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Background: Geniposidic acid (GPA) alleviates oxidative stress and inflammation in mice However, whether it can effectively regulate lipid accumulation and prevent hyperlipidemia requires further investigation., Purpose: This study combined the untargeted metabolomics of cells and a Caenorhabditis elegans model to evaluate the anti-hyperlipidemic potential of GPA by modulating oxidative stress and regulating lipid metabolism. A golden hamster model of hyperlipidemia was used to further validate the lipid-lowering effect and mechanism of action of GPA., Methods: Chemical staining, immunofluorescence, and flow cytometry were performed to examine the effects of GPA on lipid accumulation and oxidative stress. Untargeted metabolomic analysis of cells and C. elegans was performed using ultra-performance liquid chromatography coupled with quadrupole electrostatic field Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap MS) to identify biomarkers altered by GPA action, analyze the affected metabolic pathways, and validate the mechanisms by which GPA regulates lipid metabolism and oxidative stress. A golden hamster model of hyperlipidemia was established to test the lipid-lowering effects of GPA. Body weight, biochemical markers, rate-limiting enzymes, and key proteins were assessed. Hematoxylin and eosin (H&E) and Oil Red O staining were performed., Results: Phenotypic data showed that GPA decreased free fatty acid (FFA)-induced lipid buildup and high reactive oxygen species (ROS) levels, reversed the decrease in mitochondrial membrane potential (MMP), and increased the cellular reduced glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio. GPA also reduces high glucose-induced lipid build-up and ROS production in C. elegans. Metabolomic analysis showed that GPA affected purine, lipid, and amino acid metabolism. Moreover, GPA inhibited xanthine oxidase (XOD), glutamate dehydrogenase (GLDH), fatty acid synthase (FAS), phosphorylation of P38 MAPK, and upregulated the expression of SIRT3 and CPT1A protein production to control lipid metabolism and produce antioxidant benefits in cells and golden hamsters., Conclusion: Current evidence suggests that GPA can effectively regulate lipid metabolism and the oxidative stress response, and has the potential to prevent hyperlipidemia. This study also provided an effective method for evaluating the mechanism of action of GPA., Competing Interests: Declaration of competing interest The authors declare that they are no conflicts of interest., (Copyright © 2023. Published by Elsevier GmbH.)

In this work, surface molecularly imprinted polymers based on magnetic multi-walled carbon nanotubes were prepared for the specific recognition and adsorption of resveratrol. The functionalization of magnetic multi-walled carbon nanotubes and the synthesis process of surface molecularly imprinted polymers were optimized. Characterizations were performed to demonstrate the successful synthesis of the imprinted materials. The imprinted materials showed satisfactory adsorption capacity of resveratrol (45.73 ± 1.72 mg/g) and excellent selectivity (imprinting factor 2.89 ± 0.15). In addition, the imprinted materials were used as adsorbents in molecularly imprinted solid-phase extraction for the purification of resveratrol from crude extracts of some food and medicinal resources, achieving recoveries of 93.69%-95.53% with high purities of 88.37%-92.33%. Moreover, the purified products exhibited extremely strong free radical scavenging activity compared with crude extracts. Overall, this work provided a promising approach for the highly selective purification of resveratrol from natural resources, which would contribute to the application of this valuable compound in the food/nutraceutical fields., (© 2024 Wiley-VCH GmbH.)

