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Baculiferins are a group of marine sponge-derived polycyclic alkaloids with anti-HIV (human immunodeficiency virus) activities. To identify additional baculiferin-based congeners for SAR analysis and to investigate the mode of action, a total of 18 new baculiferin-type derivatives were synthesized. The inhibitory activities of the congeners against the HIV-1 virus were evaluated in vitro, and the relevant SAR was discussed. Compound 18 exerted the most potent activity toward VSV-G-pseudotyped HIV-1 (IC50 of 3.44 μM) and HIV-1 strain SF33 (IC50 of 2.80 μM) in vitro. To identify the cellular targets, three photoaffinity baculiferin probes were simultaneously synthesized. Photoaffinity labeling experiments together with LC-MS/MS data identified aspartate-tRNA ligase (DARS) as a putative target protein of 18. The overexpression and knockdown of DARS in HEK293T cells provided additional data to demonstrate that DARS is a potential target protein in the regulation of HIV virus infection. The modes of antiviral baculiferins 13 and 18 binding to DARS were determined by a molecular docking simulation. Thus, baculiferin 18 is considered a promising lead as a new molecular target for the development of anti-HIV agents.

Treatment of osteoarthritis (OA) by administration of corticosteroids is a commonly used method in clinics using anti-inflammatory medicine. Oral administration or intra-articular injection of corticosteroids can reduce the pain and progress of cartilage degeneration, but they are usually insufficient to show local and long-term anti-inflammatory effects because of their fast clearance in the body. In this study, we suggest an injectable anti-OA drug depot system for sustained drug release that provides long-term effective therapeutic advantages. Amphiphilic poly(organophosphazene), which has temperature-dependent nanoparticle forming and sol-gel transition behaviors when dissolved in aqueous solution, was synthesized for triamcinolone acetonide (TCA) delivery. Because hydrophobic parts of the polymer can interact with hydrophobic parts of the TCA, the TCA was encapsulated into the self-assembled polymeric nanoparticles. The TCA-encapsulated polymeric nanoparticles (TePNs) were well dispersed in an aqueous solution below room temperature so that they can be easily injected as a sol state into an intra-articular region. However, the TePNs solution transforms immediately to a viscose 3D hydrogel like a synovial fluid in the intra-articular region via the conducted body temperature. An in vitro TCA release study showed sustained TCA release for six weeks. One-time injection of the TePN hydrogel system in an early stage of OA-induced rat model showed a great inhibition effect against further OA progression. The OA-induced knees completely recovered as a healthy cartilage without any abnormal symptoms., Graphical abstract Image 1, Highlights • An injectable polymeric nanoparticle-based hydrogel loaded with TCA was developed to treat OA. • Nanoparticles via complexation of TCA/polymer were turned into hydrogel after injection and released TCA for a long time. • One-time injection of the hydrogel system showed a great inhibition effect against OA progression and cartilage regeneration.

Superhydrophobic coating solutions were prepared using fumed silica nanoparticles and trimethylethoxysilane (TMES) as precursors. At this time, the surface of silica nanoparticles was modified by TMES from hydrophilic to hydrophobic in various types of catalysts and organic solvents. The prepared coating solutions were coated on a cold rolled steel sheet by using a spin coater, and then superhydrophobic coating films were prepared by thermal curing. In this process, the effects of the amount of silica nanoparticles added, the type of catalysts, and the type of organic solvents were observed on the hydrophobicity of the coating films. As the content of silica nanoparticles added increased from 0 g to 0.08 g, the contact angle of the coating films increased from 93o to 151o, and when 0.08 g of silica nanoparticle was added, it showed superhydrophobicity of 151o. On the other hand, when nitric acid and hydrochloric acid, strong acids, were used as catalysts, the coating films showed low hydrophobicity of 73o and 86o, respectively. However, when oxalic acid, a weak acid, was used, the coating film showed superhydrophobicity of 151o. In addition, with methanol as an organic solvent, the coating film showed superhydrophobicity of 151o, while when i-propanol and n-butanol were used, the coating films exhibited low hydrophobicity of 97o and 91o.

Silicon (Si) has never been acknowledged as a vital nutrient though it confers a crucial role in a variety of plants. Si may usually be expressed more clearly in Si-accumulating plants subjected to biotic stress. It safeguards several plant species from disease. It is considered as a common element in the lithosphere of up to 30% of soils, with most minerals and rocks containing silicon, and is classified as a “significant non-essential” element for plants. Plant roots absorb Si, which is subsequently transferred to the aboveground parts through transpiration stream. The soluble Si in cytosol activates metabolic processes that create jasmonic acid and herbivore-induced organic compounds in plants to extend their defense against biotic stressors. The soluble Si in the plant tissues also attracts natural predators and parasitoids during pest infestation to boost biological control, and it acts as a natural insect repellent. However, so far scientists, policymakers, and farmers have paid little attention to its usage as a pesticide. The recent developments in the era of genomics and metabolomics have opened a new window of knowledge in designing molecular strategies integrated with the role of Si in stress mitigation in plants. Accordingly, the present review summarizes the current status of Si-mediated plant defense against insect, fungal, and bacterial attacks. It was noted that the Si-application quenches biotic stress on a long-term basis, which could be beneficial for ecologically integrated strategy instead of using pesticides in the near future for crop improvement and to enhance productivity.

