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The construction of intelligent near-infrared (NIR) fluorophores for high specificity to cancer cells and application in multiple therapeutic modalities is crucial for precise cancer diagnostic and therapy. In this study, an aggregation-induced emission-active NIR fluorophore (TACQ) with mitophagy-modulating activity was synthesized and developed for mitochondrial targeting multimodal cancer theranostics. The strengthened push-pull interaction extended the emission of TACQ into the NIR-II region (>1000 nm). Further, the rotor structure and twisted molecular conformation enables nanoaggregates of TACQ to balance the radiative and nonradiative decays to simultaneously exhibit bright NIR emission, high photothermal conversion efficiency (55%), and efficient generation of reactive oxygen species. The lipocationic property of TACQ allows it to selectively accumulate in the mitochondria of cancer cells. TACQ can induce mitophagy and block mitophagic flux facilitating cancer cell apoptosis. Both in vitro and in vivo evaluations revealed that TACQ is an efficient theranostic agent for NIR fluorescence and photothermal imaging-guided synergistic chemo-photothermal and photodynamic therapy.

Many lectins have been reported to have antitumor activities; identifying the glycan ligands in tumor cells of lectins is crucial for lectin clinical application. An edible mushroom galectin, Agrocybe aegerita lectin (AAL/AAGL), that has a high antitumor activity has been reported. In this paper, based on the glycan array data, it is showed that the Thomsen-Friedenreich antigen (TF antigen)-related O-glycans were found to be highly correlated with the antitumor activity of AAL/AAGL. Further glycosyltransferase quantification suggested that the ratio between GAL3ST2 and ST3GAL1 (GAL3ST2/ST3GAL1), which determined the 3′-sulfo-TF expression level, was highly correlated with the antitumor activity of AAL/AAGL. Overexpressing the enzyme of GAL3ST2 in HL60 and HeLa cell lines could increase the growth inhibition ratio of AAL/AAGL from 22.7 to 43.9% and 27.8 to 39.1%, respectively. However, ST3GAL1 in Jurkat cells could decrease the growth inhibition ratio from 44.7 to 35.6%. All the data suggested that the 3′-sulfo-TF antigen is one of the main glycan ligands that AAL/AAGL recognizes in tumor cells. AAL/AAGL may potentially serve as a reagent for cancer diagnosis and a targeted therapy for the 3′-sulfo-TF antigen.

O-GlcNAcylation is an O-linked β-N-acetyl-glucosamine (O-GlcNAc)-monosaccharide modification of serine or threonine in proteins that plays a vital role in many critical cellular processes. Owing to its low molecular weight, uncharged property, and difficulty in distinguishing from β-N-acetyl-galactosamine (GalNAc), the lack of high specificity and avidity tools and sophisticated quantification methods have always been the bottleneck in analyzing O-GlcNAc functions. Here, we compared glycan array data of the mutant of Clostridium perfringen OGA (CpOGAD298N), O-GlcNAc antibody CTD110.6, and several lectins. We found that CpOGAD298N can effectively distinguish GlcNAc from GalNAc. Glycan array analysis and isothermal titration calorimetry (ITC) show that CpOGAD298N has a GlcNAc specific binding characteristic. CpOGAD298N could be used in far-western, flow cytometry analysis, and confocal imaging to demonstrate the existence of O-GlcNAc proteins. Using the CpOGAD298N affinity column, we identified 84 highly confident O-GlcNAc modified peptides from 82 proteins in the MCF-7 cell line and 33 highly confident peptides in 33 proteins from mouse liver tissue; most of them are novel O-GlcNAc proteins and could not bind with wheat germ agglutinin (WGA). Besides being used as a facile enrichment tool, a combination of CpOGAD298N with the proximity ligation assay (PLA) is successfully used to quantify O-GlcNAc modified histone H2B, which is as low as femtomoles in MCF-7 cell lysate. These results suggest that CpOGAD298N is a specific tool for detection (far-western, flow cytometry analysis, and confocal imaging) and enrichment of O-GlcNAcylated proteins and peptides, and the CpOGAD298N-PLA method is useful for quantifying certain O-GlcNAc protein.

This letter presents a novel harmonic impedance matching technique by using a parallel LC resonate block after the combining point to design a fully integrated high-efficiency Doherty power amplifier (DPA). The second harmonic impedances of both carrier and peaking amplifiers can be matched to the optimal area with only one harmonic tuner easily. The insertion loss and size of the output matching network (OMN) can be reduced. For verification, a 4.6–5.2-GHz monolithic microwave integrated circuit DPA was designed and fabricated using a 0.25- $\mu \text{m}$ gallium nitride (GaN)-HEMT process. Experimental results show that a saturated power of 41.8–42.1 dBm, a saturated drain efficiency (DE) of 63.8%–68.4%, and a 6-dB back-off DE of 53.3%–57.4% are achieved from 4.6 to 5.2 GHz. For a 160-MHz modulated signal, a high DE of 54% with good linearity after linearization is obtained at an average output power of 35.6 dBm.

Single-atom catalysts (SACs) have attracted great attention due to their high atom-utilization and catalytic efficiency. However, a universal synthetic route is still lacking, which restricts the SAC-related investigation and application. Here, we report a simple and cost-effective method to fabricate transition metal SACs through ion exchange and annealing procedures. Benefiting from the "egg-box" structure property of alginate, the metal ion can be effectively anchored into the organic center. Using CuCl2 as a representative transition metal ion, the Cu SAC structure was synthesized and identified by aberration-corrected high-angle annular dark-field scanning transmission electron microscopy and X-ray absorption fine structure spectroscopy. Through optimizing CuCl2 concentration, the obtained Cu SAC exhibited a good oxygen reduction reaction activity, whose onset potential, half wave potential, and limiting current density are all comparable to those of 20 wt % Pt/C. Cu-N4 was identified as the responsible catalytic site. More importantly, other transition metal SACs can be easily synthesized via altering metallic solution, which proves the universality of our proposed method. This work may be valuable for the cost-effective and universal SAC synthetic method development.

Co(II) and Cu(II) complexes, [Co2(H2L)2(phen)2(H2O)4](H2O)2 (1) and [Cu2(L)0.5(phen)2Cl2]n (2) [H4L = 5,5'-(diazene-1,2-diyl)diisophthalic acid, phen = 1,10-phenanthroline], have been solvothermall...

