59,457 subjects remained, and were classified into three groups based on their weekly PA time: i.e., as NPA (no regular PA), LPA (low PA, <90 min/week) and HPA (high PA, ≥90 min/week). The primary outcome was a new diagnosis of COPD, followed up until the end of 2015 or their death. Cox proportional-hazard regression was used to assess the impact of PA on the risk of COPD., Results: The risk of COPD was more than 20% lower in the LPA and HPA groups than in the NPA group. Specifically, the adjusted hazard ratio for the risk of COPD was 0.72 in the LPA group (95% CI, 0.61-0.85, p < 0.001) and 0.79 in the HPA group (95% CI, 0.69-0.90, p < 0.001)., Conclusions: Our research uncovered an inverse relationship between PA and COPD. The findings suggest that PA might be useful as a strategy for the primary prevention of COPD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

The K + uptake system KtrAB is essential for bacterial survival in low K + environments. The activity of KtrAB is regulated by nucleotides and Na + . Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na + activates KtrAB and the Na + binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na + , as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na + binding stabilizes the ATP-bound BsKtrAB complex and enhances its K + flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na + in activating BsKtrAB is likely applicable to Na + -activated K + channels in central nervous system., (© 2024. The Author(s).)

Purpose: Ferroptosis is reported to be involved in the chronic intermittent hypoxia (CIH)-related liver damage in vivo. Nuclear factor E2-related factor 2 (Nrf2) has an essential role in the regulation of ferroptosis. This study tested the hypothesis that intermittent hypoxia (IH) could lead to hepatocyte ferroptosis in vitro and the function of Nrf2 in IH-induced hepatocyte ferroptosis., Methods: BRL-3A cells (rat liver cells) were exposed to normoxia or IH. The protocol of IH consisted of 32 cycles of 60-min hypoxic exposure with 30-min reoxygenation phase (nadir of 1% oxygen to peak of 20% oxygen). Ferroptosis was evaluated by cell viability, iron concentration, lipid reactive oxygen species (ROS), protein content of ferritin heavy chain (FTH1), and glutathione peroxidase 4 (GPX4). Both ferrostatin-1 (a ferroptosis inhibitor) and Nrf2 interfering RNA were applied to treat BRL-3A cells, respectively., Results: IH exposure induced ferroptosis in BRL-3A cells with decreased cell viability and increased total iron content and lipid ROS levels. The protein contents of GPX4 and FTH1 in IH group were markedly lower than that in normoxic control. Ferroptosis inhibitor ferrostatin-1 alleviated IH-induced ferroptosis in BRL-3A cells. IH treatment enhanced expression of Nrf2, and Nrf2 knockdown augmented IH-induced ferroptosis in BRL-3A cells., Conclusions: The results revealed that Nrf2 played a protective role during IH-induced ferroptosis in BRL-3A cells. The finding provides a therapeutic target for obstructive sleep apnea-related liver injury., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This population-based longitudinal follow-up study showed a protective effect of tea consumption against osteoporosis, particularly among women and middle-aged people. High tea consumption was also associated with a reduced risk of hip fracture., Introduction: To investigate the association of tea consumption with the risks of osteoporosis and hip fracture., Methods: This study used the Keelung Community-based Integrated Screening database and Taiwan's National Health Insurance Research Database. A total of 42,742 subjects aged 45 to 74 years were enrolled. Each was classified as no tea consumption, low tea consumption, and high tea consumption, according to the results of an eating habits questionnaire. The diagnosis of osteoporosis and hip fracture was based on BMD measured by dual-energy X-ray absorptiometry and the X-ray findings. The median follow-up time was 8.5 years., Results: As compared with the no tea consumption group, the osteoporosis HRs for the low tea consumption and high tea consumption groups were 0.88 (95% confidence interval (CI) 0.80-0.96) and 0.87 (95% CI 0.80-0.94), respectively. Among those participants aged 59 or below, the osteoporosis HRs for low tea consumption and high tea consumption (vs. no tea consumption) were 0.85 (95% CI 0.74-0.96) and 0.79 (95% CI 0.69-0.90). The HRs of hip fracture for the low tea consumption and high tea consumption groups (vs. no tea consumption) were 0.85 (95% CI 0.67-1.08) and 0.69 (95% CI 0.55-0.86), respectively., Conclusion: Tea consumption was linked to a lower risk of osteoporosis, particularly among women and middle-aged people. High tea consumption was also associated with a reduced risk of hip fracture., (© 2022. The Author(s).)