Pancreatic lipase inhibitors can reduce blood lipids by inactivating the catalytic activity of human pancreatic lipase, a key enzyme involved in triglyceride hydrolysis, which helps control some dyslipidemic diseases. The ability of Eucommia ulmoides tea to improve fat-related diseases is closely related to the natural inhibitory components of pancreatic lipase contained in the tea. In this study, fifteen pancreatic lipase inhibitors were screened and identified from Eucommia ulmoides tea by affinity-ultrafiltration combined UPLC-Q-Exactive Orbitrap/MS. Four representative components of geniposidic acid, quercetin-3-O-sambuboside, isochlorogenic acid A, and quercetin with high binding degrees were further verified by nanoscale differential scanning fluorimetry (nanoDSF) and enzyme inhibitory assays. The results of flow cytometry showed that they could significantly reduce the activity of pancreatic lipase in AR42J cells induced by palmitic acid in a concentration-dependent manner. Our findings suggest that Eucommia ulmoides tea may be a promising resource for pancreatic lipase inhibitors of natural origin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The interplay between various symmetries and electronic bands topology is one of the core issues for topological quantum materials. Spontaneous magnetism, which leads to the breaking of time-reversal symmetry, has been proven to be a powerful approach to trigger various exotic topological phases. In this Letter, utilizing the combination of angle-resolved photoemission spectroscopy, magneto-optical Kerr effect microscopy, and first-principles calculations, we present the direct evidence on the realization of the long-sought spontaneous ferromagnetism induced topological transition in soft ferromagnetic EuB_{6}. Explicitly, we reveal the topological transition is from Z_{2}=1 topological insulator in paramagnetic state to χ=1 magnetic topological semimetal in low temperature ferromagnetic state. Our results demonstrate that the simple band structure near the Fermi level and rich topological phases make EuB_{6} an ideal platform to study the topological phase physics.

In this study, a total of 179,907 blood samples from populations with suspected Brucella spp. infections were collected between 2008 and 2020 and analyzed by the Rose Bengal plate test (RBPT) and serum agglutination test (SAT). Moreover, conventional biotyping, B. abortus-melitensis-ovis-suis polymerase chain reaction (AMOS-PCR), and multiple-locus variable-number tandem repeat analysis (MLVA) was applied to characterize the isolated strains. A total of 8103 (4.50%) samples were positive in RBPT, while 7705 (4.28%, 95% confidence interval (CI) 4.19-4.37) samples were positive in SAT. There was a significant difference in seroprevalence for human brucellosis over time, in different areas and different cities (districts) (χ 2 = 2 = 32.23, 1984.14, and 3749.51, p < .05). The highest seropositivity (8.22% (4, 965/60393; 95% CI 8.00-8.44) was observed in Yulin City, which borders Inner Mongolia, Ningxia, and Gansu Province, China, regions that have a high incidence of human brucellosis. Moreover, 174 Brucella strains were obtained, including nine with B. melitensis bv. 1, 145 with B. melitensis bv. 3, and 20 with B. melitensis variants. After random selection, 132 B. melitensis were further genotyped using MLVA-16. The 132 strains were sorted into 100 MLVA-16 genotypes (GTs) (GT 1-100), 81 of which were single GTs represented by singular independent strains. The remaining 19 shared GTs involved 51 strains, and each GT included two to seven isolates from the Shaan northern and Guanzhong areas. These data indicated that although sporadic cases were a dominant epidemic characteristic of human brucellosis in this province, more than 38.6% (51/132) outbreaks were also found in the Shaan northern area and Guanzhong areas. The 47 shared MLVA-16 GTs were observed in strains (n = 71) from this study and strains (n = 337) from 19 other provinces of China. These data suggest that strains from the northern provinces are a potential source of human brucellosis cases in Shaanxi Province. It is urgent to strengthen the surveillance and control of the trade and transfer of infected sheep among regions., (© 2021 Wiley-VCH GmbH.)

In the present study, surveys of case numbers, constituent ratios, conventional biotyping, and multilocus sequence typing (MLST) were applied to characterize the incidence rate and epidemiological characteristics of human brucellosis in Shaanxi Province, China. A total of 12,215 human brucellosis cases were reported during 2008-2020, for an annual average incidence rate of 2.48/100,000. The most significant change was that the county numbers of reported cases increased from 36 in 2008 to 84 in 2020, with a geographic expansion trend from northern Shaanxi to Guanzhong, and southern Shaanxi regions; the incidence rate declined in previous epidemic northern Shaanxi regions while increasing each year in Guanzhong and southern Shaanxi regions such as Hancheng and Xianyang. The increased incidence was closely related to the development of large-scale small ruminants (goats and sheep) farms in Guanzhong and some southern Shaanxi regions. Another significant feature was that student cases (n = 261) were ranked second among all occupations, accounting for 2.14% of the total number of cases, with the majority due to drinking unsterilized goat milk. Three Brucella species were detected (B. melitensis (bv. 1, 2, 3 and variant), B. abortus bv. 3/6, and B. suis bv. 1) and were mainly distributed in the northern Shaanxi and Guanzhong regions. Three known STs (ST8, ST2, and ST14) were identified based on MLST analysis. The characteristics that had not changed were that B. melitensis strains belonging to the ST8 population were the dominant species and were observed in all nine regions during the examined periods. Strengthened human and animal brucellosis surveillance and restriction of the transfer of infected sheep (goats) as well as students avoiding drinking raw milk are suggested as optimal control strategies., (© 2021. The Author(s).)

