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Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy IkkβC46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ–IκBα–NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to IkkβWT littermates, lipopolysaccharides (LPS) could induce high mortality rate in IkkβC46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα–NF-κB signaling and inhibiting phosphorylation of 5ʹ adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix–loop–helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in IkkβC46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

High-performance Li2MnO3-like compound Li2Ni0.03Mn0.985O3 was successfully synthesized by a polyvinyl alcohol (PVA)-assisted sol–gel method. The XRD results of Li2Ni0.03Mn0.985O3 powder show that they exhibit similar XRD patterns to Li2MnO3 anode materials. EDS-HAADF, SEM, and HRTEM morphology imaging of PVA@Ni-LMO cathode materials show the two transitional metals nickel and manganese are evenly distributed throughout the samples, and the fine layered compounds can be obtained by the presence of PVA. The material synthesized with PVA not only shows a relatively high first-cycle discharge capacity of 181.9 mA h g−1, but also has excellent multiplier performance and good cycling performance. PVA@Ni-LMO samples deliver discharge capacity of 236.5 mA h g−1 after 20 cycles, which are higher than 228.3 mA h g−1 of Ni-LMO samples, maintaining a discharge capacity of 222.6 mA h g−1 after 60 cycles. EIS results show that the PVA composite material reduces charge-transfer resistance and enhances reaction kinetics, which is considered to be a major factor in improving rate performance.

As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence. Supplementary Information The online version contains supplementary material available at 10.1007/s13238-021-00879-y.

Capturing solar energy as heat for water treatment has become a substantial approach to obtain freshwater. To obtain higher performance, the understanding of the mechanism of how water molecules interact with the interface is particularly fundamental, because the migration process of water molecules on the evaporation interface will directly affect the performance of the device. Herein we regulate the number of hydroxyl groups on the surface of reduced graphene oxide quantitatively, to study the effect of different wettability of interfaces on the performance of solar water generators. The water evaporation performance displays a volcanic shape as increasing wettability. Calculated by the computational chemistry method, deviation from proper wetting humidity is not conducive to the migration of water molecules from the surface. The double-edged sword effect of wettability on performances is clarified, and the surface energy density is the key to break through the limit by the finite element method.

The immediate-early protein BRLF1 plays important roles in lytic infection of Epstein-Barr virus (EBV), in which it activates lytic viral transcription and replication. However, knowledge of the influence of BRLF1 on cellular gene expression and transcriptional reprogramming during the early lytic cycle remains limited. In the present study, deep RNA-sequencing analysis identified all differentially expressed genes (DEGs) and alternative splicing in B lymphoma cells subjected to wild-type and BRLF1-deficient EBV primary infection. The BRLF1-dependent cellular DEGs were annotated, and major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory responses, cytokine-receptor interactions and chemokine signaling and metabolic processes. Furthermore, analysis of BRLF1-binding proteins by mass spectrometry shows that BRLF1 binds to and cooperates with several transcription factors and components of the spliceosome and then influences both RNA polymerase II-dependent transcription and pre-mRNA splicing. The RTA-binding RRE motifs or specific motifs of unique cooperative transcription factors in viral and cellular DEG promoter regions indicate that BRLF1 employs different strategies for regulating viral and cellular transcription. Thus, our study characterized BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the comprehensive virus-cell interaction and alterations of transcription during EBV primary infection and lytic replication.

Adsorption of drug powder is caused by triboelectrification on the surface of starch capsule during filling process. Furthermore, high wear rate and poor water lubricity also hinder the further practical applications of traditional starch capsule. To solve these problems, a glycerol-modified starch capsule with perfect anti-triboelectrification and enhanced lubrication performance was fabricated. Hydrogen bond between glycerol and starch molecules could reduce the bound water content on the capsule surface and thus realizes anti-triboelectrification. By adding glycerol, a three-tier structure composed of starch-glycerol-water is formed through hydrogen bonding on the surface of the starch film, which has been proven to be favorable for lubrication performance. When 5% glycerol is added, the short-circuit current (Isc) of starch-based triboelectric nanogenerator (TENG) is reduced by 86%, and the wear volume of the starch film is reduced by 89%. Under water lubrication condition, the lubrication performance of the starch-glycerol film can reach the super lubricated level with a friction coefficient of about 0.005. This work provides a new route to obtain modified starch capsules with improved anti-triboelectrification property, reduced wear rate and superlubricity property.