Seven undescribed dammarane-type saponins, gypenosides LXXXI-LXXXVII, together with four known compounds, were isolated from the whole herb of Gynostemma pentaphyllum. The chemical structures of these undescribed compounds were elucidated on the basis of physical and spectroscopic analysis and comparison with literature data. All the isolates were evaluated for their proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitory activities in HepG2 cells. Among them, gypenosides LXXXII-LXXXVII, gynosaponin II, IV and VI suppressed the expression of PCSK9 in LPDS-induced HepG2 cells at 20 μM; gypenosides LXXXII, LXXXV and LXXXVII showed inhibitory activities against PCSK9 at 10 μM; notably, gypenoside LXXXII still exhibited inhibitory activity against PCSK9 at 5 μM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Backgrounds: Atherosclerotic Cardiovascular Disease (ASCVD) is defined as ischemic or endothelial dysfunction-various inflammatory diseases, which is mainly caused by excessive low-density lipoprotein cholesterol (LDL-C) in circulating blood. Gynostemma pentaphyllum is a traditional Chinese medicine, and total Gypenosides are used for the treatment of hyperlipidemia and to reduce circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) level. However, which gypenoside involved in the modulation of PCSK9 expression is still unknown., Purpose: This study aimed to discover effective PCSK9 inhibitors from Gypenosides in accordance with the 2019 ESC/EAS guidelines., Methods: HPLC was employed to determine major six components of Gypenosides. The inhibitory activity on secreted PCSK9 in HepG2 of six major compounds from Gypenosides were screened by ELISA. The level of low-density lipoprotein (LDL) receptor (LDLR) was determined by Flow cytometry and Immunofluorescence. The expression levels of PCSK9, LDLR and Sterol-regulatory element binding proteins-2 (SREBP-2) were analyzed by qPCR and Western blot. DiI-LDL was added to evaluated LDL uptake into HepG2., Results: The results suggested that the mRNA and protein levels of PCSK9 were down-regulated by Gypenoside LVI and the LDLR degradation in lysosomes system was inhibited, thereby leading to an increasing in LDL uptake into HepG2 cells. Furthermore, Gypenoside LVI decreased PCSK9 expression induced by stains. Altogether, Gypenoside LVI enhances LDL uptake into HepG2 cells by increased LDLR level on cell-surface and suppressed PCSK9 expression., Conclusion: This indicates that Gypenoside LVI can be used as a useful supplement for statins in the treatment of hypercholesterolemia. This is firstly reported that monomeric compound of G. pentaphyllum planted in Hunan province has the effect of increasing LDL-C uptake in hepatocytes via inhibiting PCSK9 expression., (Copyright © 2021. Published by Elsevier GmbH.)

Ten undescribed anthranoids, including three anthraquinone acetals as racemic mixtures, (±)-kenganthranol G-I, and seven prenylated anthranols, (±)-kenganthranol J-M and harunganol G-I, together with thirteen known compounds, were isolated from the stem bark of Harungana madagascariensis. The structures of (±)-kenganthranol G and (±)-kenganthranol J were confirmed by X-ray crystallography. (±)-Kenganthranol G was separated into (+)-kenganthranol G and (-)-kenganthranol G by chiral HPLC and their absolute configurations were established by electronic circular dichroism. (±)-Kenganthranol L displayed α-glucosidase inhibitory activity with an IC 50 of 4.4 μM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Recent research on the structure and mechanism of DNA polymerases has continued to generate fundamentally important features, including a noncanonical pathway involving "prebinding" of metal-bound dNTP (MdNTP) in the absence of DNA. While this noncanonical mechanism was shown to be a possible subset for African swine fever DNA polymerase X (Pol X) and human Pol λ, it remains unknown whether it could be the primary pathway for a DNA polymerase. Pol μ is a unique member of the X-family with multiple functions and with unusual Mn 2+ preference. Here we report that Pol μ not only prebinds MdNTP in a catalytically active conformation but also exerts a Mn 2+ over Mg 2+ preference at this early stage of catalysis, for various functions: incorporation of dNTP into a single nucleotide gapped DNA, incorporation of rNTP in the nonhomologous end joining (NHEJ) repair, incorporation of dNTP to an ssDNA, and incorporation of an 8-oxo-dGTP opposite template dA (mismatched) or dC (matched). The structural basis of this noncanonical mechanism and Mn 2+ over Mg 2+ preference in these functions was analyzed by solving 19 structures of prebinding binary complexes, precatalytic ternary complexes, and product complexes. The results suggest that the noncanonical pathway is functionally relevant for the multiple functions of Pol μ. Overall, this work provides the structural and mechanistic basis for the long-standing puzzle in the Mn 2+ preference of Pol μ and expands the landscape of the possible mechanisms of DNA polymerases to include both mechanistic pathways.