As exemplified by the growing interest in the quantum anomalous Hall effect, the research on topology as an organizing principle of quantum matter is greatly enriched from the interplay with magnetism. In this vein, we present a combined electrical and thermoelectrical transport study on the magnetic Weyl semimetal EuCd&#95;{2}As&#95;{2}. Unconventional contribution to the anomalous Hall and anomalous Nernst effects were observed both above and below the magnetic transition temperature of EuCd&#95;{2}As&#95;{2}, indicating the existence of significant Berry curvature. EuCd&#95;{2}As&#95;{2} represents a rare case in which this unconventional transverse transport emerges both above and below the magnetic transition temperature in the same material. The transport properties evolve with temperature and field in the antiferromagnetic phase in a different manner than in the paramagnetic phase, suggesting different mechanisms to their origin. Our results indicate EuCd&#95;{2}As&#95;{2} is a fertile playground for investigating the interplay between magnetism and topology, and potentially a plethora of topologically nontrivial phases rooted in this interplay.

Objective: To study the high risk factors for the transformation into acute myeloid leukemia(AML) in patients with intermediate and high risk myelodysplastic syndrome(MDS) treated by decitabine-based regimen., Methods: The clinical characterstics of 60 intermediate and high risk MDS patients and the factors of its transformed into AML were retrospectively analyzed., Results: The overall response rate(ORR) of the patients suffered from intermediate and high risk MDS treated by decitabine-based regimen was 65.0％(39/60), among the 60 cases 17 achieved complete remission(CR), 5 achieved morrow complete remission(mCR), 4 achieved partial remission(PR) and 13 achieved hematologic improvement(HI). Twenty-one cases(35.0%) were transformed into AML among 60 cases of intermediate and high risk MDS treated by decitabine-based regimen. The median time of transformation from intermediate and high risk MDS into AML was 10.0 months(1.6-32.0). χ 2 or Fisher's exact test showed that 2016 WHO MDS diagnostic subgrouping, myeloid hyperplasia markedly active, delayed interval of decitabine-based treatment associated with the transformation from intermediate to high risk MDS into AML (χ 2 =9.878，P=0.031；χ 2 =4.319，P=0.038；χ 2 =6406，P=0.011); Univariate analysis of Kaplan-Meier test showed that 2016 WHO MDS diagnostic subgroups, bone marrow blast cell ratio, bone marrow dysplasia coefficients, prolonged interval of decitabine-based treatment associated with the transformation from intermediate and high risk MDS into AML (P=0.015，P=0.008，P=0.012，P=0.032); multivariate analysis showed the bone marrow blast cell ratio and the bone marrow dysplasia coefficients were independent risk factors for the transformation from intermediate to high risk MDS into AML (P=0.022，P=0.018)., Conclusion: The bone marrow blast cell ratio and the bone marrow dysplasia coefficients are independent risk factors of transformation into AML in the patients with intermediate and high risk MDS treated by decitabine-based regimen. The regular interval of dicitabine treatment is beneficial to maintain the stability of patients conditions.

Increasing evidence demonstrate that circular RNAs (circRNAs) play critical role in regulation of gene expression, which participate in the pathogenesis of cancer, including chronic myeloid leukemia (CML). In this study, we aimed to investigate the expression profiling of circHIPK3 in CML. We found that circHIPK3 was significantly upregulated in peripheral blood mononuclear cells (PBMC) and serum samples from CML compared with healthy controls. High circHIPK3 expression predicted a poor outcome of CML patients. Further loss-function experiments suggested the oncogenic role of circHIPK3 in CML. Our findings provide insights on the role of circHIPK3 in the development and treatment of CML.

