Hepatoprotective Potential of Partially Hydrolyzed Guar Gum against Acute Alcohol-Induced Liver Injury in Vitro and Vivo

Natural polysaccharides, particularly galactomannans, are potential candidates for treatment of alcoholic liver diseases (ALD). However, applications are restricted due to the physicochemical properties associated with the high molecular weight. In this work, guar gum galactomannans were partially hydrolyzed by β-mannanase, and the molecular mechanisms of hepatoprotective effects were elucidated both in vitro and in vivo. Release of lactate dehydrogenase and cytochrome C were attenuated by partially hydrolyzed guar gum (PHGG) in HepG2 cells, due to protected cell and mitochondrial membrane integrity. PHGG co-administration decreased serum amino transaminases and cholinesterase levels of acute alcohol intoxicated mice, while hepatic pathologic morphology was depleted. Activity of superoxide dismutase, catalase, and glutathione peroxidase was recovered to 198.2, 34.5, 236.0 U/mg protein, respectively, while malondialdehyde level was decreased by 76.3% (PHGG, 1000 mg/kg∙day). Co-administration of PHGG induced a 4.4-fold increment of p-AMPK expression, and lipid metabolism was mediated. PHGG alleviated toll-like-receptor-4-mediated inflammation via the signaling cascade of MyD88 and IκBα, decreasing cytokine production. Moreover, mediated expression of Bcl-2 and Bax was responsible for inhibited acute alcohol-induced apoptosis with suppressed cleavage of caspase 3 and PARP. Findings gained suggest that PHGG can be used as functional food supplement for the treatment of acute alcohol-induced liver injury

Recent advances in bacterial therapeutics based on sense and response

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation

Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models.

Mouse models are commonly used for studying hepatocellular carcinoma (HCC) biology and exploring new therapeutic interventions. Currently three main modalities of HCC mouse models have been extensively employed in pre-clinical studies including chemically induced, transgenic and transplantation models. Among them, transplantation models are preferred for evaluating in vivo drug efficacy in pre-clinical settings given the short latency, uniformity in size and close resemblance to tumors in patients. However methods used for establishing orthotopic HCC transplantation mouse models are diverse and fragmentized without a comprehensive comparison. Here, we systemically evaluate four different approaches commonly used to establish HCC mice in preclinical studies, including intravenous, intrasplenic, intrahepatic inoculation of tumor cells and intrahepatic tissue implantation. Four parameters--the latency period, take rates, pathological features and metastatic rates--were evaluated side-by-side. 100% take rates were achieved in liver with intrahepatic, intrasplenic inoculation of tumor cells and intrahepatic tissue implantation. In contrast, no tumor in liver was observed with intravenous injection of tumor cells. Intrahepatic tissue implantation resulted in the shortest latency with 0.5 cm (longitudinal diameter) tumors found in liver two weeks after implantation, compared to 0.1cm for intrahepatic inoculation of tumor cells. Approximately 0.1cm tumors were only visible at 4 weeks after intrasplenic inoculation. Uniform, focal and solitary tumors were formed with intrahepatic tissue implantation whereas multinodular, dispersed and non-uniform tumors produced with intrahepatic and intrasplenic inoculation of tumor cells. Notably, metastasis became visible in liver, peritoneum and mesenterium at 3 weeks post-implantation, and lung metastasis was visible after 7 weeks. T cell infiltration was evident in tumors, resembling the situation in HCC patients. Our study demonstrated that orthotopic HCC mouse models established via intrahepatic tissue implantation authentically reflect clinical manifestations in HCC patients pathologically and immunologically, suggesting intrahepatic tissue implantation is a preferable approach for establishing orthotopic HCC mouse models

Correction: Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models.

[This corrects the article DOI: 10.1371/journal.pone.0148263.]

High-performance water purification and desalination by solar-driven interfacial evaporation and photocatalytic VOC decomposition enabled by hierarchical TiO2-CuO nanoarchitecture

Solar-driven interfacial evaporation for clean water generation has drawn significant attention as a promising and environmentally friendly avenue to tackle the global issue of water scarcity. The collected condensate can be free from most pollutants and impurities of diverse undrinkable water sources, such as heavy metals, organic dyes, minerals, and salts. However, when water is contaminated by volatile organic compounds (VOCs), this approach is ineffective because VOCs also evaporate and even can be enriched in the condensate. Here, we demonstrate TiO2-loaded CuO nanowire-covered Cu foam (TiO2-CuO-Cufoam) for efficient solar-driven interfacial evaporation and synchronous removal of VOCs via photocatalytic degradation. The TiO2-CuO-Cufoam nanoarchitecture possesses high solar absorption, quasi-one-dimensional water pathway, super-hydrophilicity for ultrafast water transport, long-term stability, and potential for cost-effective and scalable production for both VOC removal and desalination, meeting World Health Organization potable water standards. Our TiO2-CuO-Cufoam evaporator simultaneously demonstrates high solar evaporation efficiency of 86.6% and efficiency of 80.0% for the removal of VOCs under one sun (i.e., 1 kW m−2). This result may open new opportunities for energy-efficient, clean water generation from real-world water sources using solar energy. Novelty Statement: TiO2-loaded CuO nanowire-covered Cu foam (TiO2-CuO-Cufoam) was obtained through the facile and green synthesis process. The TiO2-CuO-Cufoam nanoarchitecture possesses high solar absorption due to surface nanostructuring, quasi-one-dimensional water pathway for localized thermal management, super-hydrophilicity for ultrafast water transport, TiO2-CuO heterojunction for enhanced photodegradation of VOCs without consumption of chemical reagents, long-term stability, and potential for cost-effective and scalable production. The nanoarchitecture is employed for clean water generation from real-world water sources.</p

