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This study aimed to evaluate the effects of curcumin by co-administration of arsenic trioxide (AsUsing Pubchem database, Traditional Chinese Medicine Information Database (TCMID) database, and Swiss target prediction database to predict compound-related targets, AML-associated targets were determined using GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. We identify overlapping common targets by comparing Compounds-related and AML-associated targets and using these targets to perform GO and KEGG functional enrichment analyses. Subsequently, these targets were input into the STRING database, and we used Cytoscape to construct protein-protein interaction (PPI) network. Finally, we used KG1-a cells and the AML mouse model to measure the anti-leukemia effects of curcumin and AsCompounds and targets screening hinted that 85 intersection targets were predicted in the curcumin treatment of AML, 75 targets in the AsOur results suggested that curcumin and As

The role of interdecadal wind stress variability in the genesis of ENSO diversity is examined by using an intermediate coupled model (ICM) in the tropical Pacific; two types of experiments are performed, one with the original ICM, and the other with interdecadal wind stress (τ𝑖𝑛𝑡𝑒𝑟𝑑𝑒) effect is explicitly represented. The τ𝑖𝑛𝑡𝑒𝑟𝑑𝑒 component is derived from NCEP/NCAR reanalysis dataset as follows. First, the ensemble empirical mode decomposition (EEMD) is used to extract the interdecadal component of wind stress anomalies on about a 10-40yr timescale. Next, an idealized interdecadal cycle of τ𝑖𝑛𝑡𝑒𝑟𝑑𝑒 is reconstructed by a principal oscillation pattern (POP) analysis based on the EEMD-extracted interdecadal wind component. A 110-yr model integration is then performed by explicitly incorporating the reconstructed τ𝑖𝑛𝑡𝑒𝑟𝑑𝑒 cycle into the ICM. Compared with the regular interannual oscillation in the original ICM, the simulated ENSO events become highly irregular with decadal variations in the amplitude and asymmetry when the τ𝑖𝑛𝑡𝑒𝑟𝑑𝑒 effect is included. Especially, the model reproduces different types of El Niño and La Niña events with different spatial distribution and temporal evolution of SST anomalies, namely Eastern-Pacific (EP) and Central-Pacific (CP) types. Further attribution analyses are performed to understand the modulating effects of τ𝑖𝑛𝑡𝑒𝑟𝑑𝑒 in the tropical Pacific using the ocean component of the ICM, forced by the added τ𝑖𝑛𝑡𝑒𝑟𝑑𝑒 effect. Two different roles of the Interdecadal Pacific Oscillation (IPO) in modulating different El Niño and La Niña events are illustrated. On the one hand, the IPO favors for the emergence of the EP type of El Niño and La Niña events, in association with the initial anomaly signals 3 occurring in the eastern equatorial Pacific, which are absent in the original ICM. On the other hand, the IPO tends to shift the El Niño/La Niña events to an CP type, with which the SST anomalies propagate eastward along the equator but cannot extend into the eastern boundary. This simple modeling study highlights the significant contributions of interdecadal wind variability to the genesis of ENSO irregularity and diversity theoretically.

How to fabricate durable superhydrophobic materials for cyclic oil/water separation to solve oil-induced pollutions is still a problem. Herein, we fabricated a durable Superhydrophobic Stainless Steel Mesh (SH-SSM) with nano/micro flower-like sheets by self-assembly of zinc stearate for the cyclic separation of various oil/water mixtures. The SH-SSM exhibits durable superhydrophobicity against static or dynamic treatments. In virtue of durable superhydrophobicity of the SH-SSM, the dusts on surface of SH-SSM can be removed completely by running water immediately showing excellent self-cleaning performance. Moreover, the SH-SSM can be used to perform gravity-driven separation of heavy oil/water and light oil/water mixtures by utilizing its superhydrophobicity that oil phase penetrates the mesh and water phase is restricted. Separation efficiencies of the SH-SSM can reach 99.99%. After 20 cycles of separation, the separation efficiencies for are > 97.00% and > 98.25% for heavy oil/water and light oil/water mixtures, respectively. Flux values of dichloromethane, hexane and petroleum ether are 2.5 × 105 L m−2 h−1, 1.7 × 105 L m−2 h−1, and 1.8 × 105 L m−2 h−1, respectively. This study proposes a facial approach to prepare durable superhydrophobic and self-cleaning material for cyclic and fast separation of oil/water.