Transition metal phosphides (TMPs) as ever-evolving electrocatalytic materials have attracted increasing attention in water splitting reactions owing to their cost-effective, highly active and stable catalytic properties. This work presents a facile synthetic route to NiCoP nanoparticles with Ru dopants which function as highly efficient electrocatalysts for oxygen evolution reaction (OER) in alkaline media. The Ru dopants induced a high content of Ni and Co vacancies in NiCoP nanoparticles, and the more defective Ru doped NiCoP phase than undoped NiCoP ones led to a greater number of catalytically active sites and improved electrical conductivity after undergoing electrochemical activation. The Ru doped NiCoP catalyst exhibited high OER catalytic performance in alkaline media with a low overpotential of 281 mV at 10 mA cm-2 and a Tafel slope of 42.7 mV dec-1 .

Nano-graphene oxide (Nano-GO) is an extensively studied multifunctional carbon nanomaterial with attractive applications in biomedicine and biotechnology. However, few studies have been conducted to assess the epithelial-to-mesenchymal transition (EMT) in the retinal pigment epithelium (RPE). We aimed to determine whether Nano-GO induces EMT by regulating phospholipase D (PLD) signaling in human RPE (ARPE-19) cells. The physicochemical characterization of Nano-GO was performed using a Zetasizer, X-ray diffraction, Fourier-transform infrared spectroscopy, and transmission electron microscopy. RPE cell viability assays were performed, and the migratory effects of RPE cells were evaluated. RPE cell collagen gel contraction was also determined. Intracellular reactive oxygen species (ROS) levels were determined by fluorescence microscopy and flow cytometry. Immunofluorescence staining and western blot analysis were used to detect EMT-related protein expression. Phospholipase D (PLD) enzymatic activities were also measured. Nano-GO significantly enhanced the scratch-healing ability of RPE cells, indicating that the RPE cell migration ability was increased. Following Nano-GO treatment, the RPE cell penetration of the chamber was significantly promoted, suggesting that the migratory ability was strengthened. We also observed collagen gel contraction and the generation of intracellular ROS in RPE cells. The results showed that Nano-GO induced collagen gel contraction and intracellular ROS production in RPE cells. Moreover, immunofluorescence staining and western blot analysis revealed that Nano-GO significantly regulated key molecules of EMT, including epithelial-cadherin, neural-cadherin, α-smooth muscle actin, vimentin, and matrix metalloproteinases (MMP-2 and MMP-9). Interestingly, Nano-GO-induced RPE cell migration and intracellular ROS production were abrogated in PLD-knockdown RPE cells, indicating that PLD activation played a crucial role in the Nano-GO-induced RPE EMT process. We demonstrate for the first time that Nano-GO promotes RPE cell migration through PLD-mediated ROS production. We provide preliminary evidence to support the hypothesis that Nano-GO has adverse health effects related to RPE damage.

The forms of arsenic (As) and lead (Pb) in coal have an important influence on their transformation during combustion. Considering that As and Pb in coal are partially associated with pyrite, pyrol...

We have previously shown that blockade of ATP-binding cassette transporter A1 (ABCA1) with cyclosporine A (CsA) stimulates the epithelial sodium channel (ENaC) in cultured distal nephron cells. Here we show that CsA elevated systolic blood pressure in both wild-type and apolipoprotein E (ApoE) knockout (KO) mice to a similar level. The elevated systolic blood pressure was completely reversed by inhibition of cholesterol (Cho) synthesis with lovastatin. Inside-out patch-clamp data show that intracellular Cho stimulated ENaC in cultured distal nephron cells by interacting with phosphatidylinositol‑4,5‑bisphosphate (PIP2), an ENaC activator. Confocal microscopy data show that both α‑ENaC and PIP2 were localized in microvilli via a Cho-dependent mechanism. Deletion of membrane Cho reduced the levels of γ‑ENaC in the apical membrane. Reduced ABCA1 expression and elevated intracellular Cho were observed in old mice, compared to young mice. In parallel, cell-attached patch-clamp data from the split-open cortical collecting ducts (CCD) show that ENaC activity was significantly increased in old mice. These data suggest that elevation of intracellular Cho due to blockade of ABCA1 stimulates ENaC, which may contribute to CsA-induced hypertension. This study also implies that reduced ABCA1 expression may mediate age-related hypertension by increasing ENaC activity via elevation of intracellular Cho.

