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The uncontrolled growth of lithium dendrites and accumulation of “dead lithium” upon cycling are among the main obstacles that hinder the widespread application of lithium metal anodes. Herein, an ionic liquid (IL) consisting of 1-methyl-1-propylpiperidinium cation (Pp13+) and bis(fluorosulfonyl)imide anion (FSI−), was chosen as the additive in propylene carbonate (PC)-based liquid electrolytes to circumvent the shortcoming of lithium metal anodes. The optimal 1% Pp13FSI acts as the role of electrostatic shielding, lithiophobic effect and participating in the formation of solid electrolyte interface (SEI) layer with enhanced properties. The in-situ optical microscopy records that the addition of IL can effectively inhibit the growth of lithium dendrites and the corrosion of lithium anode. This study delivers an effective modification to optimize electrolytes for stable lithium metal batteries.

Aims COVID-19 pandemic caused by SARS-CoV-2 has become a public health crisis worldwide. In this study, we aimed at demonstrating the neutralizing potential of the IgY produced after immunizing chicken with a recombinant SARS-CoV-2 spike protein S1 subunit. Methods and Results E. coli BL21 carrying plasmid pET28a-S1 was induced with IPTG for the expression of SARS-CoV-2 S1 protein. The recombinant His-tagged S1 was purified and verified by SDS-PAGE, Western blot and biolayer interferometry (BLI) assay. Then S1 protein emulsified with Freund's adjuvant was used to immunize layer chickens. Specific IgY against S1 (S1-IgY) produced from egg yolks of these chickens exhibited a high titer (1:25,600) and a strong binding affinity to S1 (KD = 318 nmol L−1). The neutralizing ability of S1-IgY was quantified by a SARS-CoV-2 pseudotyped virus-based neutralization assay with an IC50 value of 0.99 mg ml−1. In addition, S1-IgY exhibited a strong ability in blocking the binding of SARS-CoV-2 S1 to hACE2, and it could partially compete with hACE2 for the binding sites on S1 by BLI assays. Conclusions We demonstrated here that after immunization of chickens with our recombinant S1 protein, IgY neutralizing antibodies were generated against the SARS-CoV-2 spike protein S1 subunit; therefore, showing the potential use of IgY to block the entry of this virus. Significance and Impact of the Study IgY targeting S1 subunit of SARS-CoV-2 could be a promising candidate for pre- and post-exposure prophylaxis or treatment of COVID-19. Administration of IgY-based oral preparation, oral or nasal spray may have profound implications for blocking SARS-CoV-2.

Bearing unique redox nature and high oxygen storage capacity, ceria (CeO2) has always been a promising CO oxidation catalyst support for gold (Au) catalysts and the like. Herein, a serial of Au-CeO2-P (P stands for pH value) samples was prepared by a co-precipitation method with the assistance of an alkaline environment and amino groups functionalized ordered mesoporous polymer (OMP-NH2). Afterward, all samples described above were characterized that the Au-CeO2-P catalysts are made of Au-Ce-O solid solution and Au NPs supported on CeO2. It turns out that OMP-NH2 is not just a simple sacrificial template for mesoporous structure, but also plays an important role as an amino source, explaining the presence of rich oxygen vacancies. Due to the concentration of oxygen vacancies in Au-Ce-O solid solution is the key factor for the oxygen mobility of CO oxidation, the catalytic results also demonstrate that the catalytic activity of Au-CeO2-P catalysts is related to the concentration of their oxygen vacancies. Moreover, Au-CeO2-9.6 with a highest concentration of oxygen vacancies (as high as 13.98%) in Au-CeO2-P catalysts exhibits a best catalytic activity (complete conversion at 10 °C).

Background: The sarcoplasmic reticulum (SR) Ca 2+ -ATPase 2 (SERCA2) mediates Ca 2+ reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca 2+ release from SR and triggers contraction. Ca 2+ /CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation of PLN (phospholamban) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local Ca 2+ signals remain elusive. The objective of this study was to investigate CaMKIIδ anchoring and regulation at SERCA2-PLN and RYR. Methods: A role for AKAP18δ (A-kinase anchoring protein 18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adenoassociated virus injection, structural modeling, surface plasmon resonance, and alpha screen technology. Results: Our results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via 2 distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to the natural CaMKII inhibitor peptide and the Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent Ca 2+ threshold for kinase activation and inducing CaM trapping. While AKAP18δ-C facilitated faster Ca 2+ reuptake by SERCA2 and Ca 2+ release through RYR, AKAP18δ-N had opposite effects. We propose a model where the 2 unique AKAP18δ regions fine-tune Ca 2+ -frequency-dependent activation of CaMKIIδ at SERCA2-PLN and RYR. Conclusions: AKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge, this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP (A-kinase anchoring protein) reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP.

Folic acid (FA) supplementation in early pregnancy is recommended to protect against birth defects. But excess FA has exhibited neurodevelopmental toxicity. We previously reported that the mice treated with 2.5-fold the dietary requirement of FA one week before mating and throughout pregnancy and lactation displayed abnormal behaviors in the offspring. Here we found the levels of non-phosphorylated β-catenin (active) were increased in the brains of weaning and adult FA-exposed offspring. Meanwhile, demethylation of protein phosphatase 2 A catalytic subunit (PP2Ac), which suppresses its enzyme activity in regulatory subunit dependent manner, was significantly inhibited. Among the upstream regulators of β-catenin, PI3K/Akt/GSK-3β but not Wnt signaling was stimulated in FA-exposed brains only at weaning. In mouse neuroblastoma N2a cells, knockdown of PP2Ac or leucine carboxyl methyltransferase-1 (LCMT-1), or overexpression of PP2Ac methylation-deficient mutant decreased β-catenin dephosphorylation. These results suggest that excess FA may activate β-catenin via suppressing PP2Ac demethylation, providing a novel mechanism for the influence of FA on neurodevelopment.