Background Ferroptosis, which is characterized by lipid peroxidation and iron accumulation, is closely associated with the pathogenesis of acute renal injury (AKI). Cyanidin-3-glucoside (C3G), a typical flavonoid that has anti-inflammatory and antioxidant effects on ischemia‒reperfusion (I/R) injury, can induce AMP-activated protein kinase (AMPK) activation. This study aimed to show that C3G exerts nephroprotective effects against I/R-AKI related ferroptosis by regulating the AMPK pathway. Methods Hypoxia/reoxygenation (H/R)-induced HK-2 cells and I/R-AKI mice were treated with C3G with or without inhibiting AMPK. The level of intracellular free iron, the expression of the ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4), and the levels of the lipid peroxidation markers 4-hydroxynonenal (4-HNE), lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were examined. Results We observed the inhibitory effect of C3G on ferroptosis in vitro and in vivo, which was characterized by the reversion of excessive intracellular free iron accumulation, a decrease in 4-HNE, lipid ROS, MDA levels and ACSL4 expression, and an increase in GPX4 expression and glutathione (GSH) levels. Notably, the inhibition of AMPK by CC significantly abrogated the nephroprotective effect of C3G on I/R-AKI models in vivo and in vitro. Conclusion Our results provide new insight into the nephroprotective effect of C3G on acute I/R-AKI by inhibiting ferroptosis by activating the AMPK pathway.

Intestinal absorption of vitamin D is an important way to improve the vitamin D level in senile osteoporosis (SOP). There is a link between oral probiotics and vitamin D, but the mechanism is still unclear. We aimed to evaluate whether Lactobacillus rhamnosus GG culture supernatant (LCS) can affect cholecalciferol absorption, transport, and hydroxylation in SOP, and explore underlying mechanisms. In the study, specific-pathogen-free SAMP6 mice were randomly divided into an experimental group administered undiluted LCS and a control group administered normal drinking water. Furthermore, levels of cholecalciferol absorption were compared between Caco-2 cells cultured with varying concentrations of cholecalciferol and stimulated with LCS or de Man, Rogosa, and Sharpe (MRS) broth (control). Similarly, LCS-stimulated HepG2 cells were compared with MRS-stimulated HepG2 cells. Finally, protein levels of VD transporters in small intestine tissues and Caco-2 cells, as well as vitamin D-binding protein and 25-hydroxylase in liver tissues and HepG2 cells, were detected by western blot. The results showed that plasma concentrations of cholecalciferol and 25OHD

Distributed Denial of Service (DDoS) attacks are among the most severe threats in cyberspace. The existing methods are only designed to decide whether certain types of DDoS attacks are ongoing. As a result, they cannot detect other types of attacks, not to mention the even more challenging mixed DDoS attacks. In this paper, we comprehensively analyzed the characteristics of various types of DDoS attacks and innovatively proposed five new features from heterogeneous packets including entropy rate of IP source flow, entropy rate of flow, entropy of packet size, entropy rate of packet size, and number of ICMP destination unreachable packet to detect not only various types of DDoS attacks, but also the mixture of them. The experimental results show that the proposed fives features ranked at the top compared with other common features in terms of effectiveness. Besides, by using these features, our proposed framework outperforms the existing methods when detecting various DDoS attacks and mixed DDoS attacks. The detection accuracy improvements over the existing methods are between 21% and 53%.

Bleeding is a major adverse event during clopidogrel treatment in patients with acute coronary syndrome (ACS). However, the potential mechanism affecting bleeding among individuals is unclear. Herein, we investigated the involvement of CYP2C19*2 and CYP2C19*3, as well as 10 miRNA polymorphisms, in bleeding in Chinese patients with ACS during the first year of clopidogrel treatment. The miR-6076 rs1463411 G polymorphism was significantly associated with the risk of bleeding (P P miR-6076 significantly decreased the mRNA expression of P2RY12 (P miR-6076-G than in cells transfected with miR-6076-T (P miR-6076 targets P2RY12 mRNA and that miR-6076 rs1463411 T/G polymorphisms differentially regulate P2RY12 mRNA and protein levels in cells. rs1463411 G polymorphism may increase the risk of bleeding during clopidogrel treatment in patients with ACS.