NH3 emissions were limited strictly because of the threat for human health and sustainable development. Pt/Al2O3 and Pt/CeZrO2 were prepared by the impregnation method. Differences in surface chemical states, reduction ability, acid properties, morphological properties, reaction mechanisms, and ammonia oxidation activity were studied. It indicated that Pt species states were affected by different metal-support interactions. The homogeneously dispersed Pt species over Pt/Al2O3 exposed Pt(111) because of weak metal-support interactions; there even existed an obvious interface between Pt and Al2O3. While obscure even an overlapped interface was observed over Pt/CeZrO2, resulting in the formation of PtO because of the oxygen migration from CeZrO2 to Pt species (confirmed by CO-FTIR, the cycled H2-TPR and transmission electron microscopy results). It was noteworthy that different reaction mechanisms were induced by different states of Pt species; NH was the key intermediate species for ammonia oxidation reaction over Pt/Al2O3, but two kinds of intermediates, N2H4 and HNO, were observed for Pt/CeZrO2. It consequently resulted in the obvious distinction of the NH3-SCO catalytic performance; the light-off temperatures of NH3 over Pt/Al2O3 and Pt/CeZrO2 were 231 and 275 °C, respectively, while the maximum N2 selectivity (65%) was obtained over Pt/CeZrO2, it was obviously better than that over Pt/Al2O3.

The properties from both bulk phases (magnetism and thermal stability) and surface (composition, orientation, and stability) of iron silicide model compounds were evaluated by a theoretical study w...

The aggregation and accumulation of amyloid beta (Aβ) peptide is believed to be the primary cause of Alzheimer's disease (AD) pathogenesis. Vitamin D-binding protein (DBP) can attenuate Aβ aggregation and accumulation. A biocompatible polymer poly (D,L-lactic acid-co-glycolic acid) (PLGA) can be loaded with therapeutic agents and control the rate of their release. In the present study, a PLGA-based drug delivery system was used to examine the therapeutic effects of DBP-PLGA nanoparticles in Aβ-overexpressing (5XFAD) mice. DBP was loaded into PLGA nanoparticles and the characteristics of the DBP-PLGA nanoparticles were analyzed. Using a thioflavin-T assay, we observed that DBP-PLGA nanoparticles significantly inhibited Aβ aggregation in vitro. In addition, we found that intravenous injection of DBP-PLGA nanoparticles significantly attenuated the Aβ accumulation, neuroinflammation, neuronal loss and cognitive dysfunction in the 5XFAD mice. Collectively, our results suggest that DBP-PLGA nanoparticles could be a promising therapeutic candidate for the treatment of AD.

Two-dimensional ultrathin nickel hydroxide nanosheets with large surface area and excellent electronic properties have been considered as promising electrocatalysts for the oxygen evolution reactio...

The pollution of antibiotics, including tetracyclines (TCs), in aquatic environments has become an issue of concern in recent years. Herein, an in situ sampling of TCs in pig breeding wastewater that utilizes the technique of diffusive gradients in thin films (DGT), based on commercial nanosized ZnO (nanoZnO) particles as the potential effective binding agent and a polyethersulfone (PES) membrane as the diffusion layer, was developed. The diffusion coefficients of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC) in a PES membrane at 25 °C were (1.37 ± 0.06) × 10−6 cm2 s−1, (1.29 ± 0.05) × 10−6 cm2 s−1 and (1.94 ± 0.07) × 10−6 cm2 s−1, respectively. The results showed that the adsorption capacities of a gel disc containing 2.5 g L−1 of nanoZnO particles were as high as 3.93 ± 0.20 mg disc−1 for TC, 3.21 ± 0.20 mg disc−1 for OTC and 4.62 ± 0.22 mg disc−1 for CTC. Both a solution pH in the range of 5–9 and an ionic strength (as pNaCl) in the range of 1–3 had an insignificant influence on the TCs uptake by nanoZnO−DGT samplers. There was no significant influence of fulvic acid or tannic acid on the TC uptake by nanoZnO−DGT samplers at the tested mass ratios. For all spiked freshwater samples, there was no notable interference of matrices on the performance of the nanoZnO−DGT samplers, suggesting that the nanoZnO−DGT samplers yielded satisfactory results for the uptake of TCs at concentrations existing in the spiked freshwater samples. Field deployment of the nanoZnO−DGT samplers in pig breeding wastewater also exhibited excellent precision and accuracy, indicating that the nanoZnO−DGT samplers could be used as a promising method for the in situ sampling of TC antibiotics in aquatic environments.

Psychological stress is known to have profound effects on immune function and to promote inflammatory conditions. Elevated circulating levels of cytokines associated with stress are known to increase the risk to several diseases, but little is known about this mechanism. This study assessed the role of T cells on cytokine levels after exposure to stress in the learned helplessness paradigm. Adoptive transfer of CD4+ T cells into Rag2-/- mice did not change cytokine levels to stress while CD8+ T cells resulted in an increase in TNF-α, IL-6 and IFN-γ in stressed Rag2-/- mice. Moreover, depletion of CD8+ T cells in WT mice abolished these cytokine responses to stress. Corticosterone and behavioral stress responsiveness was impaired in Rag2-/- mice reconstituted with CD8+ T cells. Notably, depletion of these cells in WT mice had no effect on behavior or corticosterone levels. Exposure to stress did not change the expression of canonical markers of T cell activation including CD62L and CD44 or modified intracellular cytokine content, suggesting that they are not the main producers of circulating cytokines in response to stress. These results show that CD8+ T cells promote TNF-α, IL-6 and IFN-γ responses to stress, possibly by stimulating non-lymphoid cells.