Yuhua Zhan, Jiyang Han, Jing Xia, Xumei Wang Department of Psychiatry, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaCorrespondence: Xumei WangDepartment of Psychiatry, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaTel/Fax +86 0249-661566112Email xiaoyema2020@163.comBackground: Berberine has been found to inhibit the progression of depression disorder, but its specific mechanism is still unclear. MicroRNA (miRNA) is considered to play an important role in the progression of depression. However, it is unclear whether Berberine is involved in the regulation of depression progression through miRNA.Methods: The chronic unpredictable mild stress (CUMS) mice model was constructed. Mice depression behaviors were evaluated by sucrose preference test (SPT) and forced swim test (FST). Quantitative real-time PCR was employed to assess the expression of miR-34b-5p, miR-470-5p and brain-derived neurotrophic factor (BDNF). The protein expression of BDNF was examined using Western blot analysis. In addition, the viability and apoptosis of hippocampal neurons were determined using cell counting kit 8 assay, flow cytometry and TUNEL assay. The interaction between BDNF and miR-34b-5p or miR-470-5p was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay.Results: Our data indicated that Berberine could inhibit CUMS mice depression behaviors and enhance hippocampal neurons growth by targeting miR-34b-5p and miR-470-5p. In addition, we found that BDNF was a target of miR-34b-5p and miR-470-5p. Overexpressed BDNF could reverse the regulation of miR-34b-5p and miR-470-5p on CUMS mice depression behaviors and hippocampal neurons growth. Furthermore, Berberine could promote BDNF expression to regulate CUMS mice depression behaviors and hippocampal neurons growth.Conclusion: Berberine might inhibit the progression of depression disorder by regulating the miR-34b-5p/miR-470-5p/BDNF axis.Keywords: depression disorder, Berberine, miR-34b-5p, miR-470-5p, BDNF

Quench and mechanical behaviors are critical issues in high temperature superconducting coils. In this paper, the quench characteristics in the rare earth barium copper oxide (REBCO) pancake coil at 4.2 K are analyzed, and a two-dimensional (2D) axisymmetric electro-magneto-thermal model is presented. The effects of the constituent materials, background field, and coil size are analyzed. An elastoplastic mechanical model is used to study the corresponding mechanical responses during the quench propagation. The variations of the temperature and strain in superconducting layers are compared. The results indicate that the radial strain evolutions can reflect the transverse quench propagation and the tensile hoop and radial stresses in superconducting layers increase with the quench propagation. The possible damages are discussed with the consideration of the effects of the background field and coil size. It is concluded that the high background field significantly increases the maximum tensile hoop and radial stresses in quenching coils and local damage may be caused.

Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC-δ-(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC-δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3β signaling via nuclear-export signal blockage independent of PKC-δ activation. By demonstrating independent modulation of PKC-δ and PKB/GSK-3β/Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo, further supporting the potential applicability of this rationale.

The depressant-like effects of albiflorin (AF) were studied on stressed chronic restraint stress (CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer for continuous 21 d and were treated with 30 or 15 mg·kg-1 of AF for 21 d. Control rats were maintained in completely non stressed conditions. Behavioral tests and biochemical analysis were applied to investigating a regulatory mechanism of anti-stress of AF. Treatment with AF significantly restored the depressant-like behaviors. Besides, AF increased the levels of 5-hydroxytryptophan (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NE) and dopamine (DA) in the hippocampus and increased the level of brain-derived neurotrophic factor (BDNF) in serum and protein expression in hippocampus. In addition, AF decreased the levels of hypothalamo-pituitary-adrenal (HPA) cascade, reduced the level of NO and cGMP in serum and inhibited the overexpression of 5-HT2AR mRNA and protein expression. Taken together, AF can modulate the NO-mediated network pathway in the hippocampus against stress-induced depressive-like behaviors. These physiological and behavioral changes allow rats to avoid potential deleterious effects of stress that may result from chronically elevated levels of glucocorticosteroids over days.

The aim of this work is to apply Solutol® HS15 and TPGS to prepare self-assembled micelles loading with ginsenoside Rh2 to increase the solubility of ginsenoside Rh2, hence, improving the antitumor efficacy. Ginsenoside Rh2-mixed micelles (Rh2-M) were prepared by thin film dispersion method. The optimal Rh2-M was characterized by particle size, morphology, and drug encapsulation efficiency. The enhancement of in vivo anti-tumor efficacy of Rh2-M was evaluated by nude mice bearing tumor model. The solubility of Rh2 in self-assembled micelles was increased approximately 150-folds compared to free Rh2. In vitro results demonstrated that the particle size of Rh2-M is 74.72 ± 2.63 nm(PDI = 0.147 ± 0.15), and the morphology of Rh2-M is spherical or spheroid, and the EE% and LE% are 95.27 ± 1.26% and 7.68 ± 1.34%, respectively. The results of in vitro cell uptake and in vivo imaging showed that Rh2-M could not only increase the cell uptake of drugs, but also transport drug to tumor sites, prolonging the retention time. In vitro cytotoxicity and in vivo antitumor results showed that the anti-tumor effect of Rh2 can be effectively improved by Rh2-M. Therefore, Solutol® HS15 and TPGS could be used to entrapping Rh2 into micelles, enhancing solubility and antitumor efficacy.

Hydrogen is a clean fuel widely used in fuel cells, engines, rockets and many other devices. The catalytic decomposition of methane (CDM) is a COx-free hydrogen production technology from which carbon nano materials (CNMs) can be generated as a high value-added byproduct for electrode, membranes and sensors. Recent work has focused on developing a low cost catalyst that could work without rapid deactivation by carbon deposition. In this review, the economic and environmental evaluation of CDM are compared with coal gasification, steam reforming of methane, and methanol steam reforming in terms of productivity, CO2 emissions, and H2 production and cost. CDM could be a favorable technology for on-site demand-driven hydrogen production on a small or medium industrial scale. This study covers the Fe-based, Ni-based, noble metal, and carbonaceous catalysts for the CDM process. Focusing on hydrogen (or carbon) yield and production cost, Fe-based catalysts are preferable for CDM. Although Ni-based catalysts showed a much higher hydrogen yield with 0.39 molH2/gcat./h than Fe-based catalysts with 0.22 molH2/gcat./h, the hydrogen cost of the former was estimated to be 100-fold higher ($0.89/$0.009). Further, the CDM performance on different types of reactors are detailed, whereas the molten-metal catalyst/reactor is suggested to be a promising route to commercialize CDM. Finally, the formation mechanism, characterization, and utilization of carbon byproducts with different morphologies and structures are described and analyzed. Versus other reviews, this review shows that cheap Fe-based catalysts (10 tons H2/1 ton iron ore) and novel molten-metal reactors (95% methane conversion) for CDM are feasible research directions for a fundamental understanding of CDM. The CNMs by CDM could be applied to the waste water purification, lubricating oils, and supercapacitors.

Background Obesity confers increased risk for various types of cancer. PD-L1 is a key molecule in tumor immune evasion by inducing T cell exhaustion. The relationship between obesity and PD-L1 is still ambiguous. This study was designed to reveal the development of hepatocellular carcinoma and melanoma in obese mice and to investigate if adipocytes regulate PD-L1 expression and the underlying mechanism. Methods Monosodium glutamate-induced obese mice were inoculated with H22 tumor cells and High fat diet (HFD)-induced obese mice were inoculated with B16-F1 mouse melanoma cells. Human hepatoma HepG2 cells and B16-F1 cells were treated with conditional media from 3T3-L1 adipocytes (adi-CM). Neutralized anti-TNF-α and anti-IL-6 antibodies and inhibitor of NF-κB or STAT3 were used to reveal the mechanism of effect of adi-CM. Results In obese mice, H22 and B16-F1 tumor tissues grew faster and PD-L1 expression in tumor tissue was increased. Adi-CM up-regulated PD-L1 level in HepG2 and B16-F1 cells in vitro. Differentiated 3T3-L1 adipocytes secreted TNF-α and IL-6, and neutralizing TNF-α and/or IL-6 reduced PD-L1 expression in adi-CM-treated cells. p-NF-κB/NF-κB level was downregulated in HepG2 and B16-F1 cells, and p-STAT3/STAT3 level was also decreased in HepG2 cells. In addition, inhibitor of NF-κB or STAT3 reversed the effect of adi-CM on PD-L1 expression. Conclusions TNF-α and IL-6 secreted by adipocytes up-regulates PD-L1 in hepatoma and B16-F1 cells, which may be at least partially involved in the role of obesity in promoting tumor progression.

