Diet Control and Swimming Exercise Ameliorate HFD-Induced Cognitive Impairment Related to the SIRT1-NF-κB/PGC-1α Pathways in ApoE-/- Mice.

High-fat diet- (HFD-) induced neuroinflammation may ultimately lead to an increased risk of cognitive impairment. Here, we evaluate the effects of diet control and swimming or both on the prevention of cognitive impairment by enhancing SIRT1 activity. Twenty-week-old ApoE-/- mice were fed a HFD for 8 weeks and then were treated with diet control and/or swimming for 8 weeks. Cognitive function was assessed using the novel object recognition test (NORT) and Y-maze test. The expression of sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), brain-derived neurotrophic factor (BDNF), nuclear factor kappa B p65 (NF-κB p65), interleukin-1ß (IL-1ß), and tumour necrosis factor-α (TNF-α) in the hippocampus was measured by western blotting. The levels of fractional anisotropy (FA), N-acetylaspartate (NAA)/creatine (Cr) ratio, choline (Cho)/Cr ratio, and myo-inositol (MI)/Cr ratio in the hippocampus were evaluated by diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) using 7.0-T magnetic resonance imaging (MRI). Our results showed that cognitive dysfunction and hippocampal neuroinflammation appeared to be remarkably observed in apolipoprotein E (ApoE)-/- mice fed with HFD. Diet control plus swimming significantly reversed HFD-induced cognitive decline, reduced the time spent exploring the novel object, and ameliorated spontaneous alternation in the Y-maze test. Compared with the HFD group, ApoE-/- mice fed diet control and/or subjected to swimming had an increase in FA, NAA/Cr, and Cho/Cr; a drop in MI/Cr; elevated expression levels of SIRT1, PGC-1α, and BDNF; and inhibited production of proinflammatory cytokines, including NF-κB p65, IL-1ß, and TNF-α. SIRT1, an NAD+-dependent class III histone enzyme, deacetylases and regulates the activity of PGC-1α and NF-κB. These data indicated that diet control and/or swimming ameliorate cognitive deficits through the inhibitory effect of neuroinflammation via SIRT1-mediated pathways, strongly suggesting that swimming and/or diet control could be potentially effective nonpharmacological treatments for cognitive impairment.

Two new sesquiterpenoids from plant endophytic fungus Flammulina velutipes.

Two new sesquiterpenoids, flammupin A (1) and flammupin B (2), along with two known compounds, enokipodin C (3) and 5,5'-dibuthoxy-2,2'-bifuran (4) were obtained from Flammulina velutipes, an endophytic fungus isolated from the roots of Caulophyllum robustum Maxim. The structures were elucidated by the combination of HR-ESI-MS, NMR, and ECD analyses. Compound 3 exhibited moderate to potent cytotoxicity against A549, HeLa, and SMMC-7721 cells with IC50 values ranged from 3.69 to 11.84 µM.

Acrocalyenes A and B, Two New Diterpenoids from Sinomenium acutum Associated Fungus Acrocalymma sp.

We identified two new diterpenoidal acrocalyenes A (1) and B (2) through chemical investigation on Acrocalymma sp., a plant-associated fungus from the tender stem isolates of Sinomenium acutum collected from the Qinling Mountains, along with seven already-recognized compounds (3-9). The HR-ESI-TOF-MS and 1D/2D NMR data were utilized for structural elucidation of these compounds, and the single-crystal X-ray diffraction was employed for absolute configuration clarification of the novel acrocalyenes 1 and 2. Bioassays revealed that the cytotoxicities of compounds 2, 4, 6, 7, and 8 against three human carcinoma cells (RKO, HeLa and HCC-1806) were moderate to strong, with IC50 between 6.70-38.82 µM. These isolates were also evaluated for their fungal resistant potentials against Botrytis cinerea, Fusarium culmorum and Fusarium solani, in which 3 displayed significant inhibitory effects on all three phytopathogenic fungi, showing respective MIC of 50, 25 and 25 µM.

Ulmoidol, an unusual nortriterpenoid from Eucommia ulmoides Oliv. Leaves prevents neuroinflammation by targeting the PU.1 transcriptional signaling pathway.

Chronic neuroinflammation is closely associated with the development of neurodegenerative diseases, including Alzheimer's disease (AD). In the current study, 13 anti-neuroinflammatory compounds were isolated from Eucommia ulmoides Oliv. leaves. Among these compounds, trans-sinapaldehyde (6), 3',4',5,7-tetrahydroxy-3-methylflavone (7), and amarusine A (13) were isolated from E. ulmoides leaves for the first time. The ursane-type C29-triterpenoid, ulmoidol (ULM, 9), significantly inhibited the production of proinflammatory mediators and reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, ULM inhibited the cluster of differentiation 14 (CD14)/Toll-like receptor 4 (TLR4) signaling pathway and consequently limited the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Notably, electrophoretic mobility shift assay (EMSA) and molecular docking analyses indicated that ULM could prevent PU box binding-1 (PU.1) from binding to DNA, suggesting that PU.1 might be a potential ULM target. In conclusion, ULM alleviates neuroinflammatory responses in microglia, which could be partly explained by its targeting of PU.1 and the resulting suppression of the TLR4/MAPK/NF-κB signaling pathways. These results suggested that ULM may have therapeutic potential as an agent for treating neuroinflammation-related neurodegenerative diseases.