The green synthesis of inorganic nanoparticles (NPs) using bio-materials has attained enormous attention in recent years due to its simple, eco-friendly, low-cost and non-toxic nature. In this work, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) were synthesized by the marine algae extract, Sargassum serratifolium (SS). The characteristic studies of bio-synthesized SS-AgNPs and SS-AuNPs were carried out by using ultraviolet–visible (UV–Vis) absorption spectroscopy, dynamic light scattering (DLS), high-resolution transmission electron microscope (HR-TEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Phytochemicals in the algae extract, such as meroterpenoids, acted as a capping agent for the NPs’ growth. The synthesized Ag and Au NPs were found to have important catalytic activity for the degradation of organic dyes, including methylene blue, rhodamine B and methyl orange. The reduction of dyes by SS-AgNPs and -AuNPs followed the pseudo-first order kinetics.

Background Abnormalities in the extracellular matrix of tumor microenvironments support tumor progression, lead to immune dysfunction, and provide a target for cancer therapeutics. Collagens are a primary component of the extracellular matrix. Abnormal levels of collagen and of the collagen-domain containing complement component 1q (C1q) in tumor microenvironments has been proposed to disrupt anti-tumor immunity. LAIR-1 is an adhesion molecule and inhibitory receptor expressed on the cell surface of several immune cell subsets. LAIR-1 binding to collagen-like domains present in collagens and C1q inhibit immune cell function. LAIR-2 is a soluble homolog of LAIR-1 that binds to and outcompetes LAIR-1 binding to collagens and C1q and serves as a natural decoy to promote immune function. Methods Taking advantage of a natural decoy system, we designed a protein biologic, NC410, composed of LAIR-2 fused with a functional IgG1 Fc domain to target collagen-rich tumors and promote immune activation, infiltration and effector function. Results NC410 has increased avidity due to Fc mediated dimerization, and blocks LAIR-1 interactions with ligands, and LAIR-1 signaling. In vivo administration of NC410 in humanized tumor models reduced tumor growth in a dose dependent fashion. NC410 increased the numbers of infiltrating human CD8+ and CD4+ T cells in the tumor, which is associated with increased levels of chemokines in the local tumor environment. Effector function was also enhanced, as denoted by increased levels of IFN-gamma and Granzyme B in the local tumor environment. In addition, NC410 increased specific collagen degradative products in the serum of humanized tumor-bearing mice, suggesting NC410 may promote tumor microenvironment remodeling and immune accessibility to further promote anti-tumor immunity. Conclusions These data support NC410 as a novel therapeutic for targeting collagen-rich tumors and enabling normalization of the tumor-immune microenvironment. FIH studies have recently been initiated with NC410.

Collagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte associated immunoglobulin-like receptor-1 (LAIR-1). Leukocyte associated immunoglobulin-like receptor-2 (LAIR-2) is a secreted protein that can act as a decoy receptor by binding collagen with higher affinity than LAIR-1. We propose that collagens promote immune evasion by interacting with LAIR-1 and that LAIR-2 could release LAIR-1 mediated immune suppression. Analysis of public datasets shows high LAIR-2 expression being associated with a favorable outcome in certain tumors. We designed a dimeric LAIR-2 with a functional IgG1 Fc tail, NC410, and showed that NC410 reduces tumor growth and increases T cell expansion and effector function in humanized tumor models. Immunohistochemical analysis of human tumors shows that NC410 binds to collagen-rich areas where LAIR-1+immune cells are localized. Our findings show that NC410 might be a powerful new strategy for cancer immunotherapy for immune-excluded tumors.

The interaction between flue gas and ash causes the redistribution of heavy metals and affect their emission characteristics. In this study, a double-layer fixed-bed reactor was used to investigate the effect of this interaction on Pb distribution at 800–1000 °C. Obvious gaseous Pb adsorption by ash just occurred in the case of high-Pb flue gas and less ash melting. In other cases, significant Pb release from ash occurred under the action of the high-temperature flue gas. The occurrences of Pb in ash was found to be thermally stable. Ash melting is the main reason for the Pb release. Gaseous Na in the combustion flue gas and reducing components in the pyrolysis flue gas promote the Pb release via promoting the ash melting. H2S and HCl in the pyrolysis flue gas also promote the Pb release by forming PbS and PbCl2, which are more volatile.