As a type of heat dissipation material, graphite has attracted great attention due to its outstanding thermal conduction. However, the relatively poor through-plane thermal conductivity restricts its applications in certain areas. In this work, a novel thermally conductive film was developed via in situ growth of Cu microparticles between interlayers of expanded graphite (EG). The intercalation of Cu microparticles in EG improved the through-plane thermal conductivity of the film from 8.5 to 11.1 W/(m K), owing to the three-dimensional stacking architecture of Cu/EG hybrid framework, which leads to more thermal paths along the vertical direction. This Cu/EG hybrid film showed better heat spreading ability than the pristine EG film, reducing the working temperature of the LED device by 1.9 °C. Furthermore, the through-plane thermal conductivities of Cu/EG hybrid films can be controlled by the amount of Cu precursors, and the highest through-plane thermal conductivity of 11.1 W/(m K) was achieved with intercalation of 0.8–4.5 μm Cu microparticles by adding 50% Cu precursors. This thermally conductive Cu/EG hybrid film has great potential in the thermal management of electronic devices.

Catalytic decomposition of methane (CDM) is a promising technology for producing COx-free hydrogen and nano-carbon, meanwhile it is a prospective substitute to steam reforming of methane for producing hydrogen. The produced hydrogen is refined and can be applied to the field of electronic, metallurgical, synthesis of fine organic chemicals and aerospace industries. However, the CDM for COx-free hydrogen production is still in its infancy. The urgent for industrial scale of CDM is more important than ever in the current situation of huge COx emission. This review studies CDM development on Ni-based, noble metal, carbon and Fe-based catalysts, especially over cheap Fe-based catalyst to indicate that CDM would be a promising feasible method for large hydrogen production at a moderate cheap price. Besides, the recent advances in the reaction mechanism and kinetic study over metal catalysts are outlined to indicate that the catalyst deactivation rate would become more quickly with increasing temperature than the CDM rate does. This review also evaluates the roles played by various parameters on CDM catalysts performance, such as metal loading effect, influences of supports, hydrogen reduction, methane reduction and methane/hydrogen carburization. Catalysts deactivation by carbon deposition is the prime challenge found in CDM process, as an interesting approach, a molten-metal reactor to continually remove the floated surface solid carbons is put forwarded in accordance to overcome the deactivation drawback. Moreover, particular CDM reactors using substituted heating sources such as plasma and solar are detailed illustrated in this review in addition to the common electrical heating reactors of fixed bed, fluidized bed reactors. The development of high efficiency catalysts and the optimization of reactors are necessary premises for the industrial-scale production of CDM.

Phenethyl glycosides having phenolic or methoxy functions at benzene rings are substances widely occurring in nature. This kind of compounds has been shown to have anti-oxidant, anti-inflammatory, and anticancer activities. However, some of them are not naturally abundant, thus the synthesis of such molecules is desirable. In this paper, natural phenethyl glycosides 3 and 4 were first totally synthesized from easily available materials with overall yields of 50.5% and 40.1%, respectively. And a new synthetic route to obtain natural phenethyl glycoside 2 in 46.2% yield was also described.

Background Pancreatic cancer (PC) is a highly lethal malignancy worldwide. Our previous study indicated that overexpression of USP34 could promote tumor growth in PC cells. Therefore, this study aimed to further investigate the role of USP34 during the tumorigenesis of PC. Methods The level of USP34 in PANC-1 and MiaPaCa-2 cells transfected with USP34-shRNAs was detected by RT-qPCR. Moreover, transwell migration and Annexin V/PI analysis were conducted to detect cell migration and apoptosis, respectively. Results In this study, downregulation of USP34 markedly inhibited proliferation and migration, and induced apoptosis in PANC-1 cells. Moreover, silencing of USP34 obviously downregulated the levels of PRR11 and p-p38 in PANC-1 cells. An in vivo study in nude mice bearing PANC-1 cell xenografts confirmed these results. Conclusion Downregulation of USP34 could inhibit proliferation and migration in PANC-1 cells via inhibiting PRR11, and inactivating p38 MAPK signaling. Therefore, USP34 might be a potential therapeutic target for the treatment of PC.

STRA8 (Stimulated By Retinoic Acid Gene 8) is a retinoic acid (RA) induced gene that plays vital roles in spermatogonial proliferation, differentiation and meiosis. The SETD8 and STRA8 protein interaction was discovered using the yeast two‐hybrid technique using a mouse spermatogonial stem cell (SSC) cDNA library. The interaction of these two proteins was confirmed using co‐immunoprecipitation and identification of key domains governing the protein: protein complex. STRA8 and SETD8 showed a mutual transcriptional regulation pattern that provided evidence that SETD8 negatively regulated transcriptional activity of the STRA8 promoter. The SETD8 protein directly bound to the proximal promoter of the STRA8 gene. STRA8 increased the transcriptional activity of SETD8 promoter in a dose‐dependent manner. For the first time, we have discovered that STRA8 and SETD8 display a cell cycle‐dependent expression pattern in germline cells. Expression levels of SETD8 and H4K20me1 in S phase of STRA8 overexpression GC1 cells were different from that previously observed in tumour cell lines. In wild‐type mice testis, SETD8, H4K20me1 and PCNA co‐localized with STRA8 in spermatogonia. Further, our studies quantitated abnormal expression levels of cell cycle and ubiquitination‐related factors in STRA8 dynamic models. STRA8 and SETD8 may regulate spermatogenesis via Cdl4‐Clu4A‐Ddb1 ubiquitinated degradation axis in a PCNA‐dependent manner.

The functions of the glycine receptor (GlyR) and GABAA receptor (GABAAR) are both impaired in hyperekplexia, a neurological disorder usually caused by GlyR mutations. Although emerging evidence indicates that cannabinoids can directly restore normal GlyR function, whether they affect GABAAR in hyperekplexia remains unknown. Here we show that dehydroxylcannabidiol (DH-CBD), a synthetic nonpsychoactive cannabinoid, restores the GABA- and glycine-activated currents (IGABA and IGly, respectively) in HEK293 cells coexpressing a major GABAAR isoform (α1β2γ2) and GlyRα1 carrying a human hyperekplexia-associated mutation (GlyRα1R271Q). Using coimmunoprecipitation and FRET assays, we found that DH-CBD disrupts the protein interaction between GABAAR and GlyRα1R271Q. Furthermore, a point mutation of GlyRα1, changing Ser-296 to Ala-296, which is critical for cannabinoid binding on GlyR, significantly blocked DH-CBD-induced restoration of IGABA and IGly currents. This S296A substitution also considerably attenuated DH-CBD-induced disruption of the interaction between GlyRα1R271Q and GABAAR. These findings suggest that, because it restores the functions of both GlyRα1 and GABAAR, DH-CBD may represent a potentially valuable candidate drug to manage hyperekplexia.