Constitutionally adaptive chemistry of selenium-containing crown ethers (CEs) offers a new platform for controlling/switching the hydration of bolaamphiphile skeletons in water in an effective and simple manner by the virtue of covalent bonding. The adaptive behaviour of the macrocyclic bolaamphiphiles (transformations between C7SeBola and C7SeOBola) in response to redox environment was found to be a decisive factor.

N-acetyltransferase 10 (NAT10) is the key enzyme for N4-acetylcytidine (ac4C) modification of mRNA, which participates in various cellular processes and is related to many diseases. Here, we explore the relationships among osteoblast differentiation, NAT10, and ac4C, and we found that NAT0 expression and the ac4C level of total RNA were decreased in the bone tissues of bilateral ovariectomized (OVX) mice and osteoporosis patients. Adenoviruses overexpressing NAT10 reversed bone loss, and Remodelin, an NAT10 inhibitor, enhanced the loss of bone mass in OVX mice. Moreover, bone marrow-derived mesenchymal stem cells (BMSCs) with low-level ac4C modification formed fewer calcium nodules in vitro with NAT10 silencing, whereas BMSCs with high-level ac4C modification formed more calcium nodules with NAT10 overexpression. Moreover, we demonstrated that the ac4C level of runt-related transcription factor 2 (RUNX2) mRNA was increased after BMSCs were cultured in osteogenic medium (OM) and decreased after NAT10 silencing. The RUNX2 mRNA half-life and protein expression decreased after silencing NAT10 in BMSCs. Therefore, NAT10-based ac4C modification promotes the osteogenic differentiation of BMSCs by regulating the RUNX2 ac4C level. Because abnormal levels of NAT10 are probably one of the mechanisms responsible for osteoporosis, NAT10 is a new potential therapeutic target for this disease., Graphical abstract, NAT10 catalyzes the addition of ac4C to RUNX2 mRNA, which increases the half-life of RUNX2 mRNA and promotes osteogenic differentiation of BMSCs. Moreover, overexpression of NAT10 with adenovirus reversed the bone loss in OVX mice. These results indicate that NAT10 may be a new potential therapeutic target for osteoporosis.

The original magnesium slag has poor desulfurization activity, so modification treatments are needed to improve its desulfurization activity. In this article, magnesium slag was modified by quenching hydration. The crystal structure and morphology characteristics were obtained by XRD and TEM. And to further understand the relationship between crystal structure and desulfurization performance, desulfurization experiments were carried out by TGA. A theoretical basis for future development of desulfurization methods was provided, which could not only alleviate the disposal problem but also help control SO2 pollution. The results showed that the naturally cooled magnesium slag was mainly composed of γ-C2S and β-C2S. The irregular coordination of Ca2+ in β-C2S was the main reason that the hydration activity of β-C2S was higher than that of γ-C2S. With the increase of quenching temperature, the β-C2S content increased continuously, promoting the formation of C–S–H with developed pore structure. With the increasing hydration temperature, the hydration reaction of β-C2S could be promoted, and more amorphous C–S–H could be generated. The hydration product C–S–H enhanced the physical adsorption capacity, and the increase of crystal structure defects enhanced the chemical adsorption capacity. At 950 °C quenching temperature and 90 °C hydration temperature, the desulfurization activity was the highest.

Lithium (Li) metal anodes promise an ultrahigh theoretical energy density and low redox potential, thus being the critical energy material for next-generation batteries. Unfortunately, the formation of Li dendrites in Li metal anodes remarkably hinders the practical applications of Li metal anodes. Herein, the dynamic evolution of discrete Li dendrites and aggregated Li dendrites with increasing current densities is visualized by in-situ optical microscopy in conjunction with ex-situ scanning electron microscopy. As revealed by the phase field simulations, the formation of aggregated Li dendrites under high current density is attributed to the locally concentrated electric field rather than the depletion of Li ions. More specifically, the locally concentrated electric field stems from the spatial inhomogeneity on the Li metal surface and will be further enhanced with increasing current densities. Adjusting the above two factors with the help of the constructed phase field model is able to regulate the electrodeposited morphology from aggregated Li dendrites to discrete Li dendrites, and ultimately columnar Li morphology. The methodology and mechanistic understanding established herein give a significant step toward the practical applications of Li metal anodes.

Trans-active response DNA-binding protein of 43 kDa (TDP-43) promotes tau mRNA instability and tau exon 10 inclusion. Aggregation of phosphorylated TDP-43 is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Casein kinase 1ε (CK1ε) phosphorylates TDP-43 at multiple sites, enhances its cytoplasmic aggregation, and modulates its function in tau mRNA processing. To determine roles of TDP-43 site-specific phosphorylation in its localization, aggregation, and function in tau mRNA processing, TDP-43 was mutated to alanine or aspartic acid at Ser379, Ser403/404, or Ser409/410 to block or mimic phosphorylation. Site-specific phosphorylation of TDP-43 and its mutants by CK1ε was studied in vitro and in cultured cells. Cytoplasmic and nuclear TDP-43 and phospho-TDP-43 were analyzed by western blots. Aggregation of TDP-43 was assessed by immunostaining and level of radioimmunoprecipitation assay buffer-insoluble TDP-43. Green florescent protein tailed with tau 3'-untranslated region and mini-tau gene pCI/SI9-LI10 were used to study tau mRNA stability and alternative splicing of tau exon 10. We found that phospho-blocking mutations of TDP-43 at Ser379, Ser403/404, or Ser409/410 were not effectively phosphorylated by CK1ε. Compared with TDP-43, higher level of phosphorylated TDP-43 in the cytoplasm was observed. Phospho-mimicking mutations at these sites enhanced cytoplasmic aggregation of TDP-43. Green florescent protein expression was not inhibited by phospho-blocking mutants of TDP-43, but tau exon 10 inclusion was further enhanced by phospho-blocking mutations at Ser379 and Ser403/404. Phosphorylation of TDP-43 at Ser379, Ser403/404, or Ser409/410 primes its phosphorylation by CK1ε, promotes TDP-43 cytoplasmic aggregation, and modulates its function in tau mRNA processing in site-specific manner.