Background Atherosclerosis (AS) is a chronic disease characterized by abnormal blood lipid metabolism, inflammation and vascular endothelial injury. Vascular endothelial injury is the initial stage during the occurrence of AS. However, the function and mechanism of anti-AS are not well characterized. Danggui-Shaoyao-San (DGSY) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of gynecological diseases, and has been widely used in the treatment of AS in recent years. Methods ApoE−/− atherosclerosis male mice were established by feeding with high-fat diet, and then randomly divided into three groups: Atherosclerosis group (AS), Danggui-Shaoyao-San group (DGSY), and Atorvastatin calcium group (X). The mice were administered with the drugs for 16 weeks. Pathological changes in aortic vessels were examined by staining with Oil red O, Masson and hematoxylin–eosin. In addition, blood lipids were analyzed. The level of IL-6 and IL-8 in aortic vessels were detected by ELISA and the expression of ICAM-1 and VCAM-1 in the aortic vascular endothelium were measured by Immunohistochemical. The mRNA expression of interα5β1/c-Abl/YAP in the aortic vessels were measured by Real-time quantitative PCR and location of expression was assessed by immunofluorescence. Results DGSY can significantly reduce the content of TC,TG and LDL-C and increase the level of HDL-C in the serum, reduce the plaque area and inhibit the concentration of IL-6 and IL-8, down-regulate the expression of IVAM-1,VCAM-1 and interα5β1/ c-Abl/YAP in the aortic vessels. Conclusions Collectively, DGSY can alleviate vascular endothelium damage and delay the occurrence of AS, and the underlying mechanism may be related to the multi-target protective of DGSY.

The aim of this study was to quantitatively analyze the mechanical change of spinal segments (disc, muscle, and ligament) at various postures under microgravity using a full-body musculoskeletal modeling approach. Specifically, in the lumbar spine, the vertebra were modeled as rigid bodies, the intervertebral discs were modeled as 6-degree-of-freedom joints with linear force-deformation relationships, the disc swelling pressure was deformation dependent, the ligaments were modeled as piecewise linear elastic materials, the muscle strength was dependent on its functional cross-sectional area. The neutral posture and the “fetal tuck” posture in microgravity (short as “Neutral 0G” and “Fetal Tuck 0G”, in our simulation, the G constant was set to 0 for simulating microgravity), and for comparison, the relaxed standing posture in 1G and 0G gravity (short as “Neutral 1G” and “Standing 0G”) were simulated. Compared to values at Neutral 1G, the mechanical response in the lower spine changed significantly at Neutral 0G. For example, the compressive forces on lumbar discs decreased 62–70%, the muscle forces decreased 55.7–92.9%, while disc water content increased 7.0–10.2%, disc height increased 2.1–3.0%, disc volume increased 6.4–9.3%, and ligament forces increased 59.5–271.3% at Neutral 0G. The fetal tuck 0G reversed these changes at Neutral 0G back toward values at Neutral 1G, with magnitudes much larger than those at Neutral 1G. Our results suggest that microgravity has significant influences on spinal biomechanics, alteration of which may increase the risks of disc herniation and degeneration, muscle atrophy, and/or ligament failure.

Bile acid (BA) homeostasis is regulated by the extensive cross-talk between liver and intestine. Many bile-acid-activated signaling pathways have become attractive therapeutic targets for the treatment of metabolic disorders. In this study we investigated the regulatory mechanisms of BA in the intestine. We showed that the BA levels in the gallbladder and faeces were significantly increased, whereas serum BA levels decreased in systemic Krüppel-like factor 9 (Klf9) deficiency (Klf9

Most genetic studies concerning risk genes in Alzheimer’s disease (AD) are from Caucasian populations, whereas the data remain limited in the Chinese population. In this study, we systematically explored the relationship between AD and risk genes in mainland China. We sequenced 33 risk genes previously reported to be associated with AD in a total of 3604 individuals in the mainland Chinese population. Common variant (MAF ≥ 0.01) based association analysis and gene-based (MAF