To obtain astragalus polysaccharide (APS)-magnetic graphene oxide (MGO) nanoparticles (NPs), MGO was prepared by chemical co-precipitation, and then loaded with APS NPs. After the physical characterization of the material was analyzed, it was adopted to treat patients with sepsis injury to study its mechanism. Then, changes in cytokine levels in the patient’s myocardial tissue were analyzed. Giving that septic myocardial injury-related neutrophil gelatinase (neutrophil gelatinase-associated lipocalin (NGAL) and cystatin) was related to hemodynamics, changes in the patient’s hemodynamic indicators were analyzed before and after the addition of nanomaterials. Moreover, changes of the patient’s gelatinase markers before and after the preparation of nanomaterials were also analyzed. The results showed that the Fe3O4 magnetic NPs were coated on the surface of GO while successfully adsorbing APS. The sample recovery rate was more than 100%, and the relative standard deviation was 0.48%. The in vitro release showed that the NPs were easily released in an acidic environment. Clinical trials showed that the levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-β, etc.) in myocardial tissue were dramatically decreased (P < 0.05), while the levels of anti-inflammatory cytokines (IL-2, IL-4, etc.) were greatly increased (P < 0.05). The NGAL level at the arterial and venous ends both decreased remarkably (P < 0.05). The total mass transfer ratio (Mtr) increased obviously while the mass adsorption rate (Mad) decreased significantly (P < 0.05). In addition, hemodynamic indicators such as cardiac output (CO) and diastolic arterial pressure (DAP) all improved notably.

The difunctionalization of alkenes involving trifluoromethylthio group (SCF3) for the conversion of versatile and readily available olefins into more structurally complex molecules has been greatly studied. However, the disproportionate dithiolation of alkene is unknown. Herein, a transition-metal-free protocol is presented for vicinal trifluoromethylthio-thiolation of unactivated alkenes via a radical process under mild condition with broad substrate scope and excellent tolerance.

Aquaporins such as the plasma membrane intrinsic proteins (PIPs) allow water to move through cell membranes and are vital for stomatal movement in plants. Despite their importance, the dynamic changes in aquaporins during water efflux and influx have not been directly observed in real time in vivo. Here, to determine which factors regulate these changes during the bidirectional translocation of water, we examined aquaporin dynamics during the stomatal immune response to the bacterial flagellin-derived peptide flg22. The Arabidopsis (Arabidopsis thaliana) aquaporin mutant pip2;1 showed defects in the flg22-induced stomatal response. Variable-angle total internal reflection fluorescence microscopy revealed that the movement dynamics and dwell times of AQ6]GFP-AtPIP2;1 in guard cells and subsidiary cells exhibited cell type-specific dependencies on flg22. The cytoskeleton, rather than the cell wall, was the major factor regulating AtPIP2;1 dynamics, although both the cytoskeleton and cell wall might form bounded domains that restrict the diffusion of AtPIP2;1 in guard cells and subsidiary cells. Finally, our analysis revealed the different roles of cortical actin and microtubules in regulating AtPIP2;1 dynamics in guard cells, as well as subsidiary cells, under various conditions. Our observations shed light on the heterogeneous mechanisms that regulate membrane protein dynamics in plants in response to pathogens.

Plant cell elongation and expansion require the biosynthesis and remodeling of cell wall composition. Recently, Aryal et al. reported how feedback between the cell wall and the auxin response controls differential growth in apical hook development.

The transition of alveolar type II epithelial cells into fibroblasts has been reported to cause and/or aggravate pulmonary fibrosis (PF), which is characterized by fibroblast proliferation, an enhanced production and accumulation of ECM (extracellular matrix), alveolar wall damage and functional capillary unit loss. Traditional Chinese medicine Emodin has been reported to inhibit TGF‐β‐induced epithelial‐mesenchymal transition (EMT) in alveolar epithelial cells through Notch signalling. In the present study, neutrophil elastase (NE, also known as ELA2) treatment promoted EMT, Notch1 cleavage (NICD/Notch1 ratio increase) and NICD nuclear translocation in RLE‐6TN cells and A549 cells. The promotive roles of NE treatment in these events were significantly reversed by Notch1 knockdown. Traditional Chinese medicine Emodin treatment remarkably inhibited the enzyme activity of NE, suppressed EMT, Notch1 cleavage and NICD nuclear translocation within RLE‐6TN and A549 cells, while NE treatment significantly reversed the effects of Emodin. Moreover, in RLE‐6TN, the effects of NE on EMT, Notch1 cleavage and NICD nuclear translocation were remarkably attenuated by Emodin treatment and more attenuated by the combination of Emodin and neutrophil elastase inhibitor Sivelestat or notch signal pathway inhibitor DAPT. In conclusion, we revealed the involvement of NE‐induced Notch1 cleavage in the functions of Emodin suppressing NE‐caused EMT in RLE‐6TN cells and A549 cells. This novel mechanism of Emodin inhibiting EMT might extend the application of Emodin in PF treatment.

Membrane-bound transcription factors (MTFs) differ from cytosolic transcription factors (TFs) and they innately bind to membranes. Under external stimuli, MTFs are released from various membranes, ...

