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Abstract The objectives of this study were to investigate the mechanism responsible for Cd and Pb immobilization by sulfate reduction to sulfide and effectiveness of decreasing Cd2+ and Pb2+ bioavailability in culture solution and paddy soils via sulfate-reducing bacterium (SRB1-1). The SRB1-1 strain, exhibiting high resistances to Cd2+ and Pb2+, was isolated from bulk soils in the metal(loid)-contaminated paddy field. During the culture of the SRB1-1 strain, the removal percentages of Cd2+ and Pb2+ from culture solution reached 99.5% and 76.0% in 72 h, respectively. The surface morphology and composition of metal precipitates formed by SRB1-1 strain were analyzed by transmission electron microscopy (TEM) and further confirmed to be CdS and PbS by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). When living SRB1-1 strain was applied in Cd and Pb-contaminated soils, the SRB1-1 strain could stably colonize using its resistance to rifampicin, and showed significantly impact on the bacterial community composition. Cd and Pb contents in rice grains were decreased by 29.5% and 26.2%, respectively, while Cd and Pb contents in the roots, culms, leaves, and husk were also decreased ranging from 19.1% to 43%, respectively. Due to growth in highly Cd and Pb contaminated soils, Cd content of the rice grains did not meet the standard for limit of Cd and Pb, but safe production of rice plants may be obtained in slightly or moderately metal(loid)-contaminated soils in the presence of the living SRB1-1 strain. These results indicated that the SRB1-1 strain could effectively reduce the Cd and Pb bioavailability in soils and uptake in rice plants. Our results highlighted the possibility to develop a new bacterial-assisted technique for reduced metal accumulation in rice grains, and also showed potential for effective synergistic bioremediation of SRB1-1 strain and rice plants in metal(loid)-contaminated soils. Graphical abstract fx1 Highlights • The isolated SRB1-1 strain exhibiting high resistances to Cd2+ and Pb2+. • Characterization of precipitates confirmed metal sulfides formation on the SRB1-1. • Strain was effective in reducing Cd and Pb accumulation in rice grains. • Strain could colonize and alter bacterial community composition. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A facile method was developed to synthesize high-quality Na 2 (VO) 2 (PO 4) 2 F/C material. • Electrochemical Na-storage properties of Na 2 (VO) 2 (PO 4) 2 F/C were carefully investigated. • Optimized Na 2 (VO) 2 (PO 4) 2 F/C achieved excellent charge/discharge performance. Abstract Sodium vanadium fluorophosphate (Na 3 (VO) 2 (PO 4) 2 F, denoted as NVPF) has attracted particular interests as cathode for high-energy sodium-ion batteries (SIBs) owing to the high working potential, high specific capacity, and robust structural framework. However, it is challenged by the low electron conductivity and lack of available facile synthesis method. Herein, an environmentally benign, cost-effective synthesis route is reported to produce NVPF nanoparticles encapsulated in conductive graphene network (NVPF/C), involving low-temperature synthesis of NVPF nanoparticles in absolute aqueous solvents and subsequent construction of conductive network through thermally induced transformation of graphene-oxide nanosheets. The resultant product is structurally and electrochemically investigated by combining X-ray diffraction, fourier transform infrared spectroscopy, scanning electron microscope, transition electron microscope, and electrochemical analysis. Experimental results show that the optimized NVPF/C product possesses a three-dimensional graphene-encapsulation nanostructure composed of ∼100 nm NVPF nanoparticles and ∼4 nm carbon-coating layer. The unique hierarchical structure enables it cycling with excellent electrochemical performance in terms of a high reversible capacity (116.4 mA h g−1 at 0.2 C), excellent high-rate capability (87.4 mA h g−1 at 10 C) and long-term lifetime (82.1% capacity retention after 1200 cycles). It is indicated that the facile synthesis route can achieve high-performance NVPF/C material for SIBs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Emulsifier Polysorbate 80 exposure significantly exacerbated age-related cognitive decline, along with increased brain pathological proteins deposition and neuroinflammation, as well as disruption of the blood–brain barrier. • Emulsifier Polysorbate 80 exposure contributed to gut microbiota dysbiosis and the increased of deoxycholic acid in plasma and brain. • Emulsifier Polysorbate 80 induced cognitive decline and neuroinflammation via gut microbiota. • Mechanically, deoxycholic acid activates microglial cells may involve the upregulation of ABCA1-mediated cholesterol transport on lysosomes, thereby promotes the senescence-associated secretory phenotype. Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood–brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae , Lachnospiraceae , and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline. [ABSTRACT FROM AUTHOR]