Background Abnormally elevated xanthine oxidase (XO) activity has been verified to cause various pathological processes, such as gout, oxidative stress injury and metabolic syndrome. Thus, XO activators may exhibit above potential toxicological properties. Plumbagin (PLB) is an important active compound in traditional Chinese medicine (TCM), while its obvious toxic effects have been reported, including diarrhea, skin rashes and hepatic toxicity. However, the potential toxicity associated with enhancement of XO activity has not been fully illuminated so far. Methods The present study investigated the effect of PLB on XO activity by culturing mouse liver S9 (MLS9), human liver S9 (HLS9), XO monoenzyme system with PLB and xanthine. Then, the molecular docking and biolayer interferometry analysis were adopted to study the binding properties between PLB and XO. Finally, the in vivo acceleration effect also investigated by injected intraperitoneally PLB to KM mice for 3 days. Results PLB could obviously accelerate xanthine oxidation in the above three incubation systems. Both the Vmax values and intrinsic clearance values (CLint, Vmax/Km) of XO in the three incubation systems increased along with elevated PLB concentration. In addition, the molecular docking study and label-free biolayer interferometry assay displayed that PLB was well bound to XO. In addition, the in vivo results showed that PLB (2 and 10 mg/kg) significantly increased serum uric acid levels and enhanced serum XO activity in mice. Conclusion In summary, this study outlines a potential source of toxicity for PLB due to the powerful enhancement of XO activity, which may provide the crucial reminding for the PLB-containing preparation development and clinical application.

Background Fibrous dysplasia (FD) is a bone marrow stromal cell (BMSC) disease caused by activating mutations of guanine nucleotide-binding protein alpha-stimulating activity polypeptide (GNAS) and is characterized by increased proliferative activity and disrupted osteogenesis of BMSCs. However, the molecular mechanisms regulating the pathophysiologic features of BMSCs in FD remain unknown. This study aimed to identify and verify the roles of the CREB1-miR-181a-5p regulatory loop in FD pathophysiology. Methods MicroRNA (miRNA) sequencing analysis was used to identify the possible miRNAs implicated in FD. The proliferation, apoptosis, and osteogenic differentiation of BMSCs, as well as the osteoclast-induced phenotype, were measured and compared after exogenous miR-181a-5p transfection into FD BMSCs or miR-181a-5p inhibitor transfection into normal BMSCs. Chromatin immunoprecipitation and luciferase reporter assays were performed to verify the interactions between CREB1 and miR-181a-5p and their effects on the FD pathological phenotype. Results Compared to normal BMSCs, FD BMSCs showed decreased miR-181a-5p levels and exhibited increased proliferative activity, decreased apoptotic capacity, and impaired osteogenesis. FD BMSCs also showed a stronger osteoclast activation effect. miR-181a-5p overexpression reversed the pathophysiologic features of FD BMSCs, whereas miR-181a-5p suppression induced an FD-like phenotype in normal BMSCs. Mechanistically, miR-181a-5p was the downstream target of CREB1, and CREB1 was posttranscriptionally regulated by miR-181a-5p. Conclusions Our study identifies that the interaction loop between CREB1 and miR-181a-5p plays a crucial role in regulating the pathophysiologic features of FD BMSCs. MiR-181a-5p may be a potential therapeutic target for the treatment of FD.

External pressure is widely applied to the fabrication and assembling of solid-state batteries, which can reduce grain sizes, enhance solid–solid contacts, and further increase the ionic conductivi...

Raddeanin A (RA), an active triterpenoid saponin extracted from the Anemone raddeana regel, plays an essential role in the suppression of many malignancies. We aimed to investigate the effects and potential mechanisms of RA on cervical cancer (CC). RA was used to treat CC cell lines (Hela and c-33A) for 24 h and 48 h. Then, the invasion, migration and cell cycle distribution of these two cell lines with RA treatment were respectively detected by transwell, wound healing and flow cytometry. Results revealed that RA significantly inhibited the invasion, migration, promoted the cell cycle arrest and apoptosis of Hela and c-33A cells. Moreover, RA was confirmed to activate the Slit2/Robo1 signaling, and bioinformatics analysis and luciferase reporter assay verified that miR-224-3p could target Slit2. Additionally, miR-224-3p overexpression reversed the inhibitory effect of RA on invasion and migration of CC cells, and it also restored the promoting effects of RA on cell cycle arrest and apoptosis. Lastly, miR-224-3p-upregulation inactivated the expression of Slit2 and Robo1 in RA-treated Hela and c-33A cells. These findings demonstrated that RA inhibits proliferation, invasion, migration and promotes apoptosis of CC cells through miR-224-3p/Slit2/Robo1 signaling pathway, which might guide the future studies or treatment of this disease.

This study examined the impact of chitobiose (GlcN)2 and chitotriose (GlcN)3 on lipid accumulation modification and their inhibitory functionalities. (GlcN)2 and (GlcN)3 significantly inhibited the total cholesterol (TC), triglyceride (TG), and low-density lipid cholesterol (LDL-c) levels in the liver of the ob/ob-/- mice fed a non-high-fat diet. This phenomenon was associated with a reduction in the mRNA and protein expression of TG synthesis and fatty acid uptake-related signaling, significantly affecting the cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2). Furthermore, the CD36 and DGAT2 genes were overexpressed by constructing a plasmid and transfecting it into HepG2 cells, after which the phenotypic traits of lipid accumulation were assessed in vitro. Consequently, it was evident that (GlcN)2 and (GlcN)3 reduced the overexpression of these proteins and relieved cellular lipid accumulation. In conclusion, these results indicated that (GlcN)2 and (GlcN)3 acted positively against NAFLD while regulating steatosis in the non-high-fat diet NAFLD model. The potential NAFLD treatment strategies, such as targeting CD36 and DGAT2 signaling, could provide scientific insight into further applying food-derived ingredients to reduce the risk of high-fat metabolism.