Purpose. To investigate the serum changes of oxidative stress markers and the relationship between these factors and visual field (VF) progression in patients with primary angle closure glaucoma (PACG). Methods. A case-control and a prospective cohort study. A total of 94 patients with PACG and 89 normal controls were enrolled. Furthermore, 94 PACG subjects were followed up for at least two years (once every six months). All participants were evaluated for serum levels of superoxide dismutase (SOD), total antioxidant status (TAS), hydrogen peroxide (H2O2), malondialdehyde (MDA), glutathione peroxidase, glutathione reductase, and detailed eye and systematic examination. Binary logistic regression analysis and Cox regression analysis were performed. Results. The serum levels of SOD and TAS in the PACG group were significantly lower than those in the control group (p<0.001). Meanwhile, PACG subjects had significantly higher levels of MDA and H2O2 than the normal control subjects (p<0.001). Serum levels of TAS (OR=0.773, 95%CI=0.349−0.714, p<0.001), SOD (OR=0.975, 95%CI=0.955−0.995, p<0.001), MDA (OR=1.155, 95%CI=1.080−1.235, p<0.001), and H2O2 (OR=1.216, 95%CI=1.142−1.295, p<0.001) were independent risk/protective factors for PACG. TAS levels (HR=0.041, 95%CI=0.008–0.218, p<0.001), SOD levels (HR=0.983, 95%CI=0.971–0.994, p=0.003), and MDA levels (HR=1.010, 95%CI=1.001–1.018, p=0.015) at baseline were associated with visual field progression. Kaplan–Meier curves reveal that patients with TAS<0.95/SOD<143/MDA>12 had a significantly higher percentage of PACG progression (p<0.05). Conclusions. Decreased levels of TAS and SOD as well as increased levels of MDA at baseline were associated with VF progression in patients with PACG. These findings suggest that oxidative stress was involved in the onset and development of PACG.

Neutrophil extracellular traps (NETs) are characterized as extracellular DNA fibers comprised of histone and cytoplasmic granule proteins. NETs were first described as a form of innate response against pathogen invasion, which can capture pathogens, degrade bacterial toxic factors, and kill bacteria. Additionally, NETs also provide a scaffold for protein and cell binding. Protein binding to NETs further activate the coagulation system which participates in thrombosis. In addition, NETs also can damage the tissues due to the proteins they carry. Many studies have suggested that the excessive formation of NETs may contribute to a range of diseases, including thrombosis, atherosclerosis, autoimmune diseases, and sepsis. In this review, we describe the structure and components of NETs, models of NET formation, and detection methods. We also discuss the molecular mechanism of NET formation and their disease relevance. Modulation of NET formation may provide a new route for the prevention and treatment of releated human diseases.

A collinear dual-pulse laser induced breakdown spectroscopy (DP-LIBS) method was employed to analyze Chinese traditional medicine Artemisia annua. The spectral intensities and signal-to-background ...

Candida rugosa lipase was immobilized in this study using CaCl2/CMC nanoparticles that yielded a lipase loading capacity of 127 mg/g, with better thermal stability and activity of 91.8%. The hydrolysis of racemic 2-phenylpropionic acid isopropyl ester by free and immobilized Candida rugosa lipase was investigated in the mixed organic-solvent composed of isooctane and methyl tert-butyl ether (9.5:0.5, V/V). The optimal conditions were 35 °C and pH 7.5 for free Candida rugosa lipase hydrolysis. We obtained (S)-2-phenylpropionic acid with 44.85% conversion, 95.75% enantiomeric excess and enantiomeric ratio of 112. The CaCl2/CMC nanoparticles immobilized Candida rugosa lipase possesses high enantioselectivity, with E = 237 at 40 °C and pH 7.5. It was efficiently reusable in four cycles and appropriately enhanced enantioselectivity within 120–240.

NiCo2S4 nanosheet arrays have been successfully grown on carbon cloth via an easy hydrothermal way, which were then used to assemble asymmetric supercapacitors. The microstructures, the crystal structures and the electrochemical properties were carefully studied, and the NiCo2S4 nanosheet arrays exhibited impressive specific capacitance (SC) of 184.2 mAh/g at 1 A/g. The asymmetric supercapacitors (ASCs) with NiCo2S4 nanosheets as positive electrode demonstrated the energy density of 55.6 Wh/kg at 1.6 kW/kg. Furthermore, good cycle stability (93.72% after 5000 cycles) can be also possessed.

In order to investigate the influence of laser wavelength on the detection of the metals in Artemisia annua, pulsed lasers operating at wavelengths of 1064 nm and 532 nm for laser induced breakdown...