Background The marine diatom Phaeodactylum tricornutum is a commercially viable species due to its bioactive substances and lipid productivity. Increasing attention has been paid to the isolation or genetic modification of species or strains with a rapid growth rate and large quantities of lipids. Furthermore, contamination of microzooplankton has been one of the major constraints in P. tricornutum large-scale cultivation, which adversely affects growth and greatly impedes the course of biomass production industrialization. Results Here, based on our previous transcriptomics of P. tricornutum, we found a novel gene (ID: 7202015, hereafter called Pt2015) which affects morphotype of P. tricornutum. Pt2015 protein is located in the plastid, which is highly homologous to part of the sequences of exosome component. The morphotype of the Pt2015 knockout strain (termed 2015KO) using CRISPR/Cas9 method is fusiform, but the Pt2015 overexpression strain (termed oeT) demonstrates a majority triradiate morphotype (approximately 95%) which is stable and has been cultured for more than 200 generations. In addition, the oeT strain demonstrated a similar growth rate to the WT and simultaneously accumulated larger lipids droplets that increased by approximately 30% compared to that of the WT. More importantly, the grazing rate of the amoebae cultured in the oeT strain significantly decreased in comparison with that cultured in WT, suggesting that the oeT can effectively avoid being eaten by microzooplankton. Conclusions Therefore, the oeT strain not only improves our understanding of morphotype conversion in diatoms but also demonstrates potential applications for large-scale cultivation of P. tricornutum.

Background: Dietary fish-oil supplementation might attenuate the associations between fine particulate matter (PM2.5) and subclinical biomarkers. However, the molecular mechanisms remain to be elucidated. This study aimed to explore the molecular mechanisms of fish-oil supplementation against the PM2.5-induced health effects. Methods: We conducted a randomized, double-blinded, and placebo-controlled trial among healthy college students in Shanghai, China, from September 2017 to January 2018. A total of 70 participants from the Fenglin campus of Fudan University were included. We randomly assigned participants to either supplementation of 2.5-gram fish oil (n = 35) or sunflower-seed oil (placebo) (n = 35) per day and conducted four rounds of health measurements in the last two months of the trial. As a post hoc exploratory study, the present untargeted metabolomics analysis used remaining blood samples collected in the previous trial and applied a Metabolome-Wide Association Study framework to compare the effects of PM2.5 on the metabolic profile between the sunflower-seed oil and fish oil groups. Results: A total of 65 participants completed the trial (34 of the fish oil group and 31 of the sunflower-seed oil group). On average, ambient PM2.5 concentration on the day of health measurements was 34.9 µg/m3 in the sunflower-seed oil group and 34.5 µg/m3 in the fish oil group, respectively. A total of 3833 metabolites were significantly associated with PM2.5 in the sunflower-seed oil group and 1757 in the fish oil group. Of these, 1752 metabolites showed significant between-group differences. The identified differential metabolites included arachidonic acid derivatives, omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids that were related to unsaturated fatty acid metabolism, which plays a role in the inflammatory responses. Conclusion: This trial suggests fish-oil supplementation could mitigate the PM2.5-induced inflammatory responses via modulating fatty acid metabolism, providing biological plausibility for the health benefits of fish-oil supplementation against PM2.5 exposure. Trial registration: This study is registered at ClinicalTrails.gov (NCT03255187).

The medicinal plant Artemisia annua L. is presently the sole plant source of artemisinin, the key ingredient of first-line antimalarial drug. As the content of artemisinin in the native plant is very low, the growth and artemisinin biosynthesis of A. annua attract extensive attentions. Endophytic microbes, which spend their entire life spans within plant tissue are widespread in healthy A. annua plants. Although endophytes have emerged in recent years as the novel resources for secondary metabolites of antioxidant, antimicrobial and anticancer activities, the roles of endophytes in plant growth and metabolism have not been fully understood. This review presents the current development of researches into endophytes in model medicinal herb A. annua and focuses on the regulatory roles of endophytes. We introduced the isolation, cultivation and identification method for endophytes in A. annua. Distribution, biodiversity and novel bioactive metabolites of the endophytes were presented. Endophytes promoted the growth of A. annua through the enhanced photosynthesis, nutrient acquisition and phytohormones. The defense resistance against microbial pathogens of A. annua was partially involved with endophyte metabolites. The development of glandular secretory trichomes and the oxidative stress induced by endophytes could be key factors for enhanced artemisinin production. Understanding the endophyte-host partnerships has the potential to improve agricultural practices for A. annua growth and artemisinin production. The aim of this review is to shed light on the importance of endophytes in plant growth and the production of medicinally important secondary metabolites.