One key objective in electrocatalysis is to design selective catalysts, particularly in cases where the desired products require thermodynamically unfavorable pathways. Electrochemical synthesis of hydrogen peroxide (H2O2) via the two-electron water oxidation reaction (2e− WOR) requires a +0.54 V higher potential than four-electron O2 evolution. So far, best-performing electrocatalysts require considerable overpotentials before reaching peak faradaic efficiency. We present Mn-alloyed TiO2 coatings prepared by atomic layer deposition (ALD) and annealing as a stable and selective electrocatalyst for 2e− WOR. Faradaic efficiency of >90% at < 150 mV overpotentials was achieved for H2O2 production, accumulating 2.97 mM H2O2 after 8 hours. Nanoscale mixing of Mn2O3 and TiO2 resulted in a partially filled, highly conductive Mn3+ intermediate band (IB) within the TiO2 mid-gap to transport charge across the (Ti,Mn)Ox coating. This IB energetically matched that of H2O2-producing surface intermediates, turning a wide bandgap oxide into a selective electrocatalyst capable of operating in the dark. However, the high selectivity is limited to the low overpotential regime, which limits the system to low current densities and requires further research into increasing turn-over frequency per active site.

Long non‑coding RNA (lncRNA) forkhead box P4 antisense RNA 1 (FOXP4‑AS1) has been determined to function as an oncogene in various types of cancer. However, the biological function and the underlying mechanisms of FOXP4‑AS1 in mantle cell lymphoma (MCL) remain to be uncovered. The expression and the associated clinicopathological characteristics and prognostic significance of FOXP4‑AS1 were explored in MCL clinical samples. The effects of FOXP4‑AS1 on MCL cellular behaviors, including proliferation, migration and invasion were analyzed using CCK‑8, crystal violet and Transwell assays. The downstream molecules of FOXP4‑AS1 were explored using bioinformatics analysis and dual luciferase assay. Our results showed that FOXP4‑AS1 expression was upregulated in MCL patients, and that the high expression of FOXP4‑AS1 was correlated with the unfavorable prognosis of patients. Functionally, while FOXP4‑AS1 downregulation inhibited proliferation, migration and invasion of MCL cells, FOXP4‑AS1 overexpression had promotive effects on these cellular processes. Mechanistically, FOXP4‑AS1 was found to act as a competing endogenous (ce)RNA for miR‑423‑5p to regulate the expression of nucleus accumbens‑associated 1 (NACC1). The negative regulation of FOXP4‑AS1 on miR‑423‑5p compared to that of miR‑423‑5p on NACC1 was determined at the mRNA or protein levels in MCL cells. Moreover, an inverse expression correlation between FOXP4‑AS1 and miR‑423‑5p, and that between miR‑423‑5p and NACC1 was confirmed in MCL clinical samples. In addition, rescue assay showed that miR‑423‑5p upregulation or NACC1 knockdown abolished the promoting effects of FOXP4‑AS1 on MCL cell proliferation, migration and invasion. In conclusion, FOXP4‑AS1 promotes MCL progression through the upregulation of NACC1 expression by inhibiting miR‑423‑5p. FOXP4‑AS1 may serve as a novel therapeutic target for patients with MCL.

Heteroatom-doped carbon materials have been widely used as sodium (Na) and potassium (K) metal anode frameworks to achieve uniform Na and K depositions. If the origin of the Sodiophilicity and potassiophilicity of doping sites in heteroatom-doped carbon host are clearly understood, the nucleation and growth behavior of Na and K can be precisely regulated in working batteries. Herein the Sodiophilicity and potassiophilicity chemistries of carbon materials are probed through first-principles calculations. The local dipole of doping functional groups and charge transfer during Na/K deposition are regarded as key principles to reveal the sodiophilic and potassiophilic nature of doping sites. Especially, O–B, O–S, and O–P co-doping strategy are predicted to be effective methods to improve the Sodiophilicity and potassiophilicity of carbon hosts and thus render safe and dendrite-free Na and K metal anodes. This work affords a deep and insightful understanding of Sodiophilicity and potassiophilicity chemistry of Na and K anodes and establishes general principles of designing highly sodiophilic and potassiophilic carbon frameworks.

Recently, studies have shown that neuropathy target esterase (NTE) is essential to placental and normal blood vessel development. However, whether it is involved in abnormal placenta angiogenesis of pre-eclampsia remains unknown. Thus, our aim was to observe the expression of NTE in pre-eclamptic placentas and its effects and mechanism of NTE on the migration and the tube formation of human umbilical vein endothelial cells (HUVECs). Immunohistochemical staining showed that the NTE protein was intensely located in blood vessels of the normal pregnant placenta. However, western blot revealed that the expression level of NTE protein was significantly reduced in pre-eclamptic placenta. The results indicated that overexpression of NTE significantly promoted the migration and the tube formation of HUVECs compared with those of the control and scramble short hairpin RNA (shRNA) group. Conversely, NTE shRNA obviously inhibited the migration and the tube formation of HUVECs. Additionally, chromatography assay evidenced that NTE overexpression significantly reduced the level of phosphatidylcholine (PC) of HUVECs, but NTE shRNA obviously increased the level of PC of HUVECs. Furthermore, exogenous PC and lysophosphatidylcholine (LPC) significantly inhibited the tube formation of HUVECs in a dose-dependent manner. Collectively, our results suggest that reduced NTE in placenta may contribute to abnormal placenta angiogenesis of pre-eclampsia via the dysregulation of PC and LPC metabolism.