BACKGROUND Slight acidic electrolyzed water (SAEW) has been widely used in cleaning systems of fruit and vegetables. It strongly reduces microbial contamination. However, no information is available on whether SAEW offers the potential for fresh jujube cleaning. The purposes of this study were, first, to compare the effectiveness of SAEW with commercial sanitizers (i.e. sodium hypochlorite (NaClO) or calcium hypochlorite (Ca(ClO)2 )) on 'Jiancui' jujube; second, to determine the response of fruit decay, tissue calcium (Ca) content, and quality attributes to dip application of calcium nitrate (Ca(NO3 )2 ) by concentration; and third, to investigate the effects of SAEW combined with Ca(NO3 )2 or calcium acetate (Ca(OAc)2 )) on fruit Ca uptake, quality attributes, and bioactive compounds. RESULTS Fruits washed with NaClO, Ca(ClO)2 , or an SAEW solution showed no difference in reduction of decay incidence. In contrast to NaClO treatment, SAEW or Ca(ClO)2 significantly retarded losses in fruit firmness (FF), green color (hue angle), and skin lightness (L*), and maintained intact pericarp tissue structure during storage at 1 °C. Application of Ca(NO3 )2 at 5-10 g L-1 effectively promoted Ca2+ uptake and minimized declines in FF and L* value but had no effect on decay development. Adding 10 g L-1 Ca(NO3 )2 or Ca(OAc)2 to SAEW provided an additional benefit in increasing decay resistance, increasing Ca2+ into fruit and increasing levels of bioactive compounds in jujube fruit. CONCLUSION SAEW in combination with Ca(NO3 )2 or Ca(OAc)2 has commercial potential for fresh jujube disinfection and improving storage quality as a result of the cleaning processes. © 2019 Society of Chemical Industry.

As sessile organisms, plants must directly deal with an often complex and adverse environment in which hyperosmotic stress is one of the most serious abiotic factors, challenging cellular physiology and integrity. The plasma membrane (PM) is the hydrophobic barrier between the inside and outside environments of cells and is considered a central compartment in cellular adaptation to diverse stress conditions through dynamic PM remodeling. Endocytosis is a powerful method for rapid remodeling of the PM. In animal cells, different endocytic pathways are activated in response to osmotic stress, while only a few reports are related to the endocytosis response pathway and involve a mechanism in plant cells upon hyperosmotic stress. In this study, using different endocytosis inhibitors, the microdomain-specific dye di-4-ANEPPDHQ, variable-angle total internal reflection fluorescence microscopy (VA-TIRFM), and confocal microscopy, we discovered that internalized Clathrin Light Chain-Green Fluorescent Protein (CLC-GFP) increased under hyperosmotic conditions, accompanied by decreased fluorescence intensity of CLC-GFP at the PM. CLC-GFP tended to have higher diffusion coefficients and a fraction of CLC-GFP molecules underwent slower diffusion upon hyperosmotic stress. Meanwhile, an increased motion range of CLC-GFP was found under hyperosmotic treatment compared with the control. In addition, the order of the PM decreased, but the order of the endosome increased when cells were in hyperosmotic conditions. Hence, our results demonstrated that clathrin-mediated endocytosis and membrane microdomain-associated endocytosis both participate in the adaptation to hyperosmotic stress. These findings will help to further understand the role and the regulatory mechanism involved in plant endocytosis in helping plants adapt to osmotic stress.

BAY-876 is an effective antagonist of the Glucose transporter type 1 (GLUT1) receptor, a mediator of aerobic glycolysis, a biological process considered a hallmark of hepatocellular carcinoma (HCC) together with cell proliferation, drug-resistance, and metastasis. However, the clinical application of BAY-876 has faced many challenges. In the presence study, we describe the formulation of a novel microcrystalline BAY-876 formulation. A series of HCC tumor models were established to determine not only the sustained release of microcrystalline BAY-876, but also its long-acting antitumor activity. The clinical role of BAY-876 was confirmed by the increased expression of GLUT1, which was associated with the worse prognosis among advanced HCC patients. A single dose of injection of microcrystalline BAY-876 directly in the HCC tissue achieved sustained localized levels of Bay-876. Moreover, the single injection of microcrystalline BAY-876 in HCC tissues not only inhibited glucose uptake and prolonged proliferation of HCC cells, but also inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors. Thus, the microcrystalline BAY-876 described in this study can directly achieve promising localized effects, given its limited diffusion to other tissues, thereby reducing the occurrence of potential side effects, and providing an additional option for advanced HCC treatment.