Weyl fermions as emergent quasiparticles can arise in Weyl semimetals (WSMs) in which the energy bands are nondegenerate, resulting from inversion or time-reversal symmetry breaking. Nevertheless, experimental evidence for magnetically induced WSMs is scarce. Here, using photoemission spectroscopy, we observe that the degeneracy of Bloch bands is already lifted in the paramagnetic phase of EuCd 2 As 2 . We attribute this effect to the itinerant electrons experiencing quasi-static and quasi-long-range ferromagnetic fluctuations. Moreover, the spin-nondegenerate band structure harbors a pair of ideal Weyl nodes near the Fermi level. Hence, we show that long-range magnetic order and the spontaneous breaking of time-reversal symmetry are not essential requirements for WSM states in centrosymmetric systems and that WSM states can emerge in a wider range of condensed matter systems than previously thought.

Topological materials with exotic quantum properties are promising candidates for quantum spin electronics. Different classes of topological materials, including Weyl semimetal, topological superconductor, topological insulator and Axion insulator, etc., can be connected to each other via quantum phase transition. For example, it is believed that a trivial band insulator can be twisted into topological phase by increasing spin-orbital coupling or changing the parameters of crystal lattice. With the results of LDA calculation and measurement by angle-resolved photoemission spectroscopy (ARPES), we demonstrate in this work that the electronic structure of SrSn 2 As 2 single crystal has the texture of band inversion near the critical point. The results indicate the possibility of realizing topological quantum phase transition in SrSn 2 As 2 single crystal and obtaining different exotic quantum states.

Recently, theoretical studies show that layered HfTe 5 is at the boundary of weak &strong topological insulator (TI) and might crossover to a Dirac semimetal state by changing lattice parameters. The topological properties of 3D stacked HfTe 5 are expected hence to be sensitive to pressures tuning. Here, we report pressure induced phase evolution in both electronic &crystal structures for HfTe 5 with a culmination of pressure induced superconductivity. Our experiments indicated that the temperature for anomaly resistance peak (Tp) due to Lifshitz transition decreases first before climbs up to a maximum with pressure while the Tp minimum corresponds to the transition from a weak TI to strong TI. The HfTe 5 crystal becomes superconductive above ~5.5 GPa where the Tp reaches maximum. The highest superconducting transition temperature (Tc) around 5 K was achieved at 20 GPa. Crystal structure studies indicate that HfTe 5 transforms from a Cmcm phase across a monoclinic C2/m phase then to a P-1 phase with increasing pressure. Based on transport, structure studies a comprehensive phase diagram of HfTe 5 is constructed as function of pressure. The work provides valuable experimental insights into the evolution on how to proceed from a weak TI precursor across a strong TI to superconductors.

We have investigated the spin texture of surface Fermi arcs in the recently discovered Weyl semimetal TaAs using spin- and angle-resolved photoemission spectroscopy. The experimental results demonstrate that the Fermi arcs are spin polarized. The measured spin texture fulfills the requirement of mirror and time-reversal symmetries and is well reproduced by our first-principles calculations, which gives strong evidence for the topologically nontrivial Weyl semimetal state in TaAs. The consistency between the experimental and calculated results further confirms the distribution of chirality of the Weyl nodes determined by first-principles calculations.