There are only a handful of reports on indium sulfide (In2S3) in the electrochemical energy storage field without a clear electrochemical reaction mechanism. In this work, a simple electrospinning method has been used to synthesize In2S3/C nanofibers for the first time. In lithium-ion batteries (LIBs), the In2S3/C nanofiber electrode can not only deliver a high initial reversible specific capacity of 696.4 mA h g−1 at 50 mA g−1, but also shows ultra-long cycle life with a capacity retention of 80.5% after 600 cycles at 1000 mA g−1. In sodium-ion batteries (SIBs), the In2S3/C nanofibers electrode can exhibit a high initial reversible specific capacity (393.7 mA h g−1 at 50 mA g−1) and excellent cycling performance with a high capacity retention of 97.3% after 300 cycles at 1000 mA g−1. The excellent electrochemical properties mainly benefited from In2S3 being encapsulated by a carbon matrix, which buffers the volume expansion and significantly improves the conductivity of the composite. Furthermore, the structural evolution of In2S3 during the first lithiation/delithiation and sodiation/desodiation processes has been illustrated by ex situ XRD. The results confirm that the reaction mechanism of In2S3 in both LIBs and SIBs can be summarized as conversion reactions and alloying reactions, which provide theoretical support for the development of In2S3 in the field of electrochemistry.

Quantification of cell-secreted molecules, e.g., cytokines, is fundamental to the characterization of immune responses. Cytokine capture assays that use engineered antibodies to anchor the secreted molecules to the secreting cells are widely used to characterize immune responses because they allow both sensitive identification and recovery of viable responding cells. However, if the cytokines diffuse away from the secreting cells, non-secreting cells will also be identified as responding cells. Here we encapsulate immune cells in microfluidic droplets and perform in-droplet cytokine capture assays to limit the diffusion of the secreted cytokines. We use microfluidic devices to rapidly encapsulate single natural killer NK-92 MI cells and their target K562 cells into microfluidic droplets. We perform in-droplet IFN-γ capture assays and demonstrate that NK-92 MI cells recognize target cells within droplets and become activated to secrete IFN-γ. Droplet encapsulation prevents diffusion of secreted products to neighboring cells and dramatically reduces both false positives and false negatives, relative to assays performed without droplets. In a sample containing 1% true positives, encapsulation reduces, from 94% to 2%, the number of true-positive cells appearing as negatives; in a sample containing 50% true positives, the number of non-stimulated cells appearing as positives is reduced from 98% to 1%. After cells are released from the droplets, secreted cytokine remains captured onto secreting immune cells, enabling FACS-isolation of populations highly enriched for activated effector immune cells. Droplet encapsulation can be used to reduce background and improve detection of any single-cell secretion assay.

Catalytic methane decomposition was investigated over 40 wt% Fe/Al2O3 catalyst in fluidized bed reactor (FLBR). After optimization of FLBR conditions in terms of catalyst bulk density, particle size, minimum fluidization velocity, and the catalyst bed height, the catalyst activity and stability tests were conducted by comparison with a fixed bed reactor (FBR). Although a similar stable methane conversion was obtained over both reactors, the pressure drop during 35 min operation of FBR was 9 times higher than that of FLBR, which indicated the possibility of continuous operation of methane decomposition process over FLBR. Further, the influence of the space velocity, feed dilution and regeneration on catalysts reactivity was studied in FLBR to conclude that a reaction condition of 12 L/gcat∙h, feed of 20%H2–80%CH4 and CO2-regeneration of deactivated catalysts may be favourable for operating methane decomposition in FLBR continually and effectively to provide stable hydrogen.

Large soft-tissue defects are challenging to reconstruct surgically. Expansion of soft tissue using an external volume expansion (EVE) device is a noninvasive method to improve such reconstruction; however, the underlying mechanism is unclear. In this study, we created fat flaps in Sprague-Dawley rats, applied an external force of 3 or 6 kPa using an EVE device, and investigated the migration and differentiation of adipose-derived stem/progenitor cells (ASCs). In addition, we performed finite element analysis to explore the stiffness of adipose tissue. An external force of 3 kPa promoted the migration and adipogenic differentiation of ASCs. By comparison, an external force of 6 kPa had a larger effect on migration of ASCs, but a smaller effect on adipogenic differentiation of ASCs. External force affected adipose tissue stiffness. In conclusion, external force generated by an EVE device increases the stiffness of adipose tissue, which influences the migration and differentiation of ASCs. The size of the external force can be altered according to the tissue stiffness required at particular time points to promote long-term adipose tissue regeneration. Impact Statement Stem cell therapy in clinic mostly requires the addition of exogenous stem cells, therefore the safety and controllability is always defective. In this study, the external force of external volume expansion regulates adipose-derived stem/progenitor cells (ASCs) migration and differentiation through tissue stiffness. Using tissue engineering without exogenous ASCs can promote long-term adipose tissue regeneration. The findings of this study provide theoretical support for clinical tissue engineering applications and improvements in stem cell therapy.

Na0.44MnO2 is expected to be a cathode material with an excellent electrochemical performance for sodium ion batteries due to its unique 3-dimensional (3D) S-type tunnel structure. However, the high cut-off working potential of Na0.44MnO2 is usually restricted below 4.0 V (vs. Na/Na+) to inhibit fast capacity fading. Although pristine Na0.44MnO2 submicron rods deliver a high initial discharge capacity of 108.0 mAh g−1 at 0.4C (1C = 121 mAh g−1) in the wide voltage range of 2.0–4.5 V however the discharge capacity reduces to 80.5 mAh g−1 after 200 cycles. For improving the electrochemical properties under high voltage, Al2O3 coated Na0.44MnO2 is prepared by a wet-coating process and the coating amount is optimized. The as-prepared 2 wt% Al2O3-coated Na0.44MnO2 submicron rods possess the best electrochemical performance between 2.0 V–4.5 V, which deliver an initial discharge capacity of 109.8 mAh g−1 at 0.4C and maintain capacity retention of 93.2% after 200 cycles. Moreover, in long-term cycle performance at high current density (4C) between 2.0 and 4.5 V, 2 wt% Al2O3-coated Na0.44MnO2 can retain 79% capacity after 500 cycles. The mechanism of elevated electrochemical performance for Al2O3-coated Na0.44MnO2 submicron rods in high voltage is systematically investigated.

Living cells have the capability to synthesize molecular components and precisely assemble them from the nanoscale to build macroscopic living functional architectures under ambient conditions. The emerging field of living materials has leveraged microbial engineering to produce materials for various applications but building 3D structures in arbitrary patterns and shapes has been a major challenge. Here we set out to develop a bioink, termed as “microbial ink” that is produced entirely from genetically engineered microbial cells, programmed to perform a bottom-up, hierarchical self-assembly of protein monomers into nanofibers, and further into nanofiber networks that comprise extrudable hydrogels. We further demonstrate the 3D printing of functional living materials by embedding programmed Escherichia coli (E. coli) cells and nanofibers into microbial ink, which can sequester toxic moieties, release biologics, and regulate its own cell growth through the chemical induction of rationally designed genetic circuits. In this work, we present the advanced capabilities of nanobiotechnology and living materials technology to 3D-print functional living architectures., Living cells can precisely assemble to build 3D functional architectures. Here the authors produce an extrudable microbial ink entirely from the engineered cells, which can be further programmed to 3D print functional living materials.