Wet starch noodle (moisture content: 51.38 ± 1.29%) as a retrograded starch-gel product was produced on an industrial scale and investigated to learn the role of long-term storage and storage temperature in its water characteristics, physicochemical properties, sensorial properties and structure changes. During twelve weeks' storage, moisture content, hardness, water absorption index, brightness, and overall acceptability of wet starch noodles dwindled with increasing storage time, accompanied by the increased cooking loss and water mobility transformation from “freezable” to “un-freezable”. In particular, storage temperature was found to have significant correlations with moisture loss, textural performance and appearance color of wet starch noodles during long-term storage. Although refrigeration temperature increased the color stability of wet starch noodles, it would weaken the internal linkage strength and increase cooking loss and broken noodles. Comparatively, wet starch noodles stored at 25 °C exhibited more ordered arrays and smooth cross-section evidenced by SEM, as well as favorable sensorial properties after twelve weeks’ storage. These findings provide beneficial insights into storage stability of wet starch noodles and its correlation with storage temperature, thus giving guiding information for manufacturers and suppliers in selecting of appropriate storage conditions for this industrial-scale product.

Collagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte-associated immunoglobulin-like receptor (LAIR)-1. LAIR-2 is a secreted protein that can act as a decoy receptor by binding collagen with higher affinity than LAIR-1. We propose that collagens promote immune evasion by interacting with LAIR-1 expressed on immune cells, and that LAIR-2 releases LAIR-1-mediated immune suppression. Analysis of public human datasets shows that collagens, LAIR-1 and LAIR-2 have unique and overlapping associations with survival in certain tumors. We designed a dimeric LAIR-2 with a functional IgG1 Fc tail, NC410, and showed that NC410 increases human T cell expansion and effector function in vivo in a mouse xenogeneic-graft versus-host disease model. In humanized mouse tumor models, NC410 reduces tumor growth that is dependent on T cells. Immunohistochemical analysis of human tumors shows that NC410 binds to collagen-rich areas where LAIR-1+ immune cells are localized. Our findings show that NC410 might be a novel strategy for cancer immunotherapy for immune-excluded tumors.

Traumatic brain injury (TBI) is a complex and serious disease as its multifaceted pathophysiological mechanisms remain vague. The molecular changes of hippocampal and cortical dysfunction in the process of TBI are poorly understood, especially their chronic effects on metabolic profiles. Here we utilize metabolomics-based liquid chromatography coupled with tandem mass spectrometry coupled with bioinformatics method to assess the perturbation of brain metabolism in rat hippocampus and cortex on day 7. The results revealed a signature panel which consisted of 13 identified metabolites to facilitate targeted interventions for subacute TBI discrimination. Purine metabolism change in cortical tissue and taurine and hypotaurine metabolism change in hippocampal tissue were detected. Furthermore, the associations between the metabolite markers and the perturbed pathways were analyzed based on databases: 64 enzyme and one pathway were evolved in TBI. The findings represented significant profiling changes and provided unique metabolite-protein information in a rat model of TBI following the subacute phase. This study may inspire scientists and doctors to further their studies and provide potential therapy targets for clinical interventions.

The epithelial sodium channel (ENaC) regulates blood pressure by fine-tuning distal nephron sodium reabsorption. Our previous work has shown that ENaC gating is regulated by anionic phospholipid phosphates, including phosphatidylinositol 4,5-bisphosphate (PIP2). The PIP2-dependent regulation of ENaC is mediated by the myristoylated alanine-rich protein kinase C substrate-like protein-1 (MLP-1). MLP-1 binds to and is a reversible source of PIP2at the plasma membrane. We examined MLP-1 regulation of ENaC in distal convoluted tubule clonal cell line DCT-15 cells. Wild-type MLP-1 runs at an apparent molecular mass of 52 kDa despite having a predicted molecular mass of 21 kDa. Native MLP-1 consists of several distinct structural elements: an effector domain that is highly positively charged, sequesters PIP2, contains serines that are the target of PKC, and controls MLP-1 association with the membrane; a myristoylation domain that promotes association with the membrane; and a multiple homology 2 domain of previously unknown function. To further examine MLP-1 in DCT-15 cells, we constructed several MLP-1 mutants: WT, a full-length wild-type protein; S3A, three substitutions in the effector domain to prevent phosphorylation; S3D mimicked constitutive phosphorylation by replacing three serines with aspartates; and GA replaced the myristoylation site glycine with alanine, so GA could not be myristoylated. Each mutant was tagged with either NH2-terminal 3XFLAG or COOH-terminal mCherry or V5. Transfection with MLP mutants modified ENaC activity in DCT-15 cells: activity was highest in S3A and lowest in S3D, and the activity after transfection with either construct was significantly different from WT. In Western blots, when transfected with 3XFLAG-tagged MLP-1 mutants, the expression of the full length of MLP-1 at 52 kDa increased in mutant S3A-MLP-1-transfected DCT-15 cells and decreased in S3D-MLP-1-transfected DCT-15 cells. Several lower molecular mass bands were also detected that correspond to potential presumptive calpain cleavage products. Confocal imaging shows that the different mutants localize in different subcellular compartments consistent with their preferred location in the membrane or in the cytosol. Activation of protein kinase C increases phosphorylation of endogenous MLP-1 and reduces ENaC activity. Our results suggest a complicated role for proteolytic processing in MLP-1 regulation of ENaC.