Prunella vulgaris (PV) has a long history of application in traditional Chinese and Western medicine as a remedy for the treatment of subacute thyroiditis (SAT). This study applied network pharmacology to elucidate the mechanism of the effects of PV against SAT. Components of the potential therapeutic targets of PV and SAT-related targets were retrieved from databases. To construct a protein-protein interaction (PPI) network, the intersection of SAT-related targets and PV-related targets was input into the STRING platform. Gene ontology (GO) analysis and KEGG pathway enrichment analysis were carried out using the DAVID database. Networks were constructed by Cytoscape for visualization. The results showed that a total of 11 compounds were identified according to the pharmacokinetic parameters of ADME. A total of 126 PV-related targets and 2207 SAT-related targets were collected, and 83 overlapping targets were subsequently obtained. The results of the KEGG pathway and compound-target-pathway (C-T-P) network analysis suggested that the anti-SAT effect of PV mainly occurs through quercetin, luteolin, kaempferol, and beta-sitosterol and is most closely associated with their regulation of inflammation and apoptosis by targeting the PIK3CG, MAPK1, MAPK14, TNF, and PTGS2 proteins and the PI3K-Akt and TNF signaling pathways. The study demonstrated that quercetin, luteolin, kaempferol, and beta-sitosterol in PV may play a major role in the treatment of SAT, which was associated with the regulation of inflammation and apoptosis, by targeting the PI3K-Akt and TNF signaling pathways.

Based on a comprehensive study of the pyrolysis characteristics, pore structure, surface chemical functional groups, organic carbon framework structure, microcrystalline morphology and lattice char...

Summary Building stable electrolytes is one of the key technologies for sodium (Na)-metal batteries as the reactive nature and the dendritic growth of Na-metal anodes. Herein, a paradigmatic and rational strategy of cation additive was proposed to stabilize electrolytes for Na metal batteries. Three principles, including the electrode potential of introduced cations, the lowest unoccupied molecular orbital energy level decrease of solvents after coordinating with cations, and the interaction strength between cations and solvents, were proved through first-principles calculations and molecular dynamics simulations. Li+ was predicted to be a good cation additive candidate for Na metal batteries. Finite element method simulations, in situ optical microscopic observations, and electrochemical tests further validated the resisted Na dendritic growth due to the electrostatic shield effect and enhanced electrolyte stability after introducing Li+ additives. The proven cation additive strategy affords emerging chances for rational electrolyte design for stable and safe Na metal batteries.

Herein, we report that highly chemoselective and enantioselective reduction of 2-vinyl-substituted pyridines has been achieved for the first time. The reaction, which uses chiral spiro-bicyclic bisboranes as catalysts and HBpin and an acidic amide as reducing reagents, proceeds through a cascade process involving 1,4-hydroboration followed by transfer hydrogenation of a dihydropyridine intermediate. The retained double bond in the reduction products permits their conversion to natural products and other useful heterocyclic compounds by simple transformations.

Glutathione peroxidases (GPxs) belong to a family of enzymes that is important in organisms; these enzymes promote hydrogen peroxide metabolism and protect cell membrane structure and function from oxidative damage. Based on the establishment and development of the theory of the pathological roles of free radicals, the role of GPxs has gradually attracted researchers’ attention, and the involvement of GPxs in the occurrence and development of malignant tumors has been shown. On the other hand, the incidence of breast cancer in increasing, and breast cancer has become the leading cause of cancer-related death in females worldwide; breast cancer is thought to be related to the increased production of reactive oxygen species, indicating the involvement of GPxs in these processes. Therefore, this article focused on the molecular mechanism and function of GPxs in the occurrence and development of breast cancer to understand their role in breast cancer and to provide a new theoretical basis for the treatment of breast cancer.

The zeolite Cu(I)Y is promising for adsorptive removal of thiophenic sulfur compounds from transportation fuels. However, its application is seriously hindered by the instability of Cu(I), which is easily oxidized to Cu(II) even under atmospheric environment due to the coexistence of moisture and oxygen. Here, we report the adjustment of zeolite microenvironment from hydrophilic to superhydrophobic status by coating polydimethylsiloxane (yielding Cu(I)Y@P), which isolates moisture entering the pores and subsequently stabilizes Cu(I) despite the presence of oxygen. Cu(I) in Cu(I)Y@P is stable upon exposure to humid atmosphere for 6 months, while almost all Cu(I) is oxidized to Cu(II) in Cu(I)Y for only 2 weeks. The optimized Cu(I)Y@P material after moisture exposure can remove 532 μmol g−1 of thiophene and is much superior to Cu(I)Y (116 μmol g−1), regardless of similar uptakes for unexposed adsorbents. Remarkably, Cu(I)Y@P shows excellent adsorption capacity of desulfurization for water-containing model fuel., Zeolite Cu(I)Y is attractive for adsorptive removal of sulfur compounds from fuel, however practical application is limited by instability of Cu(I). Here the authors use a coating to achieve superhydrophobicity in the zeolite, leading to improved Cu(I) stability against oxidation and thiophene removal.

Vibrio parahaemolyticus is an important pathogenic bacterium in both food safety management and mariculture. Rapid and accurate detection technologies are critical for effective control of its outbreak and spreading. Conventional technologies and polymerase chain reaction (PCR)-based approaches have limited usage because of the requirement of laboratory instruments and trained personnel. Using the isothermal recombinase polymerase amplification (RPA) technology, several detection assays have been developed with added convenience. Combining the lateral flow strip (LFS) test with RPA can further simplify the detection. In this study, an improved RPA assay using LFS for visual detection of V. parahaemolyticus was developed. Primers were designed targeting the virulence genes and screened for amplification efficiency, nonspecific amplification, and primer-dimer formation. Probes were designed for the best primer pairs, and the weakness of LFS tests, being easily affected by primer-dependent artifacts, was overcome by sequence modifications on primers and probe. The RPA-LFS assay took 25 min at 35 to 45 °C, and showed excellent specificity. It detected as low as one colony forming unit (CFU) of V. parahaemolyticus per reaction without DNA purification, or 10 CFU/10 g spiked food samples with 2 hr of enrichment. The detection limit was better than the currently available RPA-based detection methods. Application of the RPA-LFS assay for simulated samples or real clinical samples showed accurate and consistent detection results compared to bioassay and quantitative PCR. The RPA-LFS assay provided a rapid, accurate, and convenient V. parahaemolyticus detection method suitable for on-site detection in resource-limited conditions. PRACTICAL APPLICATION: This research developed a rapid and visual detection technology for Vibrio parahaemolyticus that is not dependent on complicated equipment. The detection process takes 25 min and the result is read with the naked eye. A detection kit can be developed based on this technology for on-site detection of V. parahaemolyticus in resource-limited regions for food safety management and mariculture.