High-performance aqueous zinc batteries are expected to be realized, rooting from component synergistic effects of the hierarchical composite electrode materials. Herein, hierarchical crystalline Ni–Co phosphide coated with amorphous phosphate nanoarrays (C-NiCoP@A-NiCoPO4) self-supporting on the Ni foam are constructed as cathode material of an aqueous zinc battery. In this unique core–shell structure, the hexagonal phosphide with high conductivity offers ultra-fast electronic transmission and amorphous phosphate with high stability, and open-framework provides more favorable ion diffusivity and a stable protective barrier. The synergistic effects of this intriguing core–shell structure endow the electrode material with outstanding reaction kinetics and structural stability, which is theoretically confirmed by density functional theory (DFT) calculations. As a result, the C-NiCoP@A-NiCoPO4 electrode exhibits a higher specific capacity of 350.6 mA h g−1 and excellent cyclic stability with 92.6% retention after 10 000 cycles. Moreover, the C-NiCoP@A-NiCoPO4 is coupled with Zn anode to assemble an aqueous pouch battery that delivers ultra-high energy density (626.33 W h kg−1 at 1.72 kW kg−1) with extraordinary rate performance (452.05 W h kg−1 at 33.56 kW kg−1). Moreover, the corresponding quasi-solid flexible battery with polyacrylamide hydrogel electrolyte exhibits favorable durability under frequent mechanical strains, which indicates the great promise of crystalline/amorphous hierarchical electrodes in the field of energy storage.

Background Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumour that is prevalent in Southern China and other Southeast Asian countries. In previous studies, Kinesin Family Member 3A (KIF3A) was shown to play a dual role in cancers. However, the biological role of KIF3A in NPC and the underlying mechanism have not been reported. Methods The KIF3A mRNA and protein expressions in NPC were analyzed by qRT-PCR (Quantitative real-time polymerase chain reaction), Western blotting and immunohistochemistry. CCK-8, EDU incorporation assay, Colony formation, cell cycle assay, Wound-Healing Assay, Transwell verified KIF3A regulates the proliferation, migration, invasion of NPC cells. The in vivo effect of KIF3A on proliferation was elucidated with a xenograft mouse model. COIP (Co-immunoprecipitation) assay showed KIF3A interacts with β-catenin. Confocal microscopy colocalization assay confirmed colocalization of KIF3A and β-catenin in NPC cells. Nuclear and cytoplasmic extraction assays were performed to analyze the distribution of β-catenin in the nuclei and cytoplasm. Results In this study, we found that KIF3A interacts with β-catenin, suppressing the intranuclear aggregation of β-catenin, then inactivating the Wnt/β-catenin signaling pathway as well as the downstream cell cycle factors and EMT signal to inhibit NPC proliferation, migration, and invasion. Conclusions These findings suggest that KIF3A interacts with β-catenin and attenuates the malignant progression of NPC by inhibiting β-catenin intranuclear aggregation. KIF3A may be a promising therapeutic target for NPC patients.

SummaryThe receptor-like kinase (RLK) FERONIA (FER) senses peptide ligands in the plasma membrane (PM), modulates plant growth and development, and integrates biotic and abiotic stress signaling for downstream adaptive response. However, the molecular interplay of these diverse processes is largely unknown.Here, we show that FER, the receptor of Rapid Alkalinization Factor 1 (RALF1), physically interacts with C2 domain ABA–related (CAR) proteins to control the nano-organization of the PM inArabidopsis.During this process, the RALF1–FER pathway upregulates CAR protein translation, and then more CAR proteins are recruited to PM. This acts as a rapid feedforward loop to stabilize PM liquid-ordered phase. FER interacts with and phosphorylates CARs, and reducing their lipid-binding ability, which breaks the feedback regulation CAR activity at latter time point.Similar to FER mutant, pentuplecar14569mutants inhibit flg22-induced FLS2-BAK1 immune complex formation, which depends on the integrity of nanodomains.Together, we propose that the FER-CAR module controls the formation of the PM nano-organization during RALF signaling through a self-contained amplifying loop including both positive and negative feedbacks.

Few studies, especially those related to field tests, have examined the bending behaviors of drilled shafts with partial casings (DSPCs). This work reports the results of experimental studies on the behavior of DSPCs under lateral loads, including an in situ test and a set of laboratory tests. First, a DSPC with a diameter of 2 m and length of 87.9 m was studied in clay beds, and a steel casing with a diameter of 2.0 m and length of 33 m was used. In this test, strain gauges were distributed along the steel rebars in the concrete pile and the wall of the steel tube at different depths, and thus the longitudinal strains of the concrete pile and the steel tube could be studied. Second, laboratory experiments were implemented with reinforced concrete-filled steel tubular columns under pure bending conditions. In these tests, strain gauges were distributed along the steel rebars in the concrete pile and the walls of the steel tubes at the pure bending section of the specimens. Different wall thicknesses and drilling fluid conditions were considered. The field test results show that the strain of the concrete piles and the steel tubes were linearly distributed at the same cross-section. This means that a DSPC remains a flat plane after it deforms. Whereas a correction coefficient related to the loading level need to be considered in the calculation of the bending stiffness. Laboratory studies show that the strain of DSPCs was linearly distributed at a small bending moment under the best bond-quality condition, whereas obvious nonlinear behaviors were shown under a large bending moment with poor bond-quality conditions.