This study was aimed to investigate the effects of the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA) on DLC-1 gene transcription regulation and molecular biological behaviours in the human multiple myeloma RPMI-8226 cells. The cells were treated respectively with 5-Aza-CdR and TSA alone, or the both combination; the cell proliferation and apoptosis, DLC-1 expression, the protein expression of Ras homolog family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac1) were examined by CCK-8 method, RT-PCR and ELISA, respectively. The results showed that the 5-Aza-CdR and TSA had cell growth inhibitory and apoptosis-inducing effects in dose-dependent manner (P < 0.05). Compared with a single drug (5-Aza-CdR or TSA alone), the effects were significantly enhanced after treatment with the combination of 5-Aza-CdR and TSA (P < 0.05). DLC-1 was weakly expressed in the control group; the treatment with 5-Aza-CdR alone enhanced its re-expression dose-dependently (P < 0.05). Compared with 5-Aza-CdR alone, 5-Aza-CdR plus TSA enhanced DLC-1 re-expression significantly.Compared with the control, 5-Aza-CdR and TSA significantly decreased RhoA and Rac1 protein expression (P < 0.05). It is concluded that 5-Aza-CdR and TSA can effectively reverse DLC-1 expression of RPMI-8226 cells; TSA has a synergistic effect on its re-expression. 5-Aza-CdR and TSA have significant cell growth inhibitory and apoptosis-inducing effects on RPMI-8226 cells. These effects may be related to the inhibition of Rho/Rho kinase signalling pathway.

Background: How to find an effective gene locus resistant to atherosclerosis has become a hotspot of today's medicine. Membrane attack complex (MAC) has proved to be related with the occurrence and development of atherosclerosis. Complement regulatory protein CD59 is a key regulator of complement MAC assembly. So this study aimed at discussing the effects of CD59 gene on occurrence and development of atherosclerosis and relative mechanism., Methods: Apolipoprotein E knockout (ApoE (-/-)) mice were randomly divided into four groups: control group, empty plasmid-treated group, 0.5 ml CD59-treated group and 1.0 ml CD59-treated group. At the end of the 12th week, CD59 mRNA levels in whole blood were determined by RT-PCR and CD59 protein expressions were detected by western blot. The biochemical indexes in blood serum were detected. The paraffin sections of aortic root of mice were made and the degrees of atherosclerotic plaques formation were observed by hematoxylin/eosin (HE) staining. The expressions of cell apoptosis-related proteins (Bcl-2 and Fas) and plaque stability related protein (MMP-2) were detected by immunohistochemistry. Then the cell apoptosis levels were detected by TUNEL, the expression of Cyclin D1 and the mRNA level of cyclin dependent protein kinase 4 (CDK4) were detected by immunofluorescence and in situ hybridization, respectively., Results: Atherosclerotic mouse model was successfully established. CD59 gene was overexpressed in blood cells and tissue cells after liposome transfection. CD59 could reduce blood lipid levels, promote the expression of anti-apoptotic Bcl-2 protein and inhibit pro-apoptotic Fas proteins, so finally lead to degradation of apoptosis levels of endothelial cells. In addition, Cyclin D1 protein and CDK4 mRNA levels were restrained by CD59 so as to inhibit the proliferation of smooth muscle cells. CD59 could inhibit the formation of atherosclerotic vulnerable plaque by suppressing the MMP-2 expression, which was further confirmed by HE staining. The anti-atherosclerotic effects were enhanced with the increase of CD59 gene dose., Conclusions: CD59 could lower blood lipid levels, positively regulate cell cycle, maintain the stability of cell proliferation and apoptosis of aorta cells, slow down the development of atherosclerotic vulnerable plaque, and finally inhibit the progress of atherosclerosis. So CD59 gene might be a new genetic locus for the therapy of atherosclerosis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The effects of C-phycocyanin (C-PC) on atherosclerosis and the regulatory effects of CD59 gene on anti-atherosclerotic roles of C-PC were investigated. Apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into four groups: control group, C-PC treatment group, CD59 transfection group and C-PC+CD59 synergy group. The mice were fed with high-fat-diet and treated with drug intervention at the same time. Results showed the atherosclerotic mouse model was successfully established. CD59 was over-expressed in blood and tissue cells. Single CD59 or C-PC could reduce blood lipid levels and promote the expression of anti-apoptotic Bcl-2 but inhibit pro-apoptotic Fas proteins in endothelial cells. The expression levels of cell cycle protein D1 (Cyclin D1) and mRNA levels of cyclin dependent protein kinase 4 (CDK4) in smooth muscle cells were restrained by CD59 and C-PC. CD59 or C-PC alone could inhibit the formation of atherosclerotic plaque by suppressing MMP-2 protein expression. In addition, C-PC could promote CD59 expression. So both CD59 and C-PC could inhibit the progress of atherosclerosis, and the anti-atherosclerotic effects of C-PC might be fulfilled by promoting CD59 expression, preventing smooth muscle cell proliferation and the apoptosis of endothelial cells, reducing blood fat levels, and at last inhibiting the development of atherosclerosis.