Green-synthesized silver nanoparticles (SNPs) have great potential for biomedical applications, due to their distinctive optical, chemical, and catalytic properties. In this study, we aimed to develop green-synthesized SNPs from extracts of Cudrania tricuspidata (CT) roots (CTR), stems (CTS), leaves (CTL), and fruit (CTF) and to evaluate their physicochemical, photocatalytic, and biological properties. CTR, CTS, CTL, and CTF extracts were evaluated and compared for their total phenol and flavonoid content, reducing capacity, and antioxidant activity. The results revealed that CTR, CTS, CTL, and CTF extracts have high phenol and flavonoid content, as well as a powerful antioxidant and reducing capacity. CTR and CTS extracts showed the strongest effects. The results from UV-Vis spectra analysis, dynamic light scattering, high-resolution transmission electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and Fourier-transform infrared spectroscopy showed the successful formation of CT-SNPs with surface morphology, crystallinity, reduction capacity, capsulation, and stabilization. Synthesized CT-SNPs successfully photocatalyzed methylene blue, methyl orange, rhodamine B, and Reactive Black 5 within 20 min. The CTR- and CTS-SNPs showed better antibacterial properties against different pathogenic microbes (Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Salmonella enteritidis) than the CTL- and CTF-SNPs. CTS- and CTR-SNPs showed the most effective cytotoxicity and antiapoptosis properties in human hepatocellular carcinoma cells (HepG2 and SK-Hep-1). CT-SNPs also seemed to be more biologically active than the CT extracts. The results of this study provide evidence of the establishment of CT extract SNPs and their physicochemical, photocatalytic, and biological properties.

In this study, we identified a novel circulating recombinant form (CRF) of HIV (CRF105_0108) in a total of five patients with no obvious epidemiological linkage in Sichuan, China. Four strains were found in this study, and another strain (XC2014EU01) was reported in a previous study. The phylogenetic analysis of the five near full-length genomes showed that a CRF08_BC segment was inserted into the CRF01_AE backbone with one recombinant breakpoint in the pol region, which is the first HIV-1 CRF of CRF01_AE and CRF08_BC. Three genetic sequences had drug-resistant mutations, E138Q and V179D, indicating that there were low resistance levels to efavirenz (EFV) and nevirapine (NVP) in Liangshan Yi Autonomous Prefecture. CRF105_0108 increases the diversity and complexity of the prevalent HIV-1 CRFs in Sichuan. Simultaneously, drug-resistant mutations in this CRF may influence the efficacy of highly active antiretroviral treatments (ARTs) in Liangshan Yi Autonomous Prefecture.

Leonurine, an active alkaloid extracted from Herba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4+ T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naive CD4+ T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cells in vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1β, and tumor necrosis factor (TNF)-α and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1β, and TNF-α and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.

Microglia are rapidly activated following ischaemic stroke and participate in the induction of neuroinflammation, which exacerbates the injury of ischaemic stroke. However, the mechanisms regulating ischaemic microglia remain unclear. In the present study, middle cerebral artery occlusion and oxygen and glucose deprivation models were established for in vivo and vitro monitoring of experimental stroke. We applied recombinant human thioredoxin‐1 (rhTrx‐1) and Necrostatin‐1 (Nec‐1, inhibitor of RIPK1) to examine the role of receptor‐interacting protein kinase 1 (RIPK1) in the development of inflammation in ischaemic microglia via explored the inflammatory responses and the associated mechanisms. Molecular docking results indicated that rhTrx‐1 could directly bind to RIPK1. In vivo and vitro data revealed that rhTrx‐1 reduced necroptosis, mitochondrial membrane potential damage, reactive oxygen species accumulation and NLR Family, pyrin domain‐containing 3 protein (NLRP3) inflammasome activation and regulated the microglial M1/M2 phenotypic changes by inhibiting RIPK1 expression in ischaemic microglia. Consistent with these findings, further in vivo experiments revealed that rhTrx‐1 treatment attenuated cerebral ischaemic injury by inhibiting the inflammatory response. Our data demonstrated the role of RIPK1 in microglia‐induced neuroinflammation following cerebral ischaemia. Administration of rhTrx‐1 provides neuroprotection in ischaemic stroke‐induced microglial neuroinflammation by inhibiting RIPK1 expression.