Autophagy is usually considered as a protective mechanism against cell death, and in the meantime, leads to cell injury even apoptosis. Apoptosis and autophagy are very closely connected and may cooperate, coexist, or antagonize each other on progressive occurrence of cell death triggered by natural compounds. Therefore, the interplay between the two modes of death is essential for the overall fate of cancer cells. Our previous study revealed that curcumol induced apoptosis in nasopharyngeal carcinoma (NPC) cells. Recently, curcumol was found to induce autophagy in cancer cells. However, whether curcumol can induce NPC cells autophagy and the effects of autophagy on apoptosis remain elusive. In this study, we found that curcumol induced autophagy through AMPK/mTOR pathway in CNE-2 cells. Moreover, inhibiting autophagy by autophagy inhibitor 3-methyladenine (3-MA) or apoptosis inhibitor z-VAD-fmk significantly increased proliferation while attenuated apoptosis and autophagy compared with the curcumol 212 μM group. In contrast, combining curcumol with autophagy agonist rapamycin and apoptosis inducer MG132 synergized the apoptotic and autophagic effect of curcumol. Taken together, our study demonstrates that curcumol promotes autophagy in NPC via AMPK/mTOR pathway, induces autophagy enhances the activity of curcumol in NPC cells; the combination of autophagy inducer and curcumol can be a new therapeutic strategy for NPC.

The extravagant osteoclast formation and resorption is the main cause of osteoporosis. Inhibiting the hyperactive osteoclastic resorption is considered as an efficient treatment for osteoporosis. Rhaponticin (RH) is a small molecule that has been reported to possess anti-inflammatory, anti-allergic, anti-fibrotic, and anti-diabetic activities. However, the influence of RH on osteoclasts differentiation and function is still unclear. To this end, an array of assays including receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL) induced osteoclastogenesis, tartrate-resistant acidic phosphatase (TRAcP) staining, immunofluorescence, and hydroxyapatite resorption were performed in this study. It was found that RH had significant anti-catabolic effects by inhibiting osteoclastogenesis and bone resorption without cytotoxicity. Mechanistically, the expression of NADPH oxidase 1 (Nox1) was found to be suppressed and antioxidant enzymes including catalase, superoxide dismutase 2 (SOD-2), and heme oxygenase-1(HO-1) were enhanced following RH treatment, suggesting RH exhibited antioxidant activity by reducing the generation of reactive oxygen species (ROS) as well as enhancing the depletion of ROS. In addition, MAPKs, NF-κB, and intracellular Ca2+ oscillation pathways were significantly inhibited by RH. These changes led to the deactivation of osteoclast master transcriptional factor-nuclear factor of activated T cells 1 (NFATc1), as examined by qPCR and Western blot assay, which led to the decreased expression of downstream integrin β3, c-Fos, cathepsin K, and Atp6v0d2. These results suggested that RH could effectively suppress RANKL-regulated osteoclast formation and bone resorption. Therefore, we propose that RH can represent a novel natural small molecule for the treatment of osteoporosis by inhibiting excessive osteoclast activity.

Background Osteolytic diseases share symptoms such as bone loss, fracture and pain, which are caused by over-activated osteoclasts. Targeting osteoclast differentiation has emerged as a therapeutic strategy clinically. Dendrobine is an alkaloid isolated from Chinese herb Dendrobium nobile, with knowing effects of analgesia and anti-inflammation. The roles of dendrobine on osteoclasts and osteolysis remain unclear. Purpose Herein, the possible roles of dendrobine in osteoclastogenesis, inflammatory osteolysis and the underlying mechanism were explored. Methods Bone marrow-derived macrophages (BMMs) and RAW264.7 cells were employed to evaluate the roles of dendrobine on osteoclastogenesis, bone absorption and the underlying mechanism in vitro. LPS injection was used to cause inflammatory osteolysis in vivo. Results Dendrobine repressed osteoclastogenesis, bone resorption induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro. Mechanistically, dendrobine inhibited RANKL-upregulated intracellular (ROS), p-p38, c-Fos expression and nuclear factor of activated T cells (NFATc1) nuclear translocation. Osteoclastic genes were reduced, and among them matrix metalloproteinase 9 (MMP9) mRNA was dramatically blocked by dendrobine. Moreover, it substantially suppressed MMP9 protein expression during osteoclastogenesis in vitro. Accordingly, oral 20 mg/kg/day dendrobine was capable of preventing LPS-induced osteolysis with decreased osteoclasts in vivo. Conclusion Taken together, dendrobine suppresses osteoclastogenesis through restraining ROS, p38-c-Fos and NFATc1-MMP9 in vitro, thus attenuates inflammatory osteolysis in vivo. This finding supports the discover of dendrobine as a novel osteoclast inhibitor for impeding bone erosion in the future.