Lithium bonds are analogous to hydrogen bonds and are therefore expected to exhibit similar characteristics and functions. Additionally, the metallic nature and large atomic radius of Li bestow the Li bond with special features. As one of the most important applications of the element, Li batteries afford emerging opportunities for the exploration of Li bond chemistry. Herein, the historical development and concept of the Li bond are reviewed, in addition to the application of Li bonds in Li batteries. In this way, a comprehensive understanding of the Li bond in Li batteries and an outlook on its future developments is presented.

A highly enantioselective hydrogenation of α,β-unsaturated boronate esters catalyzed by Rh-(S)-DTBM-Segphos complex has been developed. Both (Z)-α,β- and β,β-disubstituted substrates can be successfully hydrogenated to afford chiral boronates with excellent enantioselectivities, up to 98 % ee. Furthermore, the obtained chiral boronate esters, as important versatile synthetic intermediates are successfully transformed to the corresponding chiral alcohols, amines and other important derivatives with maintained enantioselectivities.

GSTP1 has been considered to be a marker for malignancy in many tissues. However, the existing GST fluorescent probes are unfavorable for in vivo imaging because of the limited emission wavelength or insufficient fluorescence enhancement (six-fold). The limited fluorescence enhancement of GST fluorescent probes is mainly ascribed to the high background signals resulting from the spontaneous reaction between GSH and the probes. In this work, a highly specific GST probe with NIR emission has been successfully developed through optimization of the essential unit of the probe to repress the spontaneous reaction. The novel GST probe exhibits over 100-fold fluorescence enhancement upon incubation with GSTP1/GSH and high selectivity over other potential interference. In addition, the probe has been proved to be capable of tracking endogenous GST in A549 cells. Finally, the in vivo imaging results demonstrate that the probe can be used for effective imaging of endogenous GST activity in subcutaneous tumor mouse with high contrast.

Reactive oxygen species (ROS)-mediated cell apoptosis has been a significant strategy for tumor oxidative damage, while tumor hypoxia is a major bottleneck for efficiency. Here, a novel TiO-porphyrin nanosystem (FA-TiOPs) is designed by encapsulating TiO-porphyrin (TiOP) in folate-liposome. The nanosysytem can photocatalyze H

Organo-hydrogels are widely used in various fields, due to functional organic ingredients immobilized by the gel network or stored and protected by the gels. Herein, cellulose acetoacetate (CAA) served as reactive natural polymer emulsifier to stabilize thyme oil-in-water (O/W) emulsions. Hydroxypropyl chitosan (HPCS) was added to the continuous phase in emulsions to achieve the organo-hydrogel via the enamine bonds under mild conditions. The thyme@CAA emulsion with different loadings of the inner phase (up to 50%) displayed uniform droplets distribution (3–5 μm) and favorable stability. The organo-hydrogel was systematically analyzed by Fourier transform infrared spectroscopy, optical microscope, rheology analyses. The emulsion droplets evenly dispersed in the three-dimensional network. The modulus of organo-hydrogels depended on the viscosity of precursor emulsions and the crosslinking density. The resulting organo-hydrogel displayed favorable antibacterial activity against E. coli and S. aureus. CAA, as the reactive emulsifier and crosslinking agent, was a promising alternative candidate to fabricate a series of organo-hydrogel.

Gene therapy aimed at malignant gliomas has shown limited success to date due in part to the inability of conventional gene vectors to achieve widespread and specific gene transfer throughout the highly disseminated tumor zone within the brain. Herein, cationic micelles assembled from vitamin E succinate-grafted ε-polylysine (VES-g-PL) polymers were first exploited to condense TRAIL plasmids (pDNA). Thereafter, the condensed pDNA was further encapsulated into liposomes camouflaged with tumor cellular membrane. The condensed pDNA was successfully encapsulated into the inner aqueous compartments of the liposomes instead of the surface, which was proved based on the TEM morphology and decreased cytotoxicity toward HUVEC and PC-12 cells. Moreover, glioma cell membrane (CM) was easily inlaid into the lipid layer of the pDNA-loaded liposomes to form T@VP-MCL, as shown via TEM, AFM, and SDS-PAGE analysis. T@VP-MCL exhibited good particle size stability at strong ion strength and effectively protected pDNA from DNase I induced degradation. Owing to the CM-associated proteins, T@VP-MCL specifically targeted not only ICAM-1 overexpressed in glioma RBMECs but also homogenous glioma cells. Moreover, in vivo imaging showed that T@VP-MCL was effectively located in orthotopic gliomas of rats after intravenous administration, resulting in effective tumor growth inhibition, prolonging the lives of the rats. The mechanism of T@VP-MCL traversing the BBB was highly associated with the down-regulation of the tight junction-associated proteins ZO-1 and claudin-5. Conclusively, T@VP-MCL designed herein may be a potential carrier for therapeutic genes.