This report demonstrated the utility of high-performance liquid chromatography (HPLC)-fluorescence detection for selective separation and sensitive quantification of multiple microRNAs (miRNAs). A duplex specific nuclease (DSN)-assisted target recycling amplification strategy was developed to enhance the signals of miRNAs, which alleviates the low sensitivity of conventional HPLC to nucleic acids. To separate the signals of different miRNAs, DNA probes with different lengths and base sequences were immobilized on magnetic beads. The application of an effective magnetic separation minimized the background signal and extended the dynamic range. This assay achieved a limit of detection of 0.39 fM for miRNA-122, 0.30 fM for miRNA-155, and 0.26 fM for miRNA-21, respectively. The proposed assay was successfully applied to detect simultaneously miRNA-122, miRNA-155, and miRNA-21 in serum samples from healthy persons and cervical cancer patients, and the results were then compared with those of quantitative real-time-polymerase chain reaction amplification.

Capped chelating organic molecules are presented as a design principle for tuning heterogeneous nanoparticles for electrochemical catalysis. Gold nanoparticles (AuNPs) functionalized with a chelating tetradentate porphyrin ligand show a 110-fold enhancement compared to the oleylamine-coated AuNP in current density for electrochemical reduction of CO2 to CO in water at an overpotential of 340 mV with Faradaic efficiencies (FEs) of 93 %. These catalysts also show excellent stability without deactivation (

To overcome colloidal instability of calcium phosphate nanoparticles in gene delivery, colloidally stable and endosomolytic Ca2+-based pDNA nanocomplexes (NCs) were designed by a surface coating of biocompatible polycations (PCs; low molecular weight branched polyethyleneimine [bPEI], protamine sulfate and e-polylysine) and the addition of natural and endosomolytic ATP, respectively. Without remarkable cytotoxicity and colloidal instability, Ca2+/ATP-pDNA/bPEI1.8 kDa NCs having [bPEI1.8 kDa] = 3.6 μg showed 5.8-fold and 4.4-fold higher transfection efficiencies than bPEI25 kDa/pDNA NCs in HepG2 cells and dental pulp stem cells, respectively. In conclusion, pH-sensitive endosomolytic ATP and Ca2+-based gene complexes could be potentials as effective and safe gene delivery vectors in various cells.

We report herein the first catalytic strategy to harness amidyl radicals derived from N-chloroamides for C-C bond formation, allowing for the discovery of the first catalytic benzylic C-H difluoromethylation. Under copper-catalyzed conditions, a wide variety of N-chlorocarboxamides and N-chlorocarbamates direct selective benzylic C-H difluoromethylation with a nucleophilic difluoromethyl source at room temperature. This scalable protocol exhibits a broad substrate scope and functional group tolerance, enabling late-stage difluoromethylation of bioactive molecules. This copper-catalyzed, chloroamide-directed strategy has also been extended to benzylic C-H pentafluoroethylation and trifluoromethylation. Mechanistic studies on the difluoromethylation reactions support that the reactions involve the formation of benzylic radicals via intramolecular C-H activation, followed by the copper-mediated transfer of difluoromethyl groups to the benzylic radicals.

The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function. Gain of TRPC6 function and loss of podocin function induce podocyte injury. We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown. Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose. High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys. The decreased podocin was diminished in TRPC6 knockdown podocytes. High glucose elevated intracellular Ca2+in control podocytes but not in TRPC6 knockdown podocytes. High glucose also elevated the expression of a tight junction protein, zonula occludens-1, and induced the redistribution of zonula occludens-1 and loss of podocyte processes. These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.

SiO(silicon monoxide) anode have received widespread attention owing to the great potential for the development of modern society. Although SiO has a large Li capacity, the short cycle life, poor rate capability and low coulombic efficiency limits its wide applications. In this paper, we adopt hydrothermal mixing and sintering process to form a ball milling bm-SiO based, Ni doped and rGO recombined composite (bm-SiO/Ni/rGO) anode material, which shows excellent cycle performance with the initial columbic efficiency of 65%, the discharge capacity of 720 mAh g−1 at 100 mA g−1 current density after 100 cycles and good rate performance. The improvement of electrochemical performance can be ascribed to the interaction effects of the limited damage of volume change, the open structure of reduced graphene oxide, and the cycle stability with the Ni doping.

Rehum emodi is an important medicinal herbal and has been reported to exhibit tremendous pharmacological potential. The present study was designed to evaluate the antibacterial activity of hydromethanolic extract of rhizome of Rehum emodi against the acute gastroenteriti bacterial strains. The antimicrobial activity was determined by micro-dilution method. Antioxidant activity was determined by DPPH assay and cytotoxicity by MTT assay. Phytochemical analysis was carried out by LC/MS analysis. The results of the present study showed that hydromethanolic extract of rhizome of Rehum emodi (REE) exhibited significant antimicrobial activity against the gastroenteriti bacterial strains. The MIC values ranged from 25 μg/ml to 125 μg/ml. Moreover, the cytotoxicity of the REE was evaluated against the human breast cell line FR-2 and it was observed that REE exerted minimal cytotoxic effects on these cells with an IC50 of 250 μg/ml indicating that this extract is non-toxic to human cells. The phytochemical analysis revealed the presence of several secondery metabolites such as anthroquinones (anthrone, emodin, aloe emodin and rhein) flavonoids (quercetin, and naringenin) and phenolics (sinapinic acid and gallic acid) which could potentially be responsible for the activity of the extract. In conclusion REE could potentially prove to be useful in the treatment of acute gastroenteritis.