China has witnessed a drop in the speed of its economic development from 14% to 6% since 2007. The literature has attributed "the miracle of China's economic growth" over the past four decades to the compatibility of political incentives and fiscal incentives. However, as the central government shifts its priorities from "development is the last word" to "lucid waters and lush mountains are invaluable assets", can local officials' political and financial incentives still achieve incentive compatibility? Theoretically and empirically, this paper examines the impact of the compatibility of political and financial incentives on local governments' environmental governance in different stages. We find that environmental performance has consistently been an important political promotion incentive for officials, especially after 2007. We also find that officials in cities with incentive compatibility have no promotion advantages over their opponents because incentive compatibility restrained the development of the manufacturing industry, leading to a suppression of the economic growth rate. Local governments sacrifice a certain economic growth rate – in other words, local fiscal revenue – in exchange for environmental quality improvements and adopt strategic actions to cater to the central government's new performance evaluation system, which focuses mainly on environmental protection assessment through strategic behavior. • There are dynamic roles of compatibility between political and financial incentives. • An equilibrium model can capture the change in central and local governments. • The incentive compatibility phenomenon has no promotion advantage for local officials. • Environmental performance may be achieved at the expense of the economic growth rate. [ABSTRACT FROM AUTHOR]

• Nerves injury can induce the upregulation of miR-21-5p in neuron. • Neuron-exosomes with high miR-21-5p expression induced microglia polarization. • Inflammation factors released by polarized microglia further aggravated nerves injury. Neuroinflammation is a characteristic pathological change of acute neurological deficit and chronic traumatic encephalopathy (CTE) after traumatic brain injury (TBI). Microglia are the key cell involved in neuroinflammation and neuronal injury. The type of microglia polarization determines the direction of neuroinflammation. MiR-21-5p elevated in neurons and microglia after TBI in our previous research. In this study, we explore the influence of miR-21-5p for neuroinflammation by regulating microglia polarization. In this study, PC12 and BV2 used to instead of neuron and microglia respectively. The co-cultured transwell system used to simulate interaction of PC12 and BV2 cells in vivo environment. We found that PC12-derived exosomes with containing miR-21-5p were phagocytosed by microglia and induced microglia polarization, meanwhile, the expression of miR-21-5p was increased in M1 microglia cells. Polarization of M1 microglia aggravated the release of neuroinflammation factors, inhibited the neurite outgrowth, increased accumulation of P-tau and promoted the apoptosis of PC12 cells, which formed a model of cyclic cumulative damage. Simultaneously, we also got similar results in vivo experiments. PC12-derived exosomes with containing miR-21-5p is the essential of this cyclic cumulative damage model. Therefore, regulating the expression of miR-21-5p or the secretion of exosomes may be an important novel strategy for the treatment of neuroinflammation after TBI. [ABSTRACT FROM AUTHOR]

A series of novel enterovirus A71 inhibitors with an aminothiazole scaffold were identified. The best compound 12s displayed low- to sub-micromolar activity against enterovirus replication without significant cytotoxicity. Microscale thermophoresis (MST) experiment and co-localization assay indicated that 12s exhibited antiviral activity by targeting EV-A71 capsid protein (K d = 0.149 μM) and disturbing the binding between VP1 and receptor hSCARB2. [Display omitted] • A series of novel enterovirus A71 inhibitors with an aminothiazole scaffold were identified. • 12 s showed broad-spectrum anti-enterovirus activity (low to sub-micromolar) without significant cytotoxicity. • Systematic mechanism studies showed that 12 s might interact with the EV-A71 capsid protein by disturbing the binding between VP1 and the host receptor hSCARB2. Enterovirus A71 (EV-A71), one of the major pathogens that causes hand, foot and mouth disease (HFMD), has seriously threatened the health and safety of young children. In this study, aminothiazole derivatives were synthesized and screened against EV-A71 in Rhabdomyosarcoma (RD) cells. The best compound (12 s), with a biphenyl group, showed activity against EV-A71 (EC 50 : 0.27 μM) but also against a series of different human enteroviruses without significant cytotoxicity (CC 50 > 56.2 μM). Mechanistic studies including time-of-drug-addition assays, viral entry assays and microscale thermophoresis (MST) experiments, showed that 12 s binds to EV-A71 capsid and blocks the binding between the viral protein VP1 and the relevant human scavenger receptor class B member 2 (hSCARB2). [ABSTRACT FROM AUTHOR]