High-efficiency measurement of nitrite (NO2−) is of significant importance for both food safety and the management of health problems. In the present study, we established a fluorescent sensor for the selective detection of nitrite using 3-acetoacetyl-7-diethylaminocoumarin (ADC) and 3-aminophenol (3-Aph) based on a simplified Griess reaction and inner filter effect (IFE). Under strong acidic conditions, the rapid reaction between 3-Aph and nitrite formed an azoic compound (AZO) with the color changing from colorless to brown. The complementary spectral overlap between the absorption of AZO and the excitation of ADC induced IFE, leading to the fluorescence quenching of ADC. Under the selected optimal conditions, the proposed sensor exhibited a good linear relationship in the range from 0.1 μM to 50 μM (R2 = 0.9938) with the detection limit of 24.6 nM. Besides, the detection of nitrite in real pickle and bacon samples was successful and showed a maximum of 5% relative error with acceptable recoveries, demonstrating that this promising strategy can be employed for nitrite analysis in real-time applications.

T helper 17 (Th17) cells that express interleukin-17 (IL-17) play a key role in various inflammatory diseases, such as multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE). The retinoic acid receptor-related orphan receptors γt (RORγt) have an indispensable effect on the differentiation of this cell type, and are thus considered a valuable target in the treatment of Th17-related disorders. In this study, we found that eriodictyol (EDT), a natural flavonoid abundant in citrus fruits and peanuts, was located directly in the binding pocket of RORγt, and induced a conformational change that resulted in the effective suppression of the receptor's activity, thus offering insight into the transcriptional inhibition of RORγt-dependent genes. Consistent with this, EDT dose-dependently (5-10 μM) blocked murine Th17 differentiation, and markedly reduced IL-17A secretion in vitro. Furthermore, this compound has been found to have novel properties for directly inhibiting Th1 cell development and promoting Treg cell differentiation at high doses (≥10 μM). EDT administration significantly decreased the clinical severity in the EAE model, with inhibited demyelination and reduced inflammatory responses in the periphery and in the central nervous system (CNS). In the adoptive transfer model, EDT also remarkably suppressed the Th17 cell infiltration and pathogenicity. Collectively, our data demonstrated that EDT, as an agent for the pharmacological inhibition of RORγt, has great potential for immunomodulation, and for use in the treatment of Th17-mediated autoimmune disease.

The GLUT4 and PI3K/AKT signaling pathways are the key sensors of energy status and they regulate glucose and lipid metabolism. Phloretin activates the PI3K/AKT pathway by promoting GLUT4 translocation and expression, thereby improving glucose consumption and tolerance. As metformin can regulate glucose metabolism, we hypothesized that phloretin can amplify its gluco-regulatory effects. Male Sprague Dawley rats were fed with a high-fat and high-sugar diet for 8 weeks and injected with a low dose of streptozotocin to induce type 2 diabetes. The diabetic rats were randomized to receive phloretin (100 mg kg-1 d-1), metformin (250 mg kg-1 d-1), or phloretin + metformin via oral gavage for another 4 weeks. Random blood glucose, serum insulin, free fatty acid, total cholesterol, triglyceride, and low-density lipoprotein levels were detected in type 2 diabetic rats. Hematoxylin-eosin and Oil Red O staining were used to observe the pathological changes in the liver, pancreas, and adipose tissues of type 2 diabetic rats. The expression levels of IRS-1, PI3K, P-AKT, and GLUT4 in skeletal muscle were detected using western blotting. Phloretin plus metformin improved fasting blood glucose levels, glucose tolerance, and insulin sensitivity in type 2 diabetic rats. In addition, this combination reduced lipid accumulation, improved the pathological changes in the liver, pancreas, and adipose tissue, and increased IRS-1, PI3K, P-AKT, and GLUT4 expression in skeletal muscle and the liver of type 2 diabetic rats. Thus, phloretin can be used in a potential combination therapy with metformin for the prevention and rescue of type 2 diabetes.

BackgroundMany patients with pancreatic cancer (PC) suffer from abdominal pain and back pain. However, the cause of pain associated with PC is largely unclear. In this study, we tested the potential influence of the sonic hedgehog (sHH) signaling pathway on PC pain.MethodsSubstance P (SP) and calcitonin gene-related peptide (CGRP) expression was measured in cultured PC cells and dorsal root ganglions (DRG) by real-time PCR, western blotting analysis and ELISA. Small interfering RNA transfection and plasmid constructs were used to regulate the expression of sHH in the AsPc-1 and Panc-1 cell lines. Pain-related behavior was observed in an orthotopic tumor model in nude mice.ResultsIn this study, the results show that sHH increased the expression of SP and CGRP in DRGs in a concentration and time-dependent manner. Additionally, sHH secretion from PC cells could activate the sHH signaling pathway and, in turn, increase the expression of nerve growth factor (NGF), P75, and TrkA in DRGs. Furthermore, the sHH signaling pathway and NGF/NGF receptor contributed to pain sensitivity in a nude mouse model.ConclusionOur results demonstrate that PC pain originates from the sHH signaling pathway, and NGF mediates the pain mechanism via regulating SP and CGRP.

Purpose Long non-coding RNAs (lncRNAs) have been proved to act crucial parts in the progress of human tumor. However, the role of lncRNAs in drug resistance of tumor cells remains to be further elucidated. The present study aimed to explore whether lncRNA NCK-AS1 could affect the cisplatin (DDP) resistance in human osteosarcoma cell and the underlying molecular mechanism. Methods The expression of NCK1-AS1 and miR-137 in osteosarcoma cells was detected by qRT-PCR. CCK-8 assay, colony formation assay, Western blotting, wound healing assay and transwell assay were employed to assess the cell proliferation, migration and invasion. In addition, CCK-8 assay, flow cytometry, qRT-PCR and resistance gene activity analysis were performed to assess the DDP sensitivity of osteosarcoma cells. The interaction between NCK1-AS1 and miR-137 was identified using a dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Results The results revealed that NCK1-AS1 was significantly upregulated in osteosarcoma cells, as well as in DDP-resistant osteosarcoma cells. NCK1-AS1 silence inhibited the proliferation, migration and invasion of osteosarcoma cells, whereas enhanced the sensitivity of osteosarcoma cells to DDP. Furthermore, NCK1-AS1 directly interacted with miR-137 and overexpression of miR-137 suppressed the proliferation, migration and invasion of osteosarcoma cells. Most importantly, miR-137 overexpression enhanced the sensitivity of osteosarcoma cells to DDP, and high expression of NCK1-AS1 reversed the influences of miR-137 overexpression on DDP-resistant cells. Conclusion In short, NCK1-AS1 knockdown enhanced DDP sensitivity of osteosarcoma cells by regulating miR-137, which may be a novel potential target for anti-DDP resistance in human osteosarcoma.