We investigate the rheological properties of interpenetrating networks reconstituted from the main cytoskeletal components: filamentous actin, microtubules, and vimentin intermediate filaments. The elastic modulus is determined largely by actin, with little contribution from either microtubules or vimentin. However, vimentin dramatically impacts the relaxation, with even small amounts significantly increasing the relaxation time of the interpenetrating network. This highly unusual decoupling between dissipation and elasticity may reflect weak attractive interactions between vimentin and actin networks.

BackgroundPrevious studies have shown that ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) may be an inhibitor of the insulin signalling pathway, and insulin resistance (IR) is believed to be the core mechanism in the pathophysiology of polycystic ovarian syndrome (PCOS). This study aimed to investigate the expression of ENPP1 in different tissues of PCOS rats and to analyse its potential role in the pathophysiology of PCOS.MethodsEighteen 23-day-old Sprague-Dawley rats were divided into the PCOS and control groups (n= 9/group). Serum, ovaries, skeletal muscle, and subcutaneous and visceral fat were collected after 20 days. Pathological examination, immunofluorescence and western blotting analyses were performed. Serum indicator levels were measured, including ENPP1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), monocyte chemoattractant protein-1 (MCP-1), fasting blood glucose (FBG), fasting insulin (FINS), free fatty acids (FFAs), adiponectin (ADP), leptin, and serum lipids. ResultsThe levels of ENPP1, T, MCP-1, FBG, FINS, homeostasis model assessment of IR (HOMA-IR), FFAs, leptin, cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the PCOS group, while ADP and high-density lipoprotein cholesterol (HDL-C) were significantly lower than in the control group. Spearman’s rank correlation analysis showed that ENPP1 was correlated with T, MCP-1, HOMA-IR, FFAs, leptin, serum lipids and ADP. The mRNA levels of ENPP1, BAX, and IRS1 were higher in the ovaries, skeletal muscle, subcutaneous fat, and visceral fat of PCOS rats, and the protein expression of ENPP1 was significantly higher in the ovaries. ConclusionENPP1 is highly associated with IR and lipid metabolism-related molecules, which may promote pathophysiological changes in PCOS.

The chronic low-grade inflammation of adipose tissues, primarily mediated by adipose tissue macrophages (ATMs), is the key pathogenic link between obesity and metabolic disorders. Oleanolic acid (OA) is a natural triterpenoid possessing anti-diabetic and anti-inflammation effects, but the machinery is poorly understood. This study investigated the detailed mechanisms of OA on adipose tissue inflammation in obese mice. C57BL/6J mice were fed with high-fat diet (HFD) for 12 weeks, then daily intragastric administrated with vehicle, 25 and 50 mg/kg OA for 4 weeks. Comparing with vehicle, OA administration in obese mice greatly improved insulin resistance, and reduced adipose tissue hypertrophy, ATM infiltration as well as the M1/M2 ratio. The pro-inflammatory markers were significantly down-regulated by OA in both adipose tissue of obese mice and RAW264.7 macrophages treated with interferon gamma/lipopolysaccharide (IFN-γ/LPS). Furthermore, it was found that OA suppressed activation of mitogen-activated protein kinase (MAPK) signaling and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome through decreasing voltage dependent anion channels (VDAC) expression and reactive oxygen species (ROS) production. This is the first report that oleanolic acid exerts its benefits by affecting mitochondrial function and macrophage activation.

OBJECTIVES The accelerated shedding of extracellular domains of syndecan-4 (SDC4) is associated with central obesity and insulin resistance, while the association between serum SDC4 and nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to examine the association between SDC4 and NAFLD. METHODS Adults undergoing a health examination from 1 June 2019 to 31 December 2019 were enrolled. A diagnosis of NAFLD was made with an abdominal ultrasound. Logistic regression models and the receiver operating characteristic (ROC) curves were used to evaluate the role of SDC4 in predicting NAFLD. RESULTS In total, 533 eligible participants were finally enrolled, among them 157 (29.46%) had NAFLD. The proportion of patients with NAFLD increased with the increasing quartiles of serum SDC4. With the increase of serum SDC4 levels, metabolic features including waist circumference, serum triglyceride, total cholesterol, fasting blood glucose, fasting insulin and homeostasis model assessment of insulin resistance were significantly increased. SDC4 was an independent factor for NAFLD (odds ratio 1.963, 95% confidence interval [CI] 1.628-2.367, P

Activated persulfate oxidation has been proven to be an efficient advanced sludge treatment technique to improve sludge dewaterability. This study investigates the influence of persulfate on the transformation of phosphorus (P) and heavy metals (HMs) during the hydrothermal treatment of sewage sludge. The hydrothermal temperature, time, and persulfate concentration are optimized by a Box-Behnken design to obtain the best sludge dewaterability, which is expressed by capillary suction time (CST). The highest CST reduction efficiency is 90.5% at the optimal hydrothermal temperature, time and concentration of persulfate, which are 145 °C, 2 h, and 150 mg/g DS, respectively. The distribution and transformation of P and HMs with different persulfate concentrations (100-200 mg/g DS) during the hydrothermal process are investigated. Results show that more than 90% of the P and HMs in the sludge are retained in sludge cakes after the hydrothermal treatment. The addition of SPS can make the P in the sludge cakes transform into more stable P species according to the extraction capacity of sequential extracts. It can be found from the ecological risk indexes of the HMs that the addition of SPS during the hydrothermal treatment of sludge can reduce the environmental risk of HMs. This study provides insights into the P and HM distribution and transformation during hydrothermal treatment with persulfate, providing a reference for sludge recovery strategies.

Unbalanced copper (Cu2+ ) homeostasis is associated with the developmental defects of vertebrate myogenesis, but the underlying molecular mechanisms remain elusive. In this study, it was found that Cu2+ stressed zebrafish embryos and larvae showed reduced locomotor speed as well as loose and decreased myofibrils in skeletal muscle, coupled with the downregulated expression of muscle fiber markers mylpfa and smyhc1l and the irregular arrangement of myofibril and sarcomere. Meanwhile, the Cu2+ stressed zebrafish embryos and larvae also showed significant reduction in the expression of H3K4 methyltransferase smyd1b transcripts and H3K4me3 protein as well as in the binding enrichment of H3K4me3 on gene mylpfa promoter in skeletal muscle cells, suggesting that smyd1b-H3K4me3 axis mediates the Cu2+ -induced myofibrils specification defects. Additionally, whole genome DNA methylation sequencing unveiled that the gene smyd5 exhibited significant promoter hyper-methylation and increased expression in Cu2+ stressed embryos, and the ectopic expression of smyd5 in zebrafish embryos also induced the myofibrils specification defects as those observed in Cu2+ stressed embryos. Moreover, Cu2+ was shown to suppress myofibrils specification and smyd1b promoter transcriptional activity directly independent of the integral function of copper transporter cox17 and atp7b. All these data may shed light on the linkage of unbalanced copper homeostasis with specific gene promoter methylation and epigenetic histone protein modification as well as the resultant signaling transduction and the myofibrillogenesis defects.