Constituents with potent α-glucosidase inhibitory activity from Pueraria lobata (Willd.) ohwi.

One new flavone hydrate named lobatflavate (1), one new chromone named lobatchrosin (2), and one new isoflavone named 3S,4R-tuberosin (3), along with four known isoflavone analogues (4-7), were isolated from the traditional Chinese medicinal plant of Pueraria lobata (Willd.) ohwi. Their structures were elucidated by extensive spectroscopic methods of IR, UV, HR-ESI-MS, 1D and 2D NMR. The absolute configuration of 3 was determined by CD spectrum associated with TD-DFT calculation analysis. All compounds except for 2 were assayed the inhibitory activity against α-glucosidase. Every tested compound was proved to be more active than positive control of acarbose. Of which 1 and 4 showed significant activity with IC50 value of 1.79µM and 23.01µM (IC50 of acarbose was 1998.79µM). Enzyme kinetic experiments revealed that 1 was irreversible whereas 4 was reversible and non-competitive α-glucosidase inhibitors. Moreover, structure-activity relationship was discussed and the docking studies of 1, 3 and 4 were also carried out.

Knowledge, attitude, and practice of critical care nurses and their influence on acute skin failure patients in China: A multicenter cross-sectional study.

AIM: Acute skin failure (ASF) can happen in critically ill patients. Therefore, adequate knowledge and skills regarding ASF are essential to manage this disorder. The aim of this work was to investigate the nurses' knowledge, attitude, and practice (KAP) regarding ASF patients and to analyze its influencing factors in the intensive care unit. METHODS: A multicenter cross-sectional study was performed in 10 tertiary hospitals in March 2022. Eligible nurses received a survey with a self-designed questionnaire about their KAP regarding ASF, which included three dimensions and a maximum score of 120. A higher score corresponded to better KAP. RESULTS: A total of 255 nurses participated in this study. The mean KAP score was 75.6 ± 16.9. The mean scores of the knowledge, attitude, and practice dimensions were 26.2 ± 10.6, 38.2 ± 6.1, and 11.3 ± 4.3, respectively. The dimensions were ranked according to score (from low to high) as follows: knowledge (2.6 ± 1.1), practice (2.8 ± 1.1), and attitude (3.8 ± 0.6). Multivariate linear regression analysis showed that more training sessions and an advanced professional title were associated with higher KAP scores. CONCLUSIONS: The overall KAP score on ASF was low in nurses. Nurses had a positive attitude towards ASF, but their knowledge and practice required significant improvement. Those who had received more training and held a more advanced professional title exhibited higher KAP scores regarding ASF. Therefore, nurse managers should establish a relevant knowledge training system, strengthen relevant training, and improve nursing practices for ASF in order to achieve a high level of KAP in nurses who treat ASF patients.

Structures and absolute configurations of butenolide derivatives from the isopod-associated fungus Pidoplitchkoviella terricola.

In this research, twenty aromatic and branched aliphatic polyketides, including seven previously undescribed butenolide derivatives, piterriones A-G and one known analogue, along with twelve known altenusin derivatives, were isolated from the isopod-associated fungus Pidoplitchkoviella terricola. Their structures were elucidated by analysis of NMR (1D and 2D) and mass spectrometry data, and their absolute configurations were determined by Mosher's method, microscale derivatization, and comparison of their specific rotations and ECD spectra. Dihydroaltenuene B exhibited mushroom tyrosinase inhibitory activity with an IC50 value of 38.33 ± 1.59 µM, which was comparable to that of the positive control, kojic acid (IC50 = 39.72 ± 1.34 µM). A molecular-docking study disclosed the hydrogen bonding interactions between the 3-OH and 4'-OH of dihydroaltenuene B and the His244, Met280 and Gly281 residues of tyrosinase.

Alkylated Salicylaldehydes and Prenylated Indole Alkaloids from the Endolichenic Fungus Aspergillus chevalieri and Their Bioactivities.

Sixteen metabolites, including seven C7-alkylated salicylaldehyde derivatives (1-7) and nine prenylated indole alkaloids (8-16), three of which are new, namely, asperglaucins A and B (1 and 2) and neoechinulin F (8), were separated from the endolichenic fungus Aspergillus chevalieri SQ-8. Asperglaucin A (1) represents an unusual phthalide-like derivative with a benzo[c]thiophen-1(3H)-one scaffold. All compounds were assessed in vitro for antibacterial, antineuroinflammatory, and antioxidant activities. Notably, asperglaucins A and B exhibited potent antibacterial activities against two plant pathogens Pseudomonas syringae pv actinidae (Psa) and Bacillus cereus, with an MIC value of 6.25 µM; further SEM analyses illustrated that the possible bacteriostatic mechanisms for compounds 1 and 2 were to alter the external structure of B. cereus and Psa, and to cause the rupture or deformation of the cell membranes, respectively, and the results suggest that compounds 1 and 2 may serve as potential promising candidates for lead compounds of agrochemical bactericides. Furthermore, compounds 6 and 10 significantly inhibited nitric oxide production with an IC50 value of ca. 12 µM, and the possible anti-inflammatory mechanisms involved were also studied by molecular docking. Finally, the tested phenolics 3-5 showed significant antioxidative effects. Thus, strain SQ-8 represents a novel resource of these bioactive metabolites to be utilized.