In this work, CuNi/CoMoO4 nanozyme was synthesized the hydrothermal method, followed by calcination and impregnation techniques, which had laccase-like activity and could be used as peroxymonosulfate (PMS) activator. Thus, the total antioxidant capacity (TAC) of commercial beverage measurement and phenolic pollutants degradation were studied systematically. Besides, the portable smartphone platform integrated with an intelligence analysis APP and colorimetric signals was further established for on-site determination of epinephrine (a typical phenol). Simultaneously, as PMS activator, CuNi/CoMoO4 could activate PMS to yield ·OH and SO4·−, which was applied for organic pollutants (acid fuchsin, AF) degradation, and the degradation efficiency could reach up to 99.45% within 40 min. The results displayed that CuNi/CoMoO4 had practical value in anti-oxidant food quality evaluation and pollution degradation. Furthermore, the theoretical calculation revealed that the activation energy of the rate-determining step over Cu/CoMoO4 was decreased from 0.819 eV to 0.524 eV due to the enhanced interaction between Cu(I) of CuNi/CoMoO4 and 2,4-dichlorophenol (2,4-DCP). It not only provided a multifunctional catalyst for evaluating oxidative capacity in food quality and pollutant degradation, but also provided some new evidences for further study of laccase-like mechanism.

Temperature-induced structural variations of retrograded starch gel during long-term storage were investigated in a real food system (wet starch noodles). Fresh starch noodles presented a B-type XRD pattern containing 8.82% crystallinity and 16.04% double helices. In the first 2 weeks, double helices of starch chain formed long-range ordered structure leading to increased crystallinity, and such structural transformation was positively correlated with increasing storage temperature (from 4 °C to 35 °C) and storage time. However, with the extension of storage time to 12 weeks, the disorganization of supra-molecular structure was likely to be observed by decreased crystallinity, double helix and water mobility. Besides, we propose that the area and intensity of Raman band at 2910 cm-1 can be a good indicator for evaluating perfection of crystallinity in starch noodles. These results contributed to a better understanding of mechanisms underlying molecular order changes of retrograded starch gel product during long-term storage.

To reduce the glistenings in the hydrophobic acrylic intraocular lens (IOL) materials, various types of hydrophilic acrylic monomers of 2-hydroxyethyl acrylate (HEA), 2-hydroxypropyl acrylate (HPA), 4-hydroxybutyl acrylate (HBA), and 2-hydroxyethyl methacrylate (HEMA) were copolymerized with a hydrophobic acrylic monomer, 2-phenoxyethyl acrylate (POEA). In this process, the effect of the types and amounts of hydrophilic acrylic monomers on the physical properties, such as glistenings, equilibrium water content (EWC), refractive index, and glass transition temperature of the resulting hydrophobic acrylic IOL materials was investigated. As the amounts of hydrophilic acrylic monomers (HEA, HPA, HBA and HEMA) increased, glistenings in the IOL materials were significantly decreased in all monomers. At the same amount of the hydrophilic acrylic monomers, the IOL materials from HEA showed the least number of glistenings, but those from HBA exhibited the largest number of glistenings, resulting in a reduction of glistenings in the following order of HEA > HPA > HEMA > HBA. The EWCs of the IOL materials decreased in the order of HEA > HPA > HEMA > HBA with the same amount of hydrophilic monomers. From the above results, it can be seen that the greater the degree of hydrophilicity, such as the amounts and EWCs of the hydrophilic acrylic monomers, the greater the effect of glistening reduction of the resulting IOL materials.

Camptothecin (CPT) has been used as antitumor drug against a wide range of cancer cells. However, its clinical application is greatly hindered by insolubility and instability issues under physiological condition. Therefore, an appropriate CPT administration technique directed for living system is greatly anticipated. In this study, a delivery method for CPT in the form of thermoresponsive system was prescribed. A conjugate of cyclotriphosphazene and CPT was synthesized by substituting hexachlorocyclotriphosphazene with sodium salt of methoxy-poly (ethylene glycol) (Mw = 350), 20-O-trifluoroglycinylCPT, and isoleucine ethyl ester, respectively. The resulting cyclotriphosphazene-CPT was characterized via multinuclear (1H and 31P) NMR as well as FT-IR. The current conjugate showed temperature induced phase transition (solution to suspension) with a lower critical solution temperature at 31 °C. Our result indicated that the stability issue related to the use of CPT in aqueous solution could be handled by acylation at 20-OH moiety. Additionally, antitumor activity of cyclotriphosphazene-CPT, to some extent, was found to be more profound than that of CPT alone as evaluated against human colorectal cancer cell HCT-116. Altogether, the current cyclotriphosphazene-CPT conjugate might offer a facile method in delivering CPT as a minimally invasive system for treating cancer.