Photosynthetic organisms have evolved photoprotective mechanisms to acclimate to light intensity fluctuations in their natural growth environments. Photosystem (PS) II subunit S (PsbS) and light-harvesting complex (LHC) stress-related proteins (LhcSR) are essential for triggering photoprotection in vascular plants and green algae, respectively. The activity of both proteins is strongly enhanced in the moss Physcomitrella patens under high-light conditions. However, their role in regulating photosynthesis acclimation in P. patens under fluctuating light (FL) conditions is still unknown. Here, we compare the responses of wild-type (WT) P. patens and mutants lacking PsbS (psbs KO) or LhcSR1 and 2 (lhcsr KO) to FL conditions in which the low-light phases were periodically interrupted with high-light pulses. lhcsr KO mutant showed a strong reduction in growth with respect to WT and psbs KO under FL conditions. The lack of LhcSR not only decreased the level of non-photochemical quenching, resulting in an over-reduced plastoquinone pool, but also significantly increased the PSI acceptor limitation values with respect to WT and psbs KO under FL conditions. Moreover, in lhcsr KO mutant, the abundance of PSI core and PSI-LHCI complex decreased greatly under FL conditions compared with the WT and psbs KO. We proposed that LhcSR in P. patens play a crucial role in moss acclimation to dynamic light changes.

In order to enhance degradation of harmful organic pollutants like Rhodamine B (RhB) dye under visible-light irradiation (λ >420 nm), a silver iodide/reduced graphene oxide/bismuth molybdate (AgI/rGO/Bi2MoO6) Z-scheme heterojunction photocatalyst was synthesized by a solvothermal process combined with an in-situ precipitation technique. The AgI (15 wt.%)/rGO/Bi2MoO6 (AGBMO-15) photocatalyst with a dosage of 0.5 g/L exhibited the highest photocatalytic activity with 98.0% RhB removal under an initial concentration of 10 mg/L within 30 min. This removal rate was approximately 65.8%, 57.7%, and 72.7% higher than that for a rGO/Bi2MoO6 (GBMO) binary composite, pure AgI powder, and pristine Bi2MoO6 nanoplates, respectively. The novel photocatalyst achieved approximately three times higher photocatalytic degradation within a shorter period of visible-light irradiation than pure Bi2MoO6. Through photoluminescence analysis and trapping experiments, this outstanding performance was attributed to the efficient separation of photogenerated electron-hole pairs owing to an internal electric field at the contact interface of AgI and Bi2MoO6, which generated more superoxide radical anions (•O2–) as primary reactive species to promote RhB degradation. Meanwhile, the rGO participated in the capture of visible-light and played a role of solid electronic medium at the AgI/Bi2MoO6 interface, which realized an effective Z-scheme electron transfer path, avoided the self oxidation of photocatalyst and prolonged the carrier life. Furthermore, the AGBMO-15 photocatalyst exhibited excellent photocatalytic degradation stability, maintaining an RhB removal rate of 96.2% after four cycles of reuse. Due to its simplicity, reusability, and controllability, the proposed photocatalyst has excellent application potential for the environmental remediation of wastewater.

Background The pathogenesis of inflammatory bowel diseases (IBD) is multifactorial, and diagnostic and treatment strategies for IBD remain to be developed. RhoB regulates multiple cell functions; however, its role in colitis is unexplored. Results Here, we found RhoB was dramatically increased in colon tissues of ulcerative colitis (UC) patients and mice with DSS-induced colitis. Compared with wild type mice, RhoB+/− and RhoB−/− mice developed milder DSS-induced colitis and increased goblet cell numbers and IEC proliferation. Decreased RhoB promoted goblet cell differentiation and epithelial regeneration through inhibiting Wnt signaling pathway and activating p38 MAPK signaling pathway. Moreover, increased SCFA-producing bacteria and SCFA concentrations were detected in intestinal microbiome of both RhoB+/− and RhoB−/− mice and upregulated SCFA receptor expression was also observed. Conclusions Taken together, a higher level of RhoB is associated with UC, which also contributes to UC development through modulating cell signaling and altering intestinal bacterial composition and metabolites. These observations suggest that RhoB has potential as a biomarker and a treatment target for UC.