Adoptive chimeric antigen receptor (CAR)-modified T or NK cells (CAR-T/NK) have emerged as a novel form of disease treatment. Lentiviral vectors (LVs) are commonly employed to engineer T/NK cells for the efficient expression of CARs. This study reported for the first time the influence of single-promoter and dual-promoter LVs on the CAR expression and cytotoxicity of engineered NK cells. Our results demonstrated that the selected CAR exhibits both a higher expression level and a higher coexpression concordance with the GFP reporter in HEK-293T or NK92 cells by utilizing the optimized single-promoter pCDHsp rather than the original dual-promoter pCDHdp. After puromycin selection, the pCDHsp produces robust CAR expression and enhanced in vitro cytotoxicity of engineered NK cells. Therefore, infection with a single-promoter pCDHsp lentivector is recommended to prepare CAR-engineered cells. This research will help to optimize the production of CAR-NK cells and improve their functional activity, to provide CAR-NK cell products with better and more uniform quality.

Upon viral RNA recognition, the RIG-I signalosome continuously generates IFNs and cytokines, leading to neutrophil recruitment and inflammation. Thus, attenuation of excessive immune and inflammatory responses is crucial to restore immune homeostasis and prevent unwarranted damage, yet few proresolving mediators have been identified. In the present study, we demonstrated that RTN3 is strongly upregulated during RNA viral infection and acts as an inflammation-resolving regulator. Increased RTN3 aggregates on the endoplasmic reticulum and interacts with both TRIM25 and RIG-I, subsequently impairing K63-linked polyubiquitination and resulting in both IRF3 and NF-κB inhibition. Rtn3 overexpression in mice causes an obvious inflammation resolving phenomenon when challenged with VSV, Rtn3-overexpressing mice display significantly decreased neutrophil numbers and inflammatory cell infiltration, which is accompanied by reduced tissue edema in the liver and thinner alveolar interstitium. Taken together, our findings identify RTN3 as a conserved proresolving mediator of immune and inflammatory responses and provide insights into the negative feedback that maintains immune and inflammatory homeostasis.SummaryRTN3 is upregulated upon RNA viral infection due to inflammation and ER stress, in turn suppresses antiviral responses by impairing TRIM25-mediated RIG-I K63-linked polyubiquitination and consequently decreases neutrophil populations and inflammatory infiltration, representing a novel mechanism of negative inflammatory resolution.

Vinylboronates and alkylboronates are key components in variegated transformations in all aspects of chemical science. This work describes a sequential radical difunctionalization strategy for the construction of fluorine-containing vinylboronates and alkylboronates with the integrated redox-active reagent N-trifluoromethylthiophthalimide. This multifunctional N-S precursor offers a scalable and practical protocol for the trifluoromethylthiolation-borylation of unsaturated hydrocarbons in a highly regio- and stereoselective fashion, which can be further converted into valuable synthons via boryl migration.

Functionalized N-heteroarenes are highly desired motifs in medicinal chemistry and pharmaceutical industry. Minisci-type reactions usually require a protonated N-heteroarene for the alkyl radical t...

A highly active and stable MOF-199-supported ionic liquid [Hnmp][H2PO4] (IL-NP) adsorbent (Py/MOF) was successfully synthesized and characterized via XRD, SEM and TEM, TG-DTG, FT-IR, BET, and XPS t...

Background Current chemotherapy for acute myeloid leukemia (AML) mainly involves cytotoxic agents such as doxorubicin (DNR), mitoxantrone (Mito) or 2‐aminopurine‐6‐thiol (6‐TG). However, because these agents are relatively ineffective, discovering other more effective drugs for AML treatment would be valuable. Methods The in vitro antitumor effect of lenvatinib on AML cells was examined using the colorimetric MTT assay for assessing cell metabolic activity. AML cells mixed with Poloxamer 407 were injected into nude mice to form subcutaneous tumors. Tumor‐bearing mice received lenvatinib by oral administration. The antitumor effect of lenvatinib was established by measuring tumor volumes and weights. Results Lenvatinib inhibited the growth of AML cells in a dose‐dependent manner. We used AML cells to establish subcutaneous tumor tissues by mixing the cell suspension with Poloxamer 407. Poloxamer 407 alone did not influence the subcutaneous growth of AML cells. Treatment of lenvatinib inhibited in vivo tumor growth of AML cells. Conclusion The multiple‐kinase inhibitor lenvatinib inhibits the in vitro proliferation of AML cells, and restricts the in vivo growth of AML tumors.