Background: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside Rk3 (Rk3) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rk3 on cyclophosphamide-induced myelosuppression. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting. Results: Both Re and Rk3 could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of G0/G1 phase cells, and increase the proliferation index. Finally, Re and Rk3 could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. Conclusion: Re and Rk3 could improve the hematopoietic function of myelosuppressed mice. The effect of Rk3 was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and Rk3 on myelosuppression. Keywords: Chemotherapy, Ginsenoside Re, Ginsenoside Rk3, Myelosuppression

Dual-trap optical tweezers have been used to directly measure the interaction forces between two silica particles upon controlling the concentration of the ionic surfactant sodium dodecylbenzenesulfonate (SDBS). By capturing two silica particles in one spot optical trap and one linear optical trap and controlling the linear trap to bring one particle to approach another sufficiently closer, the interaction forces between these two particles can be measured as the separation distance changes. Results showed that with increasing concentrations of SDBS, the interaction force between the two silica particles emerges at closer surface distance between two silica particles. Only repulsive force exists between silica particles below the critical micelle concentration (cmc) of SDBS and it could be well-fitted using the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. However, the depletion attraction force appears above the cmc of SDBS which is induced by the generation of SDBS micelles. By in situ measurement of the interaction force between two silica particles in the presence of different concentrations of SDBS, the depletion force can be quantitatively calculated.

Ultrasound-responsive chemistry was exploited in manufacture of drug delivery nanoparticulates for pursuit of on-demand ultrasound-stimulated drug release function. In principle, the ultrasound-labile oxyl-alkylhydroxylamine (-oa-) linkage was tailored between the segments of amphiphiles. Consequently, the hydrophobic chemotherapeutic doxorubicin could be readily assembled with the hydrophobic segments of amphiphiles into interior compartments, whereas the hydrophilic segments represented as the external surroundings. Upon ultrasonication, the proposed phase-segregated self-assemblies were determined to be subjected to evident structural rearrangement as a consequence of -oa- cleavage. Simultaneously, the release rate of doxorubicin payloads appeared to accelerate due to the ultrasound-induced structural destabilization, consequently eliciting potent cytotoxic efficacy at the affected cells. Another noteworthy characteristic of the proposed self-assemblies was poly (lactobionamidoethyl methacrylate) (pLAMA) as the hydrophilic components of the amphiphiles, characterized to possess galactosylated residues. In view of the specific affinity of galactosylated residues (and lactosylated residues) to asialoglycoprotein receptors (overexpressed on the surface of intractable hepatocellular carcinoma), the proposed self-assemblies were determined to impart preferential affinities to hepatocellular carcinoma. Together with the strategic ultrasound-stimulated drug release property, our proposed drug delivery system demonstrated appreciably pharmaceutical efficacy on hepatocellular carcinoma.

Anammox and autotrophic desulfurization-denitrification (AADD) process is feasible for the nitrogen and sulfide removal in the same reactor, and the influence of excess nitrate produced by anammox could also be alleviated simultaneously. This study firstly proposed a novel strategy with inoculating single anammox sludge to start up the AADD process. Results demonstrated that the 90% nitrogen removal efficiency (NRE), 2.55 kg m−3 d−1 nitrogen removal rate (NRR), and 95% sulfide removal efficiency (SRE) were obtained at the influent total nitrogen of 280 mg L−1 and sulfide of 221.5 mg L−1, and the final effluent nitrate concentration was as low as 8 mg L−1 under the appropriate operation conditions. Tryptophan-like and protein-like substances were characterized as the main components in bound EPS. Thiobacillus (35.68%) and Pseudoxanthomonas (11.61%) were identified as the predominant genera. This study will pave a potential avenue to promote the treatment of high concentration nitrogen and sulfide in wastewater in the future.

The surface properties of drug/gene delivery systems are critical important to their ultimate therapeutic performance. In the present studies, cytoplasmic membranes deriving from cancerous cells (Hep-G2) were attempted as the external integument onto the polycationic theranostic DNA delivery systems with the aim of diminishing unfavorable biointerfacial reactions of nanomedicine. Herein, a multiple of polycationic oligoethylenimine (OEI) segments were installed onto the surface of luminescent carbon quantum dots (CQD, facile bioimaging utilities) for complexation with plasmid DNA (pDNA) into DNA delivery constructs, followed by surface integument by cytoplasmic membranes. The subsequent investigations verified this strategic integument capable of shielding the unfavorable surface positive net charge of the polycationic DNA delivery constructs and thereby markedly diminishing the potential nonspecific reactions in biological milieu. Leadingly, improved biocompatibilities as well as additional protection of inner vulnerable DNA cargos from enzymatic degradation, have been accomplished. More importantly, preferential affinities to the homologous cells were identified as a result of this membrane integument based on facile fluorescence quantification for the intracellular CQD. Significant higher cellular uptake efficiency for the polycationic constructs based on Hep-G2 membrane integument was confirmed in the homologous Hep-G2 cells in contrast to the heterologous MCF-7 and HeLa cells (approximately 4-fold). Note that this homologous privilege was observed for the delivery constructs not only from cancerous HeLa and MCF-7 membrane integuments but also normal cells (COS-7), heralding the intriguing potentials of this membrane-integument strategy in pursuit of targeting functions. Eventually, gene expression activities were also determined to prevail in the homologous cells. Therefore, our proposed surface integument strategy by homologous cell membrane could imply an alternative facile and versatile avenue in construction of active-targeted nanomedicine.

Recently, the responses of embryos to Cu2+ or AgNP stresses have been investigated, but few studies have been performed on the common responses of embryos to both Cu2+ and AgNPs, the same kind of stressor metal. In this study, a large number of commonly down-regulated and up-regulated differentially expressed genes (DEGs) were revealed in both Cu2+- and AgNP-stressed embryos. The down-regulated DEGs were enriched in myosin complex and muscle structure development, ion transport and metal ion binding, transmission of nerve impulses, etc., and the up-regulated DEGs were enriched in heart development, iron ion binding, etc. Based on the whole-genome bisulfite sequencing (WGBS) in both Cu2+- and AgNP-stressed embryos, a total of 57 and 64 differentially methylated genes (DMGs) were identified in Cu2+ embryos and AgNP embryos, with 15 and 12 of them being common ion-relevant genes, respectively. The correlation of the gene transcriptional expression and the methylated status of some common DMGs were further verified. The integrated analysis of transcriptomes and methylomes in zebrafish embryos stressed with Cu2+ or AgNPs revealed for the first time their common transcriptional and methylomic responses to the same kind of stressor metals, and revealed that ion-relevant genes were mostly differentially expressed and methylated genes in both Cu2+- and AgNP-stressed embryos.