Tip-enhanced Raman spectroscopy can provide molecular fingerprint information with ultrahigh spatial resolution, but the tip will be easily contaminated, thus leading to artifacts. It also remains a great challenge to establish tip-enhanced fluorescence because of the quenching resulting from the proximity of the metal tip. Herein, we report shell-isolated tip-enhanced Raman and fluorescence spectroscopies by employing ultrathin shell-isolated tips fabricated by atomic layer deposition. Such shell-isolated tips not only show outstanding electromagnetic field enhancement in TERS but also exclude interference by contaminants, thus greatly promoting applications in solution. Tip-enhanced fluorescence has also been achieved using these shell-isolated tips, with enhancement factors of up to 1.7×10 3 , consistent with theoretical simulations. Furthermore, tip-enhanced Raman and fluorescence signals are acquired simultaneously, and their relative intensities can be manipulated by changing the shell thickness. This work opens a new avenue for ultrahigh resolution surface analysis using plasmon-enhanced spectroscopies., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Despite the well-documented association between diabetes and active tuberculosis, evidence of the association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent., Methods: We included observational studies that applied either the tuberculin skin test or the interferon gamma release assay for diagnosis of LTBI and that provided adjusted effect estimate for the association between diabetes and LTBI. We searched PubMed and EMBASE through 31 January 2016. The risk of bias of included studies was assessed using a quality assessment tool modified from the Newcastle-Ottawa scale., Results: Thirteen studies (1 cohort study and 12 cross-sectional studies) were included, involving 38263 participants. The cohort study revealed an increased but nonsignificant risk of LTBI among diabetics (risk ratio, 4.40; 95% confidence interval [CI], 0.50-38.55). For the cross-sectional studies, the pooled odds ratio from the random-effects model was 1.18 (95% CI, 1.06-1.30), with a small statistical heterogeneity across studies (I2, 3.5%). The risk of bias assessment revealed several methodological issues, but the overall direction of biases would reduce the positive causal association between diabetes and LTBI., Conclusions: Diabetes was associated with a small but statistically significant risk for LTBI. Findings from this review could be used to inform future cost-effectiveness analysis on the impact of LTBI screening programs among diabetics., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Glucose transporter-1 (GLUT-1) and PI3K/Akt are known to be closely involved in resistance to chemotherapy. Co-targeted therapy reducing GLUT-1 expression and PI3K/Akt pathway activity may overcome the chemoresistance of human cancers. Apigenin may inhibit the expression of GLUT-1 and the PI3K/Akt pathway. We hypothesized that over-expression of GLUT-1 and p-Akt was associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether apigenin inhibited GLUT-1 and p-Akt, resulting in sensitization of laryngeal carcinoma Hep-2 cells to cisplatin. Real-time RT-PCR and Western blotting confirmed the presence of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins in Hep-2 cells. We found that resistance or insensitivity of Hep-2 cells to cisplatin might be associated with such expression. Apigenin markedly enhanced the cisplatin-induced suppression of Hep-2 cell growth. This effect was concentration- and time-dependent. Thus apigenin may significantly reduce the levels of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins, in cisplatin-treated Hep-2 cells, in a concentration- and time-dependent manner. To conclude, overexpression of GLUT-1 mRNA may be associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. Apigenin may enhance the sensitivity to cisplatin of laryngeal carcinoma cells via inhibition of GLUT-1 and p-Akt expression.

Objective: To study the correlation between high-resolution HLA-A * 1101, HLA-A * 0201, HLA-A * 2402, HLA-B * 4001, HLA-DRB1 * 0901 with HCMV pp65 antigenemia after bone marrow transplantation (BMT) in China., Methods: 48 recipients doing BMT during 2009. 2-2010. 10 were selected in my hospital; HCMV pp65 was detected by ELISA or immunohistochemical methods. The frequency of HLA-A * 1101, HLA-A * 0201, HLA-A * 2402, HLA-B * 4001, HLA-DRB1 * 0901 alleles were determined by Polymerase chain reaction-sequence based typing (PCR - SBT)., Results: (1) The BMT recipients were HCMV pp65 antigenic positive(100%); (2) The positive rate of HLA-A * 1101, HLA-A * 0201, HLA-A * 2402, HLA-B * 4001 showed no obvious difference between 12 lower antigenemia group and 36 higher antigenemia group, the positive rate: HLA-A * 1101 were 33.3% (8/24) and 20.8% (15/72), HLA-A * 0201 were 4.2% (1/24) and 13.9% (10/72), HLA-A * 2402 were 12.5% (3/24) and 19.4% (14/72), HLA-B* 4001 were 16.7% (4/24) and 12.5% (9/72); (3) HLA-DRB1 * 0901 positive rate in higher antigenemia group was higher than the lower (P = 0.048), the positive rate were 4.2% (1/24) and 19.4% (14/72); (4) HLA-DRB1 * 0901 recipients were higher pp65 antigenemia than HLA-A * 2402 recipients (P = 0.007) and HLA-A * 1101 recipients (P = 0.028), HLA-A * 0201 recipients were higher pp65 antigenemia than HLA-A * 2402 (P = 0.02), the pp65 antigenemia showed no obvious difference among the rest of high-resolution HLA groups (P > 0.05)., Conclusion: HLA-DRB1 * 0901 alleles might be correlated with BMT recipients happened higher pp65 antigenemia, HLA-A * 2402 alleles might be correlated with BMT recipients happened lower pp65 antigenemia.