Abstract: Herpes simplex virus thymidine kinase (HSV-TK) gene and dendritic cells (DC) have been used as the pioneering in cancer therapy. HSV-TK gene can induce apoptosis and necrosis in tumor cells in the presence of the non-toxic prodrug ganciclovir (GCV). We investigated the anti-tumor effect of DC vaccination by introducing dying cells from HSV-TK gene treatment as an adjuvant. HepG2-TK cell line was established by transfecting human hepatoma cell line HepG2 (HLA-A2 positive) with HSV-TK gene. Dying tumor cells were generated by culturing HepG2-TK cells with GCV. After engulfed dying cells efficiently, immature DCs (imDC) derived from human monocytes were fully matured and elicited marked proliferation and cytotoxicity against HLA matched HepG2 cells in autologous peripheral blood mononuclear cells (PBMC). It also implied that HepG2 specific CTLs played an important role in the cytotoxicity which was primarily depended on Th1 responses. Given the feasibility of inducing dying cells by HSV-TK/GCV in vivo, our results suggest an effective method in clinical human hepatocellular carcinoma (HCC) treatment by an in vitro model of applying HSV-TK gene modified human tumor cells integrated with DC vaccination. [Copyright &y& Elsevier]

Abstract: To deplete cellular iron uptake, and consequently inhibit the proliferation of tumor cells, we attempt to block surface expression of transferrin receptor (TfR) by intracellular antibody technology. We constructed two expression plasmids (scFv-HAK and scFv-HA) coding for intracellular single-chain antibody against TfR with or without endoplasmic reticulum (ER) retention signal, respectively. Then they were transfected tumor cells MCF-7 by liposome. Applying RT-PCR, Western blotting, immunofluorescence microscopy and immunoelectron microscope experiments, we insure that scFv-HAK intrabody was successfully expressed and retained in ER contrasted to the secreted expression of scFv-HA. Flow cytometric analysis confirmed that the TfR surface expression was markedly decreased approximately 83.4±2.5% in scFv-HAK transfected cells, while there was not significantly decrease in scFv-HA transfected cells. Further cell growth and apoptosis characteristics were evaluated by cell cycle analysis, nuclei staining and MTT assay. Results indicated that expression of scFv-HAK can dramatically induce cell cycle G1 phase arrest and apoptosis of tumor cells, and consequently significantly suppress proliferation of tumor cells compared with other control groups. For the first time this study demonstrates the potential usage of anti-TfR scFv-intrabody as a growth inhibitor of TfR overexpressing tumors. [Copyright &y& Elsevier]

Abstract: The present study aimed to evaluate whether the protein transduction domain (PTD)-conjugated human tyrosine hydroxylase (TH) fusion protein was effective on the 6-hydroxydopamine (6-OHDA)-induced Parkinson’s disease (PD) model rats. An expression vector pET-PTD-TH harbouring the PTD-TH gene was constructed and transformed to the Escherichia coli BL21 cells for expression. The expressed recombinant PTD-TH with a molecular weight of 61kD was successfully transduced (1μM) into the dopaminergic SH-sy5y human neuroblastoma cells in vitro and visualized by immunohistochemical assay. An in vivo experiment in rats showed that the iv administered PTD-TH protein (8mg/kg) permeated across the blood–brain barrier, penetrated into the striatum and midbrain, and peaked at 5–8h after the injection. The behavioral effects of PTD-TH on the apomorphine-induced rotations in the PD model rats 8weeks after the 6-OHDA lesion showed that a single bolus of PTD-TH (8mg/kg) iv injection caused a decrement of 60% of the contralateral turns on day 1 and 40% on days 5–17. The results imply that iv delivery of PTD-TH is therapeutically effective on the 6-OHDA-induced PD in rats, the PTD-mediated human TH treatment opening a promising therapeutic direction in treatment of PD. [Copyright &y& Elsevier]