Nasal administration of insulin showed the attractive potential to improve the compliance of diabetic patients and alleviate mild cognitive impairment of Alzheimer's patients. However, the nasal absorption of insulin was not ideal, limiting its therapeutic effect in clinic. This study was to explore the potential of glyceryl monocaprylate–modified chitosan (CS-GMC) on the intranasal absorption of insulin via in vivo pharmacodynamic experiment in conscious rats. It was demonstrated that the absorption-enhancing effect of CS-GMC depended on the existing state of insulin in the formulation, substitution degree of GMC on chitosan and concentration of CS-GMC. Better insulin absorption was achieved when insulin existed in molecular form compared with that in polyelectrolyte complexes. CS-GMC with substitution degree 12% (CS-GMC 12%) was a preferred absorption enhancer, and its absorption enhancing effect increased linearly with the increment of its concentration in the range investigated. Compared with chitosan of the same concentration, CS-GMC12% showed remarkably enhanced and prolonged therapeutic effect up to at least 5 h under the concentration of 0.6% (w/v). CS-GMC12% showed almost no ciliotoxicity to the nasal cilia up to concentration 1.0% (w/v). In conclusion, CS-GMC was a promising absorption enhancer to improve the intranasal absorption of insulin.

Nanotubes were prepared by self-assembly of the copolymer using co-solvent evaporation method. The biocompatibility of the nanotubes was assessed in comparison with spherical micelles and filomicelles prepared from poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PEG-PLGA) and poly(ethylene glycol)-poly(L-lactide) (PEG-PLA), respectively. Several aspects of biocompatibility of the aggregates were considered, including agar diffusion and MTT assay, release of cytokines, hemolysis, protein adsorption, dynamic clotting in vitro, and Zebrafish embryonic compatibility in vivo. The nanotubes present good cell compatibility and blood compatibility in vitro, and almost no toxicity towards Zebrafish embryos development in vivo. Furthermore, dual-loading of hydrophilic cisplatin and hydrophobic paclitaxel was achieved in the nanotubes with high loading content and loading efficiency. The release of both drugs was slower from dual-loaded nanotubes than from single-loaded ones, but the total amount of released drugs in higher for dual-loaded nanotubes than from single-loaded ones. Cellular uptake and inhibition tests showed that the nanotubes were successfully taken up by tumor cells and effectively inhibited cell growth. It is thus concluded that PEG-PLA-PEG nanotubes with outstanding biocompatibility could be promising for co-delivery of hydrophilic and hydrophobic agents in combination cancer therapy. Keywords: Nanotubes, Block copolymer, Combination cancer therapy, Biocompatibility, Drug delivery

Comparison of defect formation in tungsten samples exposed only to a helium plasma and those exposed to both helium plasma and subsequent deuterium plasmas is performed via Doppler broadening spectroscopy in the positron annihilation technique (DBS-PA). The S parameters of tungsten samples after helium plasma exposure increased with the increase of the incident fluence, which indicates that low energy helium plasma could induce the formation of defects such as nano-sized helium bubbles and dislocations in tungsten. The S parameters of samples exposed to helium incident fluence of 7.9 × 1021 He/m2 enhanced after deuterium plasmas exposure, indicating that low energy deuterium plasmas could form defects in tungsten too. Unexpectedly, deuterium plasmas exposure did not significantly influence the S parameters of the tungsten sample with helium incident fluence of 3.9 × 1022 He/m2, and reduced the S parameters of the tungsten sample with helium incident fluence of 7.9 × 1022 He/m2. These variations of S parameters could be associated with the occupation of nano-sized helium bubbles by deuterium atoms. This indicates possible competition between the increased density of vacancy-type defects by deuterium plasmas exposure and the filling of nano-sized helium bubbles by deuterium atoms, reducing detectability of these defects.

Background Nowadays, liver transplantation has become a main therapy for end-stage liver disease. However, studies show that there are high mortality and severe complications after liver transplantation. Although gastrointestinal dysfunction is a common and major complication after liver transplantation, there was rarely relative research. This study aims to elucidate the factors about ileus after liver transplantation and patients’ survival. Methods We collected and analyzed the data (n = 318, 2016–2019) from the First Affiliated Hospital of Xi’an Jiaotong University. After excluding cases, a total of 293 patients were included for this study. The subjects were divided into a non-ileus group and an ileus group. We reviewed 38 variables (including preoperative, operative and postoperative relative factors). Additionally, other complications after liver transplantation and survival data were compared between two groups. Results Of the 293 patients, 23.2% (n = 68) experienced postoperative ileus. Ileus patients were not different with non-ileus patients in preoperative, operative and postoperative factors. HBV-positive patients with ileus had a lower MELD score (P = 0.025), and lower postoperative total bilirubin was correlated with ileus (P = 0.049). Besides, Child–Pugh score of HCC patients with ileus was low (P = 0.029). The complications after liver transplantation were not different between two groups. Compared with the patients without ileus, the patients with ileus had a higher mortality rate. Conclusion According to our research, ileus-patients had a lower 1-year survival rates. The preoperative MELD score and postoperative total bilirubin of HBV-positive patients with ileus were lower, and Child–Pugh score of HCC patients with ileus was also lower.

Background Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. Methods In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3ʹ-di-O-methylellagic acid 4ʹ-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets. Results DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K–Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK. Conclusion DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia. Graphical Abstract