This tutorial review discusses a new class of colloidal metal nanoparticles that is able to enhance the efficiencies of surface-enhanced Raman scattering (SERS) by as much as 10(14)-10(15) fold. This enormous enhancement allows spectroscopic detection and identification of single molecules located on the nanoparticle surface or at the junction of two particles under ambient conditions. Considerable progress has been made in understanding the enhancement mechanisms, including definitive evidence for the single-molecule origin of fluctuating SERS signals. For applications, SERS nanoparticle tags have been developed based on the use of embedded reporter molecules and a silica or polymer encapsulation layer. The SERS nanoparticle tags are capable of providing detailed spectroscopic information and are much brighter than semiconductor quantum dots in the near-infrared spectral window. These properties have raised new opportunities for multiplexed molecular diagnosis and in vivo Raman spectroscopy and imaging.

This study was aimed to explore the expression and significance of melanoma antigen gene-3 (MAGE-3) in endoplasmic reticulum stress-induced apoptosis. After the treatment of leukemia cell line K562 and its multidrug-resistant cell line K562/A02 by thapsigargin, intracellular calcium concentrations ([Ca(2+)]i) in K562 and K562/A02 were measured by fluorescence spectrophotometer with calcium sensitive fluorescence indicator Fura-2/AM; expression changes of glucose-regulated protein 78 (GRP78) were detected by Western blot; morphological change of apoptotic cell was investigated by AO/EB fluorescent staining under fluorescent microscope; apoptosis rate was determined by terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP nick end labelling (TUNEL) staining; the expression of MAGE-3 gene mRNA was detected by RT-PCR. The results showed that (1) thapsigargin induced the enhancement of [Ca(2+)]i with different extent in K562 and K562/A02 cells, and the enhancement of [Ca(2+)]i was dose-dependent in experiment range. At the same time, thapsigargin induced upregulation of GRP78 protein expression and typical apoptotic changes of K562 and K562/A02 cells, apoptotic rate was also dose-dependent in experiment range. The [Ca(2+)]i in K562/A02 cells were higher than that in K562 cells. (2) in the course of endoplasmic reticulum stress-induced apoptosis by thapsigargin, the expression of MAGE-3 gene mRNA was remarkably downregulated. Moreover, the expression of MAGE-3 gene mRNA in K562/A02 cells was higher than that in K562 cells. It is concluded that (1) thapsigargin induces endoplasmic reticulum stress-induced apoptosis of K562 and K562/A02 cells in experiment range, and this may be associated with downregulation of MAGE-3 mRNA expression or MAGE-3 gene may participates in the regulation of endoplasmic reticulum stress-induced apoptosis. (2) MAGE-3 gene may possess anti-apoptotic activity, multidrug resistance in K562/A02 cells can be associated with [Ca(2+)]i increase and upregulation of MAGE-3 expression.

We present in this report a detailed structural study of calf gamma-crystallins both in the solid state and in solution by the newly developed technique of near-infrared (IR) Fourier transform (FT)-Raman spectroscopy as well as by the conventional Raman method. In comparison with conventional laser Raman spectroscopy, the near-IR FT-Raman approach exhibits several attractive features such as fluorescence rejection capability, frequency accuracy, and the FT's multiplex and throughput advantages. These distinct characteristics combined form the basis for the particular suitability of FT-Raman in crystallin structural analysis and elucidation. We have thus obtained evidence in support of the view that native calf gamma-II crystallin does not contain a disulfide bond either in the lyophilized state or in solution. In addition, conventional Raman spectra are examined for all four gamma-crystallin fractions. gamma-S, gamma-II, gamma-III, and gamma-IV, and the results indicate a high degree of structural similarities among them. It is also found that the sulfhydryl groups in all four gamma-crystallins are highly resistant to air oxidation and are capable of maintaining their reduced state during isolation in the absence of added reductants or such chelating agents as EDTA.