Trinor- and tetranor-eremophilane sesquiterpenoids with anti-neuroinflammatory activity from cultures of the fungus Septoria rudbeckiae.

Fifteen eremophilane sesquiterpenoids, including nine undescribed congeners, septeremophilane A-H, and chaetopenoid G, together with four conjugated unsaturated polyketide fatty acids, including an undescribed derivative, were isolated from cultures of the fungus Septoria rudbeckiae, a plant pathogenic fungus isolated from the halophyte Karelinia caspia. Septeremophilane A represents an unprecedented tetranor-eremophilane sesquiterpenoid with an α,ß-unsaturated δ-lactone unit bearing a hemiacetal group, while septeremophilane B-H possesses a trinor-eremophilane skeleton. Their structures and absolute configurations were established based on spectroscopic data (NMR and HRESIMS), quantum chemical calculations and electronic circular dichroism (ECD) experiments. All metabolites were tested for nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated BV-2 microglial cells, while dendryphiellin D, septeremophilane D, and septeremophilane E were found to display significant inhibition, with IC50 values of 11.9 ± 1.0, 8.5 ± 0.1, and 6.0 ± 0.2 µM, respectively.

Physical models and limits of radionuclides for decorative building materials.

In the past, the external exposure dose model for soil (the soil's physical model) was used to calculate the doses of decorative building materials because there was no materials model. In this paper, physical models are proposed to calculate the absorbed dose rates in air from decorative building materials by Monte Carlo simulation with the EGSnrc code. The physical models of this paper greatly differ from physical models for soil. The good agreement between simulations and measured absorbed dose rate in indoor air indicates that the results obtained by the Monte Carlo simulations are realistic. The absorbed dose rates in air calculated by physical models for soil are much higher than the measured dose rates. According to the reports of UNSCEAR 2000 and ICRP 1999, the limits of radionuclides in some kinds of decorative building materials were deduced by using the physical models for materials presented in our work. The limits of every kind of decorative building material from our work are different.

Tissue Levels of Stefin A and Stefin B in Hepatocellular Carcinoma.

Stefins have been reported to be associated with the progression and metastasis of various malignant tumors. However, the expressions of stefins in hepatocellular carcinoma (HCC) have not been well-defined. In this study, the protein levels of stefin A and stefin B were assessed by immunohistochemical staining, and the mRNA levels were quantified by real-time polymerase chain reaction in 85 primary HCC tissues, 85 surrounding non-cancerous tissues, and 9 normal hepatic tissues. The immunohistochemical staining of cathepsin B and cathepsin D, and the ratio of cathepsins to stefins were assessed. The mRNA expressions of stefin A and stefin B in HCC tissues were significantly higher than surrounding noncancerous tissues and normal hepatic tissues, respectively. A significant positive relationship of stefin A and stefin B was found with node metastasis, tumor size, and Edmondson grade for HCC. Univariate and multivariate analyses revealed that Edmondson grade and stefin B expression were independent factors associated with the risk of lymph node metastasis in HCC. The ratios of cathepsin B to stefin A, cathepsin D to stefin A, cathepsin B to stefin B and cathepsin D to stefin B of the HCC group were significantly higher than that of the surrounding noncancerous group. A significant positive correlation between the ratio of cathepsins to stefins (cathepsin B/stefin A, cathepsin B/stefin B and cathepsin D/stefin B) and node metastasis was demonstrated. We concluded that high expressions of stefin A and stefin B may be an important factor contributing to the development and metastasis of HCC.

Biological treatment of TMAH (tetra-methyl ammonium hydroxide) in a full-scale TFT-LCD wastewater treatment plant.

This study evaluated biological treatment of TMAH in a full-scale methanogenic up-flow anaerobic sludge blanket (UASB) followed by an aerobic bioreactor. In general, the UASB was able to perform a satisfactory TMAH degradation efficiency, but the effluent COD of the aerobic bioreactor seemed to increase with an increased TMAH in the influent wastewater. The batch test results confirmed that the UASB sludge under methanogenic conditions would be favored over the aerobic ones for TMAH treatment due to its superb ability of handling high strength of TMAH-containing wastewaters. Based on batch experiments, inhibitory chemicals present in TFT-LCD wastewater like surfactants and sulfate should be avoided to secure a stable methanogenic TMAH degradation. Finally, molecular monitoring of Methanomethylovorans hollandica and Methanosarcina mazei in the full-scale plant, the dominant methanogens in the UASB responsible for TMAH degradation, may be beneficial for a stable TMAH treatment performance.