Effects of US7 and UL56 on Cell-to-Cell Spread of Human Herpes Simplex Virus 1

Human herpes simplex virus (HSV), a double-stranded DNA virus belonging to the Herpesviridae family and alpha herpesvirus subfamily, is one of the most epidemic pathogens in the population. Cell-to-cell spread is a special intercellular transmission mechanism of HSV that indicates the virulence of this virus. Through numerous studies on mutant HSV strains, many viral and host proteins involved in this process have been identified; however, the mechanisms remain poorly understood. Here, we evaluated the effect of the membrane protein genes US7 and UL56 on cell-to-cell spread in vitro between two HSV-1 (HB94 and HN19) strains using a plaque assay, syncytium formation assay, and the CRISPR/Cas9 technique. US7 knockout resulted in the inhibition of viral cell-to-cell spread; additionally, glycoprotein I (US7) of the HB94 strain was found to promote cell-to-cell spread compared to that of the HN19 strain. UL56 knockout did not affect plaque size and syncytium formation; however, the gene product of UL56 from the HN19 strain inhibited plaque formation and membrane infusion. This study presents preliminary evidence of the functions of US7 and UL56 in the cell-to-cell spread of HSV-1, which will provide important clues to reveal the mechanisms of cell-to-cell spread, and contributes to the clinical drugs development

Anion-kinetics-selective graphene anode and cation-energy-selective MXene cathode for high-performance capacitive deionization

Capacitive deionization (CDI) is one of the most promising energy-efficient technologies for water desalination, however its industrial translation is slow and impeded by limited electrosorption capacity, slow electrosorption rate and poor cycling stability. Herein we address the above challenges by developing and validating a new concept of unimpeded and selective full-cell anion-cation separation using custom-designed anion-kinetics-selective anode and cation-energy-selective cathode. Nanoporous graphene anode enables the selective anion kinetics, while cation selectivity on the functionalized MXene cathode is due to the difference in ion adsorption energy. These mechanisms are validated by electrochemical quartz crystal microbalance measurements. The finely-tuned balance between ion transport and adsorption causes unimpeded ion diffusion, leading to the higher electrosorption rates. These effects are guided by the atomistic and quantum chemistry simulations, and also confirmed experimentally by tuning the pore size of graphene anode and the functionalization of MXene cathode. The fabricated asymmetric CDI cell exhibits superior electrosorption capacity of 49 mg g−1 and high electrosorption rate of 2.92 mg g−1 min−1 in 5000 mg L−1 NaCl solution as well as excellent cycling stability (100 cycles), which are among the best of the current state-of-the-art CDI studies. These results demonstrate the design of advanced electrode materials for the effective control of ion kinetics and energies to achieve selective ion transport, thus providing new insights for a broader range of energy-related applications.</p

Nanoconfined fusion of g-C3N4 within edge-rich vertically oriented graphene hierarchical networks for high-performance photocatalytic hydrogen evolution utilizing superhydrophillic and superaerophobic responses in seawater

Two-dimensional photocatalysts often suffer severe aggregation due to the inevitable van der Waals forces between nanosheets, which limits their photocatalytic water-splitting efficiency. Herein, a rational design of confined synthesis of g-C3N4 nanomeshes (GCN) on N-doped vertically-oriented graphene (NVG) arrays for enhanced hydrogen evolution is reported. The aggregation of 2D g-C3N4 nanosheets is effectively avoided via physical separation by electrically conductive NVG networks. Well-defined hierarchical architecture of the GCN/NVG photocatalyst endows with superaerophobicity and simultaneously enhanced light absorption. Experimental and ab initio simulation results suggest that the protruding graphene edges induce charge redistribution, thus enhancing interfacial charge separation. The GCN/NVG samples demonstrate a high areal hydrogen evolution rate of 41.7 μmol h−1 cm−2 (225 L m−2 in 24 h, STP) in water and 45.8 μmol h−1 cm−2 (246.2 L m−2 in 24 h, STP) in simulated seawater. This work creates further opportunities for the development of earth-abundant photocatalysts.</p