In chronic infectious diseases caused by gram-negative bacteria, such as osteomyelitis, septic arthritis, and periodontitis, osteoclastic activity is enhanced with elevated inflammation, which disturbs the bone homeostasis and results in osteolysis. Lipopolysaccharide (LPS), as a bacteria product, plays an important role in this process. Recent evidence shows that an antimalarial drug artesunate attenuates LPS-induced osteolysis independent of RANKL. In this study we evaluated the effects of artesunate on LPS-induced osteoclastogenesis in vitro and femur osteolysis in vivo, and explored the mechanisms underlying the effects of artesunate on LPS-induced osteoclast differentiation independent of RANKL. In preosteoclastic RAW264.7 cells, we found that artesunate (1.56−12.5 μM) dose dependently inhibited LPS-induced osteoclast formation accompanied by suppressing LPS-stimulated osteoclast-related gene expression (Fra-2, TRAP, Cathepsin K, β3-integrin, DC-STAMP, and Atp6v0d2). We showed that artesunate (3.125−12.5 µM) inhibited LPS-stimulated nuclear factor of activated T cells c1 (NFATc1) but not NF-κB transcriptional activity; artesunate (6.25, 12.5 μM) significantly inhibited LPS-stimulated NFATc1 protein expression. Furthermore, artesunate treatment markedly suppressed LPS-induced Ca 2+ influx, and decreased the expression of PP2B-Aα (calcineurin) and pPLCγ1 in the cells. In addition, artesunate treatment significantly decreased the expression of upstream signals TLR4 and TRAF6 during LPS-induced osteoclastogenesis. Administration of artesunate (10 mg/kg, ip) for 8 days effectively inhibited serum TNF-α levels and ameliorated LPS (5 mg/kg, ip)-induced inflammatory bone loss in vivo. Taken together, artesunate attenuates LPS-induced inflammatory osteoclastogenesis by inhibiting the expression of TLR4/TRAF6 and the downstream PLCγ1-Ca 2+ -NFATc1 signaling pathway. Artesunate is a valuable choice to treat bone loss induced by gram-negative bacteria infection or inflammation in RANKL-independent pathway.

Sustainable textile wastewater treatment strongly demands an indispensable paradigm shift from removal of contaminants to effective recovery of resources. In this work, a hybrid tight ultrafiltration (TUF) and bipolar-membrane electrodialysis (BMED) process was explored to recover resources (i.e., dye extraction, acid/base conversion, and pure water regeneration) from highly saline textile wastewater. Using a TUF membrane with 5000 Da molecular weight cutoff (MWCO) can obtain a sufficient rejection (>99.6%) of both reactive and direct dyes, due to the dye aggregation. Additionally, the considerably large pore size of the TUF membrane endowed the process with free transport of NaCl and Na2SO4 (i.e., >99.42%), exhibiting promise as an alternative means of separation of dyes and Na2SO4. Additionally, an integrated TUF-based diafiltration was designed to separate the model dye (i.e., reactive blue 194) and Na2SO4. Particularly, reactive blue 194 was remarkably concentrated from 997.9 to 7952.8 mg·L–1 by the T...

Background Recent research into skin injury and wound healing has focused mainly on post‐trauma hemostasis, infection prevention, dermal regeneration and angiogenesis. However, less attention has been paid to air permeability and moisture loss prevention which also play important roles in injury healing. Methods In the present work, we prepared a hyaluronic acid‐poloxamer (HA‐POL) hydrogel and tested the therapeutic effect of the hydrogel on skin‐wound healing. Results The HA‐POL hydrogel transformed from sol to gel at 30°C, close to body temperature, and had stable moisturizing properties. HA‐POL hydrogel promoted skin‐wound healing and increased protein accumulation in the wound area. HA‐POL hydrogel allowed greater air permeability than Band‐aid, a typical wound covering. Results from transwell assays showed that the HA‐POL hydrogel effectively isolated skin‐wounds from bacterial invasion. Conclusion This work demonstrates the advantages of using HA‐POL gel materials in the treatment of cutaneous wounds.

A hydrolysis of casein by papain was carried out to explore interaction between parachloromercuribenzoic acid (PCMB) and papain through Attenuated Total Reflection Flourier transformed Infrared Spectroscopy (ATR-FTIR), Trp intrinsic fluorescence spectroscopy and molecular docking analysis. Papain activity was almost completely inactivated when PCMB concentration reached to 10–4 mol/L or higher. The content of α-helix was decreased from 36.79% to 19.79% even up to 17%. On the other hand, the content of β-sheet was decreased from 13.41% to 11.57% by a little degree of 1.84%. However, the contents of β-turn, random coil and intermolecular β-sheet aggregates were elevated by different degree of 2.67%, 8.87% and 7.3%, respectively at the papain exposure of 10–4 mol/L PCMB solution. PCMB could bind to papain mainly through hydrophobic force and hydrogen bonding. The hydrogen bond between PCMB and Gly66; while, the hydrophobic bonds between PCMB and Trp26 in the ligand-binding pocket of papain might be the key functional groups for the inhibition of papain activity. The L-domain of papain was destructed, leading to the inactivation and fluorescence quenching of papain. The inhibition mechanism of papain activity by 10–4mol/L PCMB was involved the formation of hydrophobic force and hydrogen bond between PCMB and papain. This attempt successfully brought forth the application of computational approaches to dissect the inhibition mechanism and directed design in enzyme engineering area.