Although silver nanoparticles (AgNPs) are used in various commercial products, the biological effects of AgNPs on fish embryogenesis and the underlying molecular mechanisms are still poorly understood. In this study, both touch responses and neuron membrane potential were found to be abnormal in AgNPs-stressed embryos. Moreover, neurogenesis genes were unveiled to be down-regulated and were enriched in ligand-gated ion channel activity, dopamine receptor signaling pathway, etc. in AgNPs-stressed embryos by microarray assays. Additionally, the down-regulated expression of otpa/sncgb - gad1b/gad2 dopaminergic neurotransmitter genes, robo2 - vim and glrbb synaptic transmission genes, and motor neuron genes isl1 &isl2a was further identified in both AgNPs- and Ag+-stressed embryos by qPCR, whole-mount in situ hybridization (WISH), and by using specific promoter-derived GFP fluorescence transgenic zebrafish. Moreover, the reduced expression of gad1b, gad2, and isl1 could be recovered by adding Ag+ chelating compound l-cysteine in AgNPs stressed embryos. Our results reveal for the first time that it is through damaging the formation of neural circuits, including dopaminergic neurotransmitter, synaptic transmission, and motor activities, that AgNPs induce abnormal electrical membrane properties, leading to dysfunctional touch responses and locomotor escape responses mostly via their released Ag+ during embryogenesis.

Background Taking advantage of cellular paracrine mechanisms, the secretome of adipose-derived stem cells (ADSCs) and adipose tissue has been demonstrated to induce tissue repair and regeneration in various ischemic and impaired conditions. However, these cell-based therapies have been hindered by issues, such as inherent safety and cost-efficiency for clinical applications. In this study, we prepared a liquid cell-free extract from human adipose tissue [adipose liquid extract (ALE)] and evaluated its potential therapeutic efficacy. Methods ALE was prepared from human subcutaneous adipose tissue using a rapid and physical approach, and the protein components in ALE were identified using mass spectrometry analysis. In vivo, the therapeutic effect of this agent was investigated on wound healing in C57BL/6 mice, and wound healing rate, vessel density, and neo-adipocyte formation in wounded skins were measured at days 3, 7, 11, and 14. In vitro, the effect of ALE on the viability of human ADSCs, tube formation of human umbilical vein endothelial cells (HUVECs), and adipogenic differentiation of ADSCs were tested. Results The results demonstrated that ALE contained a variety of growth factors and did not affect cell viability. ALE-treated wounds exhibited accelerated wound healing with increased vessel density and formation of neo-adipocytes compared to that of control wounds. Moreover, when added as a cell culture supplement, ALE effectively induced tube formation of HUVECs and lipid accumulation in ADSCs. ALE-treated ADSCs also exhibited elevated levels of adipogenic gene expression. Conclusions ALE is a novel growth-rich therapeutic agent that is cell-free and easy to produce. Besides, it is also able to induce angiogenesis and adipogenesis both in vitro and in vivo, thus indicating that it could be used for wound repair and soft tissue regeneration.

Septic shock with heart dysfunction is common in intensive care units. However, the mechanism underlying myocardial depression is still unclear. Whether circular RNA (circRNA) or microRNA (miRNA) profiles differ between patients with and without myocardial depression is unknown. We generated a hypodynamic septic shock model induced by lipopolysaccharide (LPS) in adolescent rats. A total of 12 rats were utilized and heart tissue from each was collected. RNA sequencing was performed on left ventricular tissue. We focused on features of circRNAs and miRNAs, predicting their function by bioinformatic analysis and constructing circRNA-associated and miRNA-associated regulatory networks in heart tissue. We detected 851 circRNAs in heart samples, and 11 showed differential expression. A total of 639 annotated miRNAs and 91 novel miRNAs were explored including 78 showing differential expression between the two groups. We then constructed the most comprehensive circRNA-associated and miRNA-associated networks to explore their regulatory relationship in septic heart tissue, and demonstrated that different networks could potentially participate in and regulate the pathological process of sepsis. Furthermore, gene ontology term enrichment indicated miRNAs, and miRNA-mRNA networks could be associated with regulation and metabolic process, or influence cellular functions. The construction of regulator networks could improve the understanding of the basic molecular mechanisms underlying myocardial depression. It will be important for future investigations to ascertain the biological mechanisms present during the development of sepsis-induced myocardial depression to influence approaches to treatment.

Photo-responsive nitrophenyl moieties were proposed to conjugate as pendants of the pullulan backbone through labile carbamate linkage to yield amphiphilic pullulan derivatives. Note that the hydrophobicity of the conjugated nitrophenyl components in the amphiphiles enable facile their self-assembly with the hydrophobic chemotherapeutic drug (doxorubicin) as the internal drug reservoirs, whereas the hydrophilic pullulan segments existed as the biocompatible surroundings. Upon photo-illumination, the carbamate linkage was susceptible to cleavage for departure of the nitrophenyl components from the pullulan backbone owing to the photo-responsive nitrophenyl moieties. Simultaneously, the nitrophenyl components transformed into water-soluble aldehyde-terminalized nitrosophenyl derivatives, leadingly accounting for structural disassembly and liberation of the cytotoxic doxorubicin payloads. Therefore, our proposed photo-responsive strategy could address the reluctant intracellular drug release drawbacks of the conventional amphiphile-based drug delivery systems. Notably, markedly lower IC50 (half maximal inhibitory concentration) index of our constructed doxorubicin delivery systems was determined to be approximately 1.0 μg/mL upon photo-illumination, in contrast to IC50 index of 5.6 μg/mL in the absence of photo-illumination (approximate fivefold), thereby representing as a facile spatiotemporal artifice to execute on-demand drug release to the photo-imposed cells.

Cellulase has many potential applications in ethanol production, extraction of medicinal ingredients, food, brewing, oil exploration, environmental protection. However, the widespread use of cellulase is limited by its relatively high production costs and low biological activity. Therefore, we studied the enzymatic properties and reusability of cellulase immobilized on multiwalled carbon nanotubes and sodium alginate for the first time. The results showed that the optimum temperature and pH of immobilized cellulase was 40 °C and 3.0, respectively. After 1 month of storage at 4 °C, the enzyme activity of immobilized cellulase dropped to 71.2% of the baseline. Immobilized cellulase was proved to be reusable and maintained ~ 70% of its activity after 7 cycles of repeated use. Versus free cellulase, the immobilized cellulase showed good thermal stability, pH resistance, storage stability and reusability, which could be beneficial in large-scale industrial manufacturing processes.

The anaerobic ammonium oxidation (anammox) process has the advantages of a high nitrogen removal rate, low operational cost, and small footprint and has been successfully implemented to treat high-content ammonium wastewater. However, very little is known about the toxicity of the heavy metal element Ni(II) to the anammox process. In this study, the short- and long-term effects of Ni(II) on the anammox process in an upflow anaerobic sludge blanket (UASB) reactor were revealed. The results of the short-term batch test showed that the half maximal inhibitory concentration (IC50) of Ni(II) on anammox biomass was 14.6 mg L-1. A continuous-flow experiment was performed for 150 days of operation, and the results illustrated that after domestication, the achieved nitrogen removal efficiency was up to 93±0.03% at 10 mg L-1 Ni(II). The settling velocity, specific anammox activity and EPS content decreased as the Ni(II) concentration increased. Nevertheless, the content of heme c increased as the Ni(II) increased. These results indicate that short-term exposure to Ni(II) has an adverse impact on anammox process, but the anammox system could tolerate 10 mg L-1 Ni(II) stress after acclimation during continuous-flow operation for 150 days. High-throughput sequencing results indicated that the presence of Ni(II) had an impact on the microbial community composition in the anammox reactor, especially Candidatus Kuenenia. At Ni(II) concentrations of 0-10 mg L-1, the relative abundance of Candidatus Kuenenia decreased from 36.23% to 28.46%.

In this study, polyphenols were extracted from different parts (seed husks, seeds, young and old leaves) of Toona sinensis collected from Taihe District, Anhui province, China, through ultrasound-assisted extraction. During in vitro experiments, seed husks polyphenol extracts exhibited inhibitory effects against α-amylase and α-glucosidase up to 89% and 86.7%, respectively, and these values were slightly lower than the inhibitory rates of acarbose (91% and 90.5% on each enzyme) at the same concentrations. During in vivo experiments, treatment with high-dose seed husks polyphenol extracts (120 mg/kg body weight) significantly reduced the blood glucose levels, increased the glucose tolerance and insulin tolerance of diabetic mice (P < 0.05); In addition, the contents of triglyceride, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol and low density lipoprotein cholesterol in serum could be reduced, and the influence on total cholesterol was significantly different (P < 0.01). Moreover, the activity of superoxide dismutase and glutathione could be Obviously improved, the content of malonaldehyde could be reduced in serum, among those the effect on glutathione enzyme was extremely significant (P < 0.01). The results showed that the seed husks polyphenol extracts from T. sinensis had obvious hypoglycemic effect, and the mechanism of hypoglycemic might be related to the improvement of insulin sensitivity by repairing damaged islet cells. Meanwhile, antioxidant enzyme activity was improved, oxidative stress injury was reduced, and lipid metabolism was enhanced.

The pole is the unique phenomena in the parity-time (PT) symmetry structure. To explore the application of the pole effect, a PT-symmetry resonator coupling system is designed as a gas sensor. The large transmittance and reflectance near the pole are found extraordinary sensitive to the refractive index of the polluted air in the system. Through measuring the reflectance, the refractive index of the polluted air and the concentration of gas in the air can be detected. The sensor has an extraordinary sensitivity in detecting the gases with low concentration. The maximum sensitivities $\Delta R/R$ for the methane, acetylene, and ethane are 0.112, 0.190, and 0.282, respectively. The limitation of detectable concentration change is 1/1500 for methane with the photodetector that can sense the relative change rate of the reflectance of 10−3.

In this work, tin disulfide (SnS2) embedded in nitrogen and sulfur dual-doped carbon (denoted as SnS2/NSDC) nanofibers are synthesized using a facile electrospinning technique for the first time. The exterior of the nanofibers is decorated through the SnS2 nanosheet, and the interior of carbon nanofibers is embedded with SnS2 nanoparticles. Benefit from the unique structure and morphology, SnS2/NSDC nanofibers show excellent electrochemical performance. In Na half-cell, SnS2/NSDC nanofibers electrode show superior cycling performance and the capacity remains at 380.1 mAh g−1 at 500 mA g−1 after 200 cycles. Not only that, a capacity of 310.6 mAh g−1 still was obtained when the applied current density even increased to 4000 mA g−1, which reveals good rate performance of the SnS2/NSDC nanofibers electrode. In Na full-cell, SnS2/NSDC nanofibers electrode also show good sodium storage performance, which retained 213.4 mAh g−1 capacity after 50 cycles when cycling at 50 mA g−1. The excellent sodium storage performance indicates that the SnS2/NSDC nanofibers are one of the promising anode materials for high-performance sodium-ion batteries.

The secretion of interferon-α (IFN-α) is impaired during hepatitis B virus (HBV) infection. DNA sequences purified from distinct viruses, for example, HBV versus members of Herpesviridae, have been shown to differ in their IFN-α signaling properties. The present study found that DNA from HBV inhibited, while DNA from members of Herpesviridae induced, the expression of IFN-α. Furthermore, stimulatory cytosine-phosphate-guanosine (CpG) sequences derived from these DNA viruses could induce the secretion of IFN-α, while inhibitory guanosine-rich oligodeoxynucleoti (polyG) oligonucleotide sequences derived from these DNA viruses could inhibit CpG-induced IFN-α secretion. Using a computational analysis of genomic DNA sequences, the discrimination between the genomes of HBV and those of other DNA viruses that can also cause inflammation of the liver is based on different frequencies of the CpG and polyG motifs. The underrepresentation of stimulatory CpG motifs and overrepresentation of inhibitory polyG motifs were documented in HBV genomes, whereas the DNA from other viral genomes displayed the opposite trend. Moreover, it was demonstrated that HBV could suppress the activation of IFN-α via its own DNA through the high proportion of polyG motifs. To our knowledge, this is the first demonstration of a specific role for polyG motifs in the inhibition of the IFN-α response following DNA virus infection.

The development of flexible energy storage devices is the key to widen the application of flexible electronics and wearable devices. Flexible electrodes with superior electrochemical performance are critical components for flexible energy storage devices. Herein, we propose a simple and versatile electrospinning strategy to prepare the SnS/C nanofibers (SnS/C NFs) film. By using SnS/C NFs film directly as a free-standing anode in both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs), it can provide outstanding electrochemical performance. For LIBs, it delivers high capacities of 648 and 548 mA h g-1 at 200 and 500 mA g-1 respectively after 500 cycles. It even shows outstanding cyclability for 1000 cycles. For SIBs, it retains capacity of 481 mA h g-1 after 100 cycles at 50 mA g-1. Moreover, the capacity remains as high as 349 mA h g-1 at 200 mA g-1 after 500 cycles. The outstanding electrochemical performance is mainly attributed to the fact that the fine SnS nanoparticles dispersed in one-dimensional porous nanofibers with uniform diameters around 130 nm shorten the transport path of ions and electrons, and the presence of N-doped carbon enhanced the electrical conductivity as well as relieve the volume change caused by the alloying/de-alloying reaction. Besides, the ultra-robust mechanical flexibility of SnS/C NFs film makes it a promising anode candidate for flexible LIB and SIB in future.

Hydrogen peroxide (H2O2), regarded as the byproduct of aerobic metabolism via the electron transport chain, plays a significant role in a vast array of physiological and pathological process in the organisms. Therefore, it is of great importance to develop efficient analytical approach for monitoring the H2O2 level in living systems. Herein, in this work, a NIR fluorescent probe named NDCM-HP was developed for the highly selective detection of H2O2 by introducing boronate group as the recognition unit into the 2-(3-(4-hydroxystyryl)-5,5-dimethylcyclohex-2-enylidene) malononitrile (NDCM-OH) fluorophore which is featured by strong NIR emission, large Stokes shift, and good photostability. As a matter of fact, NDCM-HP demonstrated excellent sensing performance toward H2O2 in solution samples such as high sensitivity with about 127-fold emission enhancement, low detection limit of 70.189 nM, and good selectivity over biologically related species. Furthermore, it could be employed for detecting endogenous H2O2 fluctuation in living cells induced by different stimulators such as Phorbol myristate acetate (PMA), N-Acetylcysteine (NAC), indicating